The Neurocritic

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Born in West Virginia in 1980, The Neurocritic embarked upon a roadtrip across America at the age of thirteen with his mother. She abandoned him when they reached San Francisco and The Neurocritic descended into a spiral of drug abuse and prostitution. At fifteen, The Neurocritic's psychiatrist encouraged him to start writing as a form of therapy.

The Neurocritic
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  • August 18, 2013
  • 03:43 AM
  • 445 views

Remembering the Work of Dr. Patricia Goldman-Rakic

by The Neurocritic in The Neurocritic

A touching and comprehensive review article in Cerebral Cortex commemorates the life and work of Dr. Patricia Goldman-Rakic on the ten year anniversary of her death (Arnsten, 2013). The author of over 600 publications, Goldman-Rakic worked at NIMH from 1965-1979 and was a professor at Yale from 1979-2003. She served as President of the Society for Neuroscience in 1989-90 and was elected to the National Academy of Sciences in 1990. The review was written by one of her former post-docs, Dr. Amy F.T. Arnsten, herself a professor at Yale.Keeping a Life "in mind" Dr. Goldman-Rakic is best known for her research on working memory and the prefrontal cortex (PFC). Working memory is a transient form of memory that actively maintains and manipulates information for brief periods of time (Goldman-Rakic, 1995):Working memory in its most elementary form, the ability to keep events "in mind" for short periods of time, has been studied in nonhuman primates by delayed-response paradigms. Whereas in humans, facts and events accessed from long-term memory stores can be instigated by verbal instructions, in experiments with animals, the information to be processed has to be provided by the experimenter.Building on the work of Fuster and colleagues, her studies demonstrated that neurons in the dorsolateral portion of the PFC fire more rapidly when a spatial location cue is removed from the visual field and must be remembered over a brief delay. The sample neuron in the figure below codes for targets located at 270 degrees and not for targets at other locations. Note that the neurons's response is specifically enhanced over the delay period (D).Fig 1 (modified from Goldman-Rakic, 1995). Neuron during the Many Trials over Which a Monkey Performed an Oculomotor Delayed-Response Working Memory Task. The neuron's response for all trials at the preferred target location is shown as a histogram of the average response per unit time for that location. The activity is also shown in relation to task events (C, cue; D, delay; R, response) on a trial-by-trial basis. These neurons are located in the dorsal bank of the principal sulcus in monkey dorsolateral PFC, equivalent to Brodmann area 46 in humans. Goldman-Rakic and colleagues conducted extensive neuroanatomical tracing studies in the 1980's to map out the connections of this region and the posterior parietal cortex, major hubs in the brain's larger scheme of visuospatial processing.Fig. 2 (Arnsten, 2013). The cortical circuitry for spatial cognition, based on the work of Goldman-Rakic and Selemon. Note that both the dlPFC (area 46) and parietal cortex have many shared connections to subcortical structures that are not shown in this illustration, as well as “nonshared” connections that are not included in this diagram {from L. Selemon}.Goldman-Rakic's work was enormously influential, as shown in the figure below.Fig. 1 (Arnsten, 2013). Timeline of the discoveries of the PFC role in working memory (WM) and the key contributions of Goldman-Rakic. The graph shows the number of papers cited on PubMed using the search term “prefrontal cortex” for each decade ending in the year noted. Key publications by Goldman-Rakic and other early pioneers are indicated. Other major areas of research reviewed by Arnsten (2013) include the Key Role of Dopamine and Neuromodulation (e.g., D1 vs. D2 Receptor Actions, the D1 Receptor “inverted-U” Dose–Response), the Neurobiological Foundations of Schizophrenia (e.g., Insults to dlPFC Microcircuitry), and the dlPFC Microcircuits that Generate Mental Representations. The tribute article is open access and can be read freely by all.A Life of the Mind, Shaped by Working Memory The significance of working memory for higher cortical function is not necessarily self-evident. Perhaps even the quality of its transient nature misleads us into thinking it is somehow less important than the more permanent archival nature of long-term memory. However, the brain’s working memory function, i.e., the ability to bring to mind events in the absence of direct stimulation, may be its inherently most flexible mechanism and its evolutionarily most significant achievement. Thus, working memory confers the ability to guide behavior by representations of the outside world rather than by immediate stimulation, and thus to base behavior on ideas and thoughts.- Pat Goldman-Rakic (1991)ReferencesArnsten AF (2013). The Neurobiology of Thought: The Groundbreaking Discoveries of Patricia Goldman-Rakic 1937-2003. Cerebral Cortex PMID: 23926115Goldman-Rakic PS (1995). Cellular basis of working memory. Neuron, 14 (3), 477-85 PMID: 7695894... Read more »

  • August 15, 2013
  • 11:16 PM
  • 337 views

End of Life Gamma Waves: Altered State of Consciousness or Artifactual Brain Activity?

by The Neurocritic in The Neurocritic

"I had been in labor for my daughter for 16 hours. The labor was difficult and the Dr. approached me and told me it may come down to a choice between the child or myself.  ...  The labor dragged on and on and finally they came in and broke my water. I was rushed into delivery and within minutes my heart had stopped. I remember seeing a beautiful being of light enter the room. She told me I had to return as it was not my time yet. I was sucked back into my body as they restarted my breathing. My daughter began crying the moment I opened my eyes."-Description of a near-death experience1Are you afraid to die? We all are. Fear of pain and suffering, fear of the unknown, fear of eternal damnation (for the religious), fear of nothingness (for the atheist). Fear of the end. The finality of it all.The existential fear of death is part of the human condition. For a neuroscientist, studying what happens to conscious thought during the brain's own demise is one of the most profound of all questions. Short of conducting ill-advised scifi experiments on your med school classmates, how does one go about studying such a phenomenon? By using an animal model of cardiac arrest.thanks to Chris Chambers for the video ideaSurge of neurophysiological coherence and connectivity in the dying brainA popular new study by Borjigin et al. (2013) recorded EEG activity directly from the brains of nine dying rats. This paper was widely reported in mainstream media outlets, and has been nicely covered by bloggers Ed Yong, Mark Stokes, Chris Chambers, and Shelly Fan. What I would like to do here is to more closely examine the conditions surrounding the clinical death of these rats. Fig. 1A (modified from Borjigin et al., 2013). The time scale is in seconds.The y-axis is in microvolts.The figure above shows brain waves recorded from six electrodes implanted on the cerebral cortex, along with electrical activity from the muscles (EMG) and heart (EKG). The time period is 80 minutes before and 20 minutes after cardiac arrest (at time zero), which was induced by injection of potassium chloride into the heart. On its own, potassium chloride would cause a very painful death. Along with anesthetic and paralytic agents, potassium chloride is part of the drug sequence used for lethal injection in some U.S. states. In the present study, the animals were deeply anesthetized using ketamine (a dissociative anesthetic) and xylazine (veterinary sedative/analgesic which affects alpha-2 adrenergic receptors), a commonly used method of anesthesia in rodents. Fig. 1A shows that the animals were anesthetized for 30 min before cardiac arrest. The EEG exhibits fairly constant large amplitude activity during this time, shown spread out for a small interval of time in Fig. 1B below.Fig. 1B (modified from Borjigin et al., 2013). The time scale is in seconds. CAS =  cardiac arrest state. CAS3 (from 12 sec to 30 sec after cardiac arrest) is the critical time of increased EEG activity.To briefly summarize, the rats' brains were surprisingly active during the CAS3 period, showing highly coherent neural oscillations in the low gamma frequency band for a 20 sec interval after the heart and lungs stopped working. Fig. 1C below expands the vertical gray bars in Fig. 1B to show greater detail. Of note is the high amplitude rhythmic oscillations during CAS3. This low gamma activity (35-55 Hz) was strongly coupled to EEG activity in other frequency bands (theta and alpha) -- to an even greater extent than during active waking. The authors viewed this as a state of heightened consciousness, but such speculation is premature.- click on image for a larger view - Fig. 1C (modified from Borjigin et al., 2013). CAS = cardiac arrest state.Why would the authors maintain that a dying brain can generate the neural correlates of heightened conscious processing? Gamma (aka 40 Hz activity) has been viewed as a possible solution to the "binding problem" of how consciousness arises since the late 80s. In the visual system, synchronous gamma might be how the brain combines distributed activity conveying separate aspects of a stimulus (e.g., its color, shape, and form) into a unified percept. Furthermore, gamma might account for phenomenal awareness and consciousness, according to some. However, more recent evidence suggests that gamma band responses do not reflect conscious experience.In addition, it is not at all clear how highly synchronized low gamma can index "heightened conscious processing" in deeply anesthetized dying rats. Do the rats transition from ketamine/xylazine anesthesia (associated with altered thalamocortical connectivity) to a hyperaware internal state of....?  Of what?  The CAS3 activity is so abnormal that it might be artifactual or epiphenomenal, "a tale told by an idiot, full of sound and fury, signifying nothing" (Shakespeare, 1606). Near-death experience (NDE) researcher Sam Parnia believes the low gamma activity could be caused by a massive influx of calcium, as he stated in Ed Yong's ... Read more »

Borjigin J, Lee U, Liu T, Pal D, Huff S, Klarr D, Sloboda J, Hernandez J, Wang MM, & Mashour GA. (2013) Surge of neurophysiological coherence and connectivity in the dying brain. Proceedings of the National Academy of Sciences of the United States of America. PMID: 23940340  

  • August 11, 2013
  • 12:54 AM
  • 245 views

Save Us From Misleading Press Releases

by The Neurocritic in The Neurocritic

Exposure to subliminal cues can help us choose the apple instead of the cake. Or can it...  Let's take a look.Our Brains Can (Unconsciously) Save Us from Temptation Aug. 8, 2013 — Inhibitory self control -- not picking up a cigarette, not having a second drink, not spending when we should be saving -- can operate without our awareness or intention. That was the finding by scientists at the University of Pennsylvania's Annenberg School for Communication and the University of Illinois at Urbana-Champaign. They demonstrated through neuroscience research that inaction-related words in our environment can unconsciously influence our self-control. Although we may mindlessly eat cookies at a party, stopping ourselves from over-indulging may seem impossible without a deliberate, conscious effort. However, it turns out that overhearing someone -- even in a completely unrelated conversation -- say something as simple as "calm down" might trigger us to stop our cookie eating frenzy without realizing it.The press release states that overhearing a message of restraint in a background conversation might prevent us from reaching for a second piece of cake at the holiday party. What's the evidence for this?A study by Hepler and Albarracin (2013) recorded EEG activity (brain waves) while 20 participants performed a "go/no-go" task that tests their inhibitory control abilities. The subjects responded every time they saw an "X" on the screen but refrained from responding when they saw a "Y". These target letters were preceded by a visual masking stimulus (&&&&&&) for 16.7 msec, a subliminal prime word for 33.4 msec, and then another masking stimulus (&&&&&&) for 50.1 msec. The idea here is to show the prime word very briefly and to "mask" conscious perception of the word.The prime words were general action words (go, run, move, hit, start), general inaction words (still, sit, rest, calm, stop), and control stimuli (scrambled action and inaction prime words – e.g., rnu). One obvious hypothesis would be that exposure to the masked inaction words would make you better at inhibiting a response to "Y". The authors didn't exactly say that, instead predicting that the amplitude of the P3 component extracted from averaged EEG on no-go trials would reflect the engagement of unconscious inhibitory processes.However, if behavior is unaffected by the masked inaction words, it ultimately doesn't matter what happens to the P3 component. There is nothing you can say about "resisting temptation" -- behavioral change is not the same thing as a change in the size of the P3 component. The latter may indicate that a subject's brain registered sit, rest, calm, or stop implicitly, but this neural activity wasn't enough to improve stopping ability.And in fact, this is exactly what the study demonstrated. The masked primes had a modest effect on the size of the P3 wave to the subsequent no-go stimulus, which reached its peak at around 400 msec post-stimulus (i.e., less than half a second after the "Y"). The inaction primes were significantly different from the action primes, but neither one differed from the neutral condition.1Fig. 1. (Hepler & Albarracin, 2013). Grand average waveforms at electrode Cz to correct no-go trials in Experiment 1. The authors interpreted this effect to indicate that inhibition processes were "engaged" by the subliminal primes.However, the primes had absolutely no impact on how well participants could resist responding to the no-go stimuli [F(2, 38) = .00, p = .99]. Accuracy in the inaction prime condition was exactly the same as in the action prime condition. In other words, the study showed that Our Brains Cannot (Unconsciously) Save Us from Temptation.Or as succinctly stated by Justin Kiggins on Twitter:I did not intend to nitpick about the details of this particular study or to single out the authors. But the press release provided by the University of Pennsylvania Annenberg School for Communication is completely misleading (and poorly communicated).Footnote1 This is somewhat problematic, because you'd rather see each of the experimental conditions differ from the control condition.ReferenceHepler J, & Albarracin D (2013). Complete unconscious control: Using (in)action primes to demonstrate completely unconscious activation of inhibitory control mechanisms. Cognition, 128 (3), 271-9 PMID: 23747649

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  • August 8, 2013
  • 03:37 PM
  • 249 views

Possession Trance Disorder Caused by Door-to-Door Sales

by The Neurocritic in The Neurocritic

Some companies and organizations that employ door-to-door sales tactics are known for their cult-like practices (e.g., Amway, traveling magazine sales, and Jehovah's Witnesses). An unusual psychiatric report included this religious brainwashing element in presenting the case of a 47 year old Japanese housewife who felt possessed by God after a visit by a door-to-door salesman (Saitoh et al., 1996):In Japan, psychiatry has generally regarded the possessive state as symptomatic of religion- related mental disorders. ... Recently, there has been a proliferation of direct sales enterprises that incite anxiety in prospective customers in order to sell their products. Due to the prevalence of door-to-door peddling of items such as amulets and talismans to ward off curses and misfortune, the term ‘door-to-door sales’ has come to have a religious connotation.Recently, we treated a case of possessive state accompanied with suicidal tendencies which are thought to have developed in connection with door-to-door sales. Religious factors and elements of brainwashing were seen both in the conditions that promoted the possessive state and in the state itself.The patient grew up on a family farm in the Tokyo area. She was described as laconic, withdrawn, quiet, unsocial and nervous.When the patient was 47 years old, a male she described as a ‘salesperson type’ came to her home in May. He read her palm and asked for her husband’s family name and birth date. When she gave him this information he predicted that some misfortune would befall her husband. The patient’s husband had fallen in an accident a few days earlier, and she became extremely anxious. The man then said, ‘I have a talisman, a lucky name chop (family seal) which will protect your husband from misfortune’. Although she was hesitant at first, she finally agreed... When she paid for the chop the man recommended that she go to a certain room in a hotel in Saitama prefecture for a more in-depth palm reading ... where she was one of 20 women who received a lecture on subjects such as lineage, marriage, health and happiness.Approximately 1 week later, again at the salesman’s advice, she went to a rented room in a building in Tokyo where she received a scroll called a prayer book. At the same time she was urged to buy a sculpture which was called a ‘Fortune Tree’. Two days later she went to her bank with the salesman and a woman whom she did not know and paid the ¥5,400 000. The patient went to this room twice a month during June, July and August. The room was divided by a partition and she was shown biblical videotapes. In September, she complained of an inability to sleep, and stated, ‘I can hear God’s voice. He possesses me and is controlling my bodily movements’. Thereafter, she episodically gave orders to her family in an uninflected monotone, making unrealistic assertions such as, ‘Don’t eat that or you will die’ and ‘Don’t go out or you won’t come back’. In mid-September, she filed a complaint that she had been deceived into buying the ‘Fortune Tree’ at an exorbitant price. Shortly thereafter, she was taken to a private mental hospital and treated with the antipsychotic drug haloperidol. Two weeks later, she was able to recount her ordeal:... ‘I felt like God had taken over my body. I was ordered by Him to do this or do that. Even if I wasn’t talking, my mouth just moved on its own. I didn’t go so far as to be One with God, but it was almost like that. That’s why I gave orders to my husband and child as though I were God’. The patient showed no subsequent objective signs of abnormality, and was released 2 months after admission.The authors discussed her case in terms of the DSM-IV diagnosis, Dissociative Disorder Not Otherwise Specified, along with depressive symptoms and somatic complaints. Her attendance at the video lectures was described as a form of brainwashing. More specifically, her condition would fall under the category of Dissociative Trance Disorder (possession trance), a disturbance in consciousness or identity with a culturally specific element:Dissociative trance involves narrowing of awareness of immediate surroundings or stereotyped behaviors or movements that are experienced as being beyond one's control. Possession trance involves replacement of the customary sense of personal identity by a new identity, attributed to the influence of a spirit, power, deity, or other person and associated with stereotyped involuntary movements or amnesia...This case is rare not only because of its association with a business practice, but also because possession is usually seen in more isolated communities with traditional belief systems, quite unlike contemporary Tokyo. Further ReadingPossession Trance Disorder in DSM-5ReferenceSatoh S, Obata S, Seno E, Okada T, Morita N, Saito T, Yoshikawa M, & Yamagami A (1996). A case of possessive state with onset influenced by 'door-to-door' sales. Psychiatry and clinical neurosciences, 50 (6), 313-6. PMID: 9014228

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Satoh S, Obata S, Seno E, Okada T, Morita N, Saito T, Yoshikawa M, & Yamagami A. (1996) A case of possessive state with onset influenced by 'door-to-door' sales. Psychiatry and clinical neurosciences, 50(6), 313-6. PMID: 9014228  

  • August 2, 2013
  • 05:38 AM
  • 353 views

Breakthroughs in Bipolar Treatment

by The Neurocritic in The Neurocritic

"We should continue to repurpose treatments and to recognise the role of serendipity" (Geddes & Miklowitz, 2013).That quote was from a recent review article in The Lancet, which did not hint at any impending pharmacological breakthroughs in the treatment of bipolar disorder. In other words, the future of bipolar treatment doesn't look much different from the present (at least in the immediate term). Bipolar disorder, an illness defined by the existence of manic or hypomanic highs, alternating with depressive lows, can be especially difficult to treat. And the mood episode known as a mixed state, where irritability, expansive mood, anxiety, and/or agitation occur simultaneously with depressive symptoms, is an under-recognized, moving-target diagnosis (Koukopoulos et al., 2013). Mood stabilizers such as lithium and divalproex have long been the first line pharmacological choices. But these don't always work, and polypharmacy seems to be the rule, rather than the exception.The spinning molecule above is haloperidol, a first generation antipsychotic drug developed in 1958 and approved by the FDA in 1967 as a treatment for schizophrenia. It's a dopamine blocker known for having untoward extrapyramidal side effects, or movement disorders such as tremors and tardive dyskinesia. Nonetheless, haloperidol (Haldol®) is still the most effective drug for the acute treatment of mania, and fairly well tolerated (see HAL in the figure below). The second generation (atypical) antipsychotics risperidone (RIS) and olanzapine (OLZ) also turn out pretty well in the antimanic sweepstakes. But these drugs can also have untoward side effects, notably substantial weight gain that can lead to high cholesterol, diabetes, and metabolic syndrome. Figure (Geddes & Miklowitz, 2013). Ranking of antimanic drugs according to primary outcomes derived from multiple treatment meta-analysis. Efficacy is shown as a continuous outcome against the dropout rate. Treatments toward the red section combine the worst efficacy and tolerability profiles and treatments towards the green[ish] section combine the best profiles.1 Clearly, effective medications with fewer side effects are needed. Unfortunately, there doesn't seem to be anything new on the horizon, according to Geddes and Miklowitz:Overall, advances in drug treatment remain quite modest. Antipsychotic drugs are effective in the acute treatment of mania; their efficacy in the treatment of depression is variable with the clearest evidence for quetiapine. Despite their widespread use, considerable uncertainty and controversy remains about the use of antidepressant drugs in the management of depressive episodes. Lithium has the strongest evidence for long-term relapse prevention; the evidence for anticonvulsants such as divalproex and lamotrigine is less robust and there is much uncertainty about the longer term benefits of antipsychotics.The article is actually more bullish on combining existing drugs with various psychosocial interventions (e.g., family-focused approaches, strict regulation of social and circadian schedules, etc.), which are touched on below in the Appendix (Table 1 of Geddes & Miklowitz, 2013). That table also mentions some of the usual drug suspects.To find out what else might be in the works, I looked through ClinicalTrials.gov for open interventional drug studies in adults. There were a few surprises... foremost among those was Methylphenidate for the Treatment of Acute Mania. It seems bizarre to me that methylphenidate (the stimulant drug Ritalin) would be proposed as a treatment for mania, since 40% of patients prescribed stimulants for bipolar depression (or comorbid ADHD) experienced stimulant-induced mania/hypomania (Wingo & Ghaemi, 2008).The Ritalin trial was submitted to ClinicalTrials.gov in Feb. 2012, but the study is not yet open for patient recruitment 1.5 years later. The investigators recently published the study protocol in BMC Psychiatry, however (Kluge et al., 2013). They proposed the ‘vigilance regulation model of mania’ where:Unstable vigilance induces a pathogenic circle with vigilance stabilisation syndrome leading to full-blown mania. [NOTE: huh?]The outlined model ... is related to personality theories about extraversion [9] and sensation seeking [10] which comparably explain these traits as an attempt to compensate for low central nervous system arousal. Basically, it works for ADHD, and there are a handful of uncontrolled case reports, so.... let's conduct a clinical trial.Bipolar DepressionDepressive episodes in bipolar disorder are longer in duration and considered more difficult to treat. Again, ClinicalTrials.gov did not disappoint, revealing a grab bag of "repurposed" treatments:Adjunctive Lisdexamfetamine - another stimulant for ADHD (aka Vyvanse).Adjunctive Isradipine (a calcium channel blocker prescribed for high blood pressure) - this idea — not a new one — deserves a post of its own.Adjunctive Minocycline (an antibiotic) - the proposed mechanism of action is to reduce the production of pro-inflammatory cytokines.Ceftriaxone (another antibiotic) - however, the proposed mechanism here is inactivation of the excitatory neurotransmitter glutamate, via actions on the glutamate transporter.NMDA Antagonists (i.e., club drug ketamine) - this is complicated and again deserving of its own ... Read more »

  • July 22, 2013
  • 10:00 PM
  • 353 views

Rorschach inkblots and the neuroscientific basis for pareidolia

by The Neurocritic in The Neurocritic

image via psychpsychbabyA fascinating new historical article in the Journal of Neurology, Neurosurgery, and Psychiatry reviews the aesthetic and perceptual aspects of the Rorschach inkblots and proposes a role for them in understanding pareidolia, the phenomenon of ‘seeing’ objects in amorphous shapes (Schott, 2013). The Rorschach test was developed by handsome Swiss psychoanalyst Hermann Rorschach as a Psychodiagnostic method and only later used as a "projective test" thought to reveal unconscious psychopathology. Although still in use today, it has been widely discredited and shown to be an invalid instrument for assessing personality and mental illness (e.g., see What's Wrong With The Rorschach: Science Confronts the Controversial Inkblot Test). Rorschach Card III via WikipediaRorschach himself viewed the test as perceptual (p. 16 of Lemkau & Kronenberg's 1951 translation of Rorschach, 1921 - PDF):Almost all subjects regard the experiment as a test of imagination. This conception is so general that it becomes, practically, a condition of the experiment. Nevertheless, the interpretation of the figures actually has little to do with imagination, and it is unnecessary to consider imagination a pre-requisite. ...The interpretation of the chance forms falls in the field of perception and apperception rather than imagination.Rorschach denied that it was projective in nature (p. 123, ibid):The test cannot be considered as a means of delving into the unconscious. At best, it is far inferior to the other more profound psychological methods such as dream interpretation and association experiments. This is not difficult to understand. The test does not induce a «free flow from the subconscious» but requires adaptation to external stimuli, participation in the «fonction du réel».Schott (2013) views the inkblots as both artistic entities (noting that Rorschach was a "gifted draughtsman and an excellent art critic") and as visual stimuli for scientific study. Perceptual features of the inkblots are considered in detail:The pivotal graphic features which constitute the blots, and which give rise to the blots’ perceptual effects, include: form: their amorphous shape symmetry the perception of movement: ‘Movement without Motion’ the blank spaces: figure–ground relationships the use of colour shading.Finally, the article summarizes several neuroimaging experiments that have used the inkblots as stimuli. For example, Asari and colleagues reported that unusual or unique perceptions of the blots were associated with greater activation in the right temporal pole (2008) and with larger amygdala volumes (2010).The Virgin Mary TreeThe Neuroscientific Basis for PareidoliaPareidolia is the phenomenon of perceiving a meaningful stimulus (such as a face or a hidden message) in fairly random everyday objects or sounds. We do have quite a propensity to see faces everywhere, and some religious people see the face of god (and other religious iconography) everywhere.Schott (2013) concludes by suggesting that the images merit further investigation by neuroscientists for studies of pareidolia: ...these iconic ink-blots—which straddle iconography, psychology and neuroscience—deserve further study, and may yet illuminate important aspects of cerebral function, and even dysfunction. But DO NOT use them to discriminate psychopaths from non-psychopaths in forensic populations (or for any other clinical diagnostic purpose, for that matter)...ReferencesRorschach, H. (1921). Psychodiagnostics: A Diagnostic Test Based On Perception (1951 translation).Schott, G.D. (2013). Revisiting the Rorschach ink-blots: from iconography and psychology to neuroscience. J Neurol Neurosurg Psychiatry DOI: 10.1136/jnnp-2013-305672
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  • July 13, 2013
  • 10:10 PM
  • 310 views

The Destructive Power of Shame

by The Neurocritic in The Neurocritic

Shame is a negative self-conscious emotion that encompasses the feeling that something is terribly wrong with the self as a human being. Feelings of shame are a prominent factor in suicidal thoughts, behaviors, and self-harm (Hastings et al., 2002; Gilbert et al., 2010).  Lately I've encountered several articles saying that shame really isn't that bad for you, after all. The first theme of these commentaries is the spectacle of public shaming, and the second theme concerns private shame as a means of social control.The Futility of Public ShamingOne news article bemoaned the end of shame in American politics. Sex scandals, drug use, and other egregious mistakes just don't have the same permanently negative consequences they used to. If you're a powerful male politician, that is.Where’s the shame? Scandals may no longer end political careers  WASHINGTON — Sex. Drugs. Cheating on a spouse. Those words used to add up to shame. Put them in the same sentence as a politician’s name, and they ended careers.Not anymore. The latest batch of unlikely back-from-the-swamp hopefuls are Anthony Weiner and Eliot Spitzer. Weiner resigned his New York City congressional seat two years ago after revelations that he’d tweeted a sexually suggestive picture of himself to a woman who was following him on Twitter. Spitzer left the state’s governorship in 2008 after reports surfaced that federal investigators had tagged him as “Client 9,” soliciting high-end prostitutes.Read more here: http://www.mcclatchydc.com/2013/07/11/196452/wheres-the-shame-scandals-may.html#.UeG5e20rgdp#storylink=cpyHere's the list of prominent male politicians from the article:Anthony Weiner - sent lewd twitpicsEliot Spitzer - prostitution scandalMark Sanford - disappearance and extramarital affairNewt Gingrich - serial cheater; dumper of a wife with cancer; Christian Marion Barry - smoking crackBill Clinton - Monica Lewinsky affair resulted in impeachment of sitting PresidentLarry Craig - arrested for lewd conduct in a men's restroomMark Foley - sent sexually suggestive messages to teenaged male pagesDavid Vitter - D.C. Madam scandalScott DesJarlais - pro-life doctor who had multiple affairs with patients, pushed them to have abortionsThe lesson from all this: Wind up on the ever-increasing roll of tainted celebrities and re-emerge as the friendly, professional politician that vaulted you into office in the first place, and you’ll probably be OK."You'll probably be OK"... if you're a man. Has a female politician ever emerged intact from a federal sex scandal? Or has even been involved in such a scandal? If so, the double standard of slut shaming would likely put an end to her career. One of the few women on the state and local list is:Minnesota Senate Majority Leader Amy Koch (R)... The married mother of one resigned from her leadership position and announced that she would not be seeking reelection shortly before four fellow Republicans indicated that she had been engaged in an "inappropriate" relationship with a male staffer. (2011).Shaming on the InternetHow about for obnoxious offenders in the general public? Does the public shaming of those who spew idiotic sexist, racist, and homophobic comments on social media do any good?The Public Shaming Tumblr aims to draw attention to bad actors on Twitter. Matt Binder says:I started retweeting people complaining about welfare, food stamps, etc. and then following it up with a previous tweet of theirs that makes them look hypocritical/dumb/etc.I discovered that as I would retweet these, my followers would start @replying these people and let them know they were idiots. They would then delete their offending tweet.Well, I couldn’t let that happen. So, I screenshot away.One continuous stream of vile sexist hatred was directed at Women's Wimbledon champion, Marion Bartoli. Why? Because she's not a blond model. Even BBC presenter John Inverdale took part in the insults, saying she "never going to be a looker"... to which Bartoli responded:"It doesn't matter, honestly. I am not blonde, yes. That is a fact. Have I dreamt about having a model contract? No. I'm sorry. But have I dreamed about winning Wimbledon? Absolutely, yes."This is the bottom line. She won Wimbledon, and her detractors will never accomplish anything that monumental. Does shaming the immature little boys for their pathetic cries for attention help anyone?Serious cretins:@Danwatt8 @Willshow95 @LadiesLove_BigD @maxbateman20 @rrruditaylor @Kwikz @EllisKeddie @sumandutta of http://t.co/PkDXbHnfuG— Carl Gelderloos (@CGelderloos) July 9, 2013Some of those dudes deleted their accounts (to perhaps reappear another day), but others just go on their merry way with earth-shattering pronouncements like, "I have to untangle my earphones at least 3 times a day" and "Playstation is better than Xbox."Public shaming doesn't seem to cause any lasting change. Does it?Shaming: it’s a bit crap for everyoneIt’s no surprise to anyone that Twitter and Facebook are filled with vile, racist, homophobic, bigoted awfulness. Because humanity is filled with vile, racist, homophobic bigots.. . .The consequence of these shaming sites, is that us “enlightened” folk then pile in on the bigots and abuse them and tell them how awful they are. And I’m willing to bet that the number of individuals who have rescinded what is probably years’ of built up bigotry is the same number of terrorist attacks that the Wellington airport security screeners have stopped: Zero.. . .That’s not to say we should let people get away with awfulness, but when we publicly name and shame and by proxy invite the internet to start tormenting these people, we are becoming them. No better than they are because we now have a figure to poke a stick at.The shame sweepstakes become more costly and damaging once we enter the world of mental illness, addiction, and difference. Yet some still argue in favor of shaming.Has there been a resurgence of shame as a... Read more »

Wiechelt SA. (2007) The specter of shame in substance misuse. Substance use , 42(2-3), 399-409. PMID: 17558937  

Gilbert P, McEwan K, Irons C, Bhundia R, Christie R, Broomhead C, & Rockliff H. (2010) Self-harm in a mixed clinical population: the roles of self-criticism, shame, and social rank. The British journal of clinical psychology / the British Psychological Society, 49(Pt 4), 563-76. PMID: 20109278  

Hastings ME, Northman LM, Tangney JP. (2002) Shame, Guilt, and Suicide. Suicide Science, 67-79. DOI: 10.1007/0-306-47233-3_6  

  • July 8, 2013
  • 04:57 AM
  • 499 views

A New Slant on Frontal Connectivity: the Frontal Aslant Tract

by The Neurocritic in The Neurocritic

The frontal aslant tract is shown in yellow (Fig 5, Catani et al., 2012). It's not every day that you hear about a newly described white matter pathway in the human brain. An interesting new study by a group of researchers in London and Chicago found a novel fiber tract implicated in verbal fluency impairments in patients with a lesser known neurodegenerative illness (Catani et al., 2013). This short fiber tract connects two different regions in the frontal lobe. It was recently identified using a combination of diffusion imaging and post-mortem dissection (Lawes et al., 2008; Catani et al., 2012; Thiebaut de Schotten et al., 2012). Dubbed the frontal aslant tract (FAT) by Catani and colleagues, it connects the posterior portion of the inferior frontal gyrus (IFG) to the supplementary motor area (SMA) and pre-SMA on the medial wall.1A number of experiments have already looked at the functional connectivity of these regions, during both resting state and task activation conditions. Statistically correlated fluctuations in the BOLD signal 2 are thought to reflect functional connectivity between two regions, but there is often no evidence that the two regions are directly connected anatomically. Therefore, in vivo structural MRI methods such as diffusion imaging can provide complementary data by visualizing white matter pathways to determine anatomical connections.The diffusion tractography results were then compared to blunt dissection of tracts from post-mortem brains, which helped to validate a method that some view as prone to limitations and potential artifacts.3 Fig. 10 (modified from Catani et al., 2012). Coronal slices of the ‘Digital Dejerine’ maps 4  and post-mortem blunt dissections of the corresponding tracts. E) The frontal aslant tract (FAT) connecting inferior and superior frontal gyri.A comparative study went further, showing that the results obtained from human tractography compared favorably to axonal tracing methods in monkeys (Thiebaut de Schotten et al., 2012).5  Fig. 6 (Thiebaut de Schotten et al., 2012). Reconstructions of the frontal aslant tract: comparison between post-mortem axonal tracing in monkey and human in vivo SD [Spherical Deconvolution] tractography shows simian-human similarities.However, one difference between this tract in monkeys and humans is that the FAT is lateralized in humans, being larger in the left hemisphere than in the right (Catani et al., 2012). In the left hemisphere, posterior IFG is part of Broca's area. This brings us back to the clinical importance of this basic neuoanatomical work.Verbal Fluency and the Frontal Aslant TractPrimary progressive aphasia (PPA) is a neurodegenerative disorder, the hallmark of which is the deterioration of specific speech and language functions. There are three variants, each with characteristic behavioral, neuroanatomical, and pathological features (Gorno-Tempini et al., 2011):Nonfluent/Agrammatic Variant PPA is characterized by halting, effortful speech with difficulties producing grammatical output and/or comprehending syntactically complex sentences. Word comprehension and object knowledge are intact. Atrophy in the left frontal cortex is apparent on MRI.Semantic Variant PPA is marked by impairments that include comprehending the meanings of words, naming objects and understanding their function. Motor speech production and grammatical output are spared. Atrophy is seen in the anterior temporal lobe.Logopenic Variant PPA involves word finding problems, phonological speech errors, and difficulties in repeating words and sentences. Word comprehension, object knowledge, and grammar are spared. Degeneration of left posterior temporal-parietal regions is observed.In the latest study by Catani et al. (2013), 35 patients with PPA and 29 controls participated in behavioral testing and MRI scanning. The tests included standard evaluations of language abilities including the Western Aphasia Battery, the Boston Naming Test, and the Peabody Picture Vocabulary Test. Tractography identified the frontal aslant tract and the uncinate fasciculus, which connects anterior temporal lobe regions to the IFG pars orbitalis and the orbitofrontal cortex. Quantitative measures included the number of streamlines (tract volume), fractional anisotropy, and radial diffusivity (measures of white matter integrity and axonal damage, respectively).Results indicated that patients with Nonfluent/Agrammatic PPA were impaired in a speech production task that required telling the story of Cinderella from a picture book. Poor performance in verbal fluency was associated with the extent of damage in the FAT, but grammatical deficits were not. In contrast, patients with Semantic Variant PPA showed deficits in semantic processing which correlated with degeneration in the uncinate fasciculus.What are the implications for the neuroanatomy of verbal fluency and speech output?...Patients with lesions of the pre-supplementary motor area present with various degrees of speech impairment from a total inability to initiate speech (i.e. mutism) to mild altered fluency. Our findings suggest that these medial regions of the frontal lobe could facilitate speech initiation through direct connection to the pars opercularis of the inferior frontal gyrus. Indirect support of this interpretation comes from the frequent observation of impaired fluency in patients with deep lesions in the frontal periventricular white matter. In these cases, a disconnection of the frontal aslant could explain the emergence of symptoms usually associated with frontal cortical damage. More broadly, characterizing the different pattern... Read more »

Catani M, Dell'acqua F, Vergani F, Malik F, Hodge H, Roy P, Valabregue R, & Thiebaut de Schotten M. (2012) Short frontal lobe connections of the human brain. Cortex; a journal devoted to the study of the nervous system and behavior, 48(2), 273-91. PMID: 22209688  

Catani M, Mesulam MM, Jakobsen E, Malik F, Matersteck A, Wieneke C, Thompson CK, Thiebaut de Schotten M, Dell'acqua F, Weintraub S.... (2013) A novel frontal pathway underlies verbal fluency in primary progressive aphasia. Brain : a journal of neurology. PMID: 23820597  

Gorno-Tempini ML, Hillis AE, Weintraub S, Kertesz A, Mendez M, Cappa SF, Ogar JM, Rohrer JD, Black S, Boeve BF.... (2011) Classification of primary progressive aphasia and its variants. Neurology, 76(11), 1006-14. PMID: 21325651  

Thiebaut de Schotten M, Dell'Acqua F, Valabregue R, & Catani M. (2012) Monkey to human comparative anatomy of the frontal lobe association tracts. Cortex; a journal devoted to the study of the nervous system and behavior, 48(1), 82-96. PMID: 22088488  

  • June 14, 2013
  • 05:45 AM
  • 313 views

A New Biomarker for Treatment Response in Major Depression? Not Yet.

by The Neurocritic in The Neurocritic

Is a laboratory test or brain scanning method for diagnosing psychiatric disorders right around the corner? How about a test to choose the best method of treatment? Many labs around the world are working to solve these problems, but we don't yet have such diagnostic procedures (despite what some might claim). A new study by McGrath et al. (2013) might be a step in that direction, but the results are very preliminary and await further validation.The principal investigator of that study is Dr. Helen Mayberg, a leader in neuroimaging studies of major depression. She and her colleagues have pioneered the use of deep brain stimulation (DBS) as a treatment for severe, intractable depression, which was "the culmination of 15 years of research using brain imaging technology," says Dr. Mayberg.Psychotherapy or Drugs?The choice of treatment modality in depression, as in other psychiatric disorders, is by trial and error. If one drug doesn't work, switch to another one. If your insurance covers it, a short course of evidence-based psychotherapy1 might be in order.The whole concept of a DSM-based classification scheme for mental illnesses has come under fire, especially with the release of the new Diagnostic and Statistical Manual. In the real world, psychiatric disorders don't always show such clear boundaries; overlap and co-morbidity are common. The National Institute of Mental Health has endorsed a new approach, the Research Domain Criteria project, that incorporates dimensions of observable behavior along with neurobiological measures. Here's where the new work by McGrath et al. (2013) fits in. Their goal was... To identify a candidate neuroimaging “treatment-specific biomarker” that predicts differential outcome to either medication or psychotherapy.Fewer than 40% of depressed patients remit with their first course of treatment, so this would be an important advance. A more scientific way of choosing among possible treatment options would benefit patients and society at large.The study (registered at clinicaltrials.gov, NCT00367341) enrolled a total of 82 depressed people. The neuroimaging method might surprise some of you: FDG-PET to measure glucose metabolism -- not the popular and trendy resting state fMRI to examine functional connectivity or any sort of fMRI activation study. However, the authors cite an established literature using this technique in studies of antidepressant treatment response.Patients diagnosed with moderate to severe depression (a score of 18 or more on the Hamilton Depression Rating Scale, HDRS) received a PET scan and were randomized to receive 12 weeks of either cognitive behavioral therapy (CBT, n=41) or escitalopram (Lexapro, n=39), an SSRI antidepressant. Sixty-three patients completed this phase and also had a PET scan. The endpoint considered a successful response to treatment was remission (HDRS score of 7 or less), while non-response was a change in HDRS of 30% or less. Partial responders were omitted, leaving the final groups as follows:CBT remission, n=12escitalopram remission, n=11CBT nonresponse, n=9escitalopram nonresponse, n=6Right away we see that the number of patients in each group is very small, particularly for a study designed to identify biomarkers that will generalize to a larger population. Let me repeat that: a successful biomarker must generalize to an independent population. We haven't seen that here, so any conclusions drawn from this paper must be considered very preliminary.How was the biomarker identified? The PET images were co-registered with the corresponding structural MRIs. A whole brain analysis identified regions showing a treatment × outcome interaction (at a significance level of p<.001 uncorrected). Six regions met this uncorrected standard: right anterior insula, right inferior temporal cortex, left amygdala,2 left premotor cortex, right motor cortex, and precuneus (medial superior parietal lobe). Most of these are pretty surprising, but even more surprising is that the rostral anterior cingulate (and subgenual cingulate, BA 25) were not involved:Contrary to past published studies,63 the rostral anterior cingulate did not discriminate the outcome subgroups in either the main effect or interaction analyses. A post hoc examination of responder and nonresponder differences within each treatment arm did reveal a nonsignificant rostral cingulate activity difference, with metabolism in responders greater than nonresponders, but solely in the escitalopram group. While consistent with past reports, this finding did not meet the TSB [treatment-specific biomarker] criteria defined for the current study, ie, a region whose activity can differentiate both good and poor outcomes for both treatments.- click on image for a larger view -... Read more »

McGrath CL, Kelley ME, Holtzheimer PE, Dunlop BW, Craighead WE, Franco AR, Craddock RC, & Mayberg HS. (2013) Toward a Neuroimaging Treatment Selection Biomarker for Major Depressive Disorder. JAMA psychiatry (Chicago, Ill.), 1-9. PMID: 23760393  

  • June 10, 2013
  • 05:37 AM
  • 356 views

How to Measure Female Desire

by The Neurocritic in The Neurocritic

A Sexual Laboratory of One's Own, aka A Clean Well-Lighted Place for SexPsychophysiologic studies of sexual response should be done in a comfortable, well-designed laboratory to minimize subject anxiety and discomfort (Woodard & Diamond, 2009, Fig. 5). How do scientists measure the physiological aspects of sexual arousal in women? A 2009 paper by Woodard and Diamond reviewed 45 years of research using instruments that measure female sexual function. These devices include the vaginal photoplethysmograph (right), vaginal and labial thermistors, pressure/compliance balloons, clitoral electromyography, and the electrovaginogram. For a full list, see Table 1 at the bottom of this post.The authors note that these physiological measures do not correlate very well with subjective ratings of sexual arousal. Furthermore, clinicians who treat women with sexual dysfunctions are of two minds. Some say the distinction between female desire and arousal may be artificial (see DSM-5 changes, p. 13), while others maintain that the merger of female sexual arousal disorder (FSAD) with Hypoactive Sexual Desire Disorder (HSDD) will be disastrous (Clayton et al., 2012).The previous post about Lybrido and Lybridos, the drugs in clinical trials for HSDD, talked briefly about Emotional Brain, the Dutch drug company that is developing them. Putting aside the many objections to the HSDD diagnosis for now, and the fact that the trials pathologize sexual boredom within marriage, the company has conducted some interesting studies1 to assess sexual desire. Foremost among these is the development of an at-home testing environment, or ambulatory lab, to conduct studies of sexual function (Bloemers et al., 2010).Fig. 1 (Bloemers et al., 2010). Schematic overview of the ambulatory measurement setting. (1) Generic laptop, (2) genital probe, (3) wireless sensor system, (4) handheld computer, and (5) secure central database.The participants must be so much more comfortable watching hardcore porn and measuring their own vaginal pulse amplitude and clitoral blood volume in the privacy of their homes, without the prying eyes of hoards of scientists in white lab coats (although some people might be into that).And that's what was found, for the most part (Bloemers et al., 2010):The results of this study support our hypothesis that in healthy controls, clitoral and subjective laboratory measures of sexual arousal show stronger increases to erotic stimuli in the home environment than in the environment of the institutional laboratory. This effect was apparent in response to hardcore stimuli, but not to erotic fantasy. ... To our knowledge, this is the first study that investigates ecological validity of sexual psychophysiological measures by comparing those assessed in the institutional laboratory to those assessed at home with an ambulatory laboratory. Footnote1 Albeit flawed studies, from a cognitive perspective (especially their implementation of an 'Emotional Stroop' task). I am not particularly qualified to comment on other aspects of this research.ReferencesBloemers, J., Gerritsen, J., Bults, R., Koppeschaar, H., Everaerd, W., Olivier, B., & Tuiten, A. (2010). Induction of Sexual Arousal in Women Under Conditions of Institutional and Ambulatory Laboratory Circumstances: A Comparative Study Journal of Sexual Medicine, 7 (3), 1160-1176 DOI: 10.1111/j.1743-6109.2009.01660.xWoodard, T., & Diamond, M. (2009). Physiologic measures of sexual function in women: a review Fertility and Sterility, 92 (1), 19-34 DOI: 10.1016/j.fertnstert.2008.04.041
... Read more »

  • May 27, 2013
  • 07:05 AM
  • 414 views

Can Pot Smoking Counter the Negative Metabolic Consequences of Atypical Antipsychotics?

by The Neurocritic in The Neurocritic

DISCLAIMER: This is a hypothetical question and not a medical recommendation. But it might be an idea worth investigating in epidemiological studies.Everyone knows that pot gives you the munchies. So the paradoxical finding that marijuana use is associated with a lower prevalence of obesity and diabetes came as a quite surprise to me. Now, a new study has concluded that pot smokers also have lower fasting insulin levels and smaller waistlines (Penner et al., 2013).I'll let the authors summarize the clinical significance of their study (Penner et al., 2013):Marijuana use is increasingly common, and use of medical marijuana is now legal in 19 states and the District of Colombia.Despite its associations with increased appetite and caloric intake, marijuana use also is associated with lower body mass index and prevalence of diabetes.In a nationally representative survey population, we found current use of marijuana to be associated with lower levels of fasting insulin, lower insulin resistance (homeostasis model assessment of insulin resistance), and smaller waist circumference.More complete descriptions of this article are available at Addiction Inbox and Time Healthland.Marijuana Use and Mental IllnessSome other observations that I will attempt to string together:Cannabis use (and misuse) is higher among individuals with schizophrenia and bipolar disorder (Green et al., 2005; Lev-Ran et al., 2013).I will not address the issue of whether cannabis use is a risk factor for psychosis here.1 In fact, all of my observations will be related to the metabolic effects of marijuana and not to its psychoactive properties and possible detrimental effects on mental health.People with schizophrenia and bipolar disorder are often on atypical antipsychotic drugs, which are notorious for causing significant weight gain that can lead to high cholesterol, hypertension, diabetes and metabolic syndrome. Although cigarette smoking, alcohol use, unhealthy diet, and lack of exercise may contribute to shorter life expectancy in patients with serious mental illnesses (Lawrence et al., 2013), one has to wonder about the effects of atypicals on physical health.2 These drugs can have a very positive effect on mental health, but it comes at a cost.Interestingly, cannabis use is not associated with greater mortality. In fact, the opposite has been reported by Koola et al. (2012), who "observed a lower mortality risk in cannabis-using psychotic disorder patients compared to cannabis non-users despite subjects having similar symptoms and treatments." A total of 762 patients with a psychotic disorder were included in that study. All were on atypical antipsychotics, and 39% used marijuana (although this is often under-reported). The authors speculated on the potential health benefits of cannabis, including its anti-inflammatory effects. However, they didn't mention reductions in obesity and diabetes as possible causes of lower mortality in cannabis users. This association bears further investigation, in my view.Nevertheless, eliminating marijuana to counteract the increase in appetite brought on by atypicals seems like common sense. In fact, this has been proposed as a specific behavioral intervention (Werneke et al., 2013).Those authors assumed that cannabis contributes to the weight gain caused by the prescription medication, which I also assumed (until reading the new papers cited here). But this relationship hasn't really been studied (Werneke et al., 2013):As the endocannabioid system is linked to increased appetite and cannabioid receptor antagonists can induce weight loss [15] cannabis consumption will most likely potentiate antipsychotic-associated weight gain. As the prevalence of cannabis use in people suffering from psychosis is so high, the contribution of cannabis to weight gain in this population is likely to be significant. Surprisingly, this link between cannabis and weight gain remains largely ignored at present. A recent paper in Medical Hypotheses (of all places) takes the opposite stance and proposes cannabis as a weight loss drug (Le Foll et al., 2013):We recently discovered that the prevalence of obesity is paradoxically much lower in cannabis users as compared to non-users and that this difference is not accounted for by tobacco smoking status and is still present after adjusting for variables such as sex and age. Here, we propose that this effect is directly related to exposure to the Δ9-tetrahydrocannabinol (THC) present in cannabis smoke. We therefore propose the seemingly paradoxical hypothesis that THC or a THC/cannabidiol combination drug may produce weight loss and may be a useful therapeutic for the treatment of obesity and its complications.These authors have filed a patent application for 'Use of marihuana and compounds therein for treating obesity' (which they acknowledge in the paper).One of the same authors (Le Foll) has also published on 'Cannabis use and cannabis use disorders among individuals with mental illness' (Lev-Ran et al., 2013), which they found to be particularly high in individuals with Bipolar I disorder (especially in men). Many of these bipolar cannabis users are probably on atypical antipsychotics. This information was not reported in the paper, but it might be available in the National Epidemiologic Survey on Alcohol and Related Conditions (although this is not certain).To be completely clear, I am not advocating the use of marijuana by persons with schizophrenia or bipolar disorder. Rather, I am suggesting that the relationship between atypical antipsychotics and variables such as body mass index, waist circumference, insulin, glucose, and diabetes be compared between groups who do use cannabis vs. those who don't. If there is a benefit in the pot smokers, perhaps there could be a psychiatrically safe, cannabis-derived compound for weight loss in the future. Isn't that more likely than the development of 'third generation' antipsychotics that do not cause substantial weight gain?Footnotes1 Interested readers can consult these articles and posts.2 See also Rising Mortality Rates for People with Serious Mental Illness and Improving the Physical Health of People With Serious Mental Illness.ReferencesGreen B, Young R, Kavanagh D. (2005) Cannabis use and misuse prevalence among people with psychosis. Br J Psychiatry 187:306-13. ... Read more »

  • May 22, 2013
  • 06:19 AM
  • 678 views

The Mental Health of Lonely Marijuana Users

by The Neurocritic in The Neurocritic

Mr. Lonely 1Does Smoking Pot Offer Relief to the Lonely?  A new paper by the original Tylenol and social pain researchers claims that it does (Deckman et al., 2013). Let's take a closer look.Comfortably Numb: Marijuana Use Reduces Social Pain, Research FindsMarijuana use buffers people from experiencing social pain, according to research published online on May 14 in Social Psychological and Personality Science."Prior work has shown that the analgesic acetaminophen, which acts indirectly through CB1 receptors, reduces the pain of social exclusion," Timothy Deckman of the University of Kentucky and his colleagues wrote in the study. "The current research provides the first evidence that marijuana also dampens the negative emotional consequences of social exclusion on negative emotional outcomes."You could be forgiven if you thought, as I initially did, that the University of Kentucky IRB must hold a liberal view on the administration of controlled substances to undergrads participating in psychology experiments. But that's not what happened here... the data are entirely correlational, based on self-report, and largely problematic (in my view).Marijuana Lowers Self-Worth and Worsens Mental Health in Those Who Are Not LonelyThat's my interpretation of the article, which is SO clunky compared to the fun and breezy query, Can Marijuana Reduce Social Pain? 2The paper begins with the premise that "Social and physical pain share common overlap at linguistic, behavioral, and neural levels" (Deckman et al., 2013). So let's give a pain reliever to reduce the sting of rejection!  A critique of the original work asked why the authors chose Tylenol, as opposed to an NSAID like aspirin, ibuprofen, or naproxen. In the current study they tried to develop a mechanistic account of why acetaminophen might reduce social pain:Prior research has shown that acetaminophen—an analgesic medication that acts indirectly through cannabinoid 1 receptors—reduces the social pain associated with exclusion. Yet, no work has examined if other drugs that act on similar receptors, such as marijuana, also reduce social pain.The problem is that acetaminophen's mechanism of action is surprisingly unclear (Toussaint et al., 2010). One prominent hypothesis claims that Tylenol might exert its analgesic effects through descending serotonergic pathways at the level of the spinal cord. In fact, the paper that Deckman et al. cited in favor of cannabinoid 1 (CB1) receptors describes a very complex pathway that includes indirect involvement of CB1, with actual pain suppression occurring in the spinal cord. 3An even more basic question: if acetaminophen acts through CB1 receptors, then why isn't it a potential drug of abuse, or known by experienced pharmanauts for its psychoactive properties?  The drug experience vault Erowid says:Acetaminophen is a non-salicylate analgesic and antipyretic (pain killer and fever reducer). It is a common over-the-counter pain medication found in hundreds of products around the world. At higher doses it is known to cause liver-damage and has a low therapeutic index (ratio of effective dose to toxic dose), making it dangerous when included in recreationally used pharmaceuticals [e.g., Tylenol with codeine]. It is not known to be psychoactive.On the other hand, we all know that cannabis is psychoactive. The design of the cannabis study included cross-sectional national survey data, a two year longitudinal survey of 400 high school students, and a Mechanical Turk-implemented version of cyberball, an online game to simulate social exclusion. In all cases, participants reported their marijuana use, and this was related to the variables of interest.I'll focus on the national survey data in this post, which comprised Study 1 (Marijuana Use Buffers Lonely People From Lower Self-Worth and Self-Rated Mental Health) and Study 2 (Marijuana Use Predicts Fewer Major Depressive Episodes Among the Lonely).Study 1 used data from the National Comorbidity Survey: Baseline (NCS-1), 1990-1992 (ICPSR 6693), which you can download for yourself. The survey recruited 8,098 individuals from the ages of 15 to 54 living in the U.S., and included over 4,000 variables. Only four variables were chosen for the present study: self-reported loneliness (1= often, 4 = never), marijuana use (0 = none, 1 = daily, 8 = once or twice a year), self-worth (1 = high, 4 = low), and overall mental health (1 = excellent, 5 = poor).Loneliness was used as a proxy for social pain. Contrary to what the headlines suggested, the impact of pot smoking on social pain was not directly examined. Instead, the study assessed the effects of loneliness (high, low), marijuana use (high, low) and their interaction on self-worth and mental health.Loneliness and pot smoking interacted to predict feelings of self-worth [B = 0.03, t(5609) = 2.20, p = .03]. Given the huge number of participants, this level of statistical significance is not very impressive.Fig. 1 (modified from Deckman et al., 2013). Study 1: Marijuana use moderates the relationship between loneliness and self-reported feelings of self-worth. [NOTE: items were reverse-scored for display purposes.]For lonely people, the amount of pot smoked didn't make too much of a difference in their self-worth (see red arrow above).  For socially connected people, greater marijuana use resulted in lower self-worth, although it's not clear this was significant (pairwise statistical tests were not reported).I also question how the High Marijuana Use and Low Marijuana Use groups were determined, because over 5,000 participants did not smoke pot at all in the last 12 months. Does the heavy use group combine those who smoke 6 joints a year with those who smoke daily?... Read more »

Deckman, T., DeWall, C., Way, B., Gilman, R., & Richman, S. (2013) Can Marijuana Reduce Social Pain?. Social Psychological and Personality Science. DOI: 10.1177/1948550613488949  

  • May 15, 2013
  • 04:50 PM
  • 253 views

What RDoC Research Might Look Like

by The Neurocritic in The Neurocritic

The month of May is a violent thingIn the city their hearts start to singWell, some people sing, it sounds like they're screamingI used to doubt it, but now I believe itMonth Of May   ------The Arcade FireToday is Mental Health Month Blog Day, sponsored by the American Psychological Association (APA). It's designed to:...educate the public about mental health, decrease stigma about mental illness, and discuss strategies for making lasting lifestyle and behavior changes that promote overall health and wellness.If the public has been following the recent hullabaloo about how to diagnose mental illnesses, they might be confused about the current and future direction of the field. How did we get here?As most of you know, the American Psychiatric Association (the other APA) is about to release its updated Diagnostic and Statistical Manual of Mental Disorders, the much maligned DSM-5. Weeks before the big launch, however, the National Institute of Mental Health (NIMH) stole the show by announcing that it will be re-orienting its research away from DSM categories:...While DSM has been described as a “Bible” for the field, it is, at best, a dictionary, creating a set of labels and defining each. The strength of each of the editions of DSM has been “reliability” – each edition has ensured that clinicians use the same terms in the same ways. The weakness is its lack of validity. Unlike our definitions of ischemic heart disease, lymphoma, or AIDS, the DSM diagnoses are based on a consensus about clusters of clinical symptoms, not any objective laboratory measure. Instead, the Research Domain Criteria (RDoC) framework would become the preferred method for organizing biologically-based research on mental illnesses, with the ultimate goal of constructing a new classification scheme.This caused quite a commotion, leading many to comment on NIMH's shocking repudiation of DSM-5. However, to long-time observers of RDoC's development, this was not a surprise. And the initial lack of clarity on the distinction between the RDoC Dimensional Approach for Research vs. DSM-5 for Diagnosis didn't help matters, nor did the uncertainty about whether NIMH would fund DSM-based research at all.1NIMH issued a press release on May 13 to clarify its position:DSM-5 and RDoC: Shared InterestsThomas R. Insel, M.D., director, NIMHJeffrey A. Lieberman, M.D., president-elect, APANIMH and APA have a shared interest in ensuring that patients and health providers have the best available tools and information today to identify and treat mental health issues, while we continue to invest in improving and advancing mental disorder diagnostics for the future.Today, the APA's Diagnostic and Statistical Manual of Mental Disorders (DSM), along with the International Classification of Diseases (ICD) represents the best information currently available for clinical diagnosis of mental disorders  Patients, families, and insurers can be confident that effective treatments are available and that the DSM is the key resource for delivering the best available care. The NIMH has not changed its position on DSM-5. As NIMH’s Research Domain Criteria (RDoC) project website states, “The diagnostic categories represented in the DSM-IV and the International Classification of Diseases-10 (ICD-10, containing virtually identical disorder codes) remain the contemporary consensus standard for how mental disorders are diagnosed and treated.”Yet, what may be realistically feasible today for practitioners is no longer sufficient for researchers. Looking forward, laying the groundwork for a future diagnostic system that more directly reflects modern brain science will require openness to rethinking traditional categories. It is increasingly evident that mental illness will be best understood as disorders of brain structure and function that implicate specific domains of cognition, emotion, and behavior. This is the focus of the NIMH’s Research Domain Criteria (RDoC) project. RDoC is an attempt to create a new kind of taxonomy for mental disorders by bringing the power of modern research approaches in genetics, neuroscience, and behavioral science to the problem of mental illness.So what is RDoC, and how might it be applied to new research projects? From the DSM perspective of categorical disorders (e.g, schizophrenia, major depression, and obsessive compulsive disorder), RDoC embraces diagnostic messiness. Patients previously excluded from a study due to comorbidities, or because they don't meet full criteria? Misfits from the "Not Otherwise Specified" (NOS) category? Now they're in. Specifically, the instructions for RFA-MH-14-050 state:Priority will be given to applications that have a well-justified plan to include patients from multiple diagnostic groups (including Not Otherwise Specified and forme fruste diagnoses) as appropriate for explicating the dimensions and constructs of interest in the study design. Studies that include patients from a single diagnostic group may also be considered if there is a particularly strong justification for examining constructs of interest within one diagnostic category.  A defensible approach might be to study all patients presenting themselves at a specialty clinic, e.g., mood disorders clinic, anxiety clinic, or psychotic disorders clinic, regardless of whether they meet criteria for a particular DSM diagnosis.One potential pitfall of this approach is the money required to enroll huge numbers of patients. If commonalities in cognitive function or brain circuitry or especially genetic risk factors are to emerge from studying all patients with mood disorder-like symptoms, then sample sizes must be very large to overcome potential noise in the system(s).The applicant would propose to study one or more of the five different domains, or constructs, that have been fleshed out at NIMH Workshops:Negative Valence SystemsPositive Valence SystemsCognitive SystemsSystems for Social ProcessesArousal/Regulatory SystemsThe possible units of analysis run the gamut from genes to circuits to behavior, and the studies should use specific tasks (paradigms) and self-report measures, as shown in the Negative Valence Systems matrix below.Draft Research Domain Criteria Matrix Animal ... Read more »

  • April 28, 2013
  • 08:22 AM
  • 358 views

Want to remember something? Clenching your fist doesn't help!

by The Neurocritic in The Neurocritic

Image Credits: fist and brain.You might have seen this news story the other day:Want to remember something? Clench your fists!Giving a speech and need to remember what to say? Just clench your right fist while rehearsing. Then, when it's time to give the speech, clench your left fist, and voila, you’ll recall what you rehearsed! That's what a new study found, which was published April 24 online at PLOS ONE. Sounds too easy now, doesn't it? And if you're exclaiming, "that's just too good to be true!" — then you'd be correct.The new study by Propper et al. (2013) has unleashed a torrent of criticism on Twitter, including this starter by @js_simons.What motivated such a study in the first place? I'll try to run through the authors' rationale here, starting with statements from the abstract, which are followed by my commentary.Unilateral hand clenching increases neuronal activity in the frontal lobe of the contralateral hemisphere. It's true that unilateral hand movement is executed via motor cortex activity in the opposite hemisphere, so the right hemisphere controls the left hand and vice versa.Such hand clenching is also associated with increased experiencing of a given hemisphere’s “mode of processing.”This statement is based on EEG studies that have looked at alpha power suppression recorded at scalp electrodes over left and right frontal cortex (Harmon-Jones, 2006). The hypothesis is that left hand contractions "activate" (i.e., suppress alpha waves in) the unhappy right hemisphere, thereby producing negative affect, while right hand contractions activate the happy left hemisphere, which results in positive affect. The affective "modes of processing" aspect of this research isn't directly relevant to the Propper et al. (2013) paper, and further discussion is beyond the scope of this post. I'll just say that attributing EEG activity to a specific cortical region is a dicey proposition, because the spatial resolution of the technique isn't great.1 Together, these findings suggest that unilateral hand clenching can be used to test hypotheses concerning the specializations of the cerebral hemispheres during memory encoding and retrieval.Here the EEG research on emotion is being applied to memory. We investigated this possibility by testing effects of unilateral hand clenching on episodic memory. The hemispheric Encoding/Retrieval Asymmetry (HERA) model proposes left prefrontal regions are associated with encoding, and right prefrontal regions with retrieval, of episodic memories. The Hemispheric Encoding/Retrieval Asymmetry (HERA) model of Tulving et al. (1994) postulates that the left prefrontal cortex encodes information into memory, while the right prefrontal cortex retrieves information from memory. This was back in ye olden days of PET using block designs with 40 seconds of one condition subtracted from 40 seconds of another condition. In other words, poor temporal resolution.The HERA model was revisited and confirmed by its proponents using fMRI data (Habib et al., 2003), but the evidence against it was considerable (Owen, 2003). The general consensus is that HERA has been discredited. In fact, noted memory researcher Dr. Jon Simons posted a comment at the PLOS ONE website explaining why the underlying hypothesis of Propper et al. is problematic (among other issues).It was hypothesized that right hand clenching (left hemisphere activation) pre-encoding, and left hand clenching (right hemisphere activation) pre-recall, would result in superior memory. Here we're expecting to see better memory in the R/L condition than in the control condition. There is no mention that the other fist-clenching conditions would result in worse performance than in the control condition. Results supported the HERA model. Results did NOT support the HERA model, and I'll explain why below (and you can read the PLOS ONE comment).In the experiment, participants studied a list of 36 words, engaged in a filler task, and then recalled as many words as possible. Approximately 10 subjects participated in each of 16 conditions, only five of which are reported in the paper. These involved squeezing a small pink ball in one hand (2 sets of 45 sec) before the encoding and the retrieval phases of the study. The control condition did not involve clenching, but the participants held a small pink ball in each hand.2 The five conditions are shown below, named by the hand used during encoding/retrieval. You'll notice that the number of participants in each group (n) is pretty small. I calculated standard deviations from the standard error values to determine effect sizes using this effect size calculator. 3 Although the authors reported the total number of words written down (correct or not) and the number of correct words in Figs. 1 and 2 respectively, the important result is shown in Fig. 3, which takes into account the false alarms, or incorrectly recalled words. Figure 3 (Propper et al., 2013). Corrected scores as a function of hand clench condition. [NOTE: NENR = None Encoding/None Recall, or control.]The one-way ANOVA for this comparison "did not reach traditional significance" (p=.08), but two of the post hoc comparisons did (uncorrected for multiple comparisons involving 16 groups). The p<.09 bar in the figure is in the wrong pla... Read more »

Tulving E, Kapur S, Craik FI, Moscovitch M, & Houle S. (1994) Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings. Proceedings of the National Academy of Sciences of the United States of America, 91(6), 2016-20. PMID: 8134342  

  • April 19, 2013
  • 08:25 PM
  • 342 views

Does Tylenol Exert its Analgesic Effects via the Spinal Cord?

by The Neurocritic in The Neurocritic

What do we (not) know about how paracetamol (acetaminophen) works? (Toussaint et al., 2010). . .From the beginning, the focus of the search for paracetamol’s analgesic mechanism has concentrated on the central nervous system. When administered intraventricularly [i.e., directly into the ventricular system of the brain], acetaminophen produces no significant analgesia (115, 132). This finding lead to attempts to inject acetaminophen into the spinal cord (i.t.), which produced marked dose-related antinociception (132).Yesterday’s post about Tylenol as a cure for mortality salience and existential dread got me a little worked up. The first author’s public endorsement of acetaminophen as a possible treatment for chronic anxiety disorders was too much to handle (along with the less than stellar experimental rigor). Is watching a 4 min clip of a David Lynch film really the same thing as a clinically diagnosed psychiatric disorder (Randles et al., 2013)? Why Tylenol and not other pain relievers? What is the hypothesized mechanism of action? Wouldn’t we already know by now, from epidemiological studies at the very least, if Tylenol was an effective anti-anxiety medication?So I started wondering about acetaminophen's actual mechanism of action. I was quite surprised that it's somewhat mysterious. Randles et al. cited one paper on this:Second, acetaminophen affects a number of brain regions, some of which are not directly related to physical or social distress (Toussaint et al., 2010).This led me to believe there was evidence from human neuroimaging studies. Turns out there isn't, beyond the Dewall et al. (2010) paper, which states:Although the precise mechanisms by which acetaminophen exerts an analgesic effect are still unclear, it is widely accepted that acetaminophen reduces pain through central, rather than peripheral, nervous system mechanisms (Anderson, 2008; H.S. Smith, 2009).I would like to point out that the spinal cord is part of the central nervous system. So if it's really true that acetaminophen exerts its pain-relieving effects through synapses in the spinal cord, then what does this say about providing relief from the angst of social exclusion, mortality salience, and existential dread? That it's based on nociceptive spinal cord neurons in laminae I, II, and V? For a visual illustration of this pathway, I highly recommend viewing the animation, Dissection of DLF blocks analgesia, at Neuroscience Online. One hypothesis is that Tylenol (acetaminophen) may act on descending serotonergic pathways (purple projection) at the level of the spinal cord (red synapses). Figure modified from Neuroscience Online.However, it's not that simple. The review paper by Toussaint et al. (2010) concluded, "No one mechanism has been definitively shown to account for its analgesic activity." For its proposed mechanisms of action, they presented evidence both for and against Cyclooxygenase (EC 1.14.99.1, COX) inhibition, COX-1, COX-2, 'COX-3', peroxidase, nitric oxide synthase, cannabinoid receptors, and of course serotonin:There is substantial evidence that paracetamol’s mechanism of analgesia in some manner involves the descending serotonergical pathway. 5-HT neurons, largely originating in raphe nuclei located in the brain stem (117, 118) send projections down to the spinal cord that synapse on afferent neurons entering the spinal cord. These descending projections exert an inhibitory (analgesic) effect on the incoming pain signal before it is transmited to higher CNS centres.Note that these are not the same serotonergic pathways often implicated in depression. The terminal synapses for the latter are indeed located in the brain and not the spinal cord.Last night, in real life, I followed the Watertown news live via @sethmnookin and @taylordobbs (like many others).This morning I dreamt that my workplace had transformed into an institutional fortress taken over by a gang of murderous criminals. The actual law enforcement authorities were too busy watching television talk shows to do anything about it. The thugs were threatening and torturing and killing people in the building. I managed to escape down a balcony exit and hid out for a while, avoiding detection but fearful that the thugs would find me and kill me. They were unstoppable, and there seemed to be no way out. I informed an old West-style sheriff, who managed to detain a carload of the evildoers. While continuing to hide, I wondered whether I would be able to shoot them all dead with a fully automatic weapon before they shot and killed me.Then an early morning doorbell rang and woke me up. It was an unexpected FedEx delivery. In my barely awake state, I thought it might be a bomb.Why am I telling you all this?? Because I find it very hard to believe that Tylenol, a drug that's relatively ineffective for my own headache pain, could possibly alleviate the anxiety caused by this nightmare. Or by the real life nightmare that's affected so many people in Boston.ReferencesDewall CN, Macdonald G, Webster GD, Masten CL, Baumeister RF, Powell C, Combs D, Schurtz DR, Stillman TF, Tice DM, Eisenberger NI. (2010). Acetaminophen reduces social pain: behavioral and neural evidence. Psychol Sci. 21:931-7. Randles, D., Heine, S., & Santos, N. (2013). The Common Pain of Surrealism and Death: Acetaminophen Reduces Compensatory Affirmation Following Meaning Threats. Psychological Science DOI: 10.1177/0956797612464786... Read more »

Toussaint, K., Yang, X., Zielinski, M., Reigle, K., Sacavage, S., Nagar, S., & Raffa, R. (2010) What do we (not) know about how paracetamol (acetaminophen) works?. Journal of Clinical Pharmacy and Therapeutics, 35(6), 617-638. DOI: 10.1111/j.1365-2710.2009.01143.x  

  • April 18, 2013
  • 09:02 PM
  • 363 views

Existential Dread of Absurd Social Psychology Studies

by The Neurocritic in The Neurocritic

Scene from Rabbits by David Lynch“In a nameless city, deluged by a continuous rain, three rabbits live with a fearful mystery.”The latest "elegant and breathtaking"1 paper in Psychological Science presents a rather muddled view of film aesthetics, continental philosophy, surrealism, mortality salience, and stigmatizing attitudes towards sex work (Randles et al., 2013). Oh, and how Tylenol® brand acetaminophen can ease the existential dread evoked by all of these modern horrors.The authors explained the purpose and implications of their study in the APS press release:According to lead researcher Daniel Randles and colleagues at the University of British Columbia in Canada, the new findings suggest that Tylenol may have more profound psychological effects than previously thought:“Pain extends beyond tissue damage and hurt feelings, and includes the distress and existential angst we feel when we’re uncertain or have just experienced something surreal. Regardless of the kind of pain, taking Tylenol seems to inhibit the brain signal that says something is wrong.”Randles and colleagues knew from previous research that when the richness, order, and meaning in life is threatened — with thoughts of death, for instance — people tend to reassert their basic values as a coping mechanism.The researchers also knew that both physical and social pain — like bumping your head or being ostracized from friends — can be alleviated with acetaminophen. Randles and colleagues speculated that the existentialist suffering we face with thoughts of death might involve similar brain processes. If so, they asked, would it be possible to reduce that suffering with a simple pain medicine?No!!  I think this is a ridiculous assertion that gets away with using language (and dependent measures) that not only lack precision, but also lack an analogical relation to the real phenomenon under discussion. The leaps of logic were so egregious that I don't know where to begin......so let's start with the meaning-maintenance model (MMM) that motivated the work. MMM "posits that any violation of expectations leads to an affective experience that motivates compensatory affirmation" (Randles et al., 2013). Any violation?? So all sorts of psycholinguistics experiments that involve syntactic violations 2 will motivate compensatory affirmation? If that's the case, then David Lynch films will often "motivate compensatory affirmation."But does a David Lynch film “hurt” you?...Lynch’s films have the ability to “disturb, offend or mystify” (Rodley, 2005, p. 245). Insofar as it “hurts” to watch some of Lynch’s films, as it arguably hurts whenever one is assaulted by thoughts and experiences that are at odds with one’s expectations and values, the question arises as to how this uncomfortable feeling is represented in the brain. First, David Lynch is one of my favorite directors, and I have never felt "hurt" by watching one of his films. Second, Randles et al. never, at any point in their experiments, address how Lynch-viewing is represented in the brain.What did the authors actually do? In brief, they asked ~350 young Vancouverites to participate in one of two experiments. In the first study, 121 subjects wrote about death or about dental pain. In the second study, 228 subjects watched a 4 min clip from Rabbits or from The Simpsons. In each case, half of the participants received acetaminophen, half received placebo. Why? What motivated the choice of acetaminophen, as opposed to aspirin, ibuprofen, or naproxen? This was based on a study by Dewall et al. (2010), another problematic paper3 in Psych Sci. There was no mechanistic reason for the original choice.Here's the neuro-rationale for the current study (Randles et al., 2013):The present research is predicated on four key findings in the literature: (a) Both physical and social pain are associated with activation in the dACC [dorsal anterior cingulate cortex]4 (e.g., Eisenberger et al., 2003), (b) the dACC is activated in response to anomalies (e.g., Botvinick et al., 2004), (c) social rejection can produce the same compensatory affirmation as other meaning threats (e.g., Nash et al., 2011), and (d) acetaminophen has been shown to reduce physical and social pain, as well as activation in the dACC (DeWall et al., 2010). These findings led us to predict that acetaminophen may also inhibit compensatory affirmation following meaning threats.The acetaminophen group in Dewall et al. (dose of 2,000 mg a day for 3 weeks) did show less dACC activity in response to cyberball exclusion, but they did not report lower hurt feelings in that situation. The treatment administered by Randles et al. was quite different: a single acute dose of 1,000 mg Tylenol-brand acetaminophen (Rapid Release formula) or 1,000 mg sugar placebo, given 30 min before the critical manipulation.In Exp. 1, writing two paragraphs about what will happen to your body after death was designed to trigger mortality salience, or thoughts about the inevitability of death. This in turn would lead to compensatory affirmation of cultural views. How was this measured? By assessing the severity of punitive attitudes towards women who engage in sex work! This is the worst part of the study, in my opinion.Social judgment surveyFinally, participants read a hypothetical arrest report about a prostitute and were asked to set the amount of the bail (on a scale from $0 to $999). This measure has been used in a number of other meaning-threat studies (Proulx & Heine, 2008; Proulx et al., 2010; Randles et al., 2011; Rosenblatt, Greenberg, Solomon, Pyszczynski, & Lyon, 1989). Participants are expected to increase the bond amount after experiencing a threat, because trading sex for money is both at odds with commonly held cultural views of relationships and against the law. Increasing the bond assessment provides participants n opportunity to affirm their belief that prostitution is wrong. The study took place in Vancouver, Canada. What are the laws on prostitution?In Canada, the buying and selling of sexual services are leg... Read more »

  • March 31, 2013
  • 06:56 PM
  • 417 views

Are Cognitive Factors Related to Criminal Reoffending?

by The Neurocritic in The Neurocritic

Image from Graphic SociologyCan Brain Activity Predict Criminal Reoffending?  The previous post discussed a functional MRI study suggesting that the level of error-related activation in the anterior cingulate cortex (ACC) might have value in predicting whether a recently released prisoner will be rearrested within 4 years (Aharoni et al. 2013):The odds that an offender with relatively low anterior cingulate activity would be rearrested were approximately double that of an offender with high activity in this region, holding constant other observed risk factors. These results suggest a potential neurocognitive biomarker for persistent antisocial behavior.However, using ACC activity as a dichotomous variable misclassified 40% of low ACC participants who did not reoffend and 46% of high ACC participants who did commit crimes after release, not exactly the odds you'd want for making parole decisions. Even the senior author was doubtful that an fMRI test would ever be useful for risk assessment purposes on a case by case basis.Since Aharoni and colleagues made their individual subject data available as supplementary material (Download Dataset_S01, XLSX), I was interested in how some of the demographic and performance variables might be related to recidivism, since these are obviously cheaper and easier to collect from incarcerated prisoners than MRI scans.The cognitive task performed during the fMRI experiment required responding to a frequent stimulus presented 84% of the time ("X") and inhibiting responses to a rare stimulus ("K").Fig. S4. (Aharoni et al., 2013). Go/No-Go task.The study compared brain activity on incorrect responses to "K" (commission errors) and correct responses to "X" (hits) in a region of interest in the dorsal ACC, which has been implicated in error processing (Simons, 2010), among many other things. The authors framed the results largely in the context of impulse control, but other explanations are possible (as we'll see later).Are any of the task performance variables related to recidivism? Starting with some very simple-minded t-tests, the rate of commission errors in the group of participants arrested for nonviolent offenses1 (n=40) did not differ significantly from what was seen in those not arrested again (n=56).2Data from (Aharoni et al., 2013). Commission errors in the Go/NoGo task (% incorrect responses on NoGo trials) and omission errors (% missed responses on Go trials) for inmates that went on to commit nonviolent offenses within 4 years after release (Nonviolent) and those that did not (None). The trend for the reoffenders to commit more errors was not significant (p=.09) even without correcting for multiple comparisons.Although there were data from a large control group of nonoffenders (n=102) used to set the ACC ROI, we don't have their behavioral results. I consulted an earlier fMRI paper by Kiehl et al. (2000) that used a very similar Go/NoGo task in 14 control participants. Commission errors occurred on 23.7% of NoGo Trials and omission errors on 3% of Go Trials, which is similar to what was seen in the offenders (overall means of 25.04% and 3.44%, respectively).Reaction times (RTs) did not differ between the two offender groups either, suggesting there wasn't a differential speed-accuracy tradeoff (e.g., if the reoffenders were slower yet making marginally more errors).Data from (Aharoni et al., 2013). RTs in milliseconds for commission errors (incorrect responses on NoGo trials) and hits (correct responses on Go trials) for inmates that went on to commit nonviolent offenses within 4 years after release (Nonviolent) and those that did not (None). There were no group differences.Surprisingly, RTs were slower on commission errors (358 ms) than on hits (346 ms), a small but highly significant difference (p=.0005). This is the opposite of what you'd expect if the errors were due to impulsive responses. If the participants were becoming careless and not fully evaluating the NoGo stimulus, they'd be faster on error trials. This is why I'm not convinced the ACC activations are entirely related to behavioral impulsivity. In EEG studies of error processing, the degree of ACC activity3 is related to the emphasis placed on accuracy (Gehring et al., 1993), so if the reoffenders didn't care as much about accuracy, this could account for their low ACC status. One interesting bit of data for the authors to examine would be RT and accuracy on responses following an error, which indicates the amount of behavioral adjustment after making a mistake. Did the reoffenders show a lower propensity to slow down and become more careful? If so, this might reflect a lack of concern about the consequences of their actions.However, the most puzzling thing to me were scores on Factor 2 of the Psychopathy Checklist-Revised (PCL-R) (Hare, 2003). Factor 2 is thought to reflect impulsivity, stimulation seeking, and irresponsibility (Ermer et al., 2012). The rearrested and not-rearrested groups were significantly different as expected, but in the opposite direction (unless I'm missing something here) — scores were lower in the group that was rearrested, in comparison to those who were not (p=.001).Data from (Aharoni et a... Read more »

Aharoni, E., Vincent, G., Harenski, C., Calhoun, V., Sinnott-Armstrong, W., Gazzaniga, M., & Kiehl, K. (2013) Neuroprediction of future rearrest. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1219302110  

  • March 28, 2013
  • 04:13 PM
  • 334 views

Can Brain Activity Predict Criminal Reoffending?

by The Neurocritic in The Neurocritic

Is it possible for a brain scan to predict whether a recently paroled inmate will commit another crime within 4 years? A new study by Aharoni et al. (2013) suggests that the level of activity within the anterior cingulate cortex might provide a clue to whether a given offender will be rearrested.Dress this up a bit and combine with a miniaturized brain-computer interface that continuously uploads EEG activity to the data center at a maximum security prison. There, machine learning algorithms determine with high accuracy whether a given pattern of neural oscillations signals the imminent intent to reoffend that will trigger deep brain stimulation in customized regions of prefrontal cortex, and you have the plot for a 1990s cyberpunk novel.But we're getting way ahead of ourselves here...Dr. Kent Kiehl outside the mobile scanner his group uses to look at the brains of inmates at New Mexico prisons. Credit: Nature News.The actual study in question used functional MRI to scan the brains of 96 male inmates at two New Mexico state correctional facilities while they performed a cognitive task (Aharoni et al., 2013). The task required responding to a frequent stimulus presented 84% of the time ("X") and inhibiting responses to the rare stimulus ("K").Fig. S4. (Aharoni et al., 2013). Go/No-Go task.The major comparison examined brain activity on incorrect responses to "K" (commission errors) vs. correct responses to "X" (hits). This contrast was restricted to a region of interest (ROI) in the dorsal anterior cingulate cortex (dACC), which has been associated with a wide array of cognitive and emotional control functions (Posner et al., 2007).Results from a separate group of 102 age-matched control participants (mean = 33.9 yrs) from Hartford, CT1 determined the a priori ROI, with the peak voxel located at coordinates x = −3, y = 24, z = 33 in the center of a 14 mm sphere. One control ROI was chosen in a more ventral and anterior region of medial prefrontal cortex (mPFC) at 0, 51, −6.The most strongly activated voxel in the offender group for the error vs. hit contrast was remarkably close to the one determined from the independent sample and fell well within the a priori ROI (see blue crosshairs in figure below).Fig. 2 (modified from Aharoni et al., 2013). (B) Mean hemodynamic response change in offender sample (n = 96) during commission errors vs. correct hits from sagittal (Upper Left), coronal (Right), and axial (Lower Left) orientations. Peak activation located at x = 3, y = 24, z = 33 within the anterior cingulate cortex region of interest (P < 0.00001, FWE).The dACC has been strongly implicated in error processing (Simons, 2010), and that was no different in the offenders as a group. Other regions significantly activated by commission errors included bilateral inferior frontal cortex/insula, fusiform gyrus, and cerebellum but these were not discussed.Of greatest interest is whether this dACC activity can predict recidivism. For this the authors did a survival analysis:First, a Kaplan–Meier survival function was computed to describe the proportion of participants surviving any felony rearrest over the 4-y follow-up period, ignoring the influence of any particular risk factor (Fig. S1). Cox proportional hazards regression was then used to examine (i) the zero-order effects of ACC activity on months to rearrest for any crime, (ii) the shared and unique influence of the ACC and other potential risk factors on months to rearrest for any crime, (iii) for nonviolent crimes, and (iv) the shared and unique influence of the medial prefrontal cortex (mPFC) control region and other potential risk factors on months to rearrest for any crime. ...... A significant association was found whereby, for every one unit increase in ACC activity, there was a 1.39 (i.e., 1/exp[B]) decrease in the probability of rearrest....Meaning that the participants with greater ACC activity were less likely to reoffend. The mPFC  ROI did not show this association. Then a median split divided the offender sample into high ACC and low ACC groups (survival function shown below).Fig. 1 (Aharoni et al., 2013). Cox survival function showing proportional rearrest survival rates of high (solid green) vs. low (dashed red) ACC response groups for any crime over a 4-y period. Results of this median split analysis were equivalent to that of the parametric model: bootstrapped B = 0.96; SE = 0.40; P < 0.01; 95% CI, 0.29–1.84. The mean survival times to rearrest for the low and high ACC activity groups were 25.27 (2.80) mo and 32.42 (2.73) mo, respectively. The overall probabilities of rearrest were 60% for the low ACC group and 46% for the high ACC group.So for all felonies (both violent and nonviolent), a substantial percentage of participants were likely to be rearrested within 4 years. The ACC classification scheme would wrongly condemn the 40% of low ACC parolees who did not reoffend, and would miss the 46% of high ACC parolees who did commit crimes after release. When you look at it that way, it's not all that impressive and completely inadmissable as evidence for decision-making purposes. For nonviolent felonies only, the probability of rearrest for high ACC offenders was 31%, compared to 52% for low ACC offenders.A number of other variables were considered in the regression models (and singly as predictors), including age at release, drug and alcohol use, scores on the Psychopathy Checkli... Read more »

Aharoni, E., Vincent, G., Harenski, C., Calhoun, V., Sinnott-Armstrong, W., Gazzaniga, M., & Kiehl, K. (2013) Neuroprediction of future rearrest. Proceedings of the National Academy of Sciences. DOI: 10.1073/pnas.1219302110  

  • March 15, 2013
  • 05:16 AM
  • 481 views

How Neuroscientists Scan the Media

by The Neurocritic in The Neurocritic

In case you missed it, I had a guest post this week in Nature's SpotOn NYC series on Communication and the Brain (#BeBraiNY), held in conjunction with Brain Awareness Week. The theme concerned the challenges of engaging the public's interest in cognitive sciences, and communicating the knowns (and unknowns) of brain disorders:In the current funding climate of budget cuts and sequestration, there’s a wide latitude between overselling the immediate clinical implications of "imaging every spike from every neuron" in the worm C. elegans (as in the proposed Brain Activity Map Project) and ignoring science communication entirely, leaving it up to the university press office.Who occupies the middle ground between the industry cheerleader and the disinterested academic? Science bloggers, for one. Scientist bloggers comprise a growing segment of the science communication world.Many of us have been critical of how traditional media channels can distort the actual scientific results and mislead the public. With the mainstreaming of neurocriticism, I felt this topic had been discussed extensively in recent months, so I moved on to the responsibilities we face in presenting accurate information. Some examples were drawn from my posts on unusual neurological disorders, including Prosopometamorphopsia (a condition where faces look distorted on one side) and Othello Syndrome (delusional jealousy). Both posts can turn up on the first page of a Google search, so I do feel an obligation to be factual and informative.Another example was a critique of public brain scanning on Celebrity Rehab with Dr. Drew. Although I wrote that post (and a follow-up) in 2010, readers were finding them now because former program participants Mindy McCready and Dennis Rodman were in the news, for very different reasons. My guest post concludes with:Scientist bloggers serve an important function in the continuum of science communication. We should take our responsibility for presenting high quality, ethical information very seriously, to help stem the ongoing flood of neurocrackpottery.Amidst the SpotOn NYC series extolling the virtues of science blogging came a new paper suggesting that science blogs are inferior sources of information relative to traditional media (Allgaier et al., in press):Scientists may understand that neuroscience stories in legacy media channels are likely to be of higher quality than similar narratives found in blogs. Stories in social channels are often crafted on the fly, without the help of experienced editors who can point out holes in the narrative or who can insist on rewriting and revision. Blog posts also tend to be shorter narratives, bereft of the kind of complexity and nuance possible only in long-form journalism.Obviously, there's a lot of high quality "long-form" journalism (which is never defined in the paper), but a huge number of high quality, complex and nuanced blog posts can be found as well. The passage above sparked quite the discussion on social media. Here's one initiated by respected journalist, blogger, and science writer Carl Zimmer:Blogs versus journalism in neuroscience--IT LIVES!I found passages like the one I just quoted [the one above] to be puzzling on many levels. Science blogs pretty much came into existence as a way for scientists themselves to critique bad coverage in traditional media. And, ten years later, that remains a powerful tradition.The paper presents a romantic, uncritical view of the press. Speaking as a journalist, I can say this is a view we can ill-afford.What's more, neuroscience blog posts are very often deep, nuanced, and more accurate than "churnalism" driven by glib press releases.If neuroscientists are indeed avoiding blogs for this reason (no data provided in the paper that this is true), then they are sadly misguided.Eight others joined in the discussion, which is worth reading.  One of the participants was Dominique Brossard, an author on the article in question.In brief, Allgaier et al. (in press) randomly contacted 1,248 "productive" neuroscientists who had published at least 8 articles in the preceding 2-year period. The survey participation rate was 21.3% in the US and 32.6% in Germany.The scientists responded to questions about three dimensions of public media channels, both traditional and online: (1) their personal use of these channels to “follow news and information about scientific issues”; (2) their assessment of the impact of scientific information in these channels on public opinion about science; and (3) their assessment of the impact of such information on “science-related decisions made by policymakers.” The respondents answered the questions with respect to a comprehensive list of traditional print or broadcast media, online analogs of those media channels, blogs, and content in social networks. Respondents were primarily male (78%) and over 40 (79%). Is this a typical sampling of neuroscientists? Obviously not, since it is gender-imbalanced1 and excludes most grad students and the average post-doc. The results in this group of participants suggested a preference for old media:The results of our survey indicate that the respondents in both countries remained heavily reliant on journalistic narratives, in both traditional and online forms, for information about scientific issues. Only a modest number of the surveyed neuroscientists reported that they use blogs or social networks to monitor such issues.Fig. 1a (modified from Allgaier et al., in press). Media use (in percentages) among neuroscientists in the United States and Germany. For the exact wording of the questions, detailed data, and significance information, consult supplemental table S1, available online at http://dx.doi.org/10.1525/bio.2013.63.4.8  [not online as of this writing].The over 40 crowd was more reliant on newspapers and valued online articles less than the younger set, who used social media more often as a source of popular science news. Women were less reliant on newspapers and printed pop sci magazines for science issue information than men.Do we really know if the participants consider blogs and social media to be inferior sources of information for the reasons quoted above? We do not. The authors were speculating, as they were in this paragraph (which elicited howls in the ... Read more »

Joachim Allgaier, Sharon Dunwoody, Dominique Brossard, Yin-Yueh Lo, & Hans Peter Peters. (2013) Journalism and Social Media as Means of Observing the Contexts of Science. BioScience. info:/10.1525/bio.2013.63.4.8

  • March 12, 2013
  • 02:28 AM
  • 436 views

What Is This Thing Called Neuroscience?

by The Neurocritic in The Neurocritic

"It depends upon what the meaning of the word 'is' is." -President Bill Clinton, August 17, 1998image: Brain electrodes, by laimagendelmundoDr. Vaughan Bell at Mind Hacks wrote a terrific post on The history of the birth of neuroculture as a follow-up to his Observer piece on Folk Neuroscience. That article explained how neuro talk has invaded many aspects of everyday discourse. In the new post he briefly covers the history of modern neuroscience, a necessary prelude to contemporary neuroculture:Neuroscience itself is actually quite new. Although the brain, behaviour and the nervous system have been studied for millennia the concept of a dedicated ‘neuroscience’ that attempts to understand the link between the brain, mind and behaviour only emerged in the 1960s and the term itself was only coined in 1962. Since then several powerful social currents propelled this nascent science into the collective imagination.To me, those dates seem quite recent in relation to brain research that has been conducted for centuries. Was there no neuroscience research prior to the 60s? My general perception is that ‘neuroscience’ research has been around a lot longer than that, even if it wasn't called by that precise name. It might have been called psychobiology (Yerkes, 1921), neurobiology (Brodmann, 1909),1 neurophysiology (1938) or neurochemistry (Lewis, 1948), but the types of questions asked and the experiments performed appear to be in line with much of what passes as a dedicated neuroscience in modern times. Here's Dr. Nolan D.C. Lewis speaking at the 96th Annual Session of the American Medical Association, Atlantic City, NJ, June 13, 1947 (Lewis, 1948):The actual nature of the thought processes is annoyingly elusive. What is the nature of thought? It is probably a manifestation of energy, but one can ask many questions about this. ... Do small areas of intact brain produce thoughts? Does the brain produce the mind independently or is it an instrument used by some other somatic processes or agents in the body? Does the brain itself think or is it a transmission center utilized by some other force? Is the mind the product of cerebral matter or is it dependent on something else which governs it? Can matter think? Either matter can produce mind or it cannot. Is mind a unique form of matter different from any other known forms of matter? While these questions and problems are probably not solvable by means of present technics, they are challenging, approachable and must eventually become elucidated if we are to get to the core of mental disorders.2What's in a name?I became curious enough to investigate whether the term ‘neuroscience’ was actually coined in 1962. @AliceProverbio confirmed that "Francis Schmitt used the term Neuroscience for the first time in 1962 to name his Neuroscience reserch group [at] MIT".  I found the paper in the Journal of the History of Neurosciences that clearly recognizes the role of Schmitt, but it also opined that the word might have been invented earlier (Adelman, 2010):...the word might have been coined by Ralph Gerard in the early 1950s...Does it really matter when the word itself was first used? No, not for Vaughan's history of the birth neuroculture. I'm not going to get to the bottom of who should get credit, either. But I do find it interesting to see how the word is used in various historical contexts.Not to be outdone by MIT, Harrison (2000) reviews the contributions and recollections of Five Scientists at Johns Hopkins in the Modern Evolution of Neuroscience, including those of pioneering neurophysiologist Professor Vernon Mountcastle:‘In the 1940’s, and on, this place [Johns Hopkins University] was red hot for the development of Neuroscience’.Noted historian of neuroscience Professor Stanley Finger, in his review on Women and the History of the Neurosciences, named several famous women neuroscientists of the 19th century (Finger, 2002):3 Women have been underrepresented in the early years of the neurosciences, much as they have been in other scientific endeavors. Nevertheless, the names of many important women contributors stand out if one begins in the latter part of the 19th century...Two women, who worked in part with their husbands but also achieved greatness on their own as the 19th century drew to a close and the 20th century began, are Augusta Marie (Dejerine-) Klumpke (1859-1927), who was married to Joseph Jules Dejerine (1849-1917), and Cécile Mugnier Vogt (1875-1962), who was married to Oskar Vogt (1870-1950)....Three other famous women neuroscientists from the later period are Christine Ladd-Franklin (1847-1930), Maria MichailovnaManasseina (also known as Marie de Manacéine, (1843-1903), and Margaret Floy Washburn (1871-1939). But in describing the vision of Professor Francis O. Schmitt in founding the Neurosciences Research Program at MIT, Adelman (2010) gets the last word on ‘neuroscience’:Ideally, Schmitt and his colleagues thought, the various physical, biological, and neural sciences could be brought together to attack a single goal, and what a goal — the ultimate one of all science and philosophy — how does the mind/brain work! Every field with some involvement in mind-brain studies would be included, from the molecular and subcellular areas of cell biology to the higher reaches of psychology and psychiatry. Such areas as cognitive psychology might not be able to contribute much to neurobiology; parallel fibers and psychophysical parallelism have little in common. But this field could pose major questions about higher brain function and the mechanisms of thinking, with molecular genetics perhaps providing answers about mechanisms operating at subcellular levels of the nervous system. Ha, ha! So much for the modern convergence of brain and behavioral sciences...Footnotes1 Dr. Korbinian Brodmann worked as an Assistant in the Neurobiological Laboratory of the University of Berlin.2 It goes without saying that modern techniques have opened up new avenues of study. And that ethical standards for the proper conduct of human and animal research (e.g., The Purring Center in Cats) have improved... Read more »

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