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Deconstructing the most sensationalistic recent findings in Human Brain Imaging, Cognitive Neuroscience, and Psychopharmacology

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  • September 26, 2012
  • 04:28 AM

Of Mice and Women: Animal Models of Desire, Dread, and Despair

by The Neurocritic in The Neurocritic

Scene from Mon Oncle d'Amérique by Alain ResnaisDr. James G. Pfaus, a Professor of Psychology at Concordia University in Montreal, recently wrote a post in defense of Naomi Wolf's neuroscience acumen. This is understandable, as he was one of her main sources of scientific information about the "brain-vagina connection" in Vagina: A New Biography. Wolf, as you know, has been under fire for her simplistic and gendered treatment of cortisol and dopamine, as if these chemicals have highly specific effects on adult feminist women (and their vaginas), but no one else.1 Pfaus's general reply to that line of criticism is that we should let Wolf have poetic license with her storytelling:Is Wolf right in regarding dopamine as the "ultimate feminist neurochemical"? It is certainly unlikely that sea slugs and nematode worms are feminists. But can't we allow an accomplished writer and social critic a little poetic leeway to make a point?In Who's Afraid of the Vagina-Brain Connection? Pfaus also described some of his work on the sexual behavior of female lab rats:Wolf's search took her, among other places, to my laboratory. We had been doing research on the role of clitoral and vaginocervical stimulation in the sex and reproductive lives of female rats, work that has been published in high-quality peer-reviewed scientific journals. This work revealed that such stimulation, when applied in the right way, induces a state of sexual reward that conditions place and partner preferences (the latter of which was unexpected in an allegedly promiscuous and polygamous species). Taken together with previous work from my laboratory showing the profound role of dopamine and opioid neurotransmitters in both male and female sexual behavior, and in the context of a more general scientific literature in animals and humans showing that blockade of those transmitters induces varying degrees of an "anhedonic" state akin to depression in which reward does not occur and animals do not focus their attention toward it anymore, it became clear to Wolf that these neurochemicals were important parts of the sexual desire and pleasure systems of the brain.  Pfaus is a prolific scientist whose work ranges from basic animal models and translational research to establishing definitions for human sexual disorders. Now that more of Vagina is online at Amazon, I see that Wolf relied heavily on his research (he's mentioned 26 times), and that she cited many original sources from the scientific literature (albeit not always correctly).2 Which brings us to animal models for what we typically regard as profoundly human states: longing, angst, futility.  Or Desire, Dread, and Despair. The words don't easily lend themselves to rodent analogues, because they remind us of an unrequited crush or an existential crisis. Certainly, rats don't write love letters or read Kierkegaard or appreciate Expressionist art. Dark Night of the Soul (the original poem) was written by a Roman Catholic mystic to describe the painful journey of a bride (soul) in search of her groom (God). Today it indicates a spiritual crisis, a state of profound aloneness, a crushing existential despair.The animal models of these states are more mundane and less abstract, yet important for potentially explaining the neural mechanisms underlying human suffering: addiction, anxiety, and depression. But are they really adequate stand-ins for the human condition? Of course not. My purpose here isn't to critique animal research, but rather to consider actual behaviors and how they map onto the terminology used to describe them.DesireFor our present purposes, desire is defined in terms of sexual behavior. Specifically, sexual desire includes the anticipation of and motivation for participation in sexual activity. In rats, "Desire is inferred by certain measures, such as solicitations, rates of pacing (in which female rats control the initiation and rate of copulatory contact with male rats), and the strength of operant behavior aimed at acquiring sex partners" (Pfaus, 2006).Modified from FIG. 1 (Pfaus, 2006). Incentive sequences for human and rat sexual behavior (modified from Pfaus et al., 1999). The behavioral stream moves from left to right, through appetitive, precopulatory, and consummatory phases of behavior. This conforms to the movement of animals from distal to proximal to interactive with respect to the sexual incentive.In Fig. 1 we can see that female rat Excitement (grooming, investigation, motor activation) maps onto female human Sexual Desire (fantasy, excitement). Sexual fantasy is decidedly absent from the repertoire of rats, so conditioning and preference paradigms serve that purpose. Meanwhile, female rats show subsequent stages of defensiveness and lordosis, while female humans get to have orgasms. Fig. 2 in the Pfaus paper shows four panels of appetitive and consummatory measures of copulation in a pair of rats. Solicitation, investigation, running away, pursuit, lordosis, and mounting took all of 4 seconds. This goes on for several bouts until the male ejaculates. Wolf's "Goddess Array" is nowhere to be found.Indeed, one of the places where Wolf went most astray in Vagina was in her wild extrapolations from the neurobiology of Pfaus's rats to the "Goddess Array" and what women need sexually: candles, flowers, music, or some other romantic gesture ("A whole set of words, actions, and gestures that women cannot do without"). Even if this were universally true, it obviously involves the kind of cognitive capacity well beyond rats.Nonetheless, a major goal of the animal model is to serve as a preclinical testing ground for perceived sexual dysfunction in humans, including the categories of Hypoactive Sexual Desire Disorder (HSDD) and Female Sexual Arousal Disorders, which are distinct (and yet overlapping, according to some). In his accurately (but... Read more »

Adams K. (2011) The abject self: self-states of relentless despair. International journal of group psychotherapy, 61(3), 332-64. PMID: 21728704  

James G. Pfaus. (2006) Of rats and women: preclinical insights into the nature of female sexual desire. Sexual and Relationship Therapy, 21(4), 463-476. info:/10.1080/14681990600967011

  • September 12, 2012
  • 01:12 AM

The Electroencephalogram Cocktail Party

by The Neurocritic in The Neurocritic

In 2005, filmmaker Joyce Draganosky made a short entitled The Science of Love, where......the battle between reason and emotion takes center stage. A professor, who believes she has found a way of determining scientifically whether someone is in love, clashes with her department chair, a woman who thinks love and attraction are far too complex to be mapped according to the certainties of science. The clip above highlights a hilarious event designed to determine the neural correlates of love. How does it work?"Well, the goal is to identify the part of the brain that controls lust, and to show that it is different from the part of the brain that controls love. In order to do this we had to simulate as natural an environment as possible while still being able to measure neural activity. So I have created the Electroencephalogram Cocktail Party. An EEG Mixer!!"Draganosky received an Alfred P. Sloan Foundation grant for The Science of Love. She spent a year researching the film, attending presentations and conducting interviews in the laboratory of Dr. Joy Hirsh at Columbia. "I actually audio-taped the interviews because I wanted to get all the scientist-speak perfectly right so that I could write accurate dialogue." We can certainly forgive the confusion of fMRI and EEG results for artistic sake (and comic effect) here. The lead character Syd seems to be modeled after Dr. Helen Fisher, even down to the combination of evolutionary anthropology with brain imaging.1 The Real EEG MixerNow, an actual study by Gevins and colleagues (2012) recorded EEG while 10 members of his lab attended a cocktail party furnished with food and alcohol:The cocktail party was unscripted, other than withholding drinking for the first 10 minutes to record a pre-drinking baseline. The partiers intermingled, chatted, ate sushi and hors d'oeuvres and drank vodka martinis or vodka and cranberry cocktails according to their personal inclinations. They also measured BACs [breath alcohol content], took photos and checked up on the automated data collection.The goal here was not to evaluate the effectiveness of EEG Speed Dating or to explicate a lofty Science of Love, but instead to examine the effects of alcohol on the spectral properties, or frequency composition, of EEG in a naturalistic setting. Although the technique of "hyperscanning"3 has been used in fMRI studies, the advantages of EEG recording in this context should be obvious.4 The participants served as both subjects and experimenters:Teams placed headsets simultaneously on groups of participants; total set up time was about a half hour. Data from each EEG headset was transmitted during the party via Bluetooth protocol to its own dedicated notebook computer. The data were time synchronized across computers by a start signal sent via local Ethernet from one computer to all other recording computers.They measured breath alcohol contents, took photos and checked the data collection.5 Using data obtained from two prior experiments (collected from separate groups of subjects in a more typical recording environment), multivariate divergence analyses searched for the subset of variables6 that best discriminated between the EEGs of brains on alcohol vs. brains on placebo. These equations were applied to the pre- and post-alcohol EEGs of the partygoers. Although 40% of the ambulatory cocktail party data were lost due to artifacts, the remaining data showed 80% sensitivity in recognizing alcohol and 80% specificity in recognizing no-alcohol. While mandatory Wearable Wireless EEG Fashion Accessories will not be replacing breathalyzers at sobriety stops any time soon, this was certainly a fun pilot study (especially for the participants)!Footnotes1 Recycling Alert: this paragraph contains portions of my original 2006 review of the entire 18 minute short (combined with additional information). It's only two sentences, but I need to be forthcoming in anticipation of my future blogging gigs at Wired and the New Yorker.2 It looks like Neuroskeptic has already posted coverage of this study: Cocktail-Party Neuroscience.3 The hyperscanning technique was developed by Read Montague and co-workers (Montague et al., 2002). Typically, hyperscanning involves two subjects who interact with each other while playing a "trust" game. Their brains are scanned simultaneously (in adjoining or distant magnets). Specially developed software coordinates the experiments across sites.4 You can't walk around, eat, drink, and directly interact with others while lying in a scanner.5 Who's real and who's fictional??6 Technical details:The individual frequency component powers were then averaged into 3 standard bands, theta (4–7 Hz), alpha (8–13 Hz) and beta (13–18 Hz) determined in prior studies to be sensitive to alcohol's effect on the EEG. The 3 banded powers and their standard deviations constituted a total set of 6 variables for each of the 7 electrode sites. This is a very low number of variables; compare to a recent structural MRI study that used 231 neuroanatomical variables to predict brain age.Reference... Read more »

  • August 26, 2012
  • 03:33 AM

The Art of Delicate Sadness

by The Neurocritic in The Neurocritic

Sad Noh masks (from Fig. 1 of Osaka et al., 2012).Noh is a traditional style of Japanese theater where the actors wear masks to convey facial expressions. Many of the masks are known for their ambiguity:As it is often difficult to tell the actual feelings expressed in a noh mask, it is said to be made with a “neutral” expression. The mask carver tries to instill a variety of emotions in the mask. It is up to the performer to imbue the mask with emotion. One of the techniques used in this task is to slightly tilt the mask up or down. With terasu (tilting upwards) the mask appears to be slightly smiling or laughing and the expression lightens somewhat. While kumorasu (tilting downwards), produces a slight frown and can express sadness or crying. Basically, by using minute movements, the performer is able to express very fully.Three pictures of the same nō 'hawk mask' showing how the expression changes with a tilting of the head. The mask was afixed to a wall with constant lighting and only the camera moved.Professor Michael Lyons has an excellent site explaining The Noh Mask Effect: A Facial Expression Illusion, which you really should see for yourself.Delicate SadnessA recent neuroimaging study by Osaka et al., (2012) set out to examine how the amygdala (a limbic structure important for emotion) would respond while participants viewed masks portraying "delicate sadness" -- "a Noh mask that is elegant and artistically polished, and designed to express sadness." To choose the most appropriate stimuli, a separate group of subjects rated a set of 70 masks on a scale of 1 (not at all sad) to 7 (highly sad). The six most "highly sad" masks were selected for comparison to six "neutral" masks. But as we already learned, the neutral masks can be ambiguous.The amygdala (LeDoux, 2007) is predominantly known for its role in fear conditioning, but it is also activated by other emotions (e.g., Kober et al., 2008). Therefore, the comparison of viewing sad vs. "neutral" masks in the present study could yield minimal differences in the amygdala.And that is what happened (in my estimation). However, the authors presented their results in a more positive light: a region of interest (ROI) in the right amygdala showed activation in the sad vs. neutral contrast at p<.05 (uncorrected). The ROI in the left amygdala, as well as bilateral "reward-related" ROIs in the nucleus accumbens, caudate nucleus, and putamen did not reach that level of significance. They concluded that:...viewing Noh masks with expressions of elegant sadness effectively stimulates the right amygdala of the limbic system. Thus, the sadness evoked by such masks seems to be processed by the limbic system in a way similar to the way in which it processes negative emotions such as fear and disgust. Understanding the neurological processing of these facial expressions could effectively contribute to an appreciation of Noh performances in an artistic way.But I'm not so sure the present finding illuminates the aesthetic and emotional experience of Noh theater. I think we need to understand more about how the brain processes basic emotions before we make neuroaesthetic claims.I originally thought the study was interesting from the perspective of emotional ambiguity, where even the static images of those elegantly carved masks could capture multiple expressions simultaneously. A recent über meta-analysis of neuroimaging studies of emotion did not find support for the "locationist approach" where "discrete emotion categories can be consistently and specifically localized to distinct brain regions" (Lindquist et al., 2012). Hence, looking at amygdala and striatal regions in isolation will miss important aspects of emotional and aesthetic experiences engendered by viewing traditional Japanese Noh masks.ReferencesKober H, Barrett LF, Joseph J, Bliss-Moreau E, Lindquist K, Wager TD. (2008). Functional grouping and cortical-subcortical interactions in emotion: a meta-analysis of neuroimaging studies. Neuroimage 42:998-1031.LeDoux J. (2007). The amygdala. Current Biology 17: R868-R874.Lindquist KA, Wager TD, Kober H, Bliss-Moreau E, Barrett LF. (2012). The brain basis of emotion: a meta-analytic review. Behav Brain Sci. 35:121-43.Osaka N, Minamoto T, Yaoi K, & Osaka M (2012). Neural correlates of delicate sadness: an fMRI study based on the neuroaesthetics of Noh masks. Neuroreport, 23 (1), 26-9 PMID: 22113213

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  • August 18, 2012
  • 05:25 AM

Predicting Brain Age from 231 Neuroanatomical Measures

by The Neurocritic in The Neurocritic

Is your child's brain on track to reach normal developmental milestones? A paper in Current Biology reports on a new, composite neuroanatomical metric of maturity that predicts 92% of the variance in brain age (Brown et al., 2012). Structural MRI scans were obtained from 885 healthy children and young adults ranging from 3 to 20 years of age. A set of 231 different measurements, or biomarkers, were used to determine the age that provided the best "fit" for each subject. The model made the most accurate predictions at the youngest ages, and the margin of error was 1.03 years across all ages.Figure 3 (Brown et al., 2012). Multimodal Quantitative Anatomical Prediction of Age. For 885 individuals, estimated brain age is plotted as a function of actual chronological age. Colors correspond to different sites and scanners. Symbol size represents subject sex (larger = female, smaller = male). A spline-fit curve (solid line) with 5% and 95% prediction intervals (dashed lines) is also shown.The 231 measures were chosen because they are "known or suspected to change over the ages" (Brown et al., 2012):This collection of variables was derived from T1-, T2-, and diffusion-weighted imaging and included quantitative measures of brain morphology, signal intensity, and water diffusivity within different tissue types, reflecting anatomical structural organization. Specifically, we measured cortical thickness and area, volumes of segmented subcortical structures, normalized signal intensities, and measures of diffusion magnitude and directionality within cerebral, cerebellar, and white matter fiber tract regions of interest.The data from each of these imaging modalities alone could explain 81-83% of the variance, and that number rose to 92% when the T1-, T2-, and diffusion-weighted images were combined. The relative contribution from each type of measure changed with age, as shown below.Figure 4 (adapted from Brown et al., 2012). Age-Varying Contributions of Different Imaging Measures to the Prediction of Age. The relative contributions of separate morphological, diffusivity, and signal intensity measures within different brain structures are plotted as a function of age. Colors correspond to measure and structure type (T1 cortical area; T1 cortical thickness; T1 subcortical volumes; diffusion (FA/ADC) within white matter tracts; diffusion (FA/ADC) within subcortical ROIs; T2 signal intensity within white matter tracts; T2 signal intensity within subcortical ROIs). Contributions are computed as units of the proportion of total explained variance.The data were from the Pediatric Imaging, Neurocognition, and Genetics (PING) Study database (, which is open access.The primary goal of PING has been to create a data resource of highly standardized and carefully curated MRI data, whole genome SNP genotyping data, and developmental and neuropsychological assessments for a large cohort of developing children aged 3 to 20 years. The scientific aim of the project is, by openly sharing these data, to amplify the power and productivity of investigations of healthy and disordered development in children and to increase understanding of the origins of variation in neurobehavioral phenotypes.Does it sound like the PING investigators are creating a normative database for possible diagnostic purposes in the future?Perhaps further development of techniques to quantify the complex multidimensional nature of typical brain maturation can also help to improve the early identification of individuals with abnormal developmental trajectories. Our findings suggest that a multimodal neuroanatomical imaging assessment may hold promise for making an objective, quantitative contribution to our clinical evaluations of brain development.Why yes it does. We already know this promise is not right around the corner (Where Are the Clinical Tests for Psychiatric Disorders?), and we know about the possible hazards of premature commercial ventures that make bold claims not supported by solid scientific evidence (The Dark Side of Diagnosis by Brain Scan). Returning to the first sentence of this post ["Is your child's brain on track to reach normal developmental milestones?"], you can see I was already anticipating franchised scanning facilities in strip malls ready to give worried parents the verdict on their child's neurodevelopment. Kind of like genetic testing outfits that make silly claims:...unscrupulous businesses like My Gene Profile (which offers the "Inborn Talent Genetic Test" for the low low price of $1,397) have capitalized on the public's desire for simple explanations. Now you can find out whether your child has the Split Personality Gene! The Propensity for Teenage Romance Gene! The Self Detoxifying Gene!The article in Biopolitical Times is highly recommended, especially since the url seems to be defunct.1 To conclude with some important points about the Current Biology paper, the predictive accuracy of 92% is very impressive. The authors suggest there is a "latent brain phenotype that is tightly linked to chronological age." But they also issue a caveat about psychological maturity, which cannot be inferred from their measurements:Brain scans, though informative about anatomical and physiological states, cannot be used to make inferences about an individual’s psychological maturity. Rather, these results speak only to the degree to which typically developing children differ among each other in their fundamental structural brain properties. Footnote1 Biopolitical Times also mentioned the "sprawling website" that sells the "Inborn Talent Genetic Test", which you can still view via the Wayback Machine. [NOTE: EVERYONE wants their child to be the next Tiger Woods!]ReferenceBrown, T., and 21 others. (2012). Neuroana... Read more »

  • August 11, 2012
  • 03:51 PM

Where Are the Clinical Tests for Psychiatric Disorders?

by The Neurocritic in The Neurocritic

Examination room, World War 1 (Otis Historical Archives Nat'l Museum of Health & Medicine).The lack of laboratory diagnostic tests for mental disorders, along with the shady marketing practices of the pharmaceutical industry, are often viewed as the most fatal flaws in the medical practice of psychiatry. This is especially true among critics of psychiatry, but doctors in other medical specialties tend to have a dismal opinion of psychiatry1 as well (Fazel & Ebmeier, 2009). Widespread perceptions that the field is relatively low in scientific precision, and that the patients have a poor prognosis, are among the possible reasons for this. An interesting comparison of medical students in two Spanish-speaking countries revealed greater respect for psychiatry in Barcelona than in Medellín (Pailhez et al. 2010; PDF):The differences can be partly explained by the sociocultural contexts of Barcelona and Medellín. For example, students from Barcelona (where the neuroscientific model has greater influence) agreed more with a medically oriented position of psychiatry and that psychiatry is scientific, precise, and a valid branch of medicine.This lack of respect from other medical professionals, not to mention from consumer/survivor advocates, puts neuroscientists in an awkward position. We believe in neurobiological explanations for the full gamut of human behavior,2 yet we're left to defend a specialty that relies on clinical interviews and a disputed classification system. There is in fact a large and growing literature on structural and functional differences between the brains of those with and without psychiatric disorders, but these discoveries have not yet translated into reliable diagnostic tests.Why has it taken so long for biological psychiatry to develop clinical tests?A new perspectives paper by three prominent figures in biological psychiatry (Kapur, Phillips, & Insel, 2012)3 asks this precise question. They begin by describing the scope of the problem:Biological psychiatry aims to understand mental disorders in terms of the biological function of the nervous system. By several measures it has been a tremendous success—thousands of scientific papers and hundreds of books devoted to this subject; legions of dedicated scientists and over 60 dedicated professional societies worldwide; and a profound impact on the public's perception of mental disorders. Despite these successes, it has not led to clinical tests that can be routinely used in the diagnosis and treatment of mental disorders. In the early 2000s, a series of white papers expressed hope that the advances in genetics, imaging and new technologies might lead to a biologically supported psychiatric classification and diagnostic system. But a decade later, as we stand at the threshold of a new version of the DSM, there are few biological clinical tests central to diagnosing psychiatric illnesses (other than those used to exclude physical illnesses). This article explores why this journey has been difficult for psychiatry and what can be done about it.The question of "why" revolves around the "missing gold standard" - a biologically valid concept of a specific mental illness. During the Decade of the Brain (1990-1999) there was considerable optimism that advances in neuroimaging and genetics would lead to improvements in the validity of psychiatric diagnoses. However, that didn't happen. Many of the genetic association studies in schizophrenia failed to replicate, for instance. Readers of this blog (and others) know the problems and limitations inherent in contemporary neuroimaging, no less the methods of 15-20 years ago. In the Decade after The Decade of the Brain, Dr. Thomas Insel noted that 90s-era research in biological psychiatry focused on how treatments work, rather than the causes of disease. Looking ahead, he sees new views of mental disorders as circuit disorders are one reason for renewed optimism.In the present commentary, Kapur et al. (2012) discuss how the ongoing issues with DSM-5 hinder the search for clinical tests:On the one hand, these successive editions of DSM and ICD lead to increasing psychometric precision. On the other hand, the ever increasing fractionation of mental distress into smaller and more numerous categories, without a priori biological validity, makes it harder to find specific biomedical tests that diagnose or predict the disorders.Additional problems fall under the heading of Underpowered Studies and Approximate Replications:One might expect that failure to replicate the findings would induce scientists to lose interest in the given area and to move on to findings with more robust effects. Unfortunately, an initial underpowered study is often followed by another study of similar size but with a few additional measures and variables to give it some novelty and distinction. These subsequent studies usually have only modest statistical power to decisively confirm or refute the original finding, but do have sufficient multiplicity of new measures to generate some significant finding—even though not precisely the one observed in the first study—thus providing an ‘approximate replication’.26 As a result, the ‘literature’ in the field grows without decisively replicating/rejecting the precise original finding, but instead creates a penumbra of ‘P<0.05’ findings around the first.What can be done about it?Not much, if the search is for screening tests like mammograms and Pap smears in healthy women:Few biological screening tests have been developed without a plausible and understandable link to the aetiology or pathophysiology of the disease—thus biological screening for most psychiatric disorders seems distant.How about diagnostic tests? Here, too, don't hold your breath:The prospects of ‘diagnostic tests’ for DSM entities remain distant for reasons articulated above, and it seems unlikely that we will replace the 300-disorder taxonomy of the DSM-5 with an alternative biologically based classification system anytime soon. Therefore the real opportunity for psychiatry is to use the emerging advances in genetics, molecular biology, imaging and cognitive science to supplement, rather than replace, the symptom-driven diagnosis. It is often like this in the rest of medicine [e.g., asthma, arthritis]. Instead, the goal should be to create a "stratified psychiatry" of phenotypic or genotypic subtypes - although they caution that the promise of "personalized medicine" has not been obtained in other specialties either. But they point to discovery of the gene mutation resulting in overexpression of HER2 in breast cancer, and the development of monoclonal antibody treatments, as one success story. This type of stratification doesn't require a complete understanding of the etiology of breast cancer.Within psychiatry, one can view the diagnostic category of schizophrenia (for example) as a collection of symptoms or disorders that can vary across individuals (... Read more »

  • July 27, 2012
  • 04:18 AM

Online Gaming Addiction, Dysfunctional Families, and the Striatum

by The Neurocritic in The Neurocritic

Internet addiction is perceived to be an important problem in some Asian countries, including Taiwan and Korea. Fatal marathon sessions of online gaming, in particular, have drawn a lot of media attention. Most recently, a teen in Taiwan died after playing Diablo III for 40 straight hours in an internet cafe.Yen et al. (2010) speculated on potential cultural contributions to heavy internet use:Internet addiction has been found to be more prevalent in some Asian countries than in the United States 1. Differences in sociocultural background might partly account for this difference. Among various Internet activities, online gaming is the most developed in many Asian countries. Commercial promotion for online gaming focuses on the adolescent population. Adolescents in high schools of Asian countries usually face a strong academic competition. Internet provides a virtual world in which they can temporarily forget the stress of academic performance.However, "internet addiction" is a murky and controversial diagnosis that is the subject of intense debate. It is being considered for inclusion in the DSM-5, although some critics find the entire concept to be nonsensical:1[Dr. Vaughan] Bell has argued that the Internet is not an activity, and therefore Internet addiction is a flawed idea (J Ment Health 2007;16:445–57).“Fundamentally, the Internet is a medium of communication,” says Bell, who claims that one can no more be addicted to the Internet than to radio waves. “The concept itself doesn’t make sense.”Nonetheless, internet addiction treatment programs are blossoming in the U.S. and worldwide. Although dodgy Chinese 'boot camps' are grabbing all the headlines, another school of thought looks to family dynamics as the root of the problem.Online Gaming Addiction: It's the Family's FaultAn unusual new fMRI paper by Han et al. (2012) examined brain activity in adolescents with heavy online game use, both before and after 3 weeks of intensive family therapy. In brief, the results seemed to suggest that activity in the dopamine-rich striatum was increased to family bonding cues after family therapy in the "addicted" gamers.2Since I've already mentioned dopamine, you can see where this is headed. The authors cited studies on the similarities in brain activity in response to cues of affection and addiction (e.g. Fisher et al., 2005; Frascella et al., 2010), in which the striatum figures prominently. No wonder we see so many ridiculous stories on dopamine and internet addiction in the popular media.The truth is much more nuanced. It's time to abandon the simplistic notion of dopamine as the feel-good neurotransmitter. To quote the authors of Mesolimbic Dopamine in Desire and Dread (Faure et al., 2008):It is important to understand how mesocorticolimbic mechanisms generate positive versus negative motivations. Dopamine (DA) in the nucleus accumbens is well known as a mechanism of appetitive motivation for reward. However, aversive motivations such as pain, stress, and fear also may involve dopamine in nucleus accumbens (at least tonic dopamine signals). The Neurocritic expanded on this thought in Is Mourning Rewarding?, and discussed the distinction between the "wanting" and "liking" aspects of reward (Berridge et al., 2009) in Great and Desperate Cures for Addiction. These two facets of reward can become uncoupled: you can continue to "want" something you no longer "like". But summaries of this research don't make good cover stories for Newsweek.Dysfunctional Family CircusBack to Han et al. (2012): An association between dysfunctional family structure and adolescent substance use has been suggested by several public health studies... . . . In a study of family factors contributing to internet addiction, Yen et al. (2007) reported that higher levels of parent-adolescent conflict and lower family function were associated with internet addiction. China's “left behind children,” due to parental migration from rural to urban areas for work, have been reported to be at increased risk of physical inactivity, internet addiction, and smoking (Gao et al., 2010). In a study of 1369 university students, Tsai et al. (2009) reported that deficient social support was a significant risk factor for internet addiction...The participants in their study were 15 adolescents with potentially problematic online gaming habits (mean 35 hrs/week), all from dysfunctional families, and 15 adolescents with no gaming issues (mean 3 hrs/week) from intact families. The criteria for problematic online game play were:1) game playing time greater than four hours per day and 30 hours per week; 2) Young Internet Addiction Scale (YIAS)... Read more »

  • July 14, 2012
  • 04:48 AM

Brain Responses to Virtual Reality-Induced Hallucinations in Schizophrenia

by The Neurocritic in The Neurocritic

What is it like to experience the frightening auditory and visual hallucinations characteristic of schizophrenia? Yellowlees and Cook (2006) developed a virtual reality program in Second Life based on interviews with schizophrenic patients. The researchers used this as a tool to educate the general public about schizophrenia, in order to increase understanding and reduce stigma. A video sample of the program can be viewed below.As you can see, these hallucinations are straight out of a horror movie or a terrible nightmare, except they reflect the reality of living with schizophrenia: Multiple voices, occasionally overlapping, criticizing the userA newspaper in which the word “death” would stand out in a headlineA floor that would fall away, leaving the user walking on stepping stones above a bank of cloudsA television that would play a political speech, but then criticize the user and encourage suicideA gun that would appear under a cone of light and pulse, with associated voices telling the user to take the gun and commit suicideA mirror in which a person's reflection would appear to die, becoming gaunt with bleeding eyesThe authors also provide information about accessing the Virtual Hallucination environment directly.Persons with other psychiatric disorders may be plagued by voices saying they're worthless and directing them to commit suicide, but the voice is a self-deprecating internal monologue and clearly identified as their own (as in nonpsychotic unipolar and bipolar depression). The issue in schizophrenia is one of reality monitoring, so that internal thoughts and impulses are interpreted as external to the self.The most common type of hallucination is hearing voices. To determine which brain regions are implicated, a number of neuroimaging studies have scanned participants with schizophrenia while they are actively experiencing auditory hallucinations, compared to the non-hallucinating state (Allen et al., 2008; Kompus et al., 2011; Jardri et al., 2011). A common finding is increased activation of auditory cortex in the absence of external stimulation, along with greater activity in Broca's area (speech production) and the medial temporal lobe (memory). One interpretation of this pattern is that memory retrieval triggers aberrant auditory perceptual experiences. Another is that inner speech is attributed to external sources due to defective self-monitoring.A new study by Kim and colleagues (2012) took a different approach. They constructed a virtual reality environment in the scanner to produce the illusion of burning flames, and compared the neural responses of schizophrenic and control participants. The experimental setup is shown below.Fig. 1A (adapted from Kim et al., 2012). The virtual flame illusion. A participant could see his/her body through a head-mounted display (HMD) during the “flame off” block and watched a superimposed, animated image of a virtual flame on the right or left index finger during the “flame on” block.The participants were 16 schizophrenic patients with mild to moderately severe symptoms and 17 controls. They were instructed that the purpose of the experiment was to examine the brain's response to “observing the body.” However, they were not informed about the potentially frightening illusion:Participants were not told about the virtual flame and were instructed to observe their body without closing their eyes. As shown in Fig. 1, the experiment used a blocked paradigm and consisted of two conditions: 1) a ‘flame off’ block (30 s), during which only a real-time body image was presented, and 2) a ‘flame on’ block (16 s), during which the virtual flame was generated by a computer in real-time and superimposed on the participant's index finger. The blocks were alternatively repeated 8 times, and the presentation of the flame on the left or the right finger was counterbalanced.Fig. 1B (adapted from Kim et al., 2012). fMRI task sequence. The experiment used a blocked design and alternated between ‘flame off’ blocks (30 s) and ‘flame on’ blocks (16 s).Lest you think this situation skirts the boundaries of unethical (as I did), the study was approved by the local institutional review board and subjects signed [semi-]informed consent statements.After the fMRI session was over, the participants filled out a questionnaire which indicated (A) the strength of their reactions from 1 (“not at all”) to 7 (“extremely strong”), and (B) how much their feelings changed when the blocks were repeated, rated from 1 (“severely attenuated”) to 7 (“severely augmented”):After scanning, most participants reported that they initially felt the ‘flame on their finger,’ but then the feeling disappeared after realizing that the flame was not real. . . . ...both patient and control groups showed similar subjective responses to the task stimuli: moderate strength in feeling the flame (4.6 ± 1.9 and 3.8 ± 1.8, respectively) and slight attenuation in flame strength over time (3.3 ± 1.8 and 2.6 ± 1.3, respectively). [The group differences were not statistically significant.]The data analysis strategy went beyond the standard boxcar comparison between "flame on" and "flame off." Instead, the authors......considered that the process of virtual flame-specific learning (i.e., gaining insight into the reality of a visual image) might be reflected as a linear or quadratic function of fMRI signal changes. A linear function could reflect repetition enhancement, sensitization/repetition attenuation, or habituation to the stimulus. A quadratic function could reflect transitions between repetition enhancement and repetition attenuation.The brain activation differences between groups were not all that spectacular, once you discard all the p<.001 uncorrected regions that were reported in Table 2. What was left?...only five areas including the left anterior prefrontal cortex, left occipito-temporal junction, left occipital gyrus, right amygdala, and left cerebellum were included. As depicted in Fig. 2, the control group demonstrated transitions from repetition enhancement to attenuation in these five brain regions, in contrast to the lack of enhancement and attenuation in the patient group [i.e., a flat response]. Fig. 2 (Kim et al., 2012... Read more »

Yellowlees PM, & Cook JN. (2006) Education about hallucinations using an internet virtual reality system: a qualitative survey. Academic psychiatry : the journal of the American Association of Directors of Psychiatric Residency Training and the Association for Academic Psychiatry, 30(6), 534-9. PMID: 17139026  

  • July 8, 2012
  • 08:25 PM

EMPowered to Kill

by The Neurocritic in The Neurocritic

Mentally ill killer tried vitamin therapy, court toldA man with schizophrenia killed his father and gravely injured his mother at their home in North Vancouver, British Columbia. Jordan Ramsay was off his prescribed antipsychotic medication at the time, instead taking an alternative multivitamin preparation called Truehope EMPowerplus™. He believed his parents were aliens and felt compelled to kill them. Ironically, Wendy and Donald Ramsay were in favor of their son's Truehope treatment. But Jordan Ramsay's paternal aunt and grandmother disagreed strongly with this decision:Leeann Ramsay, the aunt of the accused, believes the family's attempt to control his illness with an alternative therapy rather than his psychiatrist's prescription had a role in his state of mind at the time of the killing.. . ....just two days before the murder, a North Vancouver nurse reported, "His mother stated she wanted him on Empower Plus vitamins, and she believed she had permission to reduce his medication."Leeann Ramsay told CBC News that Jordan's grandmother had serious concerns about the alternative treatment as well."My mom had various conversations with them about Jordan weaning off his anti-psychotics and trying this alternative megavitamin therapy, and my mom was very much against it."Furthermore, Leeann Ramsay wants to launch an investigation into whether EMPowerplus™ played any role in her brother's death, subverting the antipsychiatry paradigm of blaming psychotropic medications for suicides and homicides.Truehope EMPowerplus™ is no stranger to controversy. In June 2003 Health Canada advised Canadians not to use Empowerplus, and in July 2003 they executed a search warrant to seize imports from the US. The supplement was being marketed to treat bipolar disorder, anxiety, panic attacks, ADHD, schizophrenia, autism, Tourette’s syndrome, fibromyalgia, and OCD without a doctor's supervision and without an approved Drug Identification Number (DIN).Our main concern deals with the unproven health claims being made about Empowerplus, and the recommendation that patients decrease the dose of, or eliminate altogether, medications prescribed by their doctors. This can result in serious adverse health consequences. But no matter. The company continues to make false claims. For starters, the current title of the product webpage is still "Depression symptoms reduced or eleminated [sic] by taking EMPowerplus".But what is EMPowerplus™ exactly? Truehope says it's A Revolutionary Micronutrient Formula......proven effective in reducing or eliminating the symptoms of bipolar, anxiety, depression, and ADHD. 16 medical journal publications, plus many individual doctors’ observations, have shown significant reductions in the symptoms of bipolar and other mental disorders. That's interesting. ONE formulation to treat all of these disorders? Typically, the antidepressants and stimulants used to treat anxiety/depression and ADHD (respectively) are not recommended for bipolar disorder because of the risk of triggering a manic episode. The premise of the Truehope treatment strategy is that a "chemical imbalance" causes all mental illnesses:The most common explanation for mental disorders is a chemical imbalance in the brain, but how and why these imbalances happen is not yet known. Since a complex web of nutrients, such as zinc, vitamin B6, and vitamin B12, are the building blocks that the brain needs to make the right amounts of important chemicals such as neurotransmitters, it makes sense that a lack of these nutrients could cause the chemical imbalances of mental illnes. [sic]The thing that I find so fascinating is the simultaneous reliance on a simplistic "chemical imbalance" theory of mental illness and an opposition to traditional pharmaceuticals originally purported to correct those chemical imbalances. This theory has been panned by critics of biological psychiatry and has even fallen out of favor among neuroscientists conducting both basic and clinical research.However, there is no doubt that vitamin deficiencies can produce neurological and psychiatric disturbances. For instance, a lack of B12 can damage the central nervous system via changes in cytokine and growth factor production (Scalabrino, 2009). Thiamine deficiency is well-known for causing Wernicke's encephalopathy and Korsakoff's syndrome, disorders characterized by severe memory impairments. Previous studies have suggested that vitamins and minerals do have an effect on mood and perhaps even antisocial behavior Kaplan et al., 2007; Bohannon, 2009). The question here is whether broad-spectrum micronutrient treatments (i.e., nutritional supplements) can improve or "cure" bipolar disorder.Truehope lists 17 published studies on the effectiveness of EMPowerplus™ in treating bipolar, ADHD, autism, and OCD. However, none of these studies is a randomized controlled trial that compares placebo to EMPowerplus™ in a double-blind fashion. Thus, it cannot be established that any improvements are due to the supplement, rather than to expectation or placebo effects.In one study, Gately and Kaplan (2009) presented results from 358 self-identified bipolar individuals (120 men, 238 women)1 who purchased EMPowerplus™ from the Truehope website and subsequently filled out a symptom reporting checklist using the company's Self-Monitoring Form.2 The diagnosis of bipolar disorder was not confirmed by a mental health professional. We don't know how many have bipolar I vs. bipolar II vs. cyclothymia. Here's a description of how the sample was selected:There were 682 participants who reported having been diagnosed with bipolar disorder: 378 with no other disorders, 17 with both depression and bipolar disorder,3 and 287 with bipolar disorder as well as additional diagnoses such as ADHD, OCD, anxiety-panic, or schizophrenia. The conservative selection of just the 395 reporting bipolar disorder but no additional disorder except for the 17 also reporting depression was an attempt to reduce the heterogeneity of the sample.Although physician confirmation of diagnosis was not available, 81% of the sample were taking psychiatric medications at the time they commenced taking the micronutrients, indicating that a physician considered their mood s... Read more »

Gately D, Kaplan BJ. (2009) Database Analysis of Adults with Bipolar Disorder Consuming a Micronutrient Formula. Clinical Medicine: Psychiatry, 3-16. info:/

Kaplan BJ, Crawford SG, Field CJ, & Simpson JS. (2007) Vitamins, minerals, and mood. Psychological bulletin, 133(5), 747-60. PMID: 17723028  

  • June 17, 2012
  • 08:37 PM

Textmania: a Modern Manifestation of Manic Hypergraphia?

by The Neurocritic in The Neurocritic

Continuing with the theme of reading and writing, a new study reports on the case of a 23 yr old woman with bipolar I disorder whose output of text messages was "1333.33% more" during a manic episode (Emeagwali et al., 2012):The patient reported a dramatic increase in the quantity of both texting and sex-texting (or sexting) in addition to a decrease in quality of the message content. In addition, there was a substantial increase in the number of people with whom the patient engaged in simultaneous texting conversations. This case provides evidence for the need to consider non-traditional forms of communication when evaluating a patient’s communication pattern during mania.How many texts per day are we talking about? At least 200, up from her usual 15-20 texts/day.1 In the grand scheme of things, 200 is not all that unusual, because the mean number of text messages sent by young adults in the 18-24 age group is 109.5, according to a Pew Internet Survey.2 The change in the patient's behavior is the critical factor here.Hypergraphia (an overpowering urge to write) is probably seen more frequently in mania than in temporal lobe epilepsy, but the latter gets more attention in the medical literature due to the sometimes spectacular nature of the output (e.g., the novels of Dostoevsky, a 17 million word diary, and a copious collection of rhyming poetry). The neurological case studies are often illustrated with EEG traces showing abnormal spiking activity, along with examples of the person's handwriting (Kalamangalam, 2009):The patient was observed to write for much of her waking hours. The document, a letter to her husband, numbered 29 pages by the time of her discharge from hospital and remained unfinished. The writing was cramped, dense, and used all the available space on both sides of the sheet, including the margins. The contents of the letter were rambling, though with specific details. She wrote about her hospital stay, often mentioning exact times, her intake of medications, and minor details of conversations with staff. -- click on image for a larger view --Fig 1 (left). Sleep EEG, bipolar longitudinal montage: a single spike maximum over the right anterior temporal region (arrow). Fig. 3 (right). Close up of page 16. The patient writes about her medication dosing, including minor details. (modified from Kalamangalam, 2009).You don't see such reports in the psychiatric literature.3 There are no obvious manifestations of a manic episode on EEG or PET scans where you can say, in an individual person, "oh yes, this reduced gamma coherence and inhibition of theta activity in the lateral inferior prefrontal cortex, coupled with increased dopaminergic transmission in the midbrain, are clear indicators of mania." A PubMed search for mania OR manic AND hypergraphia returns one result, while a search for temporal lobe epilepsy and hypergraphia yields 22 hits.There have of course been books on bipolar disorder and creativity, such as Touched With Fire: Manic-Depressive Illness and the Artistic Temperament by Dr. Kay Redfield Jamison. More specifically, Dr. Alice W. Flaherty covered the phenomenology and neurobiology of hypergraphia. In The Midnight Disease: The Drive to Write, Writer's Block, and the Creative Brain:Flaherty writes compellingly of her bout with manic hypergraphia, when "the sight of a computer keyboard or a blank page gave me the same rush that drug addicts get from seeing their freebasing paraphernalia." Dissecting the role of emotion in writing and the ways in which brain-body and mood disorders can lead to prodigious — or meager — creative output, Flaherty uses examples from her own life and the lives of writers from Kafka to Anne Lamott, from Sylvia Plath to Stephen King [and Fyodor Dostoevsky].And certainly the evidence for manic/hypomanic hypergraphia has been plainly obvious for as long as the internet has existed. There are thousands of bipolar bloggers and Tweeters and Facebook users and online journalers before that. Unlike PubMed, Google Blog Search returns 3,670 hits for bipolar hypergraphia and 4,230 hits for manic hypergraphia. And those are just the posts that use the term hypergraphia.4 One could envision a study on quantitative changes5 in written output on Twitter or blogs as a possible sign of bipolar cycling.So it seems that contemporary psychiatrists are not all that interested in publishing case studies about their frantically writing patients, unlike the neurologists. Perhaps it's so commonplace that they just don't see the point?Footnotes1 As you can see, the mathematical calculation quoted in the first sentence is rather imprecise.2 The median, which is less sensitive to the effects of gabby outliers, is 50 texts per day.3 This raises the issue of Neurology vs Psychiatry and the Neurological/Psychiatric Divide.4 For another interesting personal perspective see Bipolar 101 on ... Read more »

Kalamangalam, G. (2009) Hypergraphia in temporal lobe epilepsy. Annals of Indian Academy of Neurology, 12(3), 193. DOI: 10.4103/0972-2327.56323  

Emeagwali, N., Bailey, R., & Azim, F. (2012) Textmania: Text Messaging During the Manic Phase of Bipolar I Disorder. Journal of Health Care for the Poor and Underserved, 23(2), 519-522. DOI: 10.1353/hpu.2012.0062  

  • June 4, 2012
  • 07:27 PM

G r e a t e r / l e t t e r / s p a c i n g / helps reading in dyslexia

by The Neurocritic in The Neurocritic

Simply increasing the spacing between letters improves the reading ability of children with developmental dyslexia, according to a group of Italian and French researchers (Zorzi et al., 2012). Dyslexic children were 20% faster and twice as accurate when reading the altered text. This impressive result was obtained without any prior training whatsoever.The study was based on the phenomenon of crowding, where the recognition of individual letters is impaired by the close proximity of surrounding letters. Children with dyslexia are disproportionately affected by crowding, compared to normally developing children (Martelli et al., 2009). Other aspects of the printed word are known to affect reading ability, but surprisingly little is known about letter spacing. The recommendations of the British Dyslexia Association include optimizing the size and type of font, page layout, headings, type of paper, and line spacing but not letter spacing.1The collaborative effort was a deliberate attempt to compare two languages that have different types of spelling-to-sound translation. Italian has completely regular spelling rules (a transparent orthography), meaning there are no exception words. Each combination of printed letters is always pronounced in a consistent way. By contrast, written French is orthographically opaque, meaning that pesky irregular spellings can trip you up. This is true in English as well: compare the pronunciation of the word "pint" to "hint", "mint", and "lint". The /i/ sound wins out over the /ī/ sound, in terms of regularity.In the study, 34 Italian and 40 French children with dyslexia were tested on two separate occasions at least two weeks apart. They read 24 short sentences, which were written in standard text in one session and highly spaced text in the other. The order of sessions was counterbalanced to control for practice effects, with half assigned to read the spaced text at T1 and the other half at T2. Reading accuracy (number of errors) and reading speed (number of syllables per second) both interacted with test session (p<.0001), indicating a drastic improvement with the highly spaced text. This was true for both the Italian and the French children with dyslexia.Fig. 2 (Zorzi et al., 2012). (C) Reading accuracy (number of errors) in the normal and spaced text conditions for Italian dyslexics, French dyslexics, and a younger group of Italian control children matched for reading level (RL) to the Italian dyslexic sample.It came as quite a surprise to me that no one had demonstrated this letter spacing effect before. But then again, I'm not familiar with the literature on developmental reading disorders, so perhaps Professor Dorothy Bishop or Livia Blackburn can provide a more critical take on an [apparently] amazing finding.Finally, the authors have developed DYS, a free iPhone/iPad application. You can test out the spacing effect for yourself and submit your results anonymously, in the name of science! For more information, see the WSJ Health Blog.Footnote1 Also note that bold is preferable to italic, as the latter induces crowding.ReferencesMartelli M, Di Filippo G, Spinelli D, Zoccolotti P (2009). Crowding, reading, and developmental dyslexia. J Vis 9: 14, 1–18.Marco Zorzi, Chiara Barbiero, Andrea Facoetti, Isabella Lonciari, Marco Carrozzi, Marcella Montico, Laura Bravar, Florence George, Catherine Pech-Georgel, and Johannes C. Ziegler (2012). Extra-large letter spacing improves reading in dyslexia. PNAS. doi:10.1073/pnas.1205566109.

... Read more »

Marco Zorzi, Chiara Barbiero, Andrea Facoetti, Isabella Lonciari, Marco Carrozzi, Marcella Montico, Laura Bravar, Florence George, Catherine Pech-Georgel, and Johannes C. Ziegler. (2012) Extra-large letter spacing improves reading in dyslexia. PNAS. info:/

  • June 2, 2012
  • 11:05 PM

Compulsion to write caused by seizure, whether at work or at leisure

by The Neurocritic in The Neurocritic

Hypergraphia is a compulsive or overwhelming urge to write, often associated with temporal lobe epilepsy. Influential behavioral neurologist Norman Geschwind included hypergraphia as one of the personality changes that can be observed in persons with temporal lobe epilepsy.An unusual example of hypergraphia was observed by Dr. Mario F. Mendez, who reported the unique case of a 58 year old man who felt utterly compelled to write poetry (Mendez, 2005). The patient reported no previous history of being a poet until the age of 53, when he felt the urge to write in rhyme. He said that words are "continuously rhyming in [my] head" and felt the need to write them down and show them to other people. He didn't speak in verse, nor did he write nonrhyming prose or read others' poetry.Thus, his condition was a very specific hypergraphia for poetry. The rhyming condition coincided with the onset of other behavioral symptoms, namely irritability and anger. Shortly thereafter he began to have partial complex seizures, which typically have foci (or origins) in the medial temporal lobes.His seizures manifested as a sensation "rising" in his stomach followed by a brief alteration of consciousness. Seizure control with phenytoin and gabapentin ameliorated his irritability and anger but did not diminish his constant need to write in rhyme. ... The patient underwent a repeat evaluation. On examination, he was circumstantial and somewhat viscous. He repeatedly emphasized the significance of his symptom of poetry writing, and continually responded in written poetry. Language, mental status, and neurological examinations were otherwise normal except for a slightly broad-based and unsteady gait. He had right temporal spikes on electroencephalograms and small strokes in the right thalamus and the right cerebellum on neuroimaging.However, Mendez (2005) did not think the small right hemisphere strokes caused the patient's hypergraphia. The author was also skeptical that ongoing subthreshold ictal activity was solely responsible, because the seizures were well-controlled yet the poetry continued. Another possible explanation was related to persistent hypofunctioning in the right hemisphere, which could lead to disinhibition or "unmasking" of poetic abilities in the left hemisphere.1 This hypothesis assumes that the right temporal lobe maintains tonic control over neural activity in the left hemisphere, so we don't all turn into Joyce Kilmer.HYPERGRAPHIA, the movieA notoriously hypergraphic writer of poetry and prose was Arthur Crew Inman (1895-1963), who will be the subject of Hypergraphia, a forthcoming film starring John Hurt.Arthur Crew Inman was a reclusive and unsuccessful poet whose 17-million word diary, extending from 1919 to 1963, provides a panoramic record of people, events, and observations from more than four decades of the twentieth century.Footnote1 Most people are left hemisphere dominant for rhyme generation (Krach & Hartje, 2006).ReferenceMendez, M. (2005). Hypergraphia for Poetry in an Epileptic Patient Journal of Neuropsychiatry, 17 (4), 560-561. DOI: 10.1176/appi.neuropsych.17.4.560

... Read more »

  • May 18, 2012
  • 12:24 AM

Blast Wave Injury and Chronic Traumatic Encephalopathy: What's the Connection?

by The Neurocritic in The Neurocritic

Fig. 3 (Goldstein et al., 2012). Single-blast exposure induces CTE-like neuropathology in wild-type C57BL/6 mice.In a tour de force, a group of 35 Boston-area scientists1 (Goldstein et al., 2012) developed a mouse model of blast-related neurotrauma that resulted in pathological changes similar to chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease seen most often in athletes with repeated concussions. They also reported post-mortem neuropathological findings from the brains of war veterans and amateur football players who had sustained concussions and traumatic brain injuries (TBIs).Diagnosis of CTE occurs after autopsy, because the brain tissue has to be stained for characteristic protein abnormalities which cannot be visualized in a living human. A defining pathological feature is tauopathy - abnormal accumulations of the tau protein seen in other dementias (e.g., Alzheimer's disease). Aggregations of hyperphosphorylated tau into neurofibrillary tangles (NFTs) are a defining feature, as in frontotemporal lobar degeneration and amyotrophic lateral sclerosis - yet CTE is distinct from both of these (McKee et al., 2009). CTE results in cognitive and behavioral changes including memory impairments, poor impulse control, alterations in mood, suicidal behavior, disorientation, and ultimately dementia.Can Blast Waves Cause Chronic Traumatic Encephalopathy?The major conclusion drawn from the human data in this study is that exposure to blasts from IEDs causes CTE (Goldstein et al., 2012). However, my contention is that the cause of tauopathies in these military veterans is unclear. Three of the four had histories of concussion from other events.Much of what you've read about this paper in the media is wrong. The worst offender by far was Business Insider:Scientists Looked Inside The Brains Of Troops Killed By Bombs And Made This Shocking DiscoveryTrauma from exposure to a single improvised explosive device (IED) blast can result in long-term brain impairment, according to new research. The study, published today in the journal Science Translational Medicine, is the first to examine postmortem brains of U.S. military personnel who were exposed to a blast and/or a concussive injury. It found evidence that a single blast from a typical IED can cause traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE).Really?1) None of the troops were killed by bombs -- they all died from other causes.2) None of the troops had a single isolated blast exposure.3) It is not the first study to examine postmortem brains of U.S. military personnel who were exposed to a blast and/or a concussive injury. That would be the paper by Omalu, Hammers, et al. (2011). I wrote about it here.2 4) The evidence that a single IED blast can cause TBI and CTE did not come from looking inside the brains of troops, it was obtained from a mouse model of neurotrauma.Next, let's take a look at what the paper actually did.Part 1 - Human CTEThe brain banks at the Center for the Study of Traumatic Encephalopathy and the Alzheimer's Disease Center at Boston University provided the brains of 12 human subjects:4 male military veterans (ages 22-45 yrs) with histories of explosive blast and/or concussive injury 1 to 6 years before death4 male athletes (ages 17-27 yrs) with histories of repetitive concussive injury, including 3 football players and a professional wrestler4 male controls (ages 18-24 yrs) with no known blast exposure, trauma history, or neurological diseaseCase histories of the military veterans are presented below, to show that 3 of the 4 had concussions that were not due to explosive blast.Case 1, a 45-year-old male U.S. military veteran with a single close-range IED blast exposure, experienced a state of disorientation without loss of consciousness that persisted for ~30 min after blast exposure. He subsequently developed headaches, irritability, difficulty sleeping and concentrating, and depression that continued until his death 2 years later from a ruptured basilar aneurysm. His medical history is notable for a remote history of concussion associated with a motor vehicle accident at age 8 years.Case 2, a 34-year-old male U.S. military veteran without a history of previous concussive injury, sustained two separate IED blast exposures 1 and 6 years before death. Both episodes resulted in loss of consciousness of indeterminate duration. He subsequently developed depression, short-term memory loss, word-finding difficulties, decreased concentration and attention, sleep disturbances, and executive function impairments. His neuropsychiatric symptoms persisted until death from aspiration pneumonia after ingestion of prescription analgesics.Case 3, a 22-year-old male U.S. military veteran with a single close-range IED blast exposure 2 years before death. He did not lose consciousness, but reported headache, dizziness, and fatigue that persisted for 24 hours after the blast. He subsequently developed daily headaches, memory loss, depression, and decreased attention and concentration. ... He was diagnosed with PTSD 3 months before death from an intracerebral hemorrhage. His past history included 2 years of high school football and multiple concussions from fist fights. Case 4, a 28-year-old male U.S. military veteran with two combat deployments, was diagnosed with PTSD after his first deployment 3 years before death. His history was notable for multiple concussions as a civilian and in combat, but he was never exposed to blast. ... He died from a self-inflicted gunshot wound 2 years after his last concussion. In brief, Case 1 had a concussion in a car accident as a child, Case 3 had multiple concussions from football and fist fights, and ... Read more »

Goldstein, L., Fisher, A., Tagge, C., Zhang, X., Velisek, L., Sullivan, J., Upreti, C., Kracht, J., Ericsson, M., Wojnarowicz, M.... (2012) Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model. Science Translational Medicine, 4(134), 134-134. DOI: 10.1126/scitranslmed.3003716  

  • May 12, 2012
  • 05:32 PM

An Orgy of Self-Referential Blogging...

by The Neurocritic in The Neurocritic

...may follow from a new PLoS ONE paper on bloggers whose posts are aggregated at (Shema et al., 2012):The average RB blogger in our sample is male, either a graduate student or has been awarded a PhD and blogs under his own name.The Neurocritic has never been one for meta-blogging.1 I don't like to draw attention to my existence as an actual person, and I don't have time to discuss things like the pros/cons of blogging, scientific outreach, gender imbalances, scientist bloggers vs. science writer bloggers, commenting policies, and blogging networks. It's not that these aren't worthwhile topics, it's just that it's not my thing.For those issues, I recommend reading Scicurious, who has blogged thoughtfully (and extensively) about them. As you can see in the figure below, she's a major player in the RB science blogging tweeting universe.Figure 3 (modified from Shema et al., 2012). Twitter interconnections – followers.In a way, I feel like this article is the peer-reviewed equivalent of a link bait site that names you as a Top Fifty Psychology Blog, just asking for egotistical bloggers to post about it.Well I'm not falling for it...Footnote1 That said, The Neurocritic's last post jokingly mentioned self-referential processing in the context of linking to oneself, but that was only because I actually have written extensively on spindle neurons, aka von Economo neurons.ReferenceShema, H., Bar-Ilan, J., & Thelwall, M. (2012). Research Blogs and the Discussion of Scholarly Information. PLoS ONE, 7 (5) DOI: 10.1371/journal.pone.0035869

... Read more »

  • May 10, 2012
  • 08:22 AM

Spindle Neurons in Macaques?

by The Neurocritic in The Neurocritic

Spindle neurons, or Von Economo neurons (VENs), are a unique type of large, bipolar neuron found primarily in layer Vb in the anterior cingulate cortex and the frontoinsular cortex of humans.1 In 1999, Nimchinsky and colleagues discovered that among the 28 nonhuman primate species they examined, only great apes had VENs [see Spindle Neurons: The Next New Thing?].Spindle neurons are also seen in humpback, fin, sperm, and killer whales (Hof & Van der Gucht, 2007), elephants (Hakeem et al., 2009), and cetaceans such as the bottlenose dolphin, Risso’s dolphin, and the beluga whale (Butti et al., 2009).Because VENs are only found in large-brained, highly evolved social species, and are potentially implicated in certain neurological and psychiatric disorders, their hypothesized functions include empathy, conscious awareness, and self-referential processing. A 2011 review by Allman and colleagues reiterated that only great apes (bonobos, chimpanzees, gorillas, orangutans) have VENs and suggested they......may be a specialization related to very large brain size. The large size and simple dendritic structure of these projection neurons suggest that they rapidly send basic information from FI [frontoinsular cortex] and LA [limbic anterior area] to other parts of the brain, while slower neighboring pyramids send more detailed information. Selective destruction of VENs in early stages of frontotemporal dementia (FTD) implies that they are involved in empathy, social awareness, and self-control, consistent with evidence from functional imaging.VENs: Not Only for Great Apes Any More!But now, a new study has identified these special neurons in the insular cortex of macaque monkeys (Evrard et al., 2012).Figure 1 (Evrard et al., 2012). The Von Economo Neuron Is Present in Layer 5b in a Restricted Portion of the Agranular Anterior Insula in the Macaque Monkey (A) High-magnification photomicrographs demonstrating the identical morphology of the macaque and human VENs. Scale bar represents 25 μm.Why weren't they found in the earlier studies that looked for them?Three reasons: (1) they're a lot smaller in monkeys; (2) they're more fragile in monkeys; and (3) they're confined to a more limited anatomical region.First, the large human VENs unambiguously stand out at low microscope magnifications. Searching for relatively smaller VENs among the densely packed cell population in layer 5 in the monkey required the highest microscope magnification, which would be unusual for anyone accustomed to examining the more obvious VENs in hominids. Second, the cytoskeletal matrix of the small monkey VENs might be more fragile during histological processing than that of the larger human VENs. ... Third, in the major prior study, the number of VENs in humans and great apes was counted in consecutive sections that were apparently spaced at 1 mm intervals ... such a sampling paradigm would likely have been inadequate for the identification of VENs within the small VEN-containing region of the ventral AAI that measures ∼2 × 2 × 1 mm3 in macaques.The authors pointed out a major advantage of their new discovery, namely that more invasive studies are now possible (i.e., you can't do single cell neurophysiology in dolphins or bonobos).But wait... are they really VENs?The morphology, size, laminar distribution, and proportional distribution of the monkey VEN suggest that it is at least a primal anatomical homolog of the human VEN. Allman, Hof, and colleagues might have something more to say on the matter, based on their earlier findings (e.g., Allman et al., 2011):The VENs are illustrated at higher magnification in Figure 3, which shows that they have very similar morphology in the great apes and humans. In primates, the VENs are present in FI only in great apes and humans. This is the same taxonomic distribution as was found for the VENs in LA, which suggests that the VENs emerged as a specialized neuron type in the common ancestor of great apes and humans. Figure 3 (Allman et al., 2011). VENs in area FI of humans and great apes.The new paper concedes that:The presence of VENs in the macaque does not discredit prior evidence for a crucial role of the VENs and AIC in the emergence of self-awareness and social cognition in humans (Craig, 2009; Allman et al., 2011). VENs in humans appear to be disproportionally slightly larger than in macaques (see above); they may also have an enhanced immunopositivity (and perhaps gene expression) for proteins that are typically involved in homeostasis, which perhaps favors higher interoceptive sensitivity. Are they confined to the anterior insula in macaques? No, VENs were also found in the ACC, but that will be reported separately (a lesson for all you junior scientists).Now that they've been found in monkeys [and can be studied physiologically], will spindle neurons finally catch up with their more glamorous elder cousins, the mirror neurons? Are they really the next new thing? Six years ago, I pondered these points:Somehow, the "spindle neuron" meme hasn't caught on like the "mirror neuron" meme. Is it because spindle neurons have been only been described anatomically (not physiologically), while the reverse is true for mirror neurons? Anatomically speaking, do we know much about mirror neurons? Evrard, Forro, and Logothetis are all over it:...invasive studies of their organization, hodology, and physiology could provide significant insights into the evolutionary basis for self-awareness and empathy in humans. Regarding the latter, it would be particularly interesting to examine whether the VENs share functional similarities with the “mirror” neurons of the ventral premotor cortex (Gallese et al., 2004).Finally, a commentary in Neuron by Critchley and Seth (2012) wonders if studies of the macaque insula will reveal the neural mechanisms of self-referen... Read more »

  • May 5, 2012
  • 06:30 PM

Neurophysiological Explanation for the Perception of Poltergeists

by The Neurocritic in The Neurocritic

Poltergeist (1982) - IMDb 1 Poltergeists are defined as paranormal, mischievous ghostly presences that appear to a select group of people. As paranormal entities, they are beyond investigation by rational scientific means. Or are they? Odd sensations, visions, felt presences, out-of-body experiences, etc. have all been explained by unusual brain activity. Hence, neuroscientists should consider that poltergeists exist in the mind of the perceiver, not as a physical reality in the external world.A new paper by parapsychologist William G. Roll and colleagues reported on the case of a woman who experienced paranormal phenomenon after suffering a head injury (Roll et al., 2012):People who report objects moving in their presence, unusual sounds, glows around other people, and multiple sensed presences but do not meet the criteria for psychiatric disorders have been shown to exhibit electrical anomalies over the right temporal lobes. This article reports the striking quantitative electroencephalography, sLORETA results, and experimental elicitation of similar subjective experiences in a middle-aged woman who has been distressed by these classic phenomena that began after a head injury. She exhibited a chronic electrical anomaly over the right temporoinsular region. The rotation of a small pinwheel near her while she 'concentrated' upon it was associated with increased coherence between the left and right temporal lobes and concurrent activation of the left prefrontal region. The occurrence of the unusual phenomena and marked 'sadness' was associated with increased geomagnetic activity; she reported a similar mood when these variations were simulated experimentally. Our quantitative measurements suggest people displaying these experiences and possible anomalous energies can be viewed clinically and potentially treated.Previous work by Roll and Michael ["god helmet"] Persinger (2001) suggested that individuals who experience "anomalous energies" around them might have complex partial epilepsy with a temporal lobe focus, usually on the right side.The current patient, Ms. S, was in a motor vehicle accident which resulted in two days of coma and a severe brain injury. After the head injury,...the relationship with her first husband deteriorated because he insisted she was not the same person. This ‘change in personality’ is a frequent report by spouses of individuals who have sustained TBIs. According to her reports one night he tried to kill her. The anomalous phenomena began that night and have been intermittent since that time. Their intensity and frequency have increased during the last 2–3 years. The anomalous phenomena include mechanical, electronic, and visual effects. She reports experiences of sounds, perceived as ‘taps’ that she estimates to be between 3 and 4 Hz with sound pressure equivalents between 40 and 60 db. Occasionally there may be a single louder sound. The durations of clusters are often between 3 and 10 seconds with intervening periods of 4–8 or 16–24 seconds. The clusters are usually localized along her left side.. . .Ms. S. reported she feels overwhelmed by a deep sadness after the occurrence of the phenomena and cries, even if nothing ‘bad happens’. Since the beginning of these phenomena she hears voices of multiple ‘imaginary’ friends who she has named; the two major ones are identified as male. They presumably help her minimize the distress of the experiences...EEG recordings revealed chronically abnormal activity at a right temporal lobe electrode (T4), which showed persistently elevated amplitude. Strangely, this enhanced activity declined when the doors to the recording chamber were closed, as in Fig 1C below.Figure 1. Sample EEG activity over 19 channels displayed by Ms. S. Note the persistent high amplitude (100 μV) over the right temporal lobe compared to all other lobes (about 20 μV). (A and B) are separated by one day. (C) Shows the attenuation of the T4 anomaly after the doors of an acoustic chamber were closed.The authors attributed this to a reduction of geomagnetic fields, to which the TBI patient is exquisitely sensitive [supposedly]:The right temporal lobe anomaly attenuated within about 20 seconds to 1 minute after the doors to the acoustic chamber were closed. In addition to providing above average silence, this procedure reduces the static background geomagnetic field from 50,000 nT to about half that value. When the T4 anomaly was not distinguishable and she was sitting within the closed-door chamber she reported experiences as if she was ‘missing’ something that was similar to a ‘craving’.But maybe she was just more relaxed in the dim lighting and quiet environment of the chamber...From here on in, the authors resort to bizarre atmospheric explanations: instabilities in global geomagnetic activity and a K-6 level geomagnetic storm accounted for perceptions of tapping sounds in her hotel bedroom window, the presence of ‘entities’, and unusual lights around objects.Here's my suggestion: Why don't you take a closer look at her EEG activity in relation to these anomalous perceptions, independent of the spooky magnetic fields?? Is it because your research in parapsychology and neurotheology might float away into the ether?Footnote1 The young actress here, Heather O'Rourke, died at the age of 12 due to "medical error."ReferencesRoll, W. G. and Persinger, M. A. 2001. “Poltergeists and haunts”. In Hauntings and poltergeists: Multidisciplinary perspectives, Edited by: Houran, J. and Lange, R. 123–163. Jefferson, NC: McFarland & Company.... Read more »

  • April 29, 2012
  • 09:26 PM

Little Evidence for a Direct Link between PTSD and Chronic Traumatic Encephalopathy

by The Neurocritic in The Neurocritic

Fig. 2 (Omalu et al., 2011). Photomicrographs of tau-immunostained section of the frontal cortex.Nicholas Kristof wrote an op-ed piece in the New York Times the other day about an Iraq War veteran with post-traumatic stress disorder (PTSD) and alcohol use problems who ultimately took his own life.Veterans and Brain DiseaseBy NICHOLAS D. KRISTOFPublished: April 25, 2012He was a 27-year-old former Marine, struggling to adjust to civilian life after two tours in Iraq. Once an A student, he now found himself unable to remember conversations, dates and routine bits of daily life. He became irritable, snapped at his children and withdrew from his family. He and his wife began divorce proceedings.This young man took to alcohol, and a drunken car crash cost him his driver’s license. The Department of Veterans Affairs diagnosed him with post-traumatic stress disorder, or P.T.S.D. When his parents hadn’t heard from him in two days, they asked the police to check on him. The officers found his body; he had hanged himself with a belt.This tragic but all-too-common story had an unusual ending. An autopsy of the veteran's brain revealed signs of chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease seen most often in athletes with repeated concussions from contact sports such as professional football and boxing. CTE results in cognitive and behavioral changes including memory impairments, poor impulse control, alterations in mood, suicidal behavior, disorientation, and ultimately dementia (Lakhan & Kirchgessner, 2012).Diagnosis of CTE is usually post-mortem, because the brain tissue has to be stained for characteristic protein abnormalities which cannot be visualized in a living human. A defining pathological feature is tauopathy - abnormal accumulations of the tau protein seen in other dementias (e.g., Alzheimer's disease). In particular, aggregations of hyperphosphorylated tau into neurofibrillary tangles and accumulations of neuronal TAR DNA-binding protein-43 (TDP-43) are seen, as in frontotemporal lobar degeneration and amyotrophic lateral sclerosis (Lakhan & Kirchgessner, 2012).There have been a string of high profile media reports about CTE pathology found at the autopsy of several American football players: Mike Webster, Terry Long, Chris Henry, Tom McHale, Owen Thomas, and others. Dr. Bennett Omalu and his colleagues at the Brain Injury Research Institute have conducted some of these autopsies (e.g., Omalu, Bailes et al., 2011).1 Now, Omalu and colleagues have put forth the speculative idea that PTSD is on a continuum with CTE (Omalu, Hammers et al., 2011). Why? PTSD needn't be associated with concussions or traumatic brain injury (TBI) at all. The traumatic event exposure for PTSD (from DSM-IV-TR) "...must have involved both (a) loss of 'physical integrity', or risk of serious injury or death, to self or others, and (b) a response to the event that involved intense fear, horror, or helplessness (or in children, the response must involve disorganized or agitated behavior)." Head injury isn't part of the definition.Omalu's target population is soldiers and veterans with TBI from the war (not, for instance, survivors of the 2011 earthquake and tsunami in Japan):Following our elucidation of CTE in athletes, we hypothesized that PTSD in war veterans may belong to the CTE spectrum given that active military personnel are high-risk cohorts for repeated subconcussive and concussive traumatic brain injuries; for example, bomb blasts can cause traumatic brain injuries from primary pressure wave and acceleration-deceleration injury mechanisms. We expanded our CTE surveillance and brain tissue analyses to include deceased military veterans who were diagnosed with PTSD.OK, that sounds reasonable -- if there's well-documented evidence of subconcussive and concussive brain injuries. Which brings us back to Kristof's article:That Marine was the first Iraq veteran found to have C.T.E., but experts have since autopsied a dozen or more other veterans’ brains and have repeatedly found C.T.E. [NOTE: none of these cases has been published.] The findings raise a critical question: Could blasts from bombs or grenades have a catastrophic impact similar to those of repeated concussions in sports, and could the rash of suicides among young veterans be a result? “P.T.S.D. in a high-risk cohort like war veterans could actually be a physical disease from permanent brain damage, not a psychological disease,” said Bennet Omalu, the neuropathologist who examined the veteran.Oh no! Here we have an unfortunate example of mind-body dualism. PTSD is a physical brain disease, and this is independent of exposure to bomb blasts. There is ample evidence that exposure to traumatic events can physically change the brain (Sapolsky, 1996, 2001). Stress increases the levels of glucocorticoids, which in turn damage the hippocampus. This is visible on MRI scans (Bremner, 2006). The amygdala, a subcortical area involved in processing fear and other emotions, is overactive in those with PTSD while frontal lobe regions controlling the amygdala are underactive (Koenigs & Grafman, 2009).However, it needn't result in permanent brain damage! In his 2006 review, Bremner notes that effective PTSD treatments can improve memory and restore hippocampal volume.With this background in mind, let's return to the case report of the 27 yr old Marine. I believe there could be causes of CTE pathology that are unrelated to his military service in Iraq. I'll introduce these items as bullet points and then go into detail about each.Committed suicide by hanging.After deployment, played football in a league on base.One hit from the side caused him to fall to the ground; after this, he was confused and showed signs of a concussion [in my view].He continued to p... Read more »

  • April 23, 2012
  • 12:42 PM

Magic Buttons, Silver Linings, and Two-Edged Swords

by The Neurocritic in The Neurocritic

The Subjective Ups and Downs of Mood DisordersThe last post, Suffering for art is still suffering, took a critical look at studies claiming that individuals with bipolar disorder are more creative.1 And instead of romanticizing the tortured bipolar artist, it considered the toll the disorder can take on those who live with it (and the people around them).Some readers might have objected to the overly pessimistic tone of that post, prompting them to say things like, "It was a very negative post and clearly you are down on bipolar disorder, if not people who have it." That was not my intent.So why don't we take a look at the sunnier side of serious mental illness!The 'Magic Button Question'“If you could live your life again, would you press the ‘magic button’ to experience life without a mood disorder?”That's the question Parker et al. (2012) asked 885 patients attending an affective disorders clinic.2 Of that number, 335 patients (38%) returned the questionnaires: 111 with bipolar disorder and 224 with unipolar depression. The authors wanted to assess whether the respondents perceived any advantages to their disorders.Such positives are rarely volunteered, more commonly emerging only when the individual contemplates whether, if they were to live their life again, they would choose to have their mood disorder. A variant of this question was evident in Stephen Fry's BBC documentary (Wilson, 2006) where he explored his and others' experiences of a bipolar disorder. He asked several people to imagine there was “a button” that, if pressed, “…would take away every aspect of your bipolarity and cyclothymia”, and questioned whether they would press that button.The results of Parker et al.'s study are based on a biased sample of patients who returned the survey: 83% of the bipolar population was diagnosed with Bipolar II (n=92), compared to only 17% with Bipolar I (n=19). In New Zealand,3 the lifetime prevalence of Bipolar I is 1.0%, compared to 0.7% for Bipolar II (Merikangas et al., 2011; see their Table 2). In the US, the figures are 1.0% and 1.1%, respectively. So we know right away the sample is highly self-selected.Individuals with Bipolar II were three times more likely to endorse advantages to their disorder than those with Bipolar I.4 Because of the small number of individuals with Bipolar I, the authors collapsed across subtypes [which doesn't make sense] and found that 62% of bipolar people claimed some positive elements to their illness, compared to only 22% of the unipolar depressed group. "Thematic analyses" suggested that the four most common benefits named by bipolar individuals were:increased empathy (18%) 5increased creativity (14%)increased self-awareness (12%)increased productivity (8%)Not to belabor the obvious, but this means that 86% did not identify creativity as a benefit, and 92% did not see productivity as an advantage of being bipolar. Hmm. Hardly a ringing endorsement for the bipolar advantage.In the unipolar depressed group, 14% listed increased empathy as a positive aspect of depression; 9% mentioned self-awareness, 1% creativity and 0% productivity.Wait, what about the 'magic button' question? The questionnaires didn't ask directly. Despite the title of the paper and four other references to buttons, Parker et al. never did get their answer.Clouds and Silver LiningsAn older paper by Dr. Kay Redfield Jamison and colleagues didn't ask the 'magic button' question either, but it left a sunnier impression of bipolar's positive side. In 1980, Jamison et al. wrote:Although the psychiatric literature is replete with case reports, symptom checklists, and rating forms designed to assess changes during different mood states, to our knowledge there has been no systematic study of short-term, or state-dependent, positive experiences of affective, behavioral, and perceptual changes perceived by the patients themselves. Nor have patients been asked what long-term benefits they feel they derive from their mood disorders. For these reasons we did a preliminary, admittedly subjective investigation of such experiences in patients with primary affective disorders. We were interested in which changes during hypomania were evaluated as the most important and enjoyable. ... Although the usual caveats about retrospective and self-report data apply, the purpose of our study necessarily makes them less applicable than for other types of research.Their sample consisted of 61 patients attending an outpatient clinic: 35 were diagnosed as bipolar and 26 as unipolar. The format of the questionnaire was more constrained than that of Parker et al. (2012). While euthymic (asymptomatic) or only mildly depressed, the patients were asked:“Do you feel that your mood swings have resulted in overall personality characteristics that make you different from most people in the following ways?” for each of the several attributes: overall psychological sensitivity, sexual enjoyment, productivity, creativity, and social outgoingness and ease. Response choices were 1) yes, definitely, 2) probably, 3) probably not, and 4) definitely not.The bipolar individuals were queried further about specific changes they perceived during episodes of mania or hypomania. Of particular interest was whether the phenomenology of hypomania differed between men and women. The authors readily admit that the phrasing of their questions might have elicited a positive response bias, and that the participants' answers were based on perceptions (and not necessarily reality). Perhaps this can account for the much higher percentage of very positive or somewhat positive ratings for productivity and creativity (relative to the study of Parker et al., 2012), as shown below.Women in general endorsed "very much increased" positive attributes more often than men, but when collapsed across "very much" and "somewhat" increased, only productivity reached statistical significance. The authors noted is interesting that manic-depressive illness -- which ostensibly carries with it more negative social, financial, and interpersonal sequelae and results in more frequent episodes of dysfunction and mood swings (which might also account for its perceived greater influence) than unipolar illness -- is assessed by most patients as making positive contributions to their lives in one or more important ways. One issue of note for clinicians is the possibility of medication non-compliance. If manic or hypomanic episodes are very enjoyable, a bipolar individual may be inclined to go off medication so as not to blunt or eliminate such experiences.Two-Edged SwordsFinally, a recent paper in the Journal of Affective Disorders (... Read more »

  • April 13, 2012
  • 05:06 AM

Suffering for art is still suffering

by The Neurocritic in The Neurocritic

Edvard Munch, Self-Portrait in Hell (1903)"I inherited two of mankind's most frightful enemies — the inheritance of consumption and insanity — disease and madness and death were the black angels that stood at my cradle." 1 -Edvard MunchMany contemporary observers believe that Edvard Munch, the brilliant Norwegian artist best known for The Scream, had bipolar disorder. According to Rothenberg (2001):A diagnosis of bipolar disorder with psychosis is based on his own diary descriptions of visual and auditory hallucinations, a multiply documented instance of his travelling throughout Europe manifesting manic disrupted behavior that culminated in his shooting two joints off the ring finger of his left hand, and his psychiatric hospitalization in 1908 for an intensification of auditory hallucinations, depression, and suicidal urges. He also suffered from bouts of alcoholism.In the same article, the abstract expressionist painter Jackson Pollock was raised as another example of the innovative, tortured, bipolar artist. This might be taken as support for the view that creative individuals are more likely be bipolar than those in the general population. Clinical psychologist Kay Redfield Jamison, herself a prolific and talented person with bipolar disorder, has written extensively on this topic (Jamison, 1989, 1993). However, Rothenberg is actually critical of this general has been alleged that the illness makes creative persons more sensitive because of depressive diatheses and more productive while undergoing manic episodes. These allegations represent a romantic notion about creativity—the saga of the suffering artist—with little evidence to support them. Only comedians such as Jackie Gleason and Dick Van Dyke have seemed to derive direct benefit in their work from manic and hypomanic tendencies. Artistic products containing depressive or manic flight of ideas content have, only at particular times in history, been of social and aesthetic interest.He continues with specific critiques of the methods used by Andreasen (1987) and Jamison (1989). In her sample, Andreasen found that 43% of writers attending the prestigious University of Iowa Creative Writing Program were bipolar, but only 10% of the controls (who included “hospital administrators, businessmen, social workers, lawyers, medical and computer science students”). The groups were not matched for socioeconomic status, peer recognition, intelligence, or success. Finally, Rothenberg notes that "the Iowa Program has long served as a retreat for writers at times of career shifts or setbacks" -- when they might be more likely to be depressed or otherwise affected by a mental illness.He's even more scathing about Jamison's study of 47 prizewinning British artists and writers:Stating that the design of the study could not allow for systematic diagnostic inquiry regarding mania and hypomania, Jamison reported that 38% of the sample had been treated for an “affective” illness. No controls, however, were used in the study. Investigator interviews here also were not “blind” and no attempt at differential diagnosis was made. Subjects were asked only “whether or not they had received treatment, and the nature of that treatment, for a mood disorder” (p. 126), and no further diagnostic assessment was reported. This problem was compounded by the fact that subjects were self-selected which, in the absence of controls, introduces the possibility of an overrepresentation of psychiatric illness in the group.In the last few days, author and blogger David Dobbs (whom I respect and admire) has written about mental illness and creativity. In Jonah Lehrer Meets Stephen Fry – The Paradoxes of Bipolar and Creativity, he discussed Andreasen's work and the third chapter of Lehrer’s new book Imagine:...[Andreasen] adds that the ideas one comes up with during such phases tend to be quite original, as the manic person, in a set of long-distance synaptic leaps that Lehrer explains earlier, draws associations that lie beyond the reach of more ordinary modes of thought. (NB: Not everyone with bipolar gets these manic “highs.”)* 2 The ideas they come up with, in short, can be a bit crazy. If they spit them out then and published them, they’d likely be of little worth. But, as Lehrer explains, then the mania ebbs. The extravagant high descends into a profound low. While this volatility is horribly painful, it can also enable creativity, since the exuberant ideas of the manic period are refined during the depression. In other words, the emotional extremes of the illness reflect the extremes of the creative process: there is the ecstatic generation phase, full of divergent thoughts, and the attentive editing phase, in which all those ideas are made to converge. This doesn’t take away, of course, from the agony of the mental illness, and it doesn’t mean that people can create only when they’re horribly sad or manic. But it does begin to explain the significant correlations that have been repeatedly observed between depressive syndromes and artistic achievement. A new idea is borne during mania, refined when it subsides. If you read only that, you can mistakenly think bipolar disorder is a good thing to have, to let run amok. Lehrer is quick to note that but fairly quickly to move on — he’s writing a book about creativity, not depression.These ideas sparked a discussion and a follow-up post at Neuron Culture, Madness Ain’t All It’s Cracked Up to Be: A Corrective.3 David graciously included an update, saying that "These links between madness and creativity don’t make the more severe manifestations of depression or bipolar disorder any less destructive or painful." Then he quoted me: Sometimes I think those who talk about bipolar and creativity haven’t been around many severely manic individuals. There’s overspending, lying, cheating, alienating friends, paranoia, psychosis, taking off and abandoning family, etc. I don’t think there’s anything especially creative about that. Here’s another idea about bipolar and creativity: the percentage of manic people who engage in creative pursuits exceeds that in the general population. However, much of the output is incoherent. Some small percentage might be brilliant (either during or in between episodes), but then how many people are Kay Redfield Jamison or Stephen Fry (collapsing across bipolar subtypes)? At any rate, bipolar can be a very destructive illness, and I hope those that romanticize it (or are viewed as romanticizing it) truly understand that. End of rant. Kay Redfield Jamison is an extremely impressive woman, and a wonderful writer and speaker. I don't mean to detract from all she's done in her professional and personal lives to advance understanding of manic-depressive illness. But how many others (with or without bipolar) are as accomplished? You might as well ask, how many of us will win an Oscar or a Nobel Prize? Not many. Expecting that severe mental illness should confer special creativity is a mistake.In An Unquiet Mind, Jamison said: “I have often asked myself whether given the choice, I would choose to have manic depressive illness…..strangely enough I think I would” (pp 217–218).Not everyone feels this way, and the title of this post is taken from the quote below (from an anonymous person with Bipolar I disorder):"...I've read a fair bit about bipolar disorders and creativity, some interesting ... Read more »

Rothenberg, A. (2001) Bipolar Illness, Creativity, and Treatment. Psychiatric Quarterly, 72(2), 131-147. DOI: 10.1023/A:1010367525951  

  • April 8, 2012
  • 09:25 AM

tDCS Symposium Stimulates Giant Brain in Chicago

by The Neurocritic in The Neurocritic

The 2012 Cognitive Neuroscience Society Meeting was held in Chicago from March 31 to April 3. The schedule was packed with three and a half days of symposia, slide sessions, and posters. One well-attended event was Symposium Session 2, on non-invasive brain stimulation.Using Non-Invasive Brain Stimulation to Enhance Cognitive and Motor Abilities in the Typical, Atypical, and Aging Brain Chair: Roi Cohen Kadosh, University of OxfordSpeakers: Roi Cohen Kadosh, Jenny Crinion, Paulo S. Boggio, Leonardo G. CohenThe talk by Dr Jenny Crinion, a speech and language therapist who has gone over to the "dark side" of research (as she put it), drew a lot of attention and media coverage. It's no wonder, given her clinically relevant results.Jolt to brain aids language recovery Stroke patients improve on picture-naming task after stimulation treatment By Laura SandersWeb edition : Monday, April 2nd, 2012 CHICAGO — A brain zapping technique helps people recover language after a stroke, new research shows. The results may point to a better way for people to relearn how to talk after a brain injury. The "brain zapping" technique is transcranial direct current stimulation. According to a 2010 review by George and Aston-Jones, it is a very old method undergoing a recent revival:Transcranial direct current stimulation (tDCS) is perhaps one of the simplest ways of focally stimulating the brain. Similar techniques were practiced almost immediately after electricity was 'discovered' in the late 1880s. Passing a direct current through muscle, or the brain, was in vogue in Europe. For example, one of Charcot's residents, Georges Duchenne de Boulogne, traveled around Paris with a small battery and passed electricity through patients' muscles, examining the effects on numerous disorders and using it to better understand muscle–nerve innervations, particularly in the muscular dystrophies (George, 1994).How does it work?Quite simply, tDCS involves passing a weak (usually 1 mA) direct current through the brain between two electrodes. The current enters the brain from the anode, travels through the tissue, and exits out the cathode. Some researchers refer to this as either cathodal tDCS or anodal tDCS depending on which electrode is placed over the region that is being modified (Figure 5).Figure 5 (George & Aston-Jones, 2010). A tDCS device uses an anode and cathode connected to a direct current source much like a 9 V battery (a). The direct current passes through the intervening tissue, with some shunting through the skull but much of it passes through the brain and changes resting electrical charge, particularly under the cathode (b).Crinion started her talk by saying she originally wanted to use transcranial magnetic stimulation (TMS) -- another non-invasive brain stimulation technique -- but this would be too painful if applied over the left inferior frontal cortex (Broca's area). She lamented the NHS limit of 12 hours of speech therapy for stroke patients with aphasia. These individuals would benefit from more intensive therapy (e.g., phonemic cueing) for a longer period of time. From a practical standpoint, then, would tDCS maximize the results obtained during a truncated retraining period?1 What sort of behavioral and neural effects might be expected with such a regimen?She continued by describing a study in control participants that combined behavioral priming for overt picture naming, true and sham tDCS, and fMRI (Holland et al., 2011). Anodal tDCS2 was applied over the left IFC.3What are the effects of tDCS on echo planar imaging (EPI)? Any potential for artifacts, you ask? No problem! Supposedly there's signal dropout at the scalp/skull but not the brain. See?This is what I first saw on the slide. "EPI is not affected," apparently, but the images looked mighty odd to me. What the &^$% kind of brain is that??It's not a brain, it's a watermelon! Oh...Figure S1. Effects of A-tDCS on Echo-Planar Images (EPI). Field distortions from control (watermelon) and one participant.(A) Multi-slice coronal view of watermelon field distortion with indices for each slice. Blue bar indicates the location of anodal electrode... Perturbations were localized to the surface layer only of the watermelon. Here's more, from Holland et al. (2011).Figure S1. (D) Consistent with the control data, perturbations in the participants’ data were also localized to the scalp surface only. Here we illustrate in one participant’s coronal sections the effect of the anode electrode on B0 field map data.All right, so what were the effects of tDCS on picture naming times?My god, what a giant effect! Oh wait... It's more like a 25 msec improvement (see below), which is still statistically significant.4... Read more »

  • April 1, 2012
  • 09:59 AM

Critical Theory in Neurocinematics: Gaspar Noe's 'Irreversible' as Neural Network Reconfiguration

by The Neurocritic in The Neurocritic

Cinematic enfant terrible Gaspar Noé has been shocking audiences with his artistic films of graphic violence for over 20 years. In IMDb he is quoted as saying:"There is no line between art and pornography. You can make art of anything. You can make an experimental movie with that candle or with this tape recorder. You can make a piece of art with a cat drinking milk. You can make a piece of art with people having sex. There is no line. Anything that is shot or reproduced in an unusual way is considered artistic or experimental."I haven't seen a Noé film myself, so I can't offer any personal opinions. The descriptions themselves are so graphic and repellent that I've avoided them.What can Noé and neuroscience possibly have in common? Neurologist/cognitive neuroscientist Dr. Guillén Fernández and colleagues have been showing clips from Irréversible to participants in fMRI studies.The film employs a non-linear narrative and follows two men as they try to avenge a brutally raped girlfriend. ... Several reviewers declared it one of the most disturbing and controversial films of 2002.1 Why would researchers show this film to [perhaps unsuspecting]2 college students? To quickly induce a state of extreme psychological stress. In brief, Fernandez et al. are interested in studying the brain under acute stress. A PubMed search suggests there are at least 16 articles using this methodology.One such study examined rapid changes in neural network connectivity induced by the Irréversible stress-induction procedure3 (Hermans et al., 2011):During exposure to a fear-related acute stressor, responsiveness and interconnectivity within a network including cortical (frontoinsular, dorsal anterior cingulate, inferotemporal, and temporoparietal) and subcortical (amygdala, thalamus, hypothalamus, and midbrain) regions increased as a function of stress response magnitudes. The data analysis strategy employed the methods of "neurocinematics" (Hasson et al., 2008) to find inter-subject correlations (ISCs) in the BOLD response during free viewing of the film clips. Then the regions that responded to the aversive film to a greater extent were identified. These included areas associated with interoception and autonomic-neuroendocrine control, peripheral stress effector systems and catecholaminergic signaling, and sensory and attentional (re)orienting.Fig. 1 (Hermans et al., 2011). ISCs. Maps are thresholded at P < 0.05, whole-brain FWE­corrected, and overlaid onto cortical surface renderings (A and B) and a canonical structural MRI (C). FI, frontoinsular cortex; SMA; supplementary motor area; PCC, posterior cingulate cortex; (v)mPFC, (ventro)mPFC; IFG, inferior frontal gyrus; Th, thalamus; Mb, midbrain; Hy, hypothalamus. Then "multisession tensorial probabilistic independent component analysis" was used to test for functional connectivity between these regions, which overlapped with the "salience network" observed in resting state studies (Seely et al., 2007). Finally, pharmacological manipulations suggested that the stress-induced connectivity within this network was decreased by blocking β-adrenergic receptors [via propranolol], but not cortisol synthesis [via metyrapone].If you happen to be in Chicago for the 2012 CNS Meeting, you can learn more from Dr. Fernandez himself, who will be speaking in Symposium Session 1:Talk 4: Equipped to Survive: Large-Scale Functional Reorganization in Response to Threat Enables Optimal BehaviorUnfortunately, this presentation conflicts with Joshua Carp's talk, mentioned in the previous post -- How vulnerable is the field of cognitive neuroscience to bias?Footnotes1 Watch the trailer for Irreversible [NOTE: This video has been age-restricted].2 Participants with "regular exposure to extremely violent movies or computer games" are excluded from the studies.3 The presented film clips were described as follows:Fragments (both 140 s) from two different movies entitled "Irréversible" (2002), by Gaspar Noé, and "Comment j’ai tué mon père" (2001), by Anne Fontaine, were selected to serve as aversive and neutral control movie clips, respectively. ... Matching for audiovisual characteristics (see table S1) was performed by the authors by selecting aversive and neutral clips out of a set of candidate clips which best matched on the following measures: presence of faces in the foreground, presence of background actors, amount of distinct camera movements, and percentage of time the camera was moving. Selected aversive scenes contained extreme male-to-male aggressive behavior and violence in front of a crowd. Neutral control scenes also contained people interacting in the foreground in the presence of a background crowd. Fragments were equalized in luminance. Both movies are French spoken, but selected movie clips contained minimal speech.ReferencesHasson U, Landesman O, Knappmeyer B, Vallines I, Rubin N, Heeger DJ. (2008). Neurocinematics: The Neuroscience of Film. Projections 2:1-26. [PDF]... Read more »

Hermans, E., van Marle, H., Ossewaarde, L., Henckens, M., Qin, S., van Kesteren, M., Schoots, V., Cousijn, H., Rijpkema, M., Oostenveld, R.... (2011) Stress-Related Noradrenergic Activity Prompts Large-Scale Neural Network Reconfiguration. Science, 334(6059), 1151-1153. DOI: 10.1126/science.1209603  

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