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The Psychological & Neuroscientific musings of sndygautam.
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- March 20, 2009
- 04:23 PM
- 1,627 views
SES and the developing brain
by sandygautam in The Mouse Trap
I have written about poverty/SES and its effects on brain development/IQ earlier too,and this new review article by Farah and Hackman in TICS is a very good introduction to anyone interested in the issue.
The article reviews the behavioral studies that show that SES is correlated with at least the two brain systems of executive function and language abilities.It also review physiological data that shows that even when behavioral outcomes do not differ ERP can show differential activation in the brains of people with low and middle SES , thus suggesting that differences that may not be detected on behavioral measures may still exist. They also review (f)MRI data that shows no structural differences in the brains of low and middle SES children, but definite functional differences.they also review experimental manipulation of social status in labarotaories, and show how those studies also indicate that SES and executive function are correlated.
They then turn to the million dollar question of the direction of causality and for this infer indirectly based on the SES-IQ causal linkages.
What is the cause of SES differences in brain function? Is it contextual priming? Is it social causation, reflecting the influence of SES on brain development? Alternatively, is it social selection, in which abilities inherited from parents lead to lower SES? Current research on SES and brain development is not designed to answer this question. However, research on SES and IQ is relevant and supports a substantial role of SES and its correlated experience as causal factors.
Slightly less than half of the SES-related IQ variability in adopted children is attributable to the SES of the adoptive family rather than the biological. This might underestimate environmental influences because the effects of prenatal and early postnatal environment are included in the estimates of genetic influence. Additional evidence comes from studies of when poverty was experienced in a child's life. Early poverty is a better predictor of later cognitive achievement than poverty in middle- or late-childhood, an effect that is difficult to explain by genetics. SES modifies the heritability of IQ, such that in the highest SES families, genes account for most of the variance in IQ because environmental influences are in effect at ceiling in this group, whereas in the lowest SES families, variance in IQ is overwhelmingly dominated by environmental influences because these are in effect the limiting factor in this group. In addition, a growing body of research indicates that cognitive performance is modified by epigenetic mechanisms, indicating that experience has a strong influence on gene expression and resultant phenotypic cognitive traits . Lastly, considerable evidence of brain plasticity in response to experience throughout development indicates that SES influences on brain development are plausible.
Differences in the quality and quantity of schooling is one plausible mechanism that has been proposed. However, many of the SES differences summarized in this article are present in young children with little or no experience of school , so differences in formal education cannot, on their own, account for all of the variance in cognition and brain development attributable to SES. The situation is analogous to that of SES disparities in health, which are only partly explained by differential access to medical services and for which other psychosocial mechanisms are important causal factors .
The last point is really important and can be extended. Access to health services for low SES people may be a reason why , for eg, more schizophrenia incidence is found in low SES neighbourhoods. which brings us to the same chicken-and-egg question of the drift theory of schizophrenia- whether people with schizophrenia drift into low SES or low SES is a risk factor in itself. Exactly this point was brought to my attention when I was interacting with a few budding psychiatrists recently, this Martha Farah theory about the SES leading to lower IQ/ cognitive abilities. It is important to acknowledge that low SES not only leads to left hypo-frontality (another symptom of schizophrenia), schizophrenia is supposed to be due to lessened mylienation and again nutritional factors may have a role to play; also access to health care, exposure to chronic stress and lesser subjective feelings of control may all be mediating afctors that lead low SS to lead to schizophrenia/ psychosis.Also remember that schizophrenia is sort of a devlopmenetal disorder.
Well, I digressed a bit, but the idea is that not only does low SES affect 'normal' cognitive abilities, it may even increase the risk for 'abnormal' cognitive abilities that may lead to psychosis, and his effect of SES on IQ/cognitive abilities/ risk of mental diseases is mediated by the effect of SES on the developing brain. I have already covered the putative mechanisms by which SES may affect brain development, but just to recap, here I quote from the paper:
Candidate causal pathways from environmental differences to differences in brain development include lead exposure, cognitive stimulation, nutrition, parenting styles and transient or chronic hierarchy effects. One particularly promising area for investigation is the effect of chronic stress. Lower-SES is associated with higher levels of stress in addition to changes in the function of physiological stress response systems in children and adults. Changes in such systems are likely candidates to mediate SES effects as they impact both cognitive performance and brain regions, such as the prefrontal cortex and hippocampus, in which there are SES differences.
We can only hope that the evil of low SES is recognized as soon as possible and if for nothing else, than for advancing science, some intervention studies are done that manipulate the SES variables in the right direction and thus ensure that the full cognitive potential of the children flowers.
HACKMAN, D., & FARAH, M. (2009). Socioeconomic status and the developing brain Trends in Cognitive Sciences, 13 (2), 65-73 DOI: 10.1016/j.tics.2008.11.003... Read more »
HACKMAN, D., & FARAH, M. (2009) Socioeconomic status and the developing brain. Trends in Cognitive Sciences, 13(2), 65-73. DOI: 10.1016/j.tics.2008.11.003
- October 22, 2008
- 05:48 AM
- 1,560 views
IQ and Religion: is the relation mediated by wealth and feelings of control?
by sandygautam in The Mouse Trap
Last week, on the blog action day, I re posted one of my earlier posts that questioned Kanazawa's assertion that IQ causes Longevity (and implicitly that low IQ causes Poverty and not the other way round) and that SES has no effect on longevity net of IQ. That has been thoroughly dealt with earlier and I will not readdress the issue; suffice it to say that I believe (and think that I have evidence on my side) that shows that in low SES conditions, a Low SES does not lead to full flowering of genetic Intelligence potential and is thus a leading cause of low IQ amongst low SES populations. This Low IQ that is a result of Low SES also gets correlated to longevity; again which would be largely explained by the low SES of the person. But as Low SES leads to less longevity and less IQ , a correlation between IQ and Longevity would also be expected. A similar issue has cropped up , this time with respect to religion or belief in God. It has been claimed that high IQ causes atheism and that low IQ leads to superstition and belief in God. The result, this time by Lynn's team is again correlational in nature and just like Kanazawa's study partially relies on Macro-data i.e. mean IQ of a country and its mean religious belief scores.The abstract of the paper goes like:Evidence is reviewed pointing to a negative relationship between intelligence and religious belief in the United States and Europe. It is shown that intelligence measured as psychometric g is negatively related to religious belief. We also examine whether this negative relationship between intelligence and religious belief is present between nations. We find that in a sample of 137 countries the correlation between national IQ and disbelief in God is 0.60.Now, BHA science group , has written a very good rebuttal to this proposition and I urge readers to go and read the discussion there in full. For the sake of completeness, let me summarize the case against the hypothesis that high IQ causes atheism.Problems with the macro data on which this analysis is made: for countries that have about 100 (average) mean IQ, the correlation does not hold. The correlation is mainly an artifact of the fact that low mean IQ countries also have high religious belief (see accompanying figure) . We can, in my opinion, thus restrict the discussion to low (mean) IQ countries and try to explain whether its the Low mean IQ of their people that causes religiosity; or that high religiosity somehow leads to low IQ (a very counter-intuitive though indeed); or more plausibly that some other factor like SES/ feelings of control may be the underlying reason for both low IQ and high religiosity. Now, I have shown elsewhere that low SES causes low IQ and not the other way round; what remains to be shown is that low SES also causes religious faith. The latter part I'll like to break in two parts: first , I believe that it is intuitive and there would be wealth of data showing that poverty or Low SES leads to fellings of helplessness or feelings of loss of control. Thus , the first assertion is that low mean SES in these countries, leads to the average person feeling less in control of his/her life and thus to feelings of loss of control.The second part of the argument is that low feelings of control lead to religiosity/ superstition. Again I too have touched this before, but would right now like to point to this recent study that found that feelings of loss of control, lead to magical thinking/ superstitious belief and by extension (I am indeed taking a leap here) propensity towards religiosity. Of course we all know that religion is the opium of the masses (which are usaully poor) and rightly subdues the pwoerlessness and lack of control feelings that are otherwise unbearable. Thus, I rest my case, claiming that it is the low SES that leads to low IQ and high religious beliefs; the effect being mediated by nutritional/ enriched environmental factors in the former (IQ) case, while that of religion being mediated by feelings of control in the latter case. The actual correlation observed between IQ and religious faith , on the basis of low SES data , is at best spurious and due to the underlying low SES effects. Richard Lynn, John Harvey, Helmuth Nyborg (2008). Average Intelligence Predicts Atheism Rates across 137 Nations IntelligenceJ. A. Whitson, A. D. Galinsky (2008). Lacking Control Increases Illusory Pattern Perception Science, 322 (5898), 115-117 DOI: 10.1126/science.1159845... Read more »
Richard Lynn, John Harvey, Helmuth Nyborg. (2008) Average Intelligence Predicts Atheism Rates across 137 Nations. Intelligence.
J. A. Whitson, & A. D. Galinsky. (2008) Lacking Control Increases Illusory Pattern Perception. Science, 322(5898), 115-117. DOI: 10.1126/science.1159845
- March 9, 2009
- 11:03 PM
- 1,483 views
The factor structure of Religiosity and its neural substrates
by sandygautam in The Mouse Trap
A new article in PNAS by Grafman et al, argues that Religiosity can be broken down into three factors and the underlying machinery that these factors use are basic Theory Of Mind (ToM) circuitry, thus substantiating the claim that religion occurred as a byproduct of basic ToM related adaptations, although not ruling out that once established Religion may have provided adaptive advantage.
First a detour. I am more interested in this study as I had once claimed that Schizophrenics were more religious than Autistics and I have been maintaining that Religion is just one aspect of an underlying hyper-mentalizing to hyper-physicalism continuum on which these two spectrum disorders lie on opposite ends. The case for less ToM abilities in ASD seems to be fairly settled; its also becoming apparent that in Schizophrenia spectrum disorders you have excess of ToM abilities; This study by showing the ToM to Religion linkage, fills in the gaps and another puzzle piece falls in place.
On to the study. The authors first show that Religious Belief can be split into three factors. they use a novel (to me) technique of Multi Dimensional Scaling (MDS) to tease out the factors associated with religious belief. I have not checked how MDS works, but I assume it is similar to Factor analysis and can give us reliable factor structure underlying the data. They build on previous research and discovered the following three factors:
God’s perceived level of involvement,
God’s perceived emotion, and
religious knowledge source.
The first factor refers to endowing intentionality to superantural agents like God; the second factor refers to endowing emotions to God an dthe thierd factor refers to the source of the religious beliefs- whether it is doctrinal or derived from experience. Thus the trinity of intention, emotion and belief - alos the trinity involved in ToM tasks. The authors do a good job of describing the factors, so I'll let them do it.
Dimension 1 (D1) correlated negatively with God’s perceived level of involvement (–0.994), Dimension 2 (D2) correlated negatively with God’s perceived anger (–0.953) and positively with God’s perceived love (0.953), and Dimension 3 (D3) correlated positively with doctrinal (0.993) and negatively with experiential (–0.993) religious content. D1 represents a quantitative gradient of a single concept and we will be referring to it as ‘‘God’s perceived level of involvement.’’ D2 and D3 represent gradients of contrasting concepts; we will be referring to them as ‘‘God’s perceived emotion’’ (D2) and ‘‘religious knowledge source’’ (D3).
God’s perceived level of involvement (D1) organizes statements so that ‘‘God is removed from the world’’ or ‘‘Life has no higher purpose’’ have high positive coordinate values, while ‘‘God’s will guides my acts,’’ ‘‘God protects one’s life,’’ or ‘‘God is punishing’’ have high negative values. Generally speaking, on the positive end of the gradient lie statements implying the existence of uninvolved supernatural agents, and on the negative end lie statements implying involved supernatural agents.
God’s perceived emotion (D2) ranges from love to anger and organizes statements so that ‘‘God is forgiving’’ and ‘‘God protects all people’’ have high positive-coordinate values, while ‘‘God is wrathful’’ and ‘‘The afterlife will be punishing’’ have high negative values. Generally speaking, on the positive end of the gradient lie statements implying the existence of a loving (and potentially rewarding) supernatural agent, and on the negative end lie statements suggestive of wrathful (and potentially punishing) supernatural agent.
Religious knowledge (D3) ranges from doctrinal to experiential and organizes statements so that ‘‘God is ever-present’’ and ‘‘A source of creation exists’’ have high positive-coordinate values, while ‘‘Religion is directly involved in worldly affairs’’ and ‘‘Religion provides moral guiding’’ have high negative values. Generally speaking, on the positive end of the gradient lies theological content referring to abstract religious concepts, and on the negative end lies theological content with moral, social, or practical implications.
This breakup of religiosity into three factors is itself commendable, but then they go on to show, using fMRI data that these factors activate areas of brain associated with ToM abilities. I don't really understand all their fMRI data, but the results seem interesting. Here is what they conclude:
The MDS results confirmed the validity of the proposed psychological structure of religious belief. The 2 psychological processes previously implicated in religious belief, assessment of God’s level of involvement and God’s level of anger (11), as well as the hypothesized doctrinal to experiential continuum for religious nowledge, were identifiable dimensions in our MDS analysis. In addition, the neural correlates of these psychological dimensions were revealed to be well-known brain networks, mediating evolutionary adaptive cognitive functions.
This study defines a psychological and neuroanatomical framework for the (predominately explicit) processing of religious belief. Within this framework, religious belief engages well-known brain networks performing abstract semantic processing, imagery, and intent-related and emotional ToM, processes known to occur at both implicit and explicit levels (36, 39, 50). Moreover, the process of adopting religious beliefs depends on cognitive-emotional interactions within the anterior insulae, particularly among religious subjects. The findings support the view that religiosity is integrated in cognitive processes and brain networks used in social cognition, rather than being sui generis (2–4). The evolution of these networks was likely driven by their primary roles in social cognition, language, and logical reasoning (1, 3, 4, 51). Religious cognition likely emerged as a unique combination of these several evolutionarily important cognitive processes (52). Measurable individual differences in these core competencies (ToM, imagination, and so forth) may predict specific patterns of brain activation in response to religious stimuli.
As always I am excited and would like to see some field work being carried out to determine religiosity in ASD and Schizophrenia spectrum groups and see if we get the same results (less religiosity in autism and more religiosity in schizophrenics) as predicted, based on their baseline ToM abilities.
PS: I was not able to use the DOI lookup fetaure of Research Blogging, but the DOI of article is 10.1073/pnas.0811717106
* Dimitrios Kapogiannis,, * Aron K. Barbey,, * Michael Su,, * Giovanna Zamboni,, * Frank Krueger,, * and Jordan Grafman (2009). Cognitive and neural foundations of religious belief PNAS... Read more »
* Dimitrios Kapogiannis,, * Aron K. Barbey,, * Michael Su,, * Giovanna Zamboni,, * Frank Krueger,, & * and Jordan Grafman. (2009) Cognitive and neural foundations of religious belief. PNAS. DOI: http://www.pnas.org/content/early/2009/03/06/0811717106.abstract?sid
- February 17, 2009
- 01:54 AM
- 1,383 views
Support for the Aberrant Salience hypothesis of Psychosis
by sandygautam in The Mouse Trap
Last week I wrote about the aberrant salience theory of psychosis, and luckily, this week itself a new study has surfaced that corroborates that theory with some preliminary evidence.
Thanks to BPS research digest, I have come across this open source research article in Psychological Medicine, that has found evidence for the aberrant salience hypothesis.
What Rosier et al did was to administer a Salience Attribution Test to both patients with Schizophrenia and normal controls, and to look for differences in the adaptive and aberrant salience. It is important to realize that most of the patients were medicated on anti-psychotics, and as per the theory advocated by Shitij Kapur, the anti-psychotics would dampen the normal adaptive salience too as psychosis is due to hyper reactivity of dopamine system and anti-psychotics are supposed to work by attenuating that behavior. More specifically, the predictions were:
It has been hypothesized that dopamine antagonists reduce both adaptive and aberrant salience, and that in the absence of effective treatment patients with schizophrenia exhibit aberrant salience (Kapur, 2003). Therefore, our first prediction was that that medicated patients with schizophrenia would exhibit reduced adaptive salience relative to controls, representing an undesirable side-effect of anti-psychotic medication. Our second prediction was that medicated patients with schizophrenia would exhibit equivalent aberrant salience to controls, representing the beneficial effect of anti-psychotic medication, which is hypothesized to normalize aberrant salience from a previously elevated level (Kapur, 2003). Our third prediction was that those patients with persistent positive symptoms, in whom medication is not entirely effective, would exhibit greater aberrant salience than patients without positive symptoms. Our fourth prediction was that in the controls, individual differences in aberrant salience would be related to the personality trait of schizotypy, considered to be an index of psychosis proneness (Chapman et al. 1994; Claridge, 1994; Stefanis et al. 2004).
All of their predictions were supported by the test results. The SAT paradigm is really simple and depends on reaction time measures following CS+ and CS-; with CS+ reaction times quantifying adaptive salience and CS- reaction times quantifying aberrant salience attribution. Read the methods section for more on the SAT.
Interestingly in patients, those with persisting delusions as well as those high on Negative symptoms exhibited higher aberrant salience as compared to patients/ controls without any delusional symptoms.Also, in controls the introverted anhedonia subscale of schizotypy correlated signficantly with the aberrant salience, thus indicating a role for negative symptom formation/ explanation too as apart of the aberrant salience. This is how the authors interpret their findings:
Aberrant salience and positive symptoms of schizophrenia
One explanation of increased aberrant salience in patients with positive symptoms concerns aberrant dopamine signalling. Contemporary accounts of reward learning suggest that phasic dopamine firing codes reward prediction errors (Schultz et al. 1997), for example, those arising from temporal difference models of reinforcement learning (Dayan & Balleine, 2002). Such models elegantly account for changes in both the firing patterns of ventral tegmental area dopamine neurons in monkeys (Schultz, 1997), and ventral striatal responses in humans (Pessiglione et al. 2006; Seymour et al. 2007), as reward-learning progresses. If phasic dopamine release signals reinforcement prediction errors, any large stochastic fluctuation in dopamine release may disrupt learning about stimulus–reinforcement associations, generating a state in which motivational salience could be misattributed to neutral stimuli, or what might be termed a ‘false-positive’ phasic dopamine signal; such events have been proposed to result in positive symptoms (Kapur, 2003).
In the present study, patients for whom medication had effectively eliminated positive symptoms actually exhibited significantly less aberrant salience than controls, supporting the hypothesis that the beneficial effects of antipsychotic medications on positive symptoms are related to their ability to dampen-down aberrant salience (Kapur, 2003). However, independent of symptoms at the time of testing, the patients with schizophrenia exhibited significantly less adaptive salience than controls. Antipsychotic medication has long been considered to exacerbate negative symptoms in schizophrenia, which may be related to reduced adaptive salience [see discussion below and Schooler (1994) ]. Our findings support the suggestion of Kapur (2003) that this may be a necessary corollary to the beneficial effect of antipsychotic medication on positive symptoms.
Previous studies suggest that antipsychotic medication does not necessarily normalize abnormal dopamine signalling in psychotic patients. For example, functional neuroimaging studies have shown dopamine dysregulation in both medicated and unmedicated patients (Hietala et al. 1995; Abi-Dargham, 2004; McGowan et al. 2004). Therefore persistent symptoms in medicated patients might still be related to aberrant salience. Furthermore, the only other study investigating stimulus–reinforcement learning for appetitive outcomes in psychosis found that both medicated and unmedicated patients responded more quickly to a CS− than controls, a finding interpreted as aberrant salience (Murray et al. 2008). This study also reported that patients exhibited reduced haemodynamic correlates of reward prediction errors in the ventral striatum relative to controls, consistent with other findings in medicated patients (Juckel et al. 2006; Jensen et al. 2008). Nevertheless it will be important to confirm our findings in unmedicated patients.
Aberrant salience and negative symptoms of schizophrenia
Although positive symptoms were associated with increased aberrant salience, our data also suggest a link between aberrant salience and negative symptoms. Aberrant salience correlated not only with negative symptoms in the patients, but also with O-LIFE introvertive anhedonia, which relates to reduced interest and social withdrawal, in the controls. If dopamine transmission is dysregulated in psychosis (Abi-Dargham, 2004), it is possible that ‘false negatives’ in the phasic dopamine signal might occur, i.e. a reinforcement-related stimulus fails to elicit a sufficiently large phasic dopamine response. False negatives would decrease the value of motivationally salient stimuli, possibly leading to symptoms such as avolition, apathy and social withdrawal. Consistent with this explanation, other studies that investigated responses to emotionally salient images in medicated patients with schizophrenia reported decreased responding for (Heerey & Gold, 2007) and ventral striatal responses to (Taylor et al. 2005) positive emotional stimuli relative to controls.
This explanation is also consistent with data from a functional magnetic resonance imaging study investigating the effects of d-amphetamine on reward processing in healthy volunteers. Knutson et al. (2004) found that amphetamine administration paradoxically decreased the magnitude of phasic ventral striatal haemodynamic responses in response to a CS+ that signalled reward (i.e. increasing the potential for a false negative). In the same study, amphetamine administration caused significant phasic haemodynamic responses in the ventral striatum following CS+ that signalled potential monetary loss, an effect that was absent under placebo, possibly reflecting a loss of specificity of dopamine signalling (i.e. increasing the potential for a false positive). The aberrant salience model might therefore explain both positive and negative symptoms by appealing to a common neurobiological mechanism, namely a loss of signal:noise ratio in the mesolimbic dopamine system, possibly as a result of increased tonic dopamine activity (Grace, 1991; Winterer & Weinberger, 2004).I believe they are on to something, but the explanation for negative symptoms is still not fully fleshed out or convincing. and of course one has to remember that these results are juts with 20 patients so need to be replicated before being put to use/ accepted as orthodoxy.
J. P. Roiser, K. E. Stephan, H. E. M. den Ouden, T. R. E. Barnes, K. J. Friston, E. M. Joyce (2008). Do patients with schizophrenia exhibit aberrant salience? Psychological Medicine, 39 (02) DOI: 10.1017/S0033291708003863... Read more »
J. P. Roiser, K. E. Stephan, H. E. M. den Ouden, T. R. E. Barnes, K. J. Friston, & E. M. Joyce. (2008) Do patients with schizophrenia exhibit aberrant salience?. Psychological Medicine, 39(02), 199. DOI: 10.1017/S0033291708003863
- December 9, 2008
- 12:00 AM
- 1,334 views
Novelty Seeking and Reward Dependence: the dopamine white matter connection.
by Sandeep Gautam in The Mouse Trap
Discusses new research that links personality traits to white matter connectivity.... Read more »
Michael X Cohen, Jan-Christoph Schoene-Bake, Christian E Elger, & Bernd Weber. (2008) Connectivity-based segregation of the human striatum predicts personality characteristics. Nature Neuroscience. DOI: 10.1038/nn.2228
- March 22, 2009
- 08:23 AM
- 1,289 views
Self relevance and the reality-fictional blur
by sandygautam in The Mouse Trap
There is a new study in PLOS One that argues that we make reality-fictional distinction on the basis of how personally relevant the event in question is. To be fair, the study focuses on fictional, famous or familiar (friends and family) entities like Cinderella, Obama or our mother and based on the fact that these are arranged in increasing order of personal relevance, as well as represent fictional and real characters, tries to show that one of the means by which we try to distinguish fictional from real characters is by the degree of personal relevance these characters are able to invoke in us.
The authors build upon their previous work that showed that amPFC(anterior medial prefrontal cortex) and PCC (Posterior Cingulate cortex), which are part of the default brain network, are differentially recruited when people are exposed to contexts involving real as opposed to fictional entities. From this neural correlate of the regions involved in distinguishing fiction from reality, and from the known functions of these brain regions in self-referential thinking and autobiographical memory retrieval, the authors hypothesized that the reality-fictional distinction may be mediated by the relevance to self and this difference in self-relevance leads to differential engagement of these brain areas. I quote form the paper:
In the first attempt to tackle this issue using functional magnetic resonance imaging (fMRI), we aimed to uncover which brain regions were preferentially engaged when processing either real or fictional scenarios . The findings demonstrated that processing contexts containing real people (e.g., George Bush) compared to contexts containing fictional characters (e.g., Cinderella) led to activations in the anterior medial prefrontal cortex (amPFC) and the posterior cingulate cortex (PCC).
These findings were intriguing for two reasons. First, the identified brain areas have been previously implicated in self-referential thinking and autobiographical memory retrieval. This suggested that information about real people, in contrast to fictional characters, may be coded in a manner that leads to the triggering of automatic self-referential and autobiographical processing. This led to the hypothesis that information about real people may be coded in more personally relevant terms than that of fictional characters. We do, after all, occupy a common social world and have a wider range of associations in relation to famous people. These may be spontaneously triggered and processed further when reading about them. A logical extension of this premise would be that explicitly self-relevant information should therefore elicit such processing to an even greater extent.
To study the above hypothesis they used an experimental study that used behavioral measures like reaction time, correctness and perceived difficulty of judging propositions involving fictional, famous and close entities. Meanwhile they also measured , using fMRI, the differential recruitment of brain areas as the subjects performed under the different entity conditions. The experimental design is best summarized by having a look at the below figure.
What they found was that for the control condition and the fictional condition the reaction time , correctness and perceived difficulty associated with the proposition was signifciantkly different (lower RT, lower correctness and more perceived difficulty) than for the famous and friend entities condition. Thus, from the behavioral data is was apparent that real characters were judged faster , accurately and more easily than fictional characters. The FMRI data showed that , as hypothesiszed, amPFC and PCC were recruited significantly more in personal relevance contexts and showed a gradient in the expected direction. The below figure should summariz the findings:
In particular, in line with our predictions, regions in and near the amPFC (including the ventral mPFC) and PCC (including the retrosplenial cortex) were modulated by the degree of personal relevance associated with the presented entities. These regions were most strongly engaged when processing high personal relevance contexts (friend-real), secondarily for medium relevance contexts (famous-real) and least of all in the low personal relevance contexts (fiction) (high relevance>medium relevance>low relevance).The amPFC and PCC regions are known to be commonly engaged during autobiographical and episodic memory retrieval as well as during self-referential processing. Regarding their specific roles, there is evidence indicating that amPFC is comparatively more selective for self-referential processing whereas the PCC/RSC is more selective for episodic memory retrieval . The results of the present study contribute to the understanding of processes implemented in these regions by showing that the demands on autobiographical retrieval processes and self-referential mentation are affected by the degree of personal relevance associated with a processed scenario. It should additionally be noted that the extension of the activations in anterior and ventral PFC regions into subgenual cingulate areas indicates that the degree of personal relevance also modulated responsiveness in affective or emotional regions of the brain .
Here is what the authors have to say about the wider ramifications:
That core regions of the brain's default network are spontaneously modulated by the degree of stimulus-associated personal relevance is a consequential finding for two reasons. Firstly, the findings suggest that one of the factors that guide our implicit knowledge of what is real and unreal is the degree of coded personal relevance associated with a particular entity/character representation.....What this might translate to at a phenomenological level is that a real person feels more “real” to us than a fictional character because we automatically have access to far more comprehensive and multi-flavored conceptual knowledge in relation to the real people than fictional characters. This would also explain why a real person we know personally (a friend) feels more real to us than a real person who we do not know personally (George Bush).
I would say that there are other broader implications. First it is important to note that phenomenologically, Schizophrenia/psychosis is charachterized by an inability to distinguish reality from fiction. What is fictious also starts seeming real. A putative mechanism of why even fictional things start assuming 'real' dimensions may be the attribution of personal relevance or significance to those fictional entities. If something, even though fictional in nature, become highly personally relevant, then it would be easier to treat it as real. What ties things together is the fact that the default brain network is indeed overactive in the schizophrenics. If the PCC and amPFC are hyperactive, no wonder even fictional entities would be attributed personal relevance and incorporated into reality. I had earlier too discussed the delusions of reference with respect to default network hyperactivity in shizophrenics and this can be easily extended to now account for the loss of contact with reality , with the relevance and reality linkage in place. when everything is self relevant everything is real.
As always I am excited and would like some experiments done with schizophrnics/scizotypals using the same experimental paradigm and finding whether there is significant differences in the behavioral measures between controls and subjects and whether that is mediated by differential engagement of the default brain network. In autistics of course I hypothesize the opposite effects.
Needless to say I am grateful to Neuronarrative for reporting on this and helping me make one more puzzle piece fit in place.
Abraham, A., & von Cramon, D. (2009). Reality = Relevance? Insights from Spontaneous Modulations of the Brain's Default Network when Telling Apart Reality from Fiction PLoS ONE, 4 (3) DOI: 10.1371/journal.pone.0004741... Read more »
Abraham, A., & von Cramon, D. (2009) Reality . PLoS ONE, 4(3). DOI: 10.1371/journal.pone.0004741
- October 22, 2008
- 07:44 AM
- 1,277 views
Autism and Schizophrenia: a minicolumnar deficit?
by sandygautam in The Mouse Trap
It has been my long standing thesis that Autism and Schizophrenia are opposite poles on a continuum; and the most recent evidence I would like to allude to is the mini columnar structure and abnormalities associetd with it in both the diseases. Let me at the outset, say that I am not an expert on mini-columns and hardly understand them, so would be glad if somebody corrected me or pointed out errors in the analysis.First let me report on Schizophrenia from an abstract of a paper titled Mean cell spacing abnormalities in the neocortex of patients with schizophrenia by M Casanova et alIt has been postulated that the prefrontal cortices of schizophrenic patients have significant alterations in their interneuronal (neuropil) space. The present study re-examines this finding based on measurements of mean cell spacing within the cell minicolumn. The population studied consisted of 13 male schizophrenic patients (DSM-IV criteria) and 13 age-matched controls. Photomicrographs of Brodmann's areas 9, 4 (M1), 3b (S1), and 17 (V1) were analyzed with computerized image analysis to measure parameters of minicolumnar morphometry, i.e., columnarity index (CI), minicolumnar width (CW), dispersion of minicolumnar width (VCW), and mean interneuronal distance (MCS). The results indicate alterations in the mean cell spacing of schizophrenic patients according to both the lamina and cortical area examined. The lack of variation in the columnarity index argues in favor of a defect postdating the formation of the cell minicolumn.To simplify the terms, I assume that CI relates to number of minicolumns in the neocortical broadmann area under consideration; CW is generally refered to as the width of the minicolumns i.e how big a particular minicolumn is , VCW I presume is related to how widely are the minicolumns themselves spaced from each other ie. the distance between two mini-columns and the last MCS is related to how densely neurons are packed within a mini-column.Now for Schizophrenia, what I could find on the net, seems to suggest that they have reduced MCS as compared to controls i.e the neurons of schizophrenics are more densely packed within a mini-column as compared to controls . Also, it was found that the density was greatest in core region and lesser so in the outer neuropil region of the mini-column.An opposite pattern is observed in Autism. Here is the abstract of article titled: Disruption in the inhibitory architecture of the cell minicolumn: implications for Autisim. by M Casanova et al again: The modular arrangement of the neocortex is based on the cell minicolumn: a self-contained ecosystem of neurons and their afferent, efferent, and interneuronal connections. The authors' preliminary studies indicate that minicolumns in the brains of autistic patients are narrower, with an altered internal organization. More specifically, their minicolumns reveal less peripheral neuropil space and increased spacing among their constituent cells. The peripheral neuropil space of the minicolumn is the conduit, among other things, for inhibitory local circuit projections. A defect in these GABAergic fibers may correlate with the increased prevalence of seizures among autistic patients. This article expands on our initial findings by arguing for the specificity of GABAergic inhibition in the neocortex as being focused around its mini- and macrocolumnar organization. The authors conclude that GABAergic interneurons are vital to proper minicolumnar differentiation and signal processing (e.g., filtering capacity of the neocortex), thus providing a putative correlate to autistic symptomatology.Now the above clearly shows that the Autistics have an increased interneuronal space in mini-columns as opposed to normals and thus have lesser density of neurons within a minicolumn. However, they have more number of minicolumns to make up for this so that overall the number of neurons in the Broadmann area remains the same or the overall neuronal density does not differ. We can extend the results in other directions and hypothesize that 1) Autistics will have increased no. of mini-columns, narrower mini-columns, narrowly spaced minicolumns and decreased neuronal density within a mini0-column as compared to controls.2) Scchizophrenics will have lesser no. of minicolumns, wider mini-columns, widely spaced minicolumns and increased neuronal density within a mini-column as compared to controls.Some of the above hypothesis is already supported and the rest may be in press/ under lab trials. What this means for in cognitive terms and how this translates to autistic and schizophrenic behaviour is another issue that I may address later (once I understand more of this minicolumn stuff!!)D Buxhoeveden (2000). Reduced interneuronal space in schizophrenia Biological Psychiatry, 47 (7), 681-682 DOI: 10.1016/S0006-3223(99)00275-9M CASANOVA, L DEZEEUW, A SWITALA, P KRECZMANSKI, H KORR, N ULFIG, H HEINSEN, H STEINBUSCH, C SCHMITZ (2005). Mean cell spacing abnormalities in the neocortex of patients with schizophrenia Psychiatry Research, 133 (1), 1-12 DOI: 10.1016/j.psychres.2004.11.004Manuel F. Casanova, Daniel Buxhoeveden, Juan Gomez (2003). Disruption in the Inhibitory Architecture of the Cell Minicolumn: Implications for Autisim The Neuroscientist, 9 (6), 496-507 DOI: 10.1177/1073858403253552... Read more »
D Buxhoeveden. (2000) Reduced interneuronal space in schizophrenia. Biological Psychiatry, 47(7), 681-682. DOI: 10.1016/S0006-3223(99)00275-9
M CASANOVA, L DEZEEUW, A SWITALA, P KRECZMANSKI, H KORR, N ULFIG, H HEINSEN, H STEINBUSCH, & C SCHMITZ. (2005) Mean cell spacing abnormalities in the neocortex of patients with schizophrenia. Psychiatry Research, 133(1), 1-12. DOI: 10.1016/j.psychres.2004.11.004
Manuel F. Casanova, Daniel Buxhoeveden, & Juan Gomez. (2003) Disruption in the Inhibitory Architecture of the Cell Minicolumn: Implications for Autisim. The Neuroscientist, 9(6), 496-507. DOI: 10.1177/1073858403253552
- May 6, 2009
- 07:11 AM
- 1,260 views
Low Latent Inhibition, high faith in intuition and psychosis/creativity
by sandygautam in The Mouse Trap
Well, the cluster goes together. Previous research has found that Low LI and psychosis (schizophrenia) and creativity are related; previous research has also found that psychotic /some types of creative people have more faith in intuition; and this research ties things by showing that Low LI and high faith in intuition are correlated.
The research under question is by Kaufman and in it he explores the dual-process theories of cognition- the popular slow high road of deliberate conscious reasoning and the fast low road of unconscious processing. I would rather have the high road consist of both cognitive and affective factors and similarly the unconscious low road consist of both cognitive and affective factors. Kaufman focuses on the unconscious low road and his factor analysis reveal three factors: Faith in intuition: a meta cognition about ones tendency to use intuition; Holistic intuition: the cognitive factor; and affective intuition: the affective factor. with this in mind let us see what Kaufman's thesis is:
He first introduces the low road and the high road:
In recent years, dual-process theories of cognition have become increasingly popular in explaining cognitive, personality, and social processes (Evans & Frankish, 2009). Although individual differences in the controlled, deliberate, reflective processes that underlay System 2 are strongly related to psychometric intelligence (Spearman, 1904) and working memory (Conway, Jarrold, Kane, Miyake, & Towse, 2007), few research studies have investigated individual differences in the automatic, associative, nonconscious processes that underlay System 1. Creativity and intelligence researchers might benefit from taking into account dual-process theories of cognition in their models and research, especially when exploring individual differences in nonconscious cognitive processes.
Then he explain LI:
Here I present new data, using a measure of implicit processing called latent inhibition (LI; Lubow, Ingberg-Sachs, Zalstein-Orda, & Gewirtz, 1992). LI reflects the brain’s capacity to screen from current attentional focus stimuli previously tagged as irrelevant (Lubow, 1989). LI is often characterized as a preconscious gating mechanism that automatically inhibits stimuli that have been previously experienced as irrelevant from entering awareness, and those with increased LI show higher levels of this form of inhibition (Peterson, Smith, & Carson, 2002). Variation in LI has been documented across a variety of mammalian species and, at least in other animals, has a known biological basis (Lubow & Gerwirtz, 1995). LI is surely important in people’s everyday lives—if people had to consciously decide at all times what stimuli to ignore, they would quickly become overstimulated.
Indeed, prior research has documented an association between decreased LI and acute-phase schizophrenia (Baruch, Hemsley, & Gray, 1988a, 1988b; Lubow et al., 1992). It is known, however, that schizophrenia is also associated with low executive functioning (Barch, 2005). Recent research has suggested that in highfunctioning individuals (in this case, Harvard students) with high IQs, decreased LI is associated with increased creative achievement (Carson et al., 2003). Therefore, decreased LI may make an individual more likely to perceive and make connections that others do not see and, in combination with high executive functioning, may lead to the highest levels of creative achievement. Indeed, the link between low LI and creativity is part of Eysenck’s (1995) model of creative potential, and Martindale (1999) has argued that a major contributor to creative thought is cognitive disinhibition.
He then relates this to intuition and presents his thesis:
A concept related to LI is intuition. Jung’s (1923/1971, p. 538) original conception of intuition is “perception via the unconscious.” Two of the most widely used measures of individual differences in the tendency to rely on an intuitive information-processing style are Epstein’s Rational- Experiential Inventory (REI; Pacini & Epstein, 1999) and the Myers-Briggs Type Indicator (MBTI) Intuition/Sensation subscale (Myers, McCaulley, Quenk, & Hammer, 1998). Both of these measures have demonstrated correlations with openness to experience (Keller, Bohner, & Erb, 2000; McCrae, 1994; Pacini & Epstein, 1999), a construct that has in turn shown associations with a reduced LI (Peterson & Carson, 2000; Peterson et al., 2002), as well as with divergent thinking (McCrae, 1987) and creative achievement.
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The main hypothesis was that intuitive cognitive style is associated with decreased latent inhibition.
He found support for the hypothesis from his data. It seemed people with low LI were high in faith in intuition factor. Here is what he discusses:
The results of the current study suggest that faith in intuition, as assessed by the REI and the MBTI Thinking/Feeling subscale, is associated with decreased LI. Furthermore, a factor consisting of abstract, conceptual, holistic thought is not related to LI. Consistent with Pretz and Totz (2007), exploratory factor analysis revealed a distinction between a factor consisting of REI Experiential and MBTI Thinking/Feeling and a factor consisting of MBTI Intuition/Sensation and REI Rational Favorability. This further supports Epstein’s (1994) theory that the experiential system is directly tied to affect. The finding that MBTI Intuition/Sensation and REI Rational Favorability loaded on the same factor supports the idea that the type of intuition that is being measured by these tasks is affect neutral and more related to abstract, conceptual, holistic thought than to the gut feelings that are part of the Faith in Intuition factor.
Here are the broader implications:
The current study adds to a growing literature on the potential benefits of a decreased LI for creative cognition. Hopefully, with further research on the biological basis of LI, as well as its associated behaviors, including interactions with IQ and working memory, we can develop a more nuanced understanding of creative cognition. There is already promising theoretical progress in this direction.
Peterson et al. (2002) and Peterson and Carson (2000) found a significant relationship between low LI and three personality measures relating to an approach-oriented response and sensation-seeking behavior: openness to experience, psychoticism, and extraversion. Peterson et al. found that a combined measure of openness and extraversion (which was referred to as plasticity) provided a more differentiated prediction of decreased LI.
Peterson et al. (2002) argued that individual differences in a tendency toward exploratory behavior and cognition may be related to the activity of the mesolimbic dopamine system and predispose an individual to perceive even preexposed stimuli as interesting and novel, resulting in low LI. Moreover, under stressful or novel conditions, the dopamine system in these individuals will become more activated and the individual will instigate exploratory behavior. Under such conditions, decreased LI could help the individual by allowing him or her more options for reconsideration and thereby more ways to resolve the incongruity. It could also be disadvantageous in that the stressed individual risks becoming overwhelmed with possibilities. Research has shown that the combination of high IQ and reduced LI predicts creative achievement (Carson et al., 2003). Therefore, the individual predisposed to schizophrenia may suffer from an influx of experiential sensations and possess insufficient executive functioning to cope with the influx, whereas the healthy individual low in LI and open to experience (particularly an openness and faith in his or her gut feelings) may be better able to use the information effectively while not becoming overwhelmed or stressed out by the incongruity of the situation. Clearly, further research will need to investigate these ideas, but an understanding of the biological basis of individual differences in different forms of implicit processing and their relationship to openness to experience and intuition will surely increase our understanding of how certain individuals attain the highest levels of creative accomplishment.
To me this is exciting, the triad of creative/psychotic cognitive style, intuition and Latent Inhibition seem to gel together. the only grip eI have is that the author could also have measured intuition directly by using some insight problems requiring 'aha' solutions; maybe that is a project for future!... Read more »
Kaufman, S. (2009) Faith in intuition is associated with decreased latent inhibition in a sample of high-achieving adolescents. Psychology of Aesthetics, Creativity, and the Arts, 3(1), 28-34. DOI: 10.1037/a0014822
- March 25, 2009
- 01:20 AM
- 1,249 views
Children not mini-adults, at least in cognitive control
by sandygautam in The Mouse Trap
A predominant, but unstated, thinking that biases many research paradigms is the assumption that children are just mini-adults with less well developed mechanisms than adults, but fundamentally using and relying on the same unitary cognitive mechanisms as the adults use. this has proven time and again wrong, and better psychologists now agree that children view the world in a fundamentally different manner from adults. I have covered some research in the past that showed for example that while differentiating between two color hues (categorical color perception), children show a more right hemisphere domination (non-verbal); while adults rely on Left hemisphere (verbal knowledge). Over development the RH processes are shadowed by the maturing LH verbal process, as far as it relates to Categorical Perception.
This recent PNAS article , by none other than the famed Chris Catham of the Developing Intelligence fame, is an effort in the same direction, showing that children use a different mechanism than adults when it comes to using cognitive control. while Adults use a more proactive cognitive control, the children rely on a reactive cognitive control. The authors do a good job of describing the proactive and reactive cognitive control so over to them:
Although sometimes derided as ‘‘creatures of habit,’’ humans develop an unparalleled ability to adaptively control thought and behavior in accordance with current goals and plans. Dominant theories of cognitive control suggest that this flexibility is enabled by the proactive regulation of behavior through sustained inhibition of inappropriate thoughts and actions , the active biasing of task-relevant thoughts, or construction of rule-like representations. Theories of the developmental origins of cognitive control converge in positing that children engage these same proactive processes, but in a weaker form, with less strength or stability , less resistance toward habitual responses, or degraded complexity.
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However, children can be notoriously constrained to the present, raising the possibility that the temporal dynamics of immature cognitive control are fundamentally different from that of adults. Specifically, we hypothesized that young children may show ‘‘reactive’’ as opposed to ‘‘proactive’’ context processing , characterized by a failure to proactively prepare for even the predictable future and a tendency to react to events only as they occur, retrieving information from memory as needed in the moment. For lack of age-appropriate methods, the possibility of this qualitative developmental shift has not been directly tested.
They also describe the paradigm used beautifully so again quoting from the article:
In the AX-CPT, subjects provide a target response to a particular probe (‘‘X’’) if it follows a specific contextual cue (‘‘A’’). Nontarget responses are provided to other cue–probe sequences (‘‘A’’ then ‘‘Y,’’ ‘‘B’’ then ‘‘X,’’ or ‘‘B’’ then ‘‘Y’’), each occurring with lower probability than the target pair. This asymmetry in trial type frequency is critical for revealing distinct behavioral profiles for proactive versus reactive control. Proactive control supports good BX trial performance at the expense of AY trials. Maintenance of the ‘‘B’’ cue supports a nontarget response to the subsequent ‘‘X’’ probe; however, maintenance of the ‘‘A’’ cue leads to anticipation of an X and thus a target response (due to the expectancy effect cultivated by the asymmetry in trial type frequencies), which can lead to false alarms in AY trials . Reactive control leads to the opposite pattern. The preceding cue is retrieved when needed, that is, in response to ‘‘X’’ probes but not to ‘‘Y’’ probes. Such retrieval renders BX trials vulnerable to retrieval-based interference; the lack of such retrieval on AY trials means that false alarms are less likely in this case. Similarly, proactive control should lead to increased delay-period effort, whereas reactive control should lead to increased effort to probes.
What they found was consistent with their hypothesis. The reaction time data, the effort data gauged from puppilometry, the speed-accuracy trade off data all pointed to the fact that children used a reactive cognitive control mechanism while adults used a proactive cognitive control mechanism. This what they conclude:
By dissociating proactive and reactive control mechanisms in children, our findings call into question a previously untested assumption of developmental theories of cognitive control, that is, relative to young adults, weaker but qualitatively similar control processes guide the task performance of children. Of course, children and even infants may be capable of sustaining context representations over shorter delays than the 1.2 s used here, but such limited proactive mechanisms would seem unlikely to strongly influence most behaviors.
Further research is needed to determine the processes that drive the developmental transition from reactive to proactive control. This qualitative shift could reflect genuinely qualitative changes, for example, in metacognitive strategies that allow children to engage proactive control. Alternatively (or additionally), the underlying mechanisms for this qualitative shift could be continuous. For example, the gradual strengthening of task-relevant representations could allow proactive control to become effective, thus supporting a shift in the temporal dynamics of control. In any case, the developmental progression to be addressed is a shift from reactive to proactive control rather than merely positing incremental improvements with development.
I think these are steps in the right direction; I lean towards a stage theory account of development so am supportive of a dramatic developmental stage whereby reactive cognitive control mechanisms are replaced by proactive ones, although both strategies may be available to the critical age children equally. However, it may be the case that the neural architecture for proactive CC develops late (just like linguistic CP) and overrides the default reactive CC circuit. that dominance of Proactive CC over reactive CC to me should mark an important developmental stage.
Thanks Chris, for your wonderful blog posts and this paper!
Chatham, C., Frank, M., & Munakata, Y. (2009). Pupillometric and behavioral markers of a developmental shift in the temporal dynamics of cognitive control Proceedings of the National Academy of Sciences DOI: 10.1073/pnas.0810002106... Read more »
Chatham, C., Frank, M., & Munakata, Y. (2009) Pupillometric and behavioral markers of a developmental shift in the temporal dynamics of cognitive control. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.0810002106
- April 3, 2009
- 06:56 AM
- 1,198 views
Low Mood and Risk Aversion: a poor State outcome?
by sandygautam in The Mouse Trap
Daniel Nettle, writes an article in Journal Of Theoretical Biology about the evolution of low mood states. Before I get to his central thesis, let us review what he reviews:
Low mood describes a temporary emotional and physiological state in humans, typically characterised by fatigue, loss of motivation and interest, anhedonia (loss of pleasure in previously pleasurable activities), pessimism about future actions, locomotor retardation, and other symptoms such as crying.
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This paper focuses on a central triad of symptoms which are common across many types of low mood, namely anhedonia, fatigue and pessimism. Theorists have argued that, whereas their opposites facilitate novel and risky behavioural projects. These symptoms function to reduce risk-taking. They do this, proximately, by making the potential payoffs seem insufficiently rewarding (anhedonia), the energy required seem too great (fatigue), or the probability of success seem insufficiently high (pessimism). An evolutionary hypothesis for why low mood has these features, then, is that is adaptive to avoid risky behaviours when one is in a relatively poor current state, since one would not be able to bear the costs of unsuccessful risky endeavors at such times .
I would like to pause here and note how he has beautifully summed up the low mood symptoms and key features; taking liberty to define using my own framework of Value X Expectancy and distinction between cognitive('wanting') and behavioral ('liking') side of things :
Anhedonia: behavioral inability to feel rewarded by previously pleasurable activities. Loss of 'liking' following the act. Less behavioral Value assigned.
Loss of motivation and interest: cognitive inability to look forward to or value previously desired activities. Loss of 'wanting' prior to the act. Less cognitive Value assigned.
Fatigue: behavioral inability to feel that one can achieve the desired outcome due to feelings that one does not have sufficient energy to carry the act to success. Less behavioral Expectancy assigned.
Pessimism: cognitive inability to look forward to or expect good things about the future or that good outcomes are possible. Less cognitive Expectancy assigned.
The reverse conglomeration is found in high mood- High wanting and liking, high energy and outlook. Thus, I agree with Nettle fully that low mood and high mood are defined by these opposed features and also that these features of low and high mood are powerful proximate mechanisms that determine the risk proneness of the individual: by subjectively manipulating the Value and Expectancy associated with an outcome, the high and low mood mediate the risk proneness that an organism would display while assigning a utility to the action. Thus, it is fairly settled: if ultimate goal is to increase risk-prone behavior than the organism should use the proximate mechanism of high mood; if the ultimate goal is to avoid risky behavior, then the organism should display low mood which would proximately help it avoid risky behavior.
Now let me talk about Nettle's central thesis. It has been previously proposed in literature that low mood (and thus risk-aversion) is due to being in a poor state wherein one can avoid energy expenditure (and thus worsening of situation) by assuming a low profile. Nettle plays the devil's advocate and argues that an exactly opposite argument can be made that the organism in a poor state needs to indulge in high risk (and high energy) activities to get out of the poor state. Thus, there is no a prior reason as to why one explanation may be more sound than the other. To find out when exactly high risk behavior pay off and when exactly low risk behaviors are more optimal, he develops a model and uses some elementary mathematics to derive some conclusions. He, of course , bases his model on a Preventive focus, whereby the organism tries to minimize getting in a state R , which is sub-threshold. He allows the S(t) to be maximized under the constraint that one does not lose sight of R. I'll not go into the mathematics, but the results are simple. When there is a lot of difference between R (dreaded state) and S (current state), then the organism adopts a risky behavioral profile. when the R and S are close, he maintains low risk behavior, however when he is in dire circumstances (R and S are very close) then risk proneness again rises to dramatic levels. To quote:
The model predicts that individuals in a good state will be prepared to take relatively large risks, but as their state deteriorates, the maximum riskiness of behaviour that they will choose declines until they become highly risk-averse. However, when their state becomes dire, there is a predicted abrupt shift towards being totally risk-prone. The switch to risk-proneness at the dire end of the state continuum is akin to that found near the point of starvation in the original optimal foraging model from which the current one is derived (Stephens, 1981). The graded shift towards greater preferred risk with improving state is novel to this model, and stems from the stipulation that if the probability of falling into the danger zone in the next time step is minimal, then the potential gain in S at the next time step should be maximised. However, a somewhat similar pattern of risk proneness in a very poor state, risk aversion in an intermediate state, and some risk proneness in a better state, is seen in an optimal-foraging model where the organism has not just to avoid the threshold of starvation, but also to try to attain the threshold of reproduction (McNamara et al., 1991). Thus, the qualitative pattern of results may emerge quite generally from models using different assumptions.
Nettle, then extrapolates the clinical significance from this by proposing that 'agitated' / 'excited' depression can be explained as when the organism is in dire straits and has thus become risk-prone. He also uses a similar logic for dysphoric mania although I don't buy that. However, I agree that euphoric mania may just be the other extreme of high mood and more risk proneness and goal achievements; while depression the normal extreme of low mood and adverse circumstances and risk aversion. To me this model ties up certain things we know about life circumstances and the risk profile and mood tone of people and contributes to deepening our understanding.
Nettle, D. (2009). An evolutionary model of low mood states Journal of Theoretical Biology, 257 (1), 100-103 DOI: 10.1016/j.jtbi.2008.10.033... Read more »
Nettle, D. (2009) An evolutionary model of low mood states. Journal of Theoretical Biology, 257(1), 100-103. DOI: 10.1016/j.jtbi.2008.10.033
- March 9, 2009
- 10:53 AM
- 1,195 views
Evidence for heightened Agency in Schizophrenia
by sandygautam in The Mouse Trap
I have been maintaining that Autism and Schizophrenia are opposites on a continuum and one dimension on which they differ is Agency , with autistics attributing too less agency to themselves (and others), while schizophrenics attributing too much agency to themselves (and others).
The case for people with ASD is fairly settled. They have deficits in theory Of Mind (ToM) and one mechanism by which this deficit seems to arise is via their attributing less agency to themselves as well as others.
For Schizophrenics too, it was speculated that they have problems with agency , but a clear illustration that they have an enhanced agency attribution device was not firmly established. This study, which dates back to 2003, in my opinion, establishes the fact that their is hyper-agency attribution (or hyper-self-menatlizing) in schizophrenics.
The study in question is one by Haggard et al , and it uses an experimental paradigm to illustrate that schizophrenics indeed have problems with self- agency attribution, and that too in the hypothesized direction.
Here is the abstract:
An abnormal sense of agency is among the most characteristic yet perplexing positive symptoms of schizophrenia. Schizophrenics may either attribute the consequences of their own actions to the intentions of others (delusions of influence), or may perceive themselves as causing events which they do not in fact control (megalomania).Previous reports have often described inaccurate agency judgments in schizophrenia, but have not identified the disordered neural mechanisms or psychological processes underlying these judgments.We report the perceived time of a voluntary action and its consequence in eight schizophrenic patients and matched controls.The patients showed an unusually strong binding effect between actions and consequences. Specifically, the temporal interval between action and consequence appeared shorter for patients than for controls. Patients may overassociate their actions with subsequent events, experiencing their actions as having unusual causal efficacy.Disorders of agency may reflect an underlying abnormality in the experience of voluntary action.
Now, let us pause and recollect that Chris Frith had postulated that the voluntary action mechanism in Scizophrenics is somewhat malformed and specifically there is a disconnect between intention attribution and voluntary action manifestation. He however had not clearly stated that there would be over-attribution of intention to voluntary actions. We all know that dopamine is associated with voluntary action (voluntary movements) and that baseline dopamine is in excess in schizophrenics. This paper ties things in together showing that excess dopamine secretion in basal ganglia and cortical areas may lead to greater biding between intentions and subsequent actions (consequences) and by this mechanism may lead to over-attribution of agency. Of course the paper doe snot establish this mechanism but just speculates on it as one of the possible mechanisms. It is also important to pause and note that schizophrenics have a jumping-to-conclusions bias and thus if an intention and action were more tightly bound (occurred in time in close proximity)_, then they are more likely to judge the two events to be related and the intention to cause the action.
Now let me get to the actual experiment. Haggard et al asked schizophrenics as well as matched controls to note subjective time (using Libets approach) when they decided to voluntarily press a computer key, and also subjective time when they first heard an auditory tone . The tone was presented 250 ms after their voluntary key press. As has been established earlier, and using controls in this experiment, people advance the key press in future (shift it towards future time from the exact time they actually pressed the key) so that subjectively the key press happens after some time form the objective key press and in the direction of the tone presentation. Thus, the effective subjective time between the key press and the tone is reduced. This binding between a voluntary action and its consequence , happens in normal individuals too, but in schizophrenics this happened significantly more in magnitude ans was dependent on two factors. first, like in normals , the voluntary key press was advanced in time towards the tone presentation, but this advance was significantly greater than in the case of controls. Secondly, the subjective auditory tone was sort of anticipated and shifted back in time towards the voluntary key press in schizophrenics. Thus, in schizophrenics, it seemed to them that the auditory tone had occurred prior to when it was actually presented. This lead to overall very significant reduction in subjective time experienced between the voluntary key press and the tone hearing, thus binding the two events strongly and leading to stronger agency inferred. to quantize the things a bit, in normal controls the voluntary key press was on the average occurring 26 ms from the actual key press, the auditory tone was heard 5 ms from the actual presentation and thus the subjective difference between the key press (intention) and tone (consequence) was 250-(26+5)= 239 ms. In schizophrenics, the key press was deemed to occur 60 ms after the actual key press, however most importantly the tone was not heard subjectively after its presentation, but was heard anticipatory 139 ms before its actual presentation, thus the actual perceived subjective time between the key press (intention) and the tone (consequence) was 250-60-139 = 51 ms only. Now , one can easily see, that if perceived subjective time between tow events is shortened in schizophrenia, then wont they end up falsely clubbing many coincidental things too together, because they seem to follow each other in close temporal proximity.
To appreciate the results, one needs to put these results in the broader context of what we know about agency in schizophrenics:
Previous laboratory studies have investigated agency using action attribution tasks. In these tasks, the patient is asked to perform an action, and is shown a visual image corresponding to that action, for example, a line drawn with a pen , a video of a hand making a manual posture , or a computerised image of a joystick moving. By introducing a mismatch between the performed action and the visual feedback, experimenters investigate the accuracy of attribution judgments. The subject has to attribute the viewed image either to an action he has just been instructed to make or to some other source. Interestingly, all these studies have found schizophrenics abnormally willing to attribute to themselves actions which in fact differ from the ones they performed. Thus, they are less sensitive than control subjects to spatial, temporal or kinematic mismatches between actions and visual feedback. The direction of these results points towards an excessive, rather than a reduced, sense of agency. Such results have been interpreted in the context of an internal forward model. Schizophrenic patients’ errors involve mostly over-attribution, implying a forward model with an unusually tolerant comparator.
Impaired judgement of agency can also be linked to the brain abnormalities underlying the disease. Agency involves forming a conscious mental association between one’s own intentional actions, and their consequences in the outside world. Thus, agency may be a conscious aspect of a more general system for instrumental or operant learning about environmental contingencies and rewards. Animal learning studies show that dopaminergic circuits, including the basal ganglia and medial forebrain are essential for associating actions with their effects, and for motivating behaviours. Brain imaging studies in man show that these same areas are active when a voluntary action produces a reward or other salient consequence . Moreover, these dopaminergic circuits are overactive in schizophrenia . Excessive dopaminergic activity might therefore explain abnormalities of conscious agency in schizophrenia, such as over-association between intentions and external events.
This is how they interpret their results:
More importantly, our schizophrenic patients seem to show an exaggerated version of the normal binding effect, or hyperbinding. These results could account for the findings of some action attribution experiments. Franck et al. asked patients and controls to move a joystick and then to observe their movements on a computer screen after a delay. The experimenters systematically varied the delay to investigate at what point the two groups ceased to accept the observed action as their own. Control subjects detected the temporal discrepancy between their action and the image with delays of around 100–150 ms. Schizophrenic subjects were much more tolerant, and accepted the viewed action as their own even for delays of 300 ms. Overall, the detection threshold for the relevant action was increased by about 150–200 ms for the patients compared to the controls. This value can be compared to the 180 ms difference between our patients and controls in the implied perceptual duration of the interval between action and tone.
The direction of the attribution effect is important: schizophrenics over-attributed events to their own agency. Our data suggests that schizophrenic patients have unusually strong associations between conscious representations of action and consequence. Thus, they might bind action and viewed image across the substantial delay periods imposed in the Franck et al. experiment, and be unaware of the artificially-induced lag between these events. There may be a critical period in which to perceive the consequence of an action. Actions and events falling in this period may be perceptually bound. A deficit in setting the duration of this critical period in schizophrenics could contribute to the shifts we found in their subjective temporal experience. This view would interpret abnormal conscious experience in schizophrenia as a problem in predicting the consequences of one’s own actions. Further work could investigate whether temporal analysis in schizophrenic patients is defective only when concerning their own actions, or also when observing actions made by others.
I am thrilled as usual and predict that if the same experimental paradigm is used with Autistic, then they will show very little or no forward movement of subjective time between their actual voluntary key-press and the subjective feel of when they decided to press the key. Also, there would be no anticipatory backwards movement of subjective time for when the tone was heard. Thus, Autistic would perceive the time gap as 250 ms only, or may even perceive the time to be more than 250 ms depending ion whether they move the voluntary key press subjective time back in time. No matter what they should show lesser binding between the intention (if they can form one) and consequence.
Haggard P, Martin F, Taylor-Clarke M, Jeannerod M, Franck N. (2003). Awareness of action in schizophrenia Neuroreport, 14 (7), 1081-1085... Read more »
Haggard P, Martin F, Taylor-Clarke M, Jeannerod M, Franck N. (2003) Awareness of action in schizophrenia. Neuroreport, 14(7), 1081-1085. DOI: http://www.neuroreport.com/pt/re/neuroreport/abstract.00001756-200305230-00035.htm;jsessionid
- March 25, 2009
- 07:51 AM
- 1,189 views
The bipolar phenotype: Excessive self-regulatory focus?
by sandygautam in The Mouse Trap
In my last post I had hinted that bipolar mania and depression may both be characterized by an excessive and overactive self-regulatory focus: with promotion focus being related to Mania and prevention focus being related to depression. It is important to pause and note that the bipolar propensity is towards more self-referential goal-directed activity resulting in excessive use of self-regulatory focus. To clarify, I am sticking my neck out and claiming that depression is marked by an excessive obsession with self-oriented goal directed activities- but with a preventive focus thus focusing more on self's responsibilities and duties , obligations etc with respect to other near and dear ones. Mania on the other hand, also has excessive self-oriented goal-directed focus, but the focus is promotional with obsession with hopes, aspirations etc, which are relatively more inward-focused and not too much dependent on significant others.
Thus, my characterization of depression as a state where regulatory reference is negative (one is focused on avoiding landing up in a negative end-state like being a burden on others), the regulatory anticipation is negative ( one anticipates pain as a result of almost any act one may perform and thus dreads day-to-day- activity) and the regulatory focus is negative (preventive focus whereby one is more concerned with duties and obligations to perform and security is a paramount need). The entire depressive syndrome can be summed up as an over activity of avoidance based mechanisms. However, please note that still there is an excess of self-referential/self-focused thinking and one is greatly motivated (although might be lacking energy) to bridge the differences between the real self and the 'ought' self. One can say that one's whole life revolves around trying to become the 'ought' self, or rather one conceptualizes oneself in terms of the 'ought' self.
Contrast this with Mania, where the regulatory reference is positive (one is focused on achieving something grandiose ) , regulatory anticipation is positive (one feels in control and believes that only good things can happen to the self) and regulatory focus is positive (promotional focus whereby one is more concerned with hopes, aspirations etc and growth / actualization needs). Still, juts like in depression there is an excess of focus on self and one is greatly motivated (and also has the energy) to bridge the difference between the real and the 'ideal' self. One can say that one's whole life revolves around trying to become the 'ideal' self , or rather one conceptualizes oneslef in terms of an 'ideal' self.
What can we predict from above: we know that brain's default network is involved in self-focused thoughts and ruminations. We can predict, and know for a fact, that the default network is overactive in schizophrenics (and thus by extension in bipolars who I believe have the same underlying pathology, at least as far as psychotic spectrum is concerned)and thus we can say with confidence that indeed the regulatory focus should be high for bipolars and this should be correlated with default network activity. We can also predict that during the Manic phase, the promotion focus related neural network should be more active and in depressive phase the prevention-related areas of the brain should be more active. this last hypothesis still needs experimentation, but lets backtrack a bit and first look at the neural correlates of the promotion and preventive regulatory self-focus.
For this, I refer the readers to an , in my view, important study that tried to dissociate the medial PFC and PCC activity (both of which belong to the default network) while people engaged in self-reflection. Here is the abstract of the study:
Motivationally significant agendas guide perception, thought and behaviour, helping one to define a ‘self’ and to regulate interactions with the environment. To investigate neural correlates of thinking about such agendas, we asked participants to think about their hopes and aspirations (promotion focus) or their duties and obligations (prevention focus) during functional magnetic resonance imaging and compared these self-reflection conditions with a distraction condition in which participants thought about non-self-relevant items. Self-reflection resulted in greater activity than distraction in dorsomedial frontal/anterior cingulate cortex and posterior cingulate cortex/precuneus, consistent with previous findings of activity in these areas during self-relevant thought. For additional medial areas, we report new evidence of a double dissociation of function between medial prefrontal/anterior cingulate cortex, which showed relatively greater activity to thinking about hopes and aspirations, and posterior cingulate cortex/precuneus, which showed relatively greater activity to thinking about duties and obligations. One possibility is that activity in medial prefrontal cortex is associated with instrumental or agentic self-reflection, whereas posterior medial cortex is associated with experiential self-reflection. Another, not necessarily mutually exclusive, possibility is that medial prefrontal cortex is associated with a more inward-directed focus, while posterior cingulate is associated with a more outward-directed, social or contextual focus.
The authors then touch upon something similar to what I have said above, that one can be too much planful or goal-directed (bipolar propensity) , but it would still make sense to find whether the focus is promotional or preventive. To quote:
The idea of variation in individuals’ regulatory focus highlights the difference between agendas and traits; two people could both be described by the trait ‘planful’, but planful about what? A person with a predominantly promotion focus would be more likely to be planful about attaining positive rewards or outcomes, while a person with a predominantly prevention focus would be more likely to be planful about avoiding negative events or outcomes. Although a promotion or prevention focus may dominate, the aspects of the self that are active change dynamically across situations (e.g. Markus and Wurf, 1987), thus most individuals have both promotion and prevention agendas. For example, the same person can hold both the hope of becoming rich (a promotion agenda) and the duty to support an aging parent (a prevention agenda), or the aspiration to be a good citizen and the obligation to be a well-informed voter. As individuals, hopes and aspirations and duties and obligations make up a large part of our mental life and constitute the motivational scaffolding for much of our behaviour.
Now comes the study design:
The present studies investigated neural activity when participants were asked to think about self-relevant agendas related to either a promotion (think about your hopes and aspirations) or prevention (think about your duties and obligations) focus. We compared neural activity associated with thinking about these two different types of self-relevant agendas and with thinking about non-self-relevant topics (distraction). We expected greater activity in anterior and/or posterior medial regions associated with these two self-reflection conditions compared with the distraction control condition because thinking about one's agendas, like thinking about one's traits, is self-referential. Such a finding would also be consistent, for example, with Luu and Tucker's (2004) proposal that both anterior cingulate and posterior cingulate cortex contribute to action regulation by representing goals and expectancies.
And this is what they found:
A double dissociation was found when participants were cued to think about promotion and prevention agendas on different trials for the first time during scanning (Experiment 2) and when they spent several minutes thinking about either promotion or prevention agendas before scanning (Experiment 1), indicating that it results from what participants are thinking about during the scan and not from some general effect (e.g. mood) carried over from the pre-scan period of self-reflection,
Here is what they discuss:
In short, the double dissociation between medial PFC and anterior/inferior medial posterior areas and our two self-reflection conditions indicates that these brain areas serve somewhat different functions during self-focus. There are a number of interesting possibilities that remain to be sorted out. Differential activity in these anterior medial and posterior medial regions as a function of the types of agendas participants were asked to think about could reflect: (i) differences in the representational content in the specific features of agendas, schemas, possible selves and so forth that constitute hopes and aspirations on the one hand and duties and obligations on the other (cf. Luu and Tucker, 2004); (ii) differences in the type(s) of component processes these agendas are likely to engage and/or the representational content they are likely to activate, for example, discovering new possibilities (hopes) vs retrieving episodic memories (e.g. Maddock et al., 2001) of past commitments (duties); (iii) differences in affective significance of hopes and aspirations (attaining the positive) and duties and obligations (avoiding the negative, Higgins, 1997; 1998); (iv) different aspects of the subjective experience of self, such as the subjective experience of control (an instrumental self) vs the subjective experience of awareness (an experiential self; Johnson, 1991; Johnson and Reeder, 1997; compare, e.g. Searle, 1992 and Weiskrantz, 1997, vs Shallice, 1978 and Umilta, 1988); (v) differences in the social significance of hopes and aspirations (more individual) and duties and obligations (involving others). This last possibility is suggested by findings linking the posterior cingulate with taking the perspective of another (Jackson et al., 2006). It may be that thinking about duties and obligations (a more outward focus) tends to involve more perspective-taking than does thinking about hopes and aspirations (a more inward focus). The greater number of mental/emotional references from the promotion group on the pre-scan essay and the tendency for a greater number of references to others from the prevention group are consistent with the hypothesis that medial PFC activity is associated with a more inward focus whereas posterior cingulate/precuneus activity is associated with a more outward, social focus. Clarifying the basis of the similarities and differences between neural activation associated with thinking about hopes and aspirations vs duties and obligations would begin to help differentiate the relative roles of brain regions in different types of self-reflective processing.
They do discuss clinical significance of their studies , but not in terms I would have loved to. I would like to see, whether there is state/trait hyperactivity and dissociation between the mPFC and PCC activation when the variable of depressive episode or manic episode subject is introduced. I'll place my bets that there would be an interaction between the type of episode and the over activity in the corresponding default-brain regions; but would like to see that data collected.
So my thesis is that the self-reflective and focused default network is overactive in biploar/psychotic spectrum people, but a bias or tilt towards promotion or preventive focus leads to their recurring and periodic episdoes of mania and depression.
Lastly let me touch upon affect in these state and what Higgins had to say about this in his paper covered yesterday. Higgins proposed that bipolar is due to a promotional focus, with mania induced when there is not much mismatch (or awareness of mismatch) between the ideal and real self; while depression or sadness and melancholia induced when one becomes aware of the discrepancy between the ideal and the real self. He proposes that 'ought' and real self discrepancy leads to anxiety and nervousness/ agitation; while a preventive focus and congruency between 'ought' and real leads to calmness/quiescence.
I disagree with his formulations, in as much as I differentiate between a regulatory focus and the corresponding awareness of discrepancies in that direction. To Higgins they are the same; if someone has a promotional focus , he would also be more aware of the discrepancies between his ideal and real self and thus be saddened. I disagree. I believe that if one has a promotional focus one is driven by goals to make the resl self as close to the ideal self as possible and if one is not able to do so, one would use defense mechanisms to delude oneself , but will not admit to its reality, as the reality of incongruence along the focused dimension is too painful. However, because on is consciously focused on promotions, one would be aware of trade-offs and will acknowledge to himself that his 'ought' self, which anyway is not too important for his self-concept, is not congruent to the real self. Thus, one wit a predominant promotion focus may be painfully aware of the discrepancy between his 'ought' and real self and thus might be nervous, agitated/ irritable- all symptoms of Mania.
A depressive person on the other hand has a predominant preventive focus and all actions/ ruminations are driven by responsibilities and obligations. Here acknowledging to oneself that one has failed in meeting obligations may be catastrophic so one will try to delude oneself that one is closer to the 'ought' self than is the case. However, one may not require any defense mechanisms when judging the discrepancy between the 'ideal' and real self as that 'ideal' self is no longer a matter of life and death! One would be aware that one is not focusing too much on hopes and aspirations and thus feel despondent/ sad/ melancholic - again classical symptoms of depression. Yet, despite the affect of sadness, all rumination would be focused on 'ought' self and thus the content be of guilt, duties, burden, responsibilities, etc.
I'm sure there is some grain of truth in my formulation, but wont be able to state emphatically unless the above proposed dissociation study involving default region and bipolar people is done. If one of you decide to do that, do let me know the results, even if they contradict the thesis.
Johnson, M. (2006). Dissociating medial frontal and posterior cingulate activity during self-reflection Social Cognitive and Affective Neuroscience, 1 (1), 56-64 DOI: 10.1093/scan/nsl004
Higgins, E. T. (1997). Beyond pleasure and pain American Psychologist (52), 1280-1300... Read more »
Johnson, M. (2006) Dissociating medial frontal and posterior cingulate activity during self-reflection. Social Cognitive and Affective Neuroscience, 1(1), 56-64. DOI: 10.1093/scan/nsl004
Higgins, E. T. (1997) Beyond pleasure and pain . American Psychologist , 1280-1300. DOI: http://www.ncbi.nlm.nih.gov/pubmed/9414606
- January 22, 2009
- 06:59 AM
- 1,176 views
Perosnality and Neurotransmitters
by sandygautam in The Mouse Trap
Although all introductory Psychology textbooks warn against any simplistic correlations between neurotransmitters and complex behavioral and cognitive measures like Personality traits, I am going to do exactly that in this post. In an earlier post , I had related personality traits to neurotransmitter systems and operant learning paradigm and here I present some corroborating evidence for the personality- neurotransmitter system linkage.
First to recap:
Nueroticism/ Harm Avoidance: Serotonin system
Conscentiousness/ novelty seeking: Dopamine system
Extarversion/ Reward Dependence: Norepinephrine system
Agreeableness/ Persistance: Epinepherine system
Openesses/ Rebeliious-conformity/self-directedness: Histamine system
First off to bat consider the following- Neuroticism is manifested as anxiety and if serotonin system is implicated , then genes affecting the serotonin system should affect the neuroticism levels of individuals . This is exactly what was found by Lesh et al.
Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.
Next comes a recent study finding that a gene variant related to NO (a neurotrasmitter) is related to Impulsiveness. Now One of the defining traits of NS/ C is Impulsiveness. This has been found related to NOS1 gene. Here is the original study.
Context Human personality is characterized by substantial heritability but few functional gene variants have been identified. Although rodent data suggest that the neuronal isoform of nitric oxide synthase (NOS-I) modifies diverse behaviors including aggression, this has not been translated to human studies.
Objectives To investigate the functionality of an NOS1 promoter repeat length variation (NOS1 Ex1f variable number tandem repeat [VNTR]) and to test whether it is associated with phenotypes relevant to impulsivity.
Design Molecular biological studies assessed the cellular consequences of NOS1 Ex1f VNTR; association studies were conducted to investigate the impact of this genetic variant on impulsivity; imaging genetics was applied to determine whether the polymorphism is functional on a neurobiological level.
Setting Three psychiatric university clinics in Germany.
Participants More than 3200 subjects were included in the association study: 1954 controls, 403 patients with personality disorder, 383 patients with adult attention-deficit/hyperactivity disorder (ADHD), 151 with familial ADHD, 189 suicide attempters, and 182 criminal offenders.
Main Outcome Measures For the association studies, the major outcome criteria were phenotypes relevant to impulsivity, namely, the dimensional phenotype conscientiousness and the categorical phenotypes adult ADHD, aggression, and cluster B personality disorder.
Results A novel functional promoter polymorphism in NOS1 was associated with traits related to impulsivity, including hyperactive and aggressive behaviors. Specifically, the short repeat variant was more frequent in adult ADHD, cluster B personality disorder, and autoaggressive and heteroaggressive behavior. This short variant came along with decreased transcriptional activity of the NOS1 exon 1f promoter and alterations in the neuronal transcriptome including RGS4 and GRIN1. On a systems level, it was associated with hypoactivation of the anterior cingulate cortex, which is involved in the processing of emotion and reward in behavioral control.
Conclusion These findings implicate deficits in neuronal signaling via nitric oxide in moderation of prefrontal circuits underlying impulsivity-related behavior in humans.
Now there does exist a relationship between NO and dopamine (but then which two neurotransmitter systems are not related) and that way I can still save my face by claiming that it is the dopamine that is finally mediating the impulsivity and not NO.
There is evidence suggesting that nitric oxide (NO) may play an important role in dopamine (DA) cell death. NO may act as a neuroprotector or neurotoxic agent in dopamine neurons, depending on cell redox status. Glutathione (GSH) depletion is the earliest biochemical alteration shown to date in brains of Parkinson's disease (PD) patients. However, data from animal models show that GSH depletion by itself is not sufficient to induce nigral degeneration. Low NO concentrations have neurotrophic effects on DA cells via a cGMP-independent mechanism that may implicate up-regulation of GSH. On the other hand, higher levels of NO induce cell death in both DA neurons and mature oligodendrocytes that is totally reverted by soluble factors released from glia. Alterations in GSH levels change the neurotrophic effects of NO in dopamine function into neurotoxic, under these conditions, NO triggers a programmed cell death with markers of both apoptosis and necrosis characterised by an early production of free radicals followed by late activation of the sGC/cGMP/PKG pathway. Arachidonic acid metabolism through the 12-lipoxygenase (12-LOX) pathway is also central for this GSH-NO interaction. Neurotrophism of NO switches into neurotoxicity after GSH depletion, due to persistent activation of the ERK-1/2 signaling pathway in glial cells. The implication of these cell death signaling pathways in pathological conditions like Parkinson's disease, where GSH depletion, glial dysfunction and NO overproduction have been documented, are discussed.
Next we move to the sociability factor underlying Extraversion/ Reward dependence. Here studies show that Noardrenaline is related to sociability/ dependence etc. Here is a study showing effects of NA on sociability.
Rationale: Treatment with antidepressants has been shown to affect social functioning, but drugs with actions on different neurotransmitters may have a different profile of effects. Objective: To study the effects of acute manipulation of two neurotransmitters, serotonin and noradrenaline, on social behaviour in healthy volunteers. Methods: Sixty volunteers were randomly assigned to a single dose of a selective noradrenaline reuptake inhibitor, reboxetine (4 mg), a selective serotonin reuptake inhibitor, citalopram (10 mg), or placebo. They socially interacted with a confederate behaving in a non-sociable manner in a stranger-dyadic social interaction paradigm 1.5 h postdrug. Social behaviour during the interaction was video recorded by a hidden camera and subsequently analysed. After the interaction, volunteers played the mixed-motive game with the confederate. This game has been shown to measure cooperative behaviour and communication. Volunteers read a short story and rated their mood predrug and before and after the interaction. Results: Subjects on reboxetine showed reduced hand fiddling during the interaction and gave significantly more cooperative communications during the mixed-motive game. More volunteers on reboxetine were classified as cooperative players. On the reading task, the speech of subjects on citalopram showed less reduction of energy variation after the social interaction. Conclusion: Reboxetine had clear effects on social behaviour. Noradrenaline was related to increased social engagement and cooperation and a reduction in self-focus. Citalopram had less effect on cooperative behaviour but serotonin may be associated with protection of the self from the negative consequences of social interaction.
Also, Zuckerman has clearly related NA to sociability and dependence.As per him:
Ellison studies the effects of chemical lesions of either dopamine or noradrenaline system in rats. ...Norepeinepherine-lesioned rats spent more time in their burrows and less time in a behavioral arena in which spontaneous social interactions could occur....
That takes us to the fourth trait of agreeableness and the related Empathy system . Here the famous Scacter- singer experiment of administering Adrenaline and then finding that the mood became congruent with that of other people has to be reinterpreted in terms of empathy at work rather than james-lange two-step appraisal of emotion. Do read the expermine in more detail at the above link.
The Experiment in a nut shell.
Independent Variables
1. Injected Adrenaline or Saline solution
2. The subjects were given a description of side-effects, misinformed about the side-effects, or told nothing.
3. The subjects were placed in a 'Euphoric' (Happy) or 'Angry' situation.
Dependent Variables
1. Observed signs of happiness
2. Observed signs of anger
3. Self-report of happiness or angerResults:
Euphoria: As expected, the adrenaline misinformed group, and the adrenaline ignorant group, reported being happiest
Anger: This didn't work. Most subjects were positive about their feelings. Schachter and Singer attribute this to the fact that they were students eager to please their tutors
It is important that those people who were placed with confederates exhibiting happy states felt happy and the same was felt by those who received adrenaline; a more valid interpretation is that adrenaline increased the empathetic feelings and lead to transmission or contagion of mood. the situational variable where one tried to induce anger by being irritable did not lead to to anger; perhaps if the confederate was irritated, they might have become irritated too due to empathy; but no anger is expected as per my interpretation that it is empathy that is primary and not the cognitive appraisal of emotional physiological state.
Finally I agree that I have not been able to find much about histamine system and how it may be affect the openness/ rebellious/conformity trait. As an exercise to reader here are some low histamine condition links.
That is it for now. would love if somebody points to some other studies that corroborate the case.
K.-P. Lesch, D. Bengel, A. Heils, S. Z. Sabol, B. D. Greenberg, S. Petri, J. Benjamin, C. R. Muller, D. H. Hamer, D. L. Murphy (1996). Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region Science, 274 (5292), 1527-1531 DOI: 10.1126/science.274.5292.1527
Wai Tse, Alyson Bond (2002). Difference in serotonergic and noradrenergic regulation of human social behaviours Psychopharmacology, 159 (2), 216-221 DOI: 10.1007/s00213-001-0926-9... Read more »
K.-P. Lesch, D. Bengel, A. Heils, S. Z. Sabol, B. D. Greenberg, S. Petri, J. Benjamin, C. R. Muller, D. H. Hamer, & D. L. Murphy. (1996) Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region. Science, 274(5292), 1527-1531. DOI: 10.1126/science.274.5292.1527
Wai Tse, & Alyson Bond. (2002) Difference in serotonergic and noradrenergic regulation of human social behaviours. Psychopharmacology, 159(2), 216-221. DOI: 10.1007/s00213-001-0926-9
- October 24, 2008
- 08:02 AM
- 1,173 views
The stage theories: are they all fiction?
by sandygautam in The Mouse Trap
I normally do not like to thrash articles or opinion pieces, but this article by Michael Shermer, in the Scientific American, has to be dealt with as it as masquerading as an authoritative debunking by one of the foremost skeptics in one of the most respected magazines. Yet, it is low on science and facts and is more towards opinions, biases and prejudices.Shermer, from the article seems to be generally antagonistic to stage theories as he thinks they are mere narratives and not science. The method he goes about discrediting stage theories is to lump all of them together (from Freud's' theories to Kohlberg's theories), and then by picking up on one of them (the stages of grief theory by Kubler-Ross) he tries to discredit them all. This is a little surprising. While I too believe (and it is one of the prime themes of this blog) that most of the stage theories have something in common and follow a general pattern, yet I would be reluctant to club developmental stage theories that usually involve stages while the child is growing; to other stage theories like stages of grief, in which no physical development is concurrent with the actual stage process, but the stages are in adults that have faced a particular situation and are trying to cope with that situation. In the former case the children are definitely growing and their brains are maturing and their is a very real substrate that could give rise to distinctive stages; in the latter case the stages may not be tied so much to development of the neural issue; as much they are to its plasticity; the question in latter case would be viz does the brain adapt to losses like a catastrophic news, death of loved one etc by reorganizing a bit and does the reorganizing happen in phases or stages. The two issues of childhood development and adult plasticity are related , but may be different too. With adult neurogenisis now becoming prominent I wont be surprised if we find neural mechanisms for some of these adult stages too, like the stages of grief, but I would still keep the issues different.Second , assuming that Shermer is right and that at the least the stage theory of grief, as proposed by Kubler-Ross is incorrect; and also that it can be clubbed with other stage theories; would it be proper to conclude that all stage theories were incorrect based on the fact that one of them was incorrect/ false. It would be like that someone proposed a modular architecture of mind; and different modules for mind were proposed accordingly; but on of the proposed modules did not stood the scrutiny of time( lets say a module for golf-playing was not found in the brain); does that say that all theories that say that the brain is organized modularity for at least some functions are wrong and all other modules are proved non-existent. Maybe the grief stages theory is wrong, but how can one generalize from that to all developmental stage theories, many of them which have been validated extensively (like Paiget's theories) and go on a general rant against all things 'stages'!!Next let me address another fallacy that Shermer commits; the causal analogy fallacy: that if two things are analogous than one thing is causing other , when in fact no directional inference can be drawn from the analogical space. He asserts that humans are pattern-seeking, story-telling primates who like to explain away there experiences with stories or narratives especially as it provides a structure over unpredictable and chaotic happenings. Now, I am all with Shermer up till this point and this has been my thesis too; but then he takes a leap here and says that this is the reason we come up with stage theories. Why 'stage' theories? Why not just theories? any theory, in as much as it is an attempt to provide a framework for understanding and explication is a potential narrative and perhaps anyone that tries to come up with a theory is guilty of story-telling by extension. The leap he is making here, is the assumption that story-telling is a 'stage' process and a typical story follows a pattern, which is, unfolding of plot in distinct stages.Now, I agree with the leap too that Shermer is making- a narrative is not just any continuous thread of yarn that the author spins- it normally involves discrete stages and though I have not touched on this before, Christopher Brooks work that delineated the eight basic story plots also deals with the five -stage unfolding of plot in all the different basic story plots. so I am not contesting the fact that story-telling is basically a stage process with distinct stages through which the protagonist pass or distinct stages of plot development; what I am contesting is the direction of causality. Is it because we have evidence of distinct stages in the lives of individuals, and in general, evidence for the eight-fold or the five-fold stages of development of various faculties, that our stories reflect distinct stages as they unfold and the mono myth has a distinct stage structure; or is it because our stories have structures in the form of stages, that the theories we develop also have stages? I believe that some theorizing in terms of stages may indeed be driven by our desire to compartmentalize everything into eight or so basic stages and environmental adaptive problems we have encountered repeatedly and which have become part of our mythical narrative structure; but most parsimoniously or mythical narrative structure is stage bound, as we have observed regularities in our development and life that can only be explained by resorting to discrete stages rather than a concept to continuous incremental improvement/ development/ unfolding.Before moving on, let me just give a brief example of the power of stage theories and how they can be traced to neural mechanisms. I'll be jumping from the very macro phenomenon I have been talking about to the very micro phenomenon of perception. One can consider the visuomotor development of a child. Early in life there is a stage when the oculomotor control is mostly due to sub cortical regions like superior colliculus and the higher cortical regions are not much involved (they are not sufficiently developed/ myelinated) . The retina of eye is such that the foveal region is underdeveloped; and all this combination means that infants are very good at orienting their eyes to moving targets in their peripheral vision, but are poor at colour and form discrimination. Also, they can perform saccades first, the capability to make antisaccades develops next and the capacity to make smooth pursuit movement comes later. There are distinct stages of oculomotor control that a child can move through and this would definitely affect its perception of the world. (for example on can recognize an disicrimintae based on form first and color later as the visual striated areas for these mature in that order. In sort, there are strong anatomical, physiological and psychological substrates for most of the developmental stage theories.Now let me address, why Shermer, whom I normally admire, has taken this perverse position. It is because his Skeptic magazine recently published an article by Russell P. Friedman, executive director of the Grief Recovery Institute in Sherman Oaks, Calif. (www.grief-recovery.com), and John W. James, of The Grief Recovery Handbook (HarperCollins, 1998), which tried to debunk an article published by JAMA that found support for the five stage grief theory. Now, that Skeptic article had received a well-deserved thrashing by some reputed blogs, see this world Of Psychology post that exposes many of the holes in Friedman and James' argument, so possibly out of desperation Shermer though why not settle the scores and expose all stage theories as pseudoscience. Unfortunately he fails miserably in defending his publication and we have seen above why!Now, let us come to the meat of the controversy: the stages of grief theory of Kubler-Ross for which the Yale group found evidence and which the Skeptics didn't like and found the evidence worth criticizing. I have read both the original JAMA paper and the skeptic article and see some merits to both side. In fact I guess the stance that Friedman et al have taken I even agree with to an extent, especially their decoupling of stages of grief from stages of dying person/ stages of adjustment to catastrophic death. Some excerpts:IN 1969 THE PSYCHIATRIST ELIZABETH KÜBLER-ROSS wrote one of the most influential books in the history of psychology, On Death and Dying. It exposed the heartless treatment of terminally-ill patients prevalent at the time. On the positive side, it altered the care and treatment of dying people. On the negative side, it postulated the now-infamous five stages of dying—Denial, Anger, Bargaining, Depression, and Acceptance (DABDA), so annealed in culture that most people can recite them by heart. The stages allegedly represent what a dying person might experience upon learning he or she had a terminal illness. “Might” is the operative word, because Kübler-Ross repeatedly stipulated that a dying person might not go through all five stages, nor would they necessarily go through them in sequence. It would be reasonable to ask: if these conditions are this arbitrary, can they truly be called stages?Many people have contested the validity of the stages of dying, but here we are more concerned with the supposed stages of grief which derived from the stages ofdying.During the 1970s, the DABDA model of stages of dying morphed into stages of grief, mostly because of their prominence in college-level sociology and psychology courses. The fact that Kübler-Ross’ theory of stages was specific to dying became obscured.Prior to publication of her famous book, Kübler-Ross hypothesized the Five Stages of Receiving Catastrophic News, but in the text she renamed them the Five Stages of Dying or Five Stages of Death. That led to the later, improper shift to stages of grief. Had she stuck with the phrase catastrophic news, perhaps the mythology of stages wouldn’t have emerged and grievers wouldn’t be encouraged to try to fit their emotions into non-existent stages. I wholeheartedly concur with the authors that it is not good to confuse stages that a dying person may go through on receiving catastrophic death of terminal illness, with grief stages that may follow once one has learned of a loss and is coping with the loss(death of someone, divorce of parents etc); in the first case the event that is of concern is in the future and would lead to different tactics, than for the latter case when the event is already in the past and has occurred. thus, as rightly pointed by the authors, denial may make sense for dying people - 'the diagnosis is incorrect, I am not going to die; I have no serious disease.'; denial may not make sense for a loos of a loved one by death, as the vent has already happened and only a very disturbed and unable to cope person would deny the factuality of the event (death). but this is a lame point; in grief (equated with loss of loved one), they stage can be rightly characterized as disbelief/dissociation/isolation, whereby one would actively avoid all thoughts of the loved one's non-existence and come up with feelings like 'I still cannot believe that my mother is no longer alive' . Similarly My personal view is that while anger and energetic searching of alternatives may be the second stage response to catastrophic prospective forecast; the second stage response to a catastrophic news (news of a loss of loved one) would be more characterized by energized yearning for the lost one and an anger towards the unavoidable circumstances and the world in general that led to the loss.The third stage is particularly problematic; in dying people it makes perfect sense to negotiate and bargain, as the event has not really happened ('I'll stop sinning, take away the cancer); but as rightly pointed out by the authors it doesn't make sense for events that have already happened.while many authoritative people have substituted yearning for the third stage in case of grief , I would propose that we replace that with regret or guilt. I know this would be controversial; but the idea is a bargaining of past events like 'God, please why didn't you take my life, instead of my young son' ; it doesn't make sense but is a normal stage of grieving - looking for and desiring alternative bad outcomes ('I wish I was dead instead of him'. The other two stages depression and acceptance do not pose as much problems, so I'll leave them for now. suffice it to say that becoming depressed / disorganized and then recovering/ becoming reorganized are normal stages that one would be expected to go through.What I would now return is to their criticism of Kubler-Ross. They first attack her saying her evidence was anecdotal and based on personal feelings then , instead of correcting this gross error and themselves providing statistical and methodological research results, present anecdotal evidence based on their helping thousands of grieving persons.Second they claim, that this stage based theories cause much harm; but I am not able to understand why a stage based theory must cause harm and , for all their good intentions, I think they are seriously confused here. On the one hand they claim (for eg in depression section) that stages lead to complacency:It is normal for grievers to experience a lowered level of emotional and physical energy, which is neither clinical depression nor a stage. But when people believe depression is a stage that defines their sad feelings, they become trapped by the belief that after the passage of some time the stage will magically end. While waiting for the depression to lift, they take no actions that might help them. and on the other hand they claim that labeling something causes over reactivity and over treatment:When medical or psychological professionals hear grievers diagnose themselves as depressed, they often reflexively confirm that diagnosis and prescribe treatment with psychotropic drugs. The pharmaceutical companies which manufacture those drugs have a vested interest in sustaining the idea that grief-related depression is clinical, so their marketing supports the continuation of that belief. The question of drug treatment for grief was addressed in the National Comorbidity Survey published in the Archives of General Psychiatry,Vol. 64, April, 2007). “Criteria For Depression Are Too Broad Researchers Say—Guidelines May Encompass Many Who Are Just Sad.” That headline trumpeted the survey’s results, which observed more than 8,000 subjects and revealed that as many as 25% of grieving people diagnosed as depressed and placed on antidepressant drugs, are not clinically depressed. The study indicated they would benefit far more from supportive therapies that could keep them from developing full-blown depression.Now, I am not clear what the problem is - is it complacency or too much concerns and over-treatment. And this argument they keep on repeating and hammering down - that stages do harm as them make people complacent that thing swill get better on its own and no treatment is needed. I don't think that is a valid assumption, we all know that many things like language develop, but their are critical times hen interventions are necessary for proper language to develop; so too is the case with grieving people, they would eventually recover, but they do need support of friends and family and all interventions, despite this being 'just a phase'. I don't think saying that someone would statistically go away in a certain time-period eases the effects one if feeling of the phenomenon right now. An analogy may help. It is statistically true, that on an average, within six months a person would get over his most recent breakup and start perhaps flirting again; that doesn't subtract from the hopelessness and feelings of futility he feels on teh days just following the breakup and most of the friends and family do provide support even though they know that this phase will get over. Same is true for other stages like stages of grief and the concerns of authors are ill-founded.The concerns of the author that I did feel sympathetic too though was the stage concept being overused in therapy and feelings like guilt being inadvertently implanted in the clients by the therapists.Grieving parents who have had a troubled child commit suicide after years of therapy and drug and alcohol rehab, are often told, “You shouldn’t feel guilty, you did everything possible.” The problem is that they weren’t feeling guilty, they were probably feeling devastated and overwhelmed, among other feelings. Planting the word guilt on them, like planting any of the stage words, induces them to feel what others suggest. Tragically, those ideas keep them stuck and limit their access to more helpful ideas about dealing with their broken hearts.Therapists have to be really careful here and not be guided by pre-existing notions of how the patient is feeling. they should listen to the client and when in doubt ask questions, not implicitly suggest and assume things. That indeed is a real danger.Lastly the criticism of stages/ common traits vs individual differences and uniqueness have to be dealt with. the claim that each grieves uniquely is not a novel claim and I do not find it lacking in evidence too. It is tautological. But still some common patterns can be elucidated and subsumed under stages. These stages are the 'normal' stages with enough room for individual aberration . I think there has to be more tolerance and acceptance of the 'abnormal' in general - if someone directly accepts and never feels and denial he too is abnormal - but one we readily accept as a resilient persons; the other who gets stuch at denial has to be shown greater care and hand-holded through the remaining stages to come to acceptance.In the end I would like to briefly touch on the Yale study that reignited this controversy. Here is the summary of An Empirical Examination of the Stage Theory of Grief by Paul K. Maciejewski, PhD; Baohui Zhang, MS; Susan D. Block, MD; Holly G. Prigerson, PhD. Context The stage theory of grief remains a widely accepted model of bereavement adjustment still taught in medical schools, espoused by physicians, and applied in diverse contexts. Nevertheless, the stage theory of grief has previously not been tested empirically.Objective To examine the relative magnitudes and patterns of change over time postloss of 5 grief indicators for consistency with the stage theory of grief.Design, Setting, and Participants Longitudinal cohort study (Yale Bereavement Study) of 233 bereaved individuals living in Connecticut, with data collected between January 2000 and January 2003.Main Outcome Measures Five rater-administered items assessing disbelief, yearning, anger, depression, and acceptance of the death from 1 to 24 months postloss.Results Counter to stage theory, disbelief was not the initial, dominant grief indicator. Acceptance was the most frequently endorsed item and yearning was the dominant negative grief indicator from 1 to 24 months postloss. In models that take into account the rise and fall of psychological responses, once rescaled, disbelief decreased from an initial high at 1 month postloss, yearning peaked at 4 months postloss, anger peaked at 5 months postloss, and depression peaked at 6 months postloss. Acceptance increased throughout the study observation period. The 5 grief indicators achieved their respective maximum values in the sequence (disbelief, yearning, anger, depression, and acceptance) predicted by the stage theory of grief.Conclusions Identification of the normal stages of grief following a death from natural causes enhances understanding of how the average person cognitively and emotionally processes the loss of a family member. Given that the negative grief indicators all peak within approximately 6 months postloss, those who score high on these indicators beyond 6 months postloss might benefit from further evaluation.I believe they have been very honest with their data and analysis. They found peak of denial, yearning, anger , depression and acceptance in that order. I belie they could have clubbed together anger and yearning together as the second stage as this study dealt with stages of grief and not stages of dying and should have introduced a new measure of regret/guilt and I predict that this new factors peak would be between the anger/yearning peak and depression peak.Thus, to summarize, my own theory of grief and dying (in eth eight basic adaptive problems framework) are :Stage theory of dying (same as Kubler-Ross):Denial: avoiding the predator; as the predator (death ) cannot be avoided , it is denied!!Anger/ Searching: Searching for resources; an energetic (and thus partly angry)efforts to find a solution to this over looming death; belief in pseudo-remedies etc.Bargaining/ negotiating: forming alliances and friendships: making a pact with the devil...or the God ...that just spare me this time and I will do whatever you want in future.Depression: parental investment/ bearing kids analogy: is it worth living/ bringing more people into this world? Acceptance: helping kin analogy: The humanity is myself. even if I die, I live via others. Stage theory of grief (any loss especially loss of a loved one) Disbelief: Avoiding the predator (loss) . I cant believe the loss happened. Let me not think about it.Anger/ Yearning: Energetic search for resources (reasons) . Why did it happen to me; can the memories and yearning substitute for the loved one?Bargaining/ regret/ guilt: forming alliances and friendships: Could this catastrophe be exchanged for another? could I have died instead of him?Depression: parental investment/ bearing kids analogy : is it worth living/ bringing more people into this world? Acceptance: helping kin analogy: Maybe I can substitute the lost one with other significant others? Maybe I should be thankful that other significant persons are still there and only one loss has occurred.Do let me know your thoughts on this issue. I obviously being a researcher in the stages paradigm was infuriated seeing the Shermer article,; others may have more balanced views. do let me know via comments, email!!Paul K. Maciejewski, PhD; Baohui Zhang, MS; Susan D. Block, MD; Holly G. Prigerson, PhD (2007). An Empirical Examination of the Stage Theory of Grief JAMA, 297 (7), 716-723... Read more »
Paul K. Maciejewski, PhD; Baohui Zhang, MS; Susan D. Block, MD; Holly G. Prigerson, PhD. (2007) An Empirical Examination of the Stage Theory of Grief. JAMA, 297(7), 716-723. DOI: http://jama.ama-assn.org/cgi/content/full/297/7/716
- February 11, 2009
- 02:28 AM
- 1,171 views
Psychosis and Salience dysregulation
by sandygautam in The Mouse Trap
Regular readers of this blog will know that I subscribe to the incentive salience theory of doapmaine propounded by Berridge et al. As per this theory dopamine mediates the salience of an internal/ external stimulus and endows and activates the motivational salience related to that stimulus. In simple words the mesolimbic dopamine systems serves to identify the importance of a stimulus to us- be it aversive or pleasurable. This conceptualization is different from the hedonic pleasure theory of dopamine and distinguishes between 'wanting/ dreading' and 'liking/ disliking'. Thus, the amount of doapminergic activity will affect the degree of dread or want associated with a stimulus, but not the actual liking/ disliking of the reward/punishment administered following the stimulus. Till now we have been talking mostly in terms of classical Pavlovian conditioning, but the same incentive salience can be extended to operant conditioning paradigm, with the external stimulus being replaced by an internal intention and the mesolimbic dopamine system activity determining whether, and to what degree, one is motivated to perform the intended action. Again the motivational component should be separated from our actual liking/disliking of the expected outcomes of the behavioral measures. Thus, we may actually like the reward at the end of operant behavior less , but still be highly motivated to perform the action depending on high dopaminergic activity that confers a very positive incentive salience to that operant behavior. Consider the gambler for whom winning the jackpot is motivationally very salient , but the actual pleasure he may derive or hedonistic value he may get from spending the lottery amount may not be that much. Or consider the carving of a drug addict for the dope- the drug administered may not feel that pleasurable , but the wanting is strong.
We also know about the reward error-prediction theory of dopamine, and that in my opinion is not incompatible with the incentive salience theory. The error coding signal of dopamine surge or ebb signals that the stimulus has become meaningful and salient and needs to be (re)coded. Thus, in most basic terms dopamine will signal whether the stimulus is meaningful for the organism and as it could be meaningful in both positive and negative sense , the dopamine activity will lead to subjective feelings of either alarm or significance associated with that stimulus. In either case, the stimulus would 'grab our attention' and become salient (this may happen unconsciously) and perhaps if the activity is sustained also become consciously significant and enter consciousness.
Now, consider a dysregulated mesolimbic dopamine system that is hyperactive and is characterized by excessive dopamine synthesis, release and synaptic presence. Here , for a given stimulus, that usually, and in normal individuals, grabs the unconscious attention and is unconsciously and automatically evaluated , the dopamenirgic activity may be sustained and lead to conscious perception of/ attention to the stimulus and a conscious evaluation or appraisal of the stimulus. The individual with such a hyperactive dopaminergic system would start paying conscious attention to many stimulus that were earlier processed subliminally and start noticing a much deeper sensory (external) and cognitive( internal) world. But the effect would not just be a richness of sensation and distractibility, the dopamine surge will also label the stimulus to which the attention has thus been directed salient and the individual will try to reason why that stimulus is significant.So first sensory (vividness) and cognitive (racing thoughts) richness arrives, along with an overwhelming subjective feeling that they are important and later with a need to create a story as to why the stimulus (internal/ external) is important comes rationalizing and delusions that serve to jutify the significance of things that were earlier not consciously significant/threatening. Thus, the delusions of grandeur and persecution. Also, sometimes the dopamine surges may happen without any associated external and internal stimulus. We know that when one is not task-oriented (either task involving external stimulus or internal goal-directed activity), then the default network that is usually associated with self-system and imagination takes over. In such conditions when the default network is active and one is just focused on self and internal imaginary world, a dopamine surge may signal that the self and imagination is very salient or important. The self thus becoming salient may get associated with other arbitrary external stimulus happening at that time and one may get delusions of reference whereby seemingly innocuous and impersonal external communications/ references are deemed to refer to the self. thus, delusions may be partly explained by stimuli becoming consciously significant and also stimuli/ self becoming salient out of context. Hallucinations might also be explained partly by the imaginative activity of the default newtrok becoming salient , meaningful, conscious and life-like and thus sort of 'real'. Thus, while many have outgrown the unconscious-becoming-conscious theories of psychosis, I see some scope for more work here and a possible mechanism too.
Of course the above incentive salience hyper activation can work in conjunction with other deficits/abnormalities like self-monitoring deficit, theory-of-mined hyperactivity, intentional attribution hyperactivity, need for more control in lieu of facing an unpredictable environment, jumping-to-conclusion bias etc to foster full fledged symptoms of psychosis in some individuals.
I am grateful to Mind Hacks for discovering the Shitij Kapur paper on the incentive dysregulation theory of psychosis and I now quote extensively form the paper.
First the paper establishes the dopamine theory of psychosis by looking at anti-psychotic drug action and also the effect of dopamine administration.
The dopamine hypothesis of schizophrenia has comprised two distinct ideas: a dopamine hypothesis of antipsychotic action and a dopamine hypothesis of psychosis. The two are related but different. The dopamine hypothesis of antipsychotic medications can be traced to the early observation that antipsychotics increase the turnover of monoamines , more specifically, dopamine , and this observation anticipated the discovery of the "neuroleptic receptor" , now called the dopamine D2 receptor, providing a mechanistic basis for the dopamine hypothesis of antipsychotic action. A central role for D2 receptor occupancy in antipsychotic action is now well established, buttressed by neuroimaging studies using positron emission tomography and single photon emission computed tomography. However, the importance of dopamine receptors in the treatment of psychosis does not by itself constitute proof of the involvement of dopamine in psychosis .
Early evidence for a role of dopamine in psychosis was the observation that psychostimulant agents that trigger release of dopamine are associated with de novo psychosis and cause the worsening of psychotic symptoms in patients with partial remissions. Further evidence came from postmortem studies that showed abnormalities in dopaminergic indexes in schizophrenia, although the interpretation of these data was always confounded by drug effects . The most compelling evidence in favor of the dopamine hypothesis emerges from neuroimaging studies . Several studies have shown that patients with schizophrenia, when psychotic, show a heightened synthesis of dopamine , a heightened dopamine release in response to an impulse , and a heightened level of synaptic dopamine . While there are some indications of a change in the number of receptors , the claim remains controversial . Thus, on balance there is reasonable evidence of heightened dopaminergic transmission, more likely a presynaptic dysregulation than a change in receptor number, in patients with schizophrenia. This role of dopamine in psychosis and schizophrenia needs to be put in perspective. First, it is quite likely that the dopaminergic abnormality in schizophrenia is not exclusive (as other systems are involved), and it may not even be primary . Second, the dopaminergic disturbance is likely a "state" abnormality associated with the dimension of psychosis-in-schizophrenia, as opposed to being the fundamental abnormality in schizophrenia . As suggested by Laruelle and Abi-Dargham , "Dopamine [is] the wind of the psychotic fire." If so, how does dopamine, a neurochemical, stoke the experience of psychosis?
After this he looks at the incentive salience theory of dopamine.
Another account of the roles of dopamine is the incentive/motivational salience hypothesis of Berridge and Robinson and similar proposals by others . This latter conceptualization provides the most plausible framework for the current discussion and will be detailed further in this article.
The motivational salience hypothesis in its current form builds on the previous ideas of Bindra and Toates , who have written about incentive motivation, and of neurobiologists such as Fibiger and Phillips , Robbins and Everitt , Di Chiara , Panksepp , and others who have speculated on the role of dopamine in these motivated behaviors. According to this hypothesis, dopamine mediates the conversion of the neural representation of an external stimulus from a neutral and cold bit of information into an attractive or aversive entity . In particular, the mesolimbic dopamine system is seen as a critical component in the "attribution of salience," a process whereby events and thoughts come to grab attention, drive action, and influence goal-directed behavior because of their association with reward or punishment . This role of dopamine in the attribution of motivational salience does not exclude the roles suggested by previous theorists; instead it provides an interface whereby the hedonic subjective pleasure, the ability to predict reward, and the learning mechanisms allow the organism to focus its efforts on what it deems valuable and allows for the seamless conversion of motivation into action . When used in this sense, the concept of motivational salience brings us a step closer to concepts such as "decision utility" that are used to explain and understand the evaluations and choices that humans make . Conceived in this way, the role of dopamine as a mediator of motivational salience provides a valuable heuristic bridge to address the brain-mind question of psychosis-in-schizophrenia.
Then he goes to his main thesis that psychosis can be considered as a disorder of salience. Note the similarities as well as differences from my conceptualization as above.
It is postulated that before experiencing psychosis, patients develop an exaggerated release of dopamine, independent of and out of synchrony with the context. This leads to the assignment of inappropriate salience and motivational significance to external and internal stimuli. At its earliest stage this induces a somewhat novel and perplexing state marked by exaggerated importance of certain percepts and ideas. Given that most patients come to the attention of clinicians after the onset of psychosis, phenomenological accounts of the onset of psychosis are largely anecdotal or post hoc. However, patients report experiences such as, "‘I developed a greater awareness of.... My senses were sharpened. I became fascinated by the little insignificant things around me’" ; "Sights and sounds possessed a keenness that he had never experienced before" ; "‘It was as if parts of my brain awoke, which had been dormant’" ; or "‘My senses seemed alive.... Things seemed clearcut, I noticed things I had never noticed before’" . Most patients report that something in the world around them is changing, leaving them somewhat confused and looking for an explanation. This stage of perplexity and anxiety has been recognized by several authors and is best captured in the accounts of patients: "‘I felt that there was some overwhelming significance in this’" ; "‘I felt like I was putting a piece of the puzzle together’" .
If this were an isolated incident, perhaps it would be no different from the everyday life experience of having one’s attention drawn to or distracted by something that is momentarily salient and then passes. What is unique about the aberrant saliences that lead to psychosis is their persistence in the absence of sustaining stimuli. This experience of aberrant salience is well captured by this patient’s account: "‘My capacities for aesthetic appreciation and heightened sensory receptiveness...were very keen at this time. I had had the same intensity of experience at other times when I was normal, but such periods were not sustained for long and had also been integrated with other feelings’" . From days to years (the prodrome) , patients continue in this state of subtly altered experience of the world, accumulating experiences of aberrant salience without a clear reason or explanation for the patient.
Delusions in this framework are a "top-down" cognitive explanation that the individual imposes on these experiences of aberrant salience in an effort to make sense of them. Since delusions are constructed by the individual, they are imbued with the psychodynamic themes relevant to the individual and are embedded in the cultural context of the individual. This explains how the same neurochemical dysregulation leads to variable phenomenological expression: a patient in Africa struggling to make sense of aberrant saliences is much more likely to accord them to the evil ministrations of a shaman, while the one living in Toronto is more likely to see them as the machinations of the Royal Canadian Mounted Police. Once the patient arrives at such an explanation, it provides an "insight relief" or a "psychotic insight" and serves as a guiding cognitive scheme for further thoughts and actions. It drives the patients to find further confirmatory evidence—in the glances of strangers, in the headlines of newspapers, and in the lapel pins of newscasters.
Hallucinations in this framework arise from a conceptually similar and more direct process: the abnormal salience of the internal representations of percepts and memories. This could account for the gradation in the severity of hallucinations, whereby to some people they seem like their own "internal thoughts," to others their own "voice," to others the voice of a third party, and to some others the voice of an alien coming from without . So long as these events (delusions and hallucinations) remain private affairs, they are not an illness by society’s standards . It is only when the patient chooses to share these mental experiences with others, or when these thoughts and percepts become so salient that they start affecting the behavior of the individual, that they cross over into the domain of clinical psychosis.
In the remaining part of the paper the author proposes how anti-psychotics work by dampening the salience of things and how they should be adjuncted with psychotherapy as the salience of delusional ideas/ hallucinations may be dampened immediately, but it takes traditional psychological work on the part of the patients to attenuate/overcome the already established beliefs/ perceptions that are no longer salient. I recommended reading the article in full as it has immense treatment implications.
Another implication of the paper is questioning the categorical diagnostic criteria of schizophrenia/ psychosis and making it more dimensional in nature by positing that the dysregulations of incentive salience happens in a continuum. this theme is more boldly covered in a recent BJP paper that argues that we rename schizophrenia to incentive dysregulation syndrome.
Analogous to the metabolic syndrome, although in need of improving on the weaknesses that since its introduction have become apparent, many people with positive psychotic experiences, that have been shown to constitute a fundamental alteration in salience attribution, also display evidence of alterations in other dimensions of psychopathology such as mania,disorganisation and developmental cognitive deficit. This may be referred to as the salience dysregulation syndrome. If the values of the dimensional components in this syndrome rise above a certain threshold, need for care (formal or informal) may arise. Depending on which combinations of dimensional psychopathology are most prominent in this salience dysregulation syndrome and taking into account which elements have been shown to possess the best diagnostic specificity, as discussed above, the categorical representation of this dimensional psychopathology may be expressed using three sub-categories: with affective expression (high in mania/depression dimension); with developmental expression (high in developmental cognitive deficit/negative symptoms); and not otherwise specified. The first two sub-categories are based on evidence of specificity and the more agnostic category of ‘not otherwise specified’ reflects the continuing gap in knowledge.
This I believe is welcome change and I have been arguing endlessly for psychosis to be seen as more of a dimensional syndrome (with autism at the other end) and in continuum with normality.
Shitij Kapur (2003). Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am J Psychiatry. (160), 13-23
J. van Os (2009). A salience dysregulation syndrome The British Journal of Psychiatry, 194 (2), 101-103 DOI: 10.1192/bjp.bp.108.054254... Read more »
Shitij Kapur. (2003) Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. Am J Psychiatry., 13-23. DOI: http://ajp.psychiatryonline.org/cgi/content/abstract/160/1/13
J. van Os. (2009) A salience dysregulation syndrome. The British Journal of Psychiatry, 194(2), 101-103. DOI: 10.1192/bjp.bp.108.054254
- October 20, 2008
- 09:00 AM
- 1,139 views
The Maudsely debates: anti-depressants and placebo
by sandygautam in The Mouse Trap
The Institute Of Psychiatry, London conducts Madusley debates on relevant psychiatric topics between distinguished psychiatrists and neuroscientists and also publishes them as a podcast. The most recent such debate consisted of the issue of whether anti-depressants are any better than Placebos in treating depression. There were knowledgeable arguments on both fronts and no matter what position you hold, hearing the debate would definitely enhance your knowledge about the issues involved.I, for one, did not knew that anti-depressants worked by addressing the automatic and unconscious attention/ perception and memory biases. While I was aware that CBT worked top-down and affected cognitive biases and brain regions different from that areas affected by anti-depressants that presumably worked on neurotransmitter levels and bottom-up, the revelation that Goodwin's team had found that anti-depressants too work on biases, but unconscious ones, while CBT works on conscious ones, was new and enriching.On the other hand I agree with many of the methodological issues raised by the speakers who claimed that anti-depressants were no good than placebos : the fact that the results lack 'clinical significance'; being psycho-active they are bound to have some effects and also the fact that the relief may be symptomatic due to 'drug' nature of anti-depressants and not specific and addressing the underlying disease, that the scale (HRSD) measuring depression may be not reflective of DSM criterion and may not be the best measure of disease severity; and I concur, but still think that the current generation of anti-depressants (other medicines) must be some good (over and above the good they bring by way of Placebo effect) especially since research has shown how they work (with a lag of few weeks before showing effects and by primarily inducing neurogenesis and affecting discrete brain areas) and how they are indeed effective at least in severely depressed people. Still all this should be taken with a pinch of salt- we have continuously been replacing outdated models of depression (like serotonin deficiency) by more and more accurate models (like neurogenesis). In my view we need to persist in that direction, though also having a healthy skepticism of what the drug companies might say and market new drugs and models for. Fortunately there are a host of unbiased pharmacists, neuroscientist and psychiatrist out there who are struggling with finding the most accurate model and the most accurate medication/ treatment like CBT for the same; so we don't need to despair. However, to blindly accepted all drugs (and models) , marketed by the Big Pharma, at their face value, and in clear evidence that they have not been proved effective beyond doubt, in clear evidence that negative finding have not been reported diligently and in view of the fact that at many time side -effects are glossed over, I would request not to be seduced overtly by the anti-depressants efficacy hype, but to moderate that with other known efficacious manes like exercise, CBT and yoga (all of which may be working by placebo effect themselves, but which definitely have lesser or no side-effects than anti-depressants. this of course does'nt mean that you give up your medicenes- at least not without consulting your psychiatrist- but supplementing them with other non-drug measures and reducing your reliance on the drugs- as they definitely have side-effects and may not be that efficacious as depicted in advertisements/ popular press.Here is the summary of the talk from the IoP website:Inspired by the recent media-frenzy at Prof Irving Kirsch?s research which suggested that antidepressants are no better than placebo, this Maudsley debate had an extremely good turnout.Professor Kirsch gave us a run through of his research, in which he claimed to have found that there was a statistically significant benefit in the use of SSRIs over placebo - but that the difference was smaller than the standard of ?clinical significance? set down by the UK?s National Institute for Clinical Excellence (NICE) for all but the most depressed patients. His team also found that patients? response to placebo across all the trials was ?exceptionally large? - an indication of the complexity of the disorder. It was only the fact that the most severely depressed patients showed a much lower response to placebo that made the drug response clinically significant in this group of patients.Against the motion, Professor Guy Goodwin argued that there were crucial flaws to the bounds that Kirsch had used to define clinical effectiveness. He pointed out that these criteria fail to contain an accurate description of depression, for example that they fail to mention persistent negative thoughts and other crucial symptoms that would be included in DSM IV.For the motion, Dr Joanna Moncrieff alluded to the idea that there may be some sort of conspiracy of complacency and wishful thinking within the psychiatric profession as to the effectiveness of anti-depressants.An impassioned speech against the motion was then given by Prof Lewis Wolpert. This was inspired by his own experiences of depression, which proved a powerful persuader as to the place that anti-depressants have in the treatment of severe depression.Prior to the debate the audience were asked to vote which side of the argument they favoured. The leaning was overwhelmingly against the motion, perhaps not surprising in a room full of psychiatrists! After the speakers had made their points votes were recounted and a minority had changed their minds and had been swayed to support the motion. However those against the motion still had the majority. The original article that sparked this debate is available online at PLOS Medicine, and I'm including the editor's summary below:Background.Everyone feels miserable occasionally. But for some people—those with depression—these sad feelings last for months or years and interfere with daily life. Depression is a serious medical illness caused by imbalances in the brain chemicals that regulate mood. It affects one in six people at some time during their life, making them feel hopeless, worthless, unmotivated, even suicidal. Doctors measure the severity of depression using the “Hamilton Rating Scale of Depression” (HRSD), a 17–21 item questionnaire. The answers to each question are given a score and a total score for the questionnaire of more than 18 indicates severe depression. Mild depression is often treated with psychotherapy or talk therapy (for example, cognitive–behavioral therapy helps people to change negative ways of thinking and behaving). For more severe depression, current treatment is usually a combination of psychotherapy and an antidepressant drug, which is hypothesized to normalize the brain chemicals that affect mood. Antidepressants include “tricyclics,” “monoamine oxidases,” and “selective serotonin reuptake inhibitors” (SSRIs). SSRIs are the newest antidepressants and include fluoxetine, venlafaxine, nefazodone, and paroxetine.Why Was This Study Done?Although the US Food and Drug Administration (FDA), the UK National Institute for Health and Clinical Excellence (NICE), and other licensing authorities have approved SSRIs for the treatment of depression, some doubts remain about their clinical efficacy. Before an antidepressant is approved for use in patients, it must undergo clinical trials that compare its ability to improve the HRSD scores of patients with that of a placebo, a dummy tablet that contains no drug. Each individual trial provides some information about the new drug's effectiveness but additional information can be gained by combining the results of all the trials in a “meta-analysis,” a statistical method for combining the results of many studies. A previously published meta-analysis of the published and unpublished trials on SSRIs submitted to the FDA during licensing has indicated that these drugs have only a marginal clinical benefit. On average, the SSRIs improved the HRSD score of patients by 1.8 points more than the placebo, whereas NICE has defined a significant clinical benefit for antidepressants as a drug–placebo difference in the improvement of the HRSD score of 3 points. However, average improvement scores may obscure beneficial effects between different groups of patient, so in the meta-analysis in this paper, the researchers investigated whether the baseline severity of depression affects antidepressant efficacy.What Did the Researchers Do and Find?The researchers obtained data on all the clinical trials submitted to the FDA for the licensing of fluoxetine, venlafaxine, nefazodone, and paroxetine. They then used meta-analytic techniques to investigate whether the initial severity of depression affected the HRSD improvement scores for the drug and placebo groups in these trials. They confirmed first that the overall effect of these new generation of antidepressants was below the recommended criteria for clinical significance. Then they showed that there was virtually no difference in the improvement scores for drug and placebo in patients with moderate depression and only a small and clinically insignificant difference among patients with very severe depression. The difference in improvement between the antidepressant and placebo reached clinical significance, however, in patients with initial HRSD scores of more than 28—that is, in the most severely depressed patients. Additional analyses indicated that the apparent clinical effectiveness of the antidepressants among these most severely depressed patients reflected a decreased responsiveness to placebo rather than an increased responsiveness to antidepressants.What Do These Findings Mean?These findings suggest that, compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression, but show significant effects only in the most severely depressed patients. The findings also show that the effect for these patients seems to be due to decreased responsiveness to placebo, rather than increased responsiveness to medication. Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective. In addition, the finding that extremely depressed patients are less responsive to placebo than less severely depressed patients but have similar responses to antidepressants is a potentially important insight into how patients with depression respond to antidepressants and placebos that should be investigated further.Irving Kirsch, Brett J. Deacon, Tania B. Huedo-Medina, Alan Scoboria, Thomas J. Moore, Blair T. Johnson (2008). Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration PLoS Medicine, 5 (2) DOI: 10.1371/journal.pmed.0050045... Read more »
Irving Kirsch, Brett J. Deacon, Tania B. Huedo-Medina, Alan Scoboria, Thomas J. Moore, & Blair T. Johnson. (2008) Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the Food and Drug Administration. PLoS Medicine, 5(2). DOI: 10.1371/journal.pmed.0050045
- May 11, 2009
- 03:52 PM
- 1,085 views
synaptic plasticity: angelman's/autism and psychosis
by sandygautam in The Mouse Trap
There is a recent article in Nature Neuroscience by Philpot et al regarding how experience-dependent synaptic plasticity is downregulated in Angelmans' syndrome and perhaps in Autism too, as the Ube3a gene involved is implicated in both disorders.
First a little history about Angelman- it is a disorder caused by deletion/lack of a maternally imprinted UBE3a gene in chromosomal region 15q11-q13 . It is typically contrasted with Prader-Willi syndrome which is caused by a paternally imprinted gene malfunction in the same chromosomal region. Christopher Badcock has used this to contrast Autism (related to Angelman) and Psychosis (more common in PWS) to argue that Autism and Psychosis are due to a genomic imprinting tug of war between fathers and mothers genes.
I have written about Badcock's and Crespi's thesis before and how it fits in with my views on Autism and Psychosis; suffice it to say that I am seeing the new study primarily from this prism of Autism and Psychosis dichotomy.
First , let us see what the study tells us:
It uses mouse model that contains silenced maternal Ube3a genes (Ube3a m-p+ mouse), thus trying to make a mouse model of Angelman.
What it found was:
1) Ube3a expression was markedly reduced in Ube3am-/p+ mice compared with wild-type mice in all three brain regions (visual neocortex, hippocampus,cerebellam). Consistent with previous observations, this attenuation was brain specific, as Ube3a was highly expressed in the liver of both Ube3am+/p- and Ube3am-/p+ mice.2) To determine the physiological consequences of Ube3a loss on neocortical development, we examined the developmental acquisition of spontaneous excitatory synaptic transmission by recording miniature excitatory postsynaptic currents (mEPSCs) in layer 2/3 pyramidal neurons of visual cortex (see Supplementary Table 1 online for intrinsic membrane properties of recorded neurons). Consistent with previous findings24, 25, mEPSC amplitudes decreased and frequency increased during development in wild-type mice . Just before eye opening (postnatal day 10, P10), mEPSC frequency and amplitude were indistinguishable between wild-type and Ube3am-/p+ mice . Thereafter, mEPSC frequency failed to develop normally in Ube3am-/p+ mice3)Although dark rearing had no measurable effect on mEPSC amplitude in wild-type mice at P25 , sensory deprivation strongly attenuated the normal developmental increase in mEPSC frequency in wild-type mice . In contrast, dark rearing did not affect mEPSC amplitude or frequency in Ube3am-/p+ mice. Consequently, mEPSC frequency in normally reared Ube3am-/p+ mice was not significantly different from that of dark-reared wild-type mice . These findings demonstrate that, although Ube3a is not necessary for the initial sensory-independent establishment of synaptic connectivity, it is selectively required for experience-dependent maturation of excitatory circuits.4)We therefore compared the properties of neocortical long-term depression (LTD) and LTP at layer 2/3 synapses in visual cortex of wild-type and Ube3am-/p+ mice at both young (P25) and adult (P100) ages. Because layer 2/3 pyramidal neurons receive major inputs from layer 4 pyramidal neurons, layer 2/3 field potentials were evoked by layer 4 stimulation . We began by measuring LTD in young mice using a standard stimulation protocol (1 Hz for 15 min). Although LTD was reliably induced in young wild-type mice, it was absent in young Ube3am-/p+ mice . We also observed deficits in LTP induction. A relatively weak induction protocol (three 1-s trains of 40-Hz stimulation) elicited LTP in young wild-type mice, but failed to reliably induce LTP in young Ube3am-/p+ mice . To test whether the neocortex of Ube3am-/p+ mice was capable of expressing LTP, we also applied a strong LTP stimulation protocol (two 1-s trains of 100-Hz stimulation). This protocol consistently induced LTP in both Ube3am-/p+ and wild-type mice. Thus, as with LTP deficits in hippocampus8, 9, the LTP induction machinery is impaired in the visual cortex of Ube3am-/p+ mice and this deficit in LTP can be overcome with strong stimulation.5)To determine whether the plasticity deficits in Angelman syndrome mice persisted into adulthood, we tested LTD and LTP in adults (P100). In adult wild-type mice, LTD induced by 1-Hz stimulation was absent, as expected27, whereas LTP could be induced with strong stimulation. In adult Ube3am-/p+ mice, however, neither of these protocols were effective at modifying synaptic strength. These results indicate that wild-type mice show attenuated neocortical plasticity as they mature and that this attenuation of plasticity is more severe in the absence of Ube3a . Furthermore, these data indicate that plasticity defects in Angelman syndrome mice persist into adulthood...and so on (go read the full paper)
In a nutshell, what they found was that in presence of visual stimuli, the plasticity (measured by LTP/LTD ) of visual cortex was adversely affected. As sensory stimulus would normally be available while developing, this would adversely affect the plasticity in adolescence/ critical periods and also continue into adulthood.
Thus, Autism/ Angelman are charechterised by less synaptic plasticity in adulthood and during critical development periods. Paradoxically, this loss of synaptic plasticity is concomitant on their it being experience-dependent or having sensory stimuli. If the organism is sensory deprived, it may still retain the normal synaptic plasticity exhibited by similar sensory deprived normal people.
How does this relate to Psychosis? If my thesis is correct that autism and Psychosis are opposites, then I would predict that in either prader-willi or in Psychosis (scheziphrenia etc) there should be excessive experience-dependent plasticity. I was glad to learn that I am not the first one to make that proposition, but someone back in 1995 has argued for Hippocampal synaptic plasticity as an endophenotyoe for Episodic Psychosis. I now quote heavily form that article.
Here is the abstract:
Structural change in the hippocampal formation has become popular as a proposed neurobiological substrate for schizophrenic disorders. It is postulated that behavioral plasticity in the form of long-term potentiation of hippocampal synaptic transmission is an attractive putative mechanism for the mediation of transient psychosis. Moreover, the disturbed hippocampal neuroarchitecture found in schizophrenic brain may be susceptible to potentiation and dysfunctional to the degree that delusions and hallucinations develop. Partial and selective blockade of the receptors mediating potentiation may prove to be an efficient means of preventing psychotic episodes and avoiding further damage to the involved network. Basic research, utilizing experimental models such as intraventricular kainic acid injection, may help to clarify the anatomical and physiological substrate of psychosis.
The Main thesis of the paper is:
1. Anatomical, physiological, pharmacological, and behavioral findings are most consistent with the view that neuropathological changes within the limbic system, specifically within the hippocampal formation, may represent a biological substrate of schizophrenia.2. The biological mechanism underlying transient psychosis may be long-term potentiation (LTP) of synaptic transmission within the hippocampal formation.3. The effects of dopamine manipulation on these behaviors may be mediated by direct actions on the compromised limbic system of the psychotic patient.Further:
Associative plasticity within hippocampus occurs in the form of long-term potentiation (LTP), an experience-dependent increase in synaptic efficacy. Experimentally, LTP is produced by tetanic stimulation of afferent systems (Bliss and Lomo 1973) and has been shown to facilitate simple associative learning (Berger 1984) but disrupt more complex forms of associative plasticity (Robinson et al 1989). Hippocampal LTP has been observed to occur as a consequence of stimulus pairings in classical conditioning (Weisz et al 1984) and appears to be mediated by N-methyl-Daspartate (NMDA) receptors (Harris et al 1984). Pharmacological blockade of NMDA receptors has been shown to disrupt learning and memory in a variety of forms, including simple associations (Stillwell and Robinson 1990), spatial learning (Morris et al 1986; Heale and Harley 1990; Shapiro and Caramanos 1990), conditioned fear (Miserendino et al 1990; Kim et al 1991), olfactory memory (Staubli et al 1989) and gustatory memory (Welzl et al 1990). Some evidence, however, suggests that deficits involve motor impairment as well as disrupted learning (Keith and Rudy 1990)
Hippocampal function is particularly sensitive to neurochemical modulation, and the expression of monoamine receptors in the temporal lobe is altered in schizophrenics (Joyce 1993). Antipsychotics that reduce e... Read more »
PORT, R., & SEYBOLD, K. (1995) Hippocampal synaptic plasticity as a biological substrate underlying episodic psychosis. Biological Psychiatry, 37(5), 318-324. DOI: 10.1016/0006-3223(94)00128-P
Koji Yashiro, Thorfinn T Riday, Kathryn H Condon, Adam C Roberts, Danilo R Bernardo, Rohit Prakash, Richard J Weinberg, Michael D Ehlers . (2009) Ube3a is required for experience-dependent maturation of the neocortex. Nature Neuroscience. DOI: http://www.nature.com/neuro/journal/vaop/ncurrent/full/nn.2327.html
- March 24, 2009
- 08:36 AM
- 1,061 views
Beyond pleasure and pain: promotion, prevention, desire and dread.
by sandygautam in The Mouse Trap
The hedonic principle says that we are motivated to approach pleasure and avoid pain. This, as per Higgins is too simplistic a formulation. He supplants this with his concepts of regulatory focus, regulatory anticipation and regulatory reference. That is too much of jargon for a single post, but let us see if we can make sense.
First, let us conceptualize a desired end-state that an organism wants to be in- say eating food and satisfying hunger. This desired end-state becomes the current goal of the organism and leads to gold-directed behavior. Now, it is proposed that given this desired end-state, the organism has two ways to go about achieving or moving towards the end-state. If the organism has promotion or achievement self-regulation focus, then it will be more sensitive to whether the positive outcome is achieved or not and will thus have an approach orientation whereby it would try to match his next state to the desired state or try approaching the desired end-sate as close as possible. On the other hand, if the organism has a prevention or safety self-regulation focus, then it will be more sensitive to the negative outcome as to whether it becomes worse off after the behavior and will have an avoidance orientation whereby it would try to minimize the mismatch between his next state and the desired state. Thus given n next states with different food availability , the person with promotion focus will choose a next state that is as close, say within a particular threshold, to the desired state of satiety ; while the person with the prevention focus will be driven by avoiding all the sates that have a sub-threshold food availability and are thus mis-matched with the end-goal of satiety. thus, the number and actual states which are available for choosing form are different for the two groups: the first set is derived from whether the states are within a particular range of the end-state; the second set is derived from excluding all the states that are not within a particular range of the end-state. Put this way it is easy to see, that these strategies of promotion or prevention focus, place different cognitive and computational demands: the former requires explortation/ maximizing, the other may be satisfied by satisficing. (see my earlier post on exploration/ exploitation and satisficers / maximisers where I believe I was slightly mistaken).
Now, that I have explained in simple terms (hopefully) the concepts of self-regulatory focus, let me quote from the article and show how Higgins arrives at the same.
The theory of self-regulatory focus begins by assuming that the hedonic principle should operate differently when serving fundamentally different needs, such as the distinct survival needs of nurturance (e.g., nourishment) and security (e.g., protection). Human survival requires adaptation to the surrounding environment, especially the social environment (see Buss, 1996). To obtain the nurturance and security that children need to survive, children must establish and maintain relationships with caretakers who provide them with nurturance and security by supporting, encouraging, protecting, and defending them (see Bowlby, 1969, 1973). To make these relationships work, children must learn how their appearance and behaviors influence caretakers' responses to them (see Bowlby, 1969; Cooley, 1902/1964; Mead, 1934; Sullivan, 1953). As the hedonic principle suggests,children must learn how to behave in order to approach pleasure and avoid pain. But what is learned about regulating pleasure and pain can be different for nurturance and security needs. Regulatory-focus theory proposes that nurturance-related regulation and security-related regulation differ in regulatory focus. Nurturance-related regulation involves a promotion focus, whereas security related regulation involves a prevention focus.
.....
People are motivated to approach desired end-states, which could be either promotion-focus aspirations and accomplishments or prevention-focus responsibilities and safety. But within this general approach toward desired end-states, regulatory focus can induce either approach or avoidance strategic inclinations. Because a promotion focus involves a sensitivity to positive outcomes (their presence and absence), an inclination to approach matches to desired end-states is the natural strategy for promotion self-regulation. In contrast, because a prevention focus involves a sensitivity to negative outcomes (their absence and presence), an inclination to avoid mismatches to desired end-states is the natural strategy for prevention self-regulation (see Higgins, Roney, Crowe, & Hymes, 1994).
Figure 1 (not shown here, go read the article for the figure) summarizes the different sets of psychological variables discussed thus far that have distinct relations to promotion focus and prevention focus (as well as some variables to be discussed later). On the input side (the left side of Figure 1), nurturance needs, strong ideals, and situations involving gain-nongain induce a promotion focus, whereas security needs, strong oughts, and situations involving nonloss-loss induce a prevention focus. On the output side (the right side of Figure 1), a promotion focus yields sensitivity to the presence or absence of positive outcomes and approach as strategic means, whereas a prevention focus yields sensitivity to the absence or presence of negative outcomes and avoidance
as strategic means.Higgins then goes on describing many experiments that support this differential regulations focus and how that is different from pleasure-pain valence based approaches. He also discusses the regulatory focus in terms of signal detection theory and here it is important to note that promotion focus leads to leaning towards (being biased towards) increasing Hits and reducing Misses ; while prevention focus means leaning more towards increasing correct rejections and reducing or minimizing false alarms. Thus,a promotion focus individual is driven by finding correct answers and minimizing errors of omission; while a preventive focused person is driven by avoiding incorrect answers and minimizing errors of commission. In Higgin's words:
Individuals in a promotion focus, who are strategically inclined to approach matches to desired end-states, should be eager to attain advancement and gains. In contrast, individuals in a prevention focus, who are strategically inclined to avoid mismatches to desired end-states, should be vigilant to insure safety and nonlosses. One would expect this difference in self-regulatory state to be related to differences in strategic tendencies. In signal detection terms (e.g., Tanner & Swets, 1954; see also Trope & Liberman, 1996), individuals in a state of eagerness from a promotion focus should want, especially, to accomplish hits and to avoid errors of omission or misses (i.e., a loss of accomplishment). In contrast, individuals in a state of vigilance from a prevention focus should want, especially, to attain correct rejections and to avoid errors of commission or false alarms (i.e., making a mistake). Therefore, the strategic tendencies in a promotion focus should be to insure hits and insure against errors of omission, whereas in a prevention focus, they should be to insure correct rejections and insure against errors of commission .
He next discusses Expectancy x Value effects in utility research. Basically , whenever one tries to decide between two or more alternative actions/ outcomes, one tries to find the utility of a particular decision/ behavioral act based on both the value and expectance of the outcome. Value means how desirable or undesirable (i.e what value is attached) that outcome is to that person. Expectancy means how probable it is that the contemplated action (that one is deciding to do) would lead to the outcome. By way of an example: If I am hungry, I want to eat food. Lets say there are two actions or decisions that have different utility that can lead to my hunger reduction. The first involves begging for food from the shopkeeper; the second involves stealing the food from the shopkeeper. The first may be having positive value (begging might not be that embarrassing) , but low expectancy (the shopkeeper is miserly and unsympathetic) ; while the second act may have negative value (I believe that stealing is wrong and would like to avoid that act) but high expectancy (I am sure I'll be able to steal the food and fulfill my hunger). the utility I impart to the two acts may determine what act I eventually decide to indulge in.
Higgins touches on research that showed that Expectancy X value have a multiplicative effect i.e as expectancy increases, and value increases the motivation to take that decision/ course of action increases non-linearly. He clarifies that this interaction effect is seen in promotion focus , but not in preventive focus:
Expectancy-value models of motivation assume not only that expectancy and value have an impact on goal commitment as independent variables but also that they combine multiplicatively (Lewin, Dembo, Festinger, & Sears, 1944; Tolman, 1955; Vroom, 1964; for a review, see Feather, 1982). The multiplicative assumption is that as either expectancy or value increases, the impact of the other variable on commitment increases. For example, it is assumed that the effect on goal commitment of higher likelihood of goal attainment is greater for goals of higher value. This assumption reflects the notion that the goal commitment involves a motivation to maximize the product of value and expectancy, as is evident in a positive interactive effect of value and expectancy. This maximization prediction is compatible with the hedonic or pleasure principle because it suggests that people are motivated to attain as much pleasure as possible.
Despite the almost universal belief in the positive interactive effect of value and expectancy, not all studies have found this effect empirically (see Shah & Higgins, 1997b). Shah and Higgins proposed that differences in the regulatory focus of decision makers might underlie the inconsistent findings in the literature. They suggested that making a decision with a promotion focus is more likely to involve the motivation to maximize the product of value and expectancy. A promotion focus on goals as accomplishments should induce an approach-matches strategic inclination to pursue highly valued goals with the highest expected utility, which maximizes Value × Expectancy. Thus, the positive interactive effect of value and expectancy assumed by classic expectancy-value models should increase as promotion focus increases.
But what about a prevention focus? A prevention focus on goals as security or safety should induce an avoid-mismatches strategic inclination to avoid all unnecessary risks by striving to meet only responsibilities that are clearly necessary. This strategic inclination creates a different interactive relation between value and expectancy. As the value of a prevention goal increases, the goal becomes a necessity, like the moral duties of the Ten Commandments or the safety of one's child. When a goal becomes a necessity, one must do whatever one can to attain it, regardless of the ease or likelihood of goal attainment. That is, expectancy information becomes less relevant as a prevention goal becomes more like a necessity. With prevention goals, motivation would still generally increase when the likelihood of goal attainment is higher, but this increase would be smaller for high-value goals (i.e., necessities) than low-value goals. Thus, the second prediction was that the positive interactive effect of value and expectancy assumed by classic expectancy value models would not be found as prevention focus increased. Specifically, as prevention focus increases, the interactive effect of value and expectancy should be negative.
And that is exactly what they found! the paper touches on many other corroborating readers and the interested reader can go to the source for more. Here I will now focus on his concepts of regulatory expectancy and regulatory reference.
Regulatory Reference is the tendency to be either driven by positive and desired end-states as a reference end-point and a goal; or to be driven by negative and undesired end-states as goals that are most prominent. For example, eating food is a desirable end-state; while being eaten by others is a undesired end-sate. now an organism may be driven by the end-sate of 'getting food' and thus would be regulating approach behavior of how to go about getting food. It is important to contrast this with regulatory focus; while searching for food, it may have promotion orientation focusing on matching the end state; or may have prevention focus i.e avoiding states that don't contain food; but it is still driven by a 'positive' or desired end-state. On the other hand, when the regulatory reference is a negative or undesirable end-state like 'becoming food', then avoidance behavior is regulated i.e. behavior is driven by avoiding the end-state. Thus, any state that keeps one away from 'being eaten' is the one that is desired; this may involve promotion focus as in approaching states that are opposite of the undesired state and provide safety from predator; or it may have a prevention focus as in avoiding states that can lead one closer to the undesired end-state. In words of Higgins:
Inspired by these latter models in particular, Carver and Scheier (1981, 1990) drew an especially clear distinction between self-regulatory systems that have positive versus negative reference values. A self-regulatory system with a positive reference value has a desired end state as the reference point. The system is discrepancy reducing and involves attempts to move one's (represented) current self-state as close as possible to the desired end-state. In contrast, a self-regulatory system with a negative reference value has an undesired end-state as the reference point. This system is discrepancy-amplifying and involves attempts to move the current self-state as far away as possible from the undesired end-state.
To me Regulatory Reference is similar to Value associated with a utility decision and determines whether when we are choosing between different actions/ goals , the end-states or goals have a positive connotation or a negative connotation.
That brings us to Regulatory anticipation: that is the now well-known Desire/ dread functionality of dopamine mediated brain regions that are involved in anticipation of pleasure and pain and drive behavior. This anticipation of pleasure or pain is driven by our Expectancies of how our actions will yield the desired/undesired outcomes and can be treated as the equivalent to Expectancy in the Utility decisions. The combination of independent factors of regulatory reference and regulatory anticipation will drive what end-state or goal is activated to be the next target for the organism. Once activated, its tendencies towards promotion focus or prevention focus would determine how it strategically uses approach/ avoidance mechanisms to archive that goal or move towards the end-state. Let us also look at regulatory anticipation as described by higgins:
Freud (1920/1950) described motivation as a "hedonism of the future." In Beyond the Pleasure Principle (Freud, 1920/1950), he postulated that people go beyond total control of the "id" that wants to maximize pleasure with immediate gratification to regulating as well in terms of the "ego" or reality principle that avoids punishments from norm violations. For Freud, then, behavior and other psychical activities were driven by anticipations of pleasure to be approached (wishes) and anticipations of pain to be avoided (fears). Lewin (1935) described how the "prospect" of reward or punishment is involved in children learning to produce or suppress, respectively, certain specific behaviors (see also Rotter, 1954). In the area of animal learning, Mowrer (1960) proposed that the fundamental principle underlying motivated learning was regulatory anticipation, specifically, approaching hoped-for desired end-states and avoiding feared undesired endstates. Atkinson's (1964) personality model of achievement motivation also proposed a basic distinction between self-regulation in relation to "hope of success" versus "fear of failure." Wicker, Wiehe, Hagen, and Brown (1994) extended this notion by suggesting that approaching a goal because one anticipates positive affect from attaining it should be distinguished from approaching a goal because one anticipates negative affect from not attaining it. In cognitive psychology, Kahneman and Tversky's (1979) "prospect theory" distinguishes between mentally considering the possibility of experiencing pleasure (gains) versus the possibility of experiencing pain (losses).
Why I have been dwelling on this and how this fits into the larger framework: Wait for the next post, but the hint is that I believe that bipolar mania as well as depression is driven by too much goal-oriented activity- in mania the focus being promotion; while in depression the focus being preventive; Higgins does discuss mania and depression in his article, but my views differ and would require a new and separate blog post. Stay tuned!
Higgins, E. T. (1997). Beyond pleasure and pain American Psychologist (52), 1280-1300... Read more »
Higgins, E. T. (1997) Beyond pleasure and pain. American Psychologist, 1280-1300. DOI: http://www.ncbi.nlm.nih.gov/pubmed/9414606
- January 21, 2009
- 06:40 AM
- 999 views
The Default Brain Network: implications for Autism and Schizophrenia
by sandygautam in The Mouse Trap
This blog post has been triggered by a recent news article that found that the default network in schizophrenics was both hyperactive and hyperconnected during rest, and it remained so as they performed demanding cognitive tasks. To quote:
The researchers were especially interested in the default system, a network of brain regions whose activity is suppressed when people perform demanding mental tasks. This network includes the medial prefrontal cortex and the posterior cingulate cortex, regions that are associated with self-reflection and autobiographical memories and which become connected into a synchronously active network when the mind is allowed to wander.
Whitfield-Gabrieli found that in the schizophrenia patients, the default system was both hyperactive and hyperconnected during rest, and it remained so as they performed the memory tasks. In other words, the patients were less able than healthy control subjects to suppress the activity of this network during the task. Interestingly, the less the suppression and the greater the connectivity, the worse they performed on the hard memory task, and the more severe their clinical symptoms.
“We think this may reflect an inability of people with schizophrenia to direct mental resources away from internal thoughts and feelings and toward the external world in order to perform difficult tasks,” Whitfield-Gabrieli explained.
The hyperactive default system could also help to explain hallucinations and paranoia by making neutral external stimuli seem inappropriately self-relevant. For instance, if brain regions whose activity normally signifies self-focus are active while listening to a voice on television, the person may perceive that the voice is speaking directly to them.
The default system is also overactive, though to a lesser extent, in first-degree relatives of schizophrenia patients who did not themselves have the disease. This suggests that overactivation of the default system may be linked to the genetic cause of the disease rather than its consequences.
The study on which this report is based , is supposedly published in advanced online PNAS edition of 19 jan, but I am unable to locate it. However, my readers know my obsession with Autism and Schizophrenia as diametrically opposed disorders theory and so I was seen reading all the other relevant studies related to default Network and especially how it may be differentially and oppositely activated in Autism and Schizophrenia.
First I would like to refer you to an extremely good overview of Default Network by Buckner, Schacter et al which is freely available. I'll now present some quotes from the paper that are relevant to my thesis. I start with the abstract:
Thirty years of brain imaging research has converged to define the brain's default network—a novel and only recently appreciated brain system that participates in internal modes of cognition. Here we synthesize past observations to provide strong evidence that the default network is a specific, anatomically defined brain system preferentially active when individuals are not focused on the external environment. Analysis of connectional anatomy in the monkey supports the presence of an interconnected brain system. Providing insight into function, the default network is active when individuals are engaged in internally focused tasks including autobiographical memory retrieval, envisioning the future, and conceiving the perspectives of others. Probing the functional anatomy of the network in detail reveals that it is best understood as multiple interacting subsystems. The medial temporal lobe subsystem provides information from prior experiences in the form of memories and associations that are the building blocks of mental simulation. The medial prefrontal subsystem facilitates the flexible use of this information during the construction of self-relevant mental simulations. These two subsystems converge on important nodes of integration including the posterior cingulate cortex. The implications of these functional and anatomical observations are discussed in relation to possible adaptive roles of the default network for using past experiences to plan for the future, navigate social interactions, and maximize the utility of moments when we are not otherwise engaged by the external world. We conclude by discussing the relevance of the default network for understanding mental disorders including autism, schizophrenia, and Alzheimer's disease.
Some snippets from the introduction:
A common observation in brain imaging research is that a specific set of brain regions—referred to as the default network—is engaged when individuals are left to think to themselves undisturbed . Probing this phenomenon further reveals that other kinds of situations, beyond freethinking, engage the default network. For example, remembering the past, envisioning future events, and considering the thoughts and perspectives of other people all activate multiple regions within the default network . These observations prompt one to ask such questions as: What do these tasks and spontaneous cognition share in common? and what is the significance of this network to adaptive function? The default network is also disrupted in autism, schizophrenia, and Alzheimer's disease, further encouraging one to consider how the functions of the default network might be important to understanding diseases of the mind. (emphasis mine)
Then they review some history including how default brain activity was recognized when it was found that metabolic demands and blood glucose consumption of brain as a whole remained the same even when the brain was at 'rest' viv-a-vis involved in an active task. They also review how when baseline PET/fMRI rest activity was compared to many disparate tasks related fMRI/ PET activity , then while some task-relevant areas showed activations related to baseline, many correlated areas of brain, the default network, showed deactivation in the task-related conditions as compared to baseline. The modern interpretation is that the default network is active at rest and places metabolic demands on the brain. They then reference the seminal work of Rachile et al and how that made the default network as a study area in itself.
They further elaborate on how the default network may be identified as an interconnected and functional brain system and list various approaches like spontaneous correlations at rest, seeding from a RoI and determining the areas correlated to activity in seed region etc, to determine the components of the default network. While dMPFC and PCC are implicated in all analysis, the case for vMPFC, IPL, HF+ and LTC is also strong.
I'll skip most of this stuff , including comparative analysis. Suffice it to note here that the default brain regions are up to 30% more metabolically demanding then the rest of the brain and are recently evolved/ selected for. this becomes significant in view of recent studies showing that schizophrenia may be a result of selection for metabolism related genes.
The interesting part begins when trying to determine the behavioral/cognitive correlates of this default brain activity. The consensus seems to be that it is used for daydreaming, reconstructing the past, simulating the future, taking other peoples perspective, self-referential processes and in general stimulus independent thought.
A shared human experience is our active internal mental life. Left without an immediate task that demands full attention, our minds wander jumping from one passing thought to next—what William James (1890) called the "stream of consciousness." We muse about past happenings, envision possible future events, and lapse into ideations about worlds that are far from our immediate surroundings. In lay terms, these are the mental processes that make up fantasy, imagination, daydreams, and thought. A central issue for our present purposes is to understand to what degree, if any, the default network mediates these forms of spontaneous cognition. The observation that the default network is most active during passive cognitive states, when thought is directed toward internal channels, encourages serious consideration of the possibility that the default network is the core brain system associated with spontaneous cognition, and further that people have a strong tendency to engage the default network during moments when they are not otherwise occupied by external tasks.
Support for the same is then provided. The next task the authors undertake is that of determining the function, usefulness and evolutionary rationale for this default brain activity. Two ,in my opinion not mutually exclusive, theories are offered. One is simulation of something that is not tied to current reality (whether it be past memories, future expectations and scenarios or other peoples intentions, beliefs, perspectives). The other theory is that the default mode is a diffused attentional/ exploration state and is suppressed by foveal attention/task focus. The over activity of default network in Schizophrenia can be related to both theories equally well.
In this section, we explore two possible functions of the network, while recognizing that it is too soon to rule out various alternatives. One possibility is that the default network directly supports internal mentation that is largely detached from the external world. Within this possibility, the default network plays a role in constructing dynamic mental simulations based on personal past experiences such as used during remembering, thinking about the future, and generally when imagining alternative perspectives and scenarios to the present. This possibility is consistent with a growing number of studies that activate components of the default network during diverse forms of self-relevant mentalizing as well as with the anatomic observation that the default network is coupled to memory systems and not sensory systems. Another possibility is that the default network functions to support exploratory monitoring of the external environment when focused attention is relaxed. This alternative possibility is consistent with more traditional ideas of posterior parietal function but does not explain other aspects of the data such as the default network's association with memory structures. It is important to recognize that the correlational nature of available data makes it difficult to differentiate between possibilities, especially because focus on internal channels of thought is almost always correlated with a change in external attention . We also explore in this section an intriguing functional property of the default network: the default network operates in opposition to other brain systems that are used for focused external attention and sensory processing. When the default network is most active, the external attention system is attenuated and vice versa.
To me both the Sentinel and the Internal Mentation hypothesis appear to be somewhat valid and relevant to Schizophrenia. One can attribute Psychosis to both increased 'watchfulness' and and increased internal mentation or mentalizing and I have written about the second hypothesis in detail previously.
The most relevant part of the paper is their discussion of Autism, Schizophrenia and Alzheimer's. I reproduce the entire autism and Schizophrenia section , highlighting a few points:
Autism Spectrum Disorders
The autism spectrum disorders (ASD) are developmental disorders characterized by impaired social interactions and communication. Symptoms emerge by early childhood and include stereotyped (repetitive) behaviors. Baron-Cohen and colleagues (1985) proposed that a core deficit in many children with ASD is the failure to represent the mental states of others, as needed to solve theory-of-mind tasks. Based on an extensive review of the functional anatomy that supports theory-of-mind and social interaction skills, Mundy (2003) proposed that the MPFC may be central for understanding the disturbances in ASD. Given the convergent evidence presented here that suggests the default network contributes to such functions, it is natural to explore whether the default network is disrupted in ASD.
Developmental disruption of the default network, in particular disruption linked to the MPFC, might result in a mind that is environmentally focused and absent a conception of other people's thoughts. The inability to interact with others in social contexts would be an expected behavioral consequence. It is important to also note that such disruptions, if identified, may not be linked to the originating developmental events that cause ASD but rather reflect a developmental endpoint. That is, dysfunction of the default network and associated symptoms may emerge as an indirect consequence of early developmental events that begin outside the network.
Many studies have explored whether ASD is associated with morphological differences in brain structure. The general conclusion from this literature is that the brain changes are complex, reflecting differences in growth rates and attenuation of growth (see Brambilla et al. 2003 for review). At certain developmental stages these differences are manifest as overgrowth and at later stages as undergrowth. Early observations have implicated the cerebellum. A further consistent observation has been that the amygdala is increased in volume in children with ASD (e.g., Abell et al. 1999, Schumann et al. 2004), perhaps as a reflection of abnormal regulation of brain growth (Courchesne et al. 2001). While not discussed earlier because of our focus on cortical regions, the amygdala is known to contribute to social cognition (Brothers 1990, Adolphs 2001, Phelps 2006) and interacts with regions within the default network. The amygdala has extensive projections to orbital frontal cortex (OFC) and vMPFC (Carmichael & Price 1995).
Of perhaps more direct relevance to the default network, dMPFC has shown volume reduction in several studies of ASD that used survey methods to explore regional differences in brain volume (Abell et al. 1999, McAlonan et al. 2005). The effects are subtle and will require further exploration, but it is noteworthy that, of those studies that have looked, several have noted dMPFC volume reductions in ASD. Of interest, a study using voxel-based morphometry to investigate grey matter differences in male adolescents with ASD noted that several regions within the default network exhibited a relative increase in grey matter volume compared to the control population (Waiter et al. 2004). Because this observation has generally not been replicated in adult ASD groups, future studies should investigate whether complex patterns of overgrowth and undergrowth of the regions within the default network exist in ASD and, if so, whether they track behavioral improvement on tests of social function (see also Carper & Courchesne 2005).
Kennedy and colleagues (2006) recently used fMRI to directly explore the functional integrity of the default network in ASD. In their study, young adults with ASD and age-matched individuals without ASD were imaged during passive tasks and demanding active tasks that elicit strong activity differences in the default network. While the control participants showed the typical pattern of activity in the default network during the passive tasks, such activity was absent in the individuals with ASD. Direct comparison between the groups revealed differences in vMPFC and PCC. Moreover, in an exploratory analysis of individual differences within the ASD group, those individuals with the greatest social impairment (measured using a standardized diagnostic inventory) were those with the most atypical vMPFC activity levels (Fig. 16). An intriguing possibility suggested by the authors of the study and extended by Iacoboni (2006) is that the failure to modulate the default network in ASD is driven by differential cognitive mentation during rest, specifically a lack of self-referential processing.
Another recent study using analysis of intrinsic functional correlations showed that the default network correlations were weaker in ASD (Cherkassky et al. 2006).Of note, the individuals with ASD showed differences in a fronto-parietal network that has been recently hypothesized to control interactions between the default network and brain systems linked to external attention (Vincent et al. 2007b). These data in ASD suggest an interesting possibility: the default network may be largely intact in ASD but under utilized perhaps because of a dysfunction in control systems that regulate its use.
Schizophrenia
Schizophrenia is a mental illness characterized by altered perceptions of reality. Auditory hallucinations, paranoid and bizarre delusions, and disorganized speech are common positive clinical symptoms (Liddle 1987). Cognitive tests also reveal negative symptoms, including impaired memory and attention (Kuperberg & Heckers 2000). These symptoms lead to questions about their relationship to the default network for a few reasons. The first reason surrounds the association of the default network with internal mentation. Many symptoms of schizophrenia stem from misattributions of thought and therefore raise the question of an association with the default network because of its functional connection with mental simulation. A second related reason has to do with the broader context of control of the default network. While still poorly understood, there appears to be dynamic competition between the default network and brain systems supporting focused external attention (Fransson 2005, Fox et al. 2005, Golland et al. 2007, Tian et al. 2007, see also Williamson 2007). Frontal-parietal systems are candidates for controlling these interactions (Vincent et al. 2007b). The complex symptoms of schizophrenia could arise from a disruption in this control system resulting in an overactive (or inappropriately active) default network. The normally strongly defined boundary between perceptions arising from imagined scenarios and those from the external world might become blurry, including the boundary between self and other (similar to that proposed by Frith 1996).
Three studies have provided preliminary data supporting the possibility that the default network is functionally overactive. Garrity and colleagues (2007) recently reported an analysis of correlations among default network regions in patients with schizophrenia. Studying a sizable data sample (21 patients and 22 controls), they explored task-associated activity modulations within the default network and identified largely similar correlations among default network regions in patients and controls. Differences were noted in specific subregions, as were differences in the dynamics of activity as measured from the timecourses of the fMRI signal. Of particular interest, they noted that within the patient group, the positive symptoms of the disease (e.g., hallucinations, delusions, and thought confusions) were correlated with increased default network activity during the passive epochs, including MPFC and PCC/Rsp. In a related analysis, Harrison et al. (2007) noted accentuated default network activity during passive task epochs in patients with schizophrenia as contrasted to controls, again suggesting an overactive default network. Moreover, within the patient group, poor performance was again correlated with MPFC activation during the passive as compared to the active tasks. Finally, Zhou and colleagues (2007) found that regions constituting the default network were functionally correlated with each other to a significantly higher degree in patients than in control participants. Thus, while the data are limited, these studies converge to suggest that patients with schizophrenia have an overactive default network, as would be expected if the boundary between imagination and reality were disrupted. Overactivity within the network correlates with task performance (Harrison et al. 2007) and clinical symptoms (Garrity et al. 2007).
I now link to two abstracts form Autism and default network research by Kennedy et al:
Several regions of the brain (including medial prefrontal cortex, rostral anterior cingulate, posterior cingulate, and precuneus) are known to have high metabolic activity during rest, which is suppressed during cognitively demanding tasks. With functional magnetic resonance imaging (fMRI), this suppression of activity is observed as “deactivations,” which are thought to be indicative of an interruption of the mental activity that persists during rest. Thus, measuring deactivation provides a means by which rest-associated functional activity can be quantitatively examined. Applying this approach to autism, we found that the autism group failed to demonstrate this deactivation effect. Furthermore, there was a strong correlation between a clinical measure of social impairment and functional activity within the ventral medial prefrontal cortex. We speculate that the lack of deactivation in the autism group is indicative of abnormal internally directed processes at rest, which may be an important contribution to the social and emotional deficits of autism.
In their discussion they make explicit the fact that in Autism, the default Netwrok may be under active.
There are two possible reasons why the ASD group failed to show the typical deactivation effect. One possibility is that midline resting network activity during both rest and task performance is high, and, thus, a subtraction between these conditions would reveal no difference in activity levels. We believe, however, that it is unlikely that high midline network activity was maintained during the cognitively demanding number task in autism for several reasons. First, as mentioned previously, behavioral performance was similar between control and ASD groups. This result, however, would be unexpected if the ASD group were carrying out additional mental processing that control subjects inhibit during cognitively demanding conditions. Second, positron-emission tomography studies of autism, which provide an absolute measure of brain metabolism, have found reduced, as opposed to increased, glucose metabolism in rACC and PCC (36) during task performance, as compared with controls. Furthermore, one positron-emission tomography study found that lower blood flow in MPFC and rACC at rest was correlated with more severe social and communicative impairments in subjects with autism (37), a finding similar to our correlational results. Third, reduced anatomical volumes and neurochemical deficiencies have consistently been observed in MPFC∕rACC in adults with autism (reviewed in ref. 26), likely indicative of a reduced functioning of these regions. Therefore, an alternative explanation, the one to which we attribute the lack of deactivation, is that midline activity is low during rest. We suggest, then, that the absence of deactivation in this network indicates that the mental processes that normally occur at rest are absent or abnormal in autism.
What are these mental processes that dominate during rest? Evidence in the literature to date seems to suggest that tasks that induce certain types of internal processing activate this resting network. Examples of such tasks are self- and other-person judgments (4, 6, 7, 19–22, 38–45), person familiarity judgments (24, 25), emotion processing (15–17, 46), perspective-taking (22, 47), passive observation of social interactions vs. nonsocial interactions (18), relaxation based on interoceptive biofeedback (48, 49), conceptual judgments (based on internal knowledge stores) vs. perceptual judgments (50), and episodic memory tasks (51), among others [moral decision making (52), joint attention experience (23), and pleasantness judgments (53)]. Therefore, the activity in these regions at rest might simply reflect the extent to which these types of internally directed thoughts are engaged at rest. In fact, a particularly intriguing behavioral study found that individuals with ASD report very different internal thoughts than control subjects (54, 55), lending support to our interpretation that an absence of this resting activity in autism may be directly related to abnormal internal thought. Admittedly, this is a speculative hypothesis but one that can be explicitly tested.
Another of their recent papers comes to the same conclusion.
Recent studies of autism have identified functional abnormalities of the default network during a passive resting state. Since the default network is also typically engaged during social, emotional and introspective processing, dysfunction of this network may underlie some of the difficulties individuals with autism exhibit in these broad domains. In the present experiment, we attempted to further delineate the nature of default network abnormality in autism using experimentally constrained social and introspective tasks. Thirteen autism and 12 control participants were scanned while making true/false judgments for various statements about themselves (SELF condition) or a close other person (OTHER), and pertaining to either psychological personality traits (INTERNAL) or observable characteristics and behaviors (EXTERNAL). In the ventral medial prefrontal cortex/ventral anterior cingulate cortex, activity was reduced in the autism group across all judgment conditions and also during a resting condition, suggestive of task-independent dysfunction of this region. In other default network regions, overall levels of activity were not different between groups. Furthermore, in several of these regions, we found group by condition interactions only for INTERNAL/EXTERNAL judgments, and not SELF/OTHER judgments, suggestive of task-specific dysfunction. Overall, these results provide a more detailed view of default network functionality and abnormality in autism.
If you want to read more about Schizophrenia - default network linkage , read here. If you want to read about Default Network in general , read here ( a very good blog I have recently discovered).
I think the case is settled that at least in the case of Default Network activations, Schizophrenia and Autism are on opposite poles. One has too much default brain activity, the other too little. Also, the function of default network suggests that it is primarily the focus on self and the ability to imagine that is disrupted in autism and heightend to dramatic effects in Schizophrenics.
R. L. BUCKNER, J. R. ANDREWS-HANNA, D. L. SCHACTER (2008). The Brain's Default Network: Anatomy, Function, and Relevance to Disease Annals of the New York Academy of Sciences, 1124 (1), 1-38 DOI: 10.1196/annals.1440.011
D. P. Kennedy, E. Courchesne (2008). Functional abnormalities of the default network during self- and other-reflection in autism Social Cognitive and Affective Neuroscience, 3 (2), 177-190 DOI: 10.1093/scan/nsn011
D. P. Kennedy (2006). Failing to deactivate: Resting functional abnormalities in autism Proceedings of the National Academy of Sciences, 103 (21), 8275-8280 DOI: 10.1073/pnas.0600674103... Read more »
R. L. BUCKNER, J. R. ANDREWS-HANNA, & D. L. SCHACTER. (2008) The Brain's Default Network: Anatomy, Function, and Relevance to Disease. Annals of the New York Academy of Sciences, 1124(1), 1-38. DOI: 10.1196/annals.1440.011
D. P. Kennedy, & E. Courchesne. (2008) Functional abnormalities of the default network during self- and other-reflection in autism. Social Cognitive and Affective Neuroscience, 3(2), 177-190. DOI: 10.1093/scan/nsn011
D. P. Kennedy. (2006) Failing to deactivate: Resting functional abnormalities in autism. Proceedings of the National Academy of Sciences, 103(21), 8275-8280. DOI: 10.1073/pnas.0600674103
- May 27, 2009
- 09:07 PM
- 992 views
How Mood and felt Energy are related to thought variability and speed
by sandygautam in The Mouse Trap
There is a recent article by Pronin and Jacobs, on the relationship between mood, thought speed and experience of 'mental motion' that builds up on their previous work.
Let us see how they describe thought speed and variability and what their hypothesis is:
1. The principle of thought speed. Fast thinking, which involves many thoughts per unit time, generally produces positive affect. Slow thinking, which involves few thoughts per unit time, generally produces less positive affect. At the extremes of thought speed, racing thoughts can elicit feelings of mania, and sluggish thoughts can elicit feelings of depression.2. The principle of thought variability. Varied thinking generally produces positive affect, whereas repetitive thinking generally produces negative affect. This principle is derived in part from the speed principle: when thoughts are repetitive, thought speed (thoughts per unit time) diminishes. At its extremes, repetitive thinking can elicit feelings of depression (or anxiety), and varied thinking can elicit feelings of mania (or reverie).
Let me clarify at the outset that they are aware of the effects of though speed on variability and vice versa; as well as the effects of mood on felt energy and vice versa; thus they know that one can confound the other. Another angle they consider is the relationship between thought speed/variability i.e the form of thought and the contents of thought (whether having emotional salience or neutral) and investigated whether the effects of speed and variability were confounded with though content; they found negative evidence for this inetrcationist view.
Let me also clarify that I differ slightly (based on my interpreation of their data) from their original hypothesis, in the sense that I believe that their data shows that speed affects felt energy and variability affects affect and that the effects of speed on mood may be mediated by the effect of speed on felt energy and similarly the effect of variability on felt energy may be mediated by its effects on mood.
Thus my claim is that:
Thought speed leads to more felt energy. Extremes of 'racing thoughts' leads to the manic feeling of being very energetic (when accompanied with positive mood, this may give rise to feelings of grandiosity- I have the energy to achieve anything), while also may lead to anxiety states (when accompanied with negative affect) in which one cannot really suppress a negative chain of thoughts - one following the other in fast succession, regarding the object of ones anxiety. The counterpart to this the state where thoughts come slowly (writer's block etc) and when accompanied with negative affect, this can easily be viewed as depression.
Thought variability leads to more positive affect: Extremes of 'tangential thoughts' leads to the manic feeling of being in a good mood (when accompanied with high energy , this manifest as feelings of euphoria); while the same tangential thoughts when accompanied by low felt energy may actually be felt as serenity/ calmness/ reverie. The counterpart to this is the state of thoughts that are stuck in a rut - when accompanied with low energy this leads to feelings of depression and sadness.
Thus, to put simply : there are two dimensions one needs to take care of - mood (thought variability) x energy (thought speed) and high and low extremes on these dimensions are all opposites of their counterpart.
Before we move on, I'll let the authors present their other two claims too:
3. The combination principle. Fast, varied thinking prompts elation; slow, repetitive thinking prompts dejection. When speed and variability oppose each other, such that one is low and the other high, individuals’ affective experience will depend on factors including which one of the two factors is more extreme. The psychological state elicited by such combinations can vary apart from its valence, as shown in Figure 1. For example, repetitive thinking can elicit feelings of anxiety rather than depression if that repetitive thinking is rapid. Notably, anxious states generally are more energetic than depressive states. Moreover, just as fast-moving physical objects possess more energy than do identical slower objects, fast thinking involves more energy (e.g., greater wakefulness, arousal, and feelings of energy) than does slow thinking.4. The content independence principle. Effects of thought speed and variability are independent of the specific nature of thought content. Powerful affective states such as depression and anxiety have been traced to irrational and dysfunctional cognitions (e.g., Beck, 1976). According to the independence principle, effects of mental motion on mood do not require any particular type of thought content.
They review a number of factors and studies that all point to a causal link between thought speed and energy and between thought variability and mood. More importantly they show the independent effects of though speed and variability from the effects of thought content on mood. I'll not go into the details of the studies and experiments they performed, as their article is available freely online and one can read for oneself (it makes for excellent reading); suffice it to say that I believe they are on the right track and have evidence to back their claims.
What are the implications of this:
The speed and repetition of thoughts, we suggest, could be manipulated in order to alter and alleviate some of the mood and energy symptoms of mental disorders. The slow and repetitive aspects of depressive thinking, for example, seem to contribute to the disorder’s affective symptoms (e.g., Ianzito et al., 1974; Judd et al., 1994; Nolen-Hoeksema, 1991; Philipp et al., 1991; Segerstrom et al., 2000). Thus, techniques that are effective in speeding cognition and in breaking the cycle of repetitive thought may be useful in improving the mood and energy levels of depressed patients. The potential of this sort of treatment is suggested by Pronin and Wegner’s (2006) study, in which speeding participants’ cognitions led to improved mood and energy, even when those cognitions were negative, self-referential, and decidedly depressing. It also is suggested by Gortner et al.’s (2006) finding that an expressive writing manipulation that decreased rumination (even while inducing thoughts about an upsetting experience) rendered recurrent depression less likely.
There also is some evidence suggesting that speeding up even low-level cognition may improve mood in clinically depressed patients. In one experiment, Teasdale and Rezin (1978) instructed depressed participants to repeat aloud one of four letters of the alphabet (A, B, C, or D) presented in random order every 1, 2, or 4 s. They found that those participants required to repeat the letters at the fastest rate experienced the most reduction in depressed mood. Similar techniques could be tested for the treatment of other mental illnesses. For example, manipulations might be designed to decrease the mental motion of manic patients, perhaps by introducing repetitive and slow cognitive stimuli. Or, in the case of anxiety disorders, it would be worthwhile to test interventions aimed at inducing slow and varied thought (as opposed to the fast and repetitive thought characteristic of anxiety). The potential effectiveness of such interventions is supported by the fact that mindfulness meditation, which involves slow but varied thinking, can lessen anxiety, stress, and arousal. hat tip: Ulterior Motives
Pronin, E., & Jacobs, E. (2008). Thought Speed, Mood, and the Experience of Mental Motion Perspectives on Psychological Science, 3 (6), 461-485 DOI: 10.1111/j.1745-6924.2008.00091.x... Read more »
Pronin, E., & Jacobs, E. (2008) Thought Speed, Mood, and the Experience of Mental Motion. Perspectives on Psychological Science, 3(6), 461-485. DOI: 10.1111/j.1745-6924.2008.00091.x
Pronin, E., & Wegner, D. (2006) Manic Thinking: Independent Effects of Thought Speed and Thought Content on Mood. Psychological Science, 17(9), 807-813. DOI: 10.1111/j.1467-9280.2006.01786.x
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