The Neurocritic

230 posts · 166,672 views

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

The Neurocritic
230 posts

this is a false account
0 posts

Sort by: Latest Post, Most Popular

View by: Condensed, Full

December 11, 2010
01:16 PM
3,471 views

Perspectives on Psychological Science: Blogs Don't Exist

by The Neurocritic in The Neurocritic

The Seductive Allure of Neuroscience ExplanationsThe previous post, Voodoo Correlations: Two Years Later, was a retrospective on the neuroimaging methods paper that was widely discussed in the blogosphere before it was considered "officially" published (Vul et al., 2009). The article, a controversial critique of the statistical analyses used by fMRI investigators in social neuroscience, made its initial appearance on Ed Vul's website once it was accepted by Perspectives in Psychological Sciences. This caused considerable consternation among the criticized authors and the journal editor (Ed Diener).Now, as part of the November 2010 issue of the journal (Diener's last as editor), six invited articles on Neuroimaging: Voodoo, New Phrenology, or Scientific Breakthrough? appear in a Special Section on fMRI (Diener, 2010). I was pleased to see that one of the articles addressed The Appeal of the Brain in the Popular Press (Beck, 2010), since this has been a major theme of my blog for almost five years. However, I was disappointed that the word "blog" was not mentioned at all in Beck's article.This should have come as no surprise, given the journal's response to bloggers in May 2009. The Editor's Introduction is worth a mention for the issues it raises about peer review and publication in these modern times.PREPUBLICATION DISSEMINATIONAs soon as I accepted the Vul et al. article, I heard from researchers about it. People around the globe saw the article on the Internet, and replies soon appeared as well. Although my plan was to publish the article with commentary, the appearance of the article on the Internet meant that researchers read the article without the accompanying commentaries and replies that I had planned to publish with it.In some fields such as economics, it is standard practice to widely disseminate articles before they are published, whereas in much of psychology this has been discouraged. An argument in favor of dissemination is that it speeds scientific communication in a fast-paced world where journal publication is often woefully slow. An argument against dissemination of articles before publication is that readers do not have the opportunity to simultaneously see commentary and replies. ... In the Internet age, the issue of prepublication distribution becomes all the more important because an article can reach thousands of readers in a few hours. Given the ability of the Internet to communicate so broadly and quickly, we need greater discussion of this issue.In reply, I wrote:Bloggers have discussed this specific issue months ago. For example, as noted in Mind Hacks,The paper was accepted by a peer-reviewed journal before it was released to the public. The idea that something actually has to appear in print before anyone is allowed to discuss it seems to be a little outdated (in fact, was this ever the case?).And The Neurocritic opined that...[The aggrieved authors] are not keeping up with the way that scientific discourse is evolving. Citing "in press" articles in the normal academic channels is a frequent event; why should bloggers, some of whom are read more widely than the authors' original papers, refrain from such a practice? Is it the "read more widely" part?-from The paper formerly known as "Voodoo Correlations in Social Neuroscience", by The NeurocriticDiener originally solicited six commentaries on the Vul et al. paper for the May 2009 issue of the journal. Ironically, authors on two of the papers have serious blogs:Statistical Modeling, Causal Inference, and Social Science is a blog written by Andrew Gelman, a Professor of Statistics and Political Science at Columbia. He was one of the first to blog about the paper in Suspiciously high correlations in brain imaging studies, with a more detailed post a month later (More on the so-called voodoo correlations in neuroscience). Lindquist and Gelman (2009) applauded the discussion engendered by "pre-publication dissemination":Their article has in a short time given rise to a spirited debate about key statistical issues at the heart of most functional neuroimaging studies. The debate provides a useful opportunity to discuss core statistical issues in neuroimaging and ultimately provides a chance for the field to grow and move forward. [citation needed] is the blog kept by Tal Yarkoni, a Post-Doc at the University of Colorado Boulder. He happens to be an expert in statistics for fMRI analysis, and another one of the authors invited to submit a paper for the Vul, Harris, Winkielman, and Pashler festschrift/verdammung (Yarkoni, 2009):In this article, I argue that Vul et al.'s primary conclusion is correct, but for different reasons than they suggest. I demonstrate that the primary cause of grossly inflated correlations in whole-brain fMRI analyses is not nonindependence, but the pernicious combination of small sample sizes and stringent alpha-correction levels. Far from defusing Vul et al.'s conclusions, the simulations presented suggest that the level of inflation may be even worse than Vul et al.'s empirical analysis would suggest. His blog started in October 2009, after the commentaries were published.The Appeal of the Brain in the Popular PressThat brings us back to the article by Diane Beck, an Assistant Professor in Psychology and Cognitive Neuroscience at the University of Illinois Urbana-Champaign. She examines the distorted media coverage of neuroimaging studies, and possible reasons for it (Beck, 2010):Since the advent of human neuroimaging, and of ... fMRI in particular, the popular press has shown an increasing interest in brain-related findings. In this article, I explore possible reasons behind this interest, including recent data suggesting that people find brain images and neuroscience language more convincing than results that make no reference to the brain (McCabe & Castel, 2008; Weisberg, Keil, Goodstein, Rawson, & Gray, 2008). I suggest that part of the allure of these data are the deceptively simply messages they afford, as well as general, but sometimes misguided, confidence in biological data. In addition to cataloging some misunderstandings by the press and public, I highlight the responsibilities of the research scientist in carefully conveying their work to the general public. While reading through the examples of poor media coverage, imagine the shock of recognition if you were to realize that you have written several trenchant blog posts criticizing these very articles. Yet all this work (and the writings of many others) is rendered invisible to the mainstream of the Association for Psychological Science.Why is blogging so non-existent in these circles? There's a large thriving community of science blogs. Go to ResearchBlogging.org and look under ... Read more »

Beck, D. (2010) The Appeal of the Brain in the Popular Press. Perspectives on Psychological Science, 5(6), 762-766. DOI: 10.1177/1745691610388779

December 15, 2011
12:51 AM
2,879 views

Born This Way?

by The Neurocritic in The Neurocritic

A group of investigators from the University of Iowa have published a case report about a 14 year old boy with severe antisocial behavior (Boes et al., 2011):He is aggressive, manipulative, and callous; features consistent with psychopathy. Other problems include: egocentricity, impulsivity, hyperactivity, lack of empathy, lack of respect for authority, impaired moral judgment, an inability to plan ahead, and poor frustration tolerance.MRI findings revealed a small congenital malformation in his left ventromedial prefrontal cortex (vmPFC), which has been associated with decision making and the regulation of emotional behavior (Grabenhorst & Rolls, 2011; Mitchell, 2011).Figure 1 (Boes et al., 2011). MRI Images. 1A. This is an oblique coronal T2 image at the level immediately anterior to the horn of the lateral ventricles. Note the hyperintense white matter just deep to the gyrus rectus (indicated by arrow) with a linear extension tapering as it courses toward the anterior horn of the ventricle. Also note the cortical thickening of the left gyrus rectus relative to the right gyrus rectus. 1B. This coronal T1 MPRAGE image shows thickening of the left ventromedial prefrontal cortex [PFC] and blurring of the gray-white interface in this same region. 1C. This is a surface rendering of B.W.'s brain viewing the medial left hemisphere surface with thickened cortex highlighted, which approximates the lesion site.The boy (patient B.W.) had MRI scans at the ages of 4, 11, and 13. The three main neuroanatomical findings remained stable across the three scans. Although the abnormalities appear to be relatively minor, the authors described them as consistent with a focal cortical dysplasia affecting portions of Brodmann areas 11, 12, 25, and 32.Did these anatomical anomalies cause B.W.'s aberrant behavior? He reached normal developmental milestones until the age of 4, when he started having seizures. He was prescribed divalproate, an anticonvulsant (and mood stabilizer) which temporarily controlled his seizures. But they returned between the ages of 6-11 yrs, when he started having complex partial seizures every few months. Complex partial seizures are typically associated with an alteration of consciousness and foci in the medial temporal lobes, although they can also originate in the frontal lobes (Williamson et al., 1985). More details of B.W.'s behavior from the case history:At age six B.W.'s parents reported the onset of defiance at home and at school, including: stealing, lying, aggression, rage, rude language, and disobedience. His parents referred to this as his 'contraband' period because he would consistently bring prohibited items to school (e.g. a pocketknife). He also stole cookies and would sell them to peers. The parents were very concerned about this behavior because it did not seem characteristic of B.W.‟s previous temperament. Moreover, neither parent nor any sibling of B.W. had similar behavioral problems. He was seen by a child psychologist and diagnosed with oppositional defiant disorder and started counseling, which was discontinued after a few visits.During ages seven to nine B.W.'s parents describe a 'cause and effect problem' in which he would behave badly and be punished and the following day would engage in the same behavior that led to the punishment. Along with his lack of response toward punishment, B.W. was impulsive and showed a lack of respect toward authority, including teachers and parents. In an effort to provide greater structure and discipline than the school could provide the parents decided to begin home-schooling B.W. and his siblings when he was nine years old... Despite behavioral problems and lack of self-motivation he was noted to be intelligent and academically capable. The following year a child psychiatrist diagnosed B.W. with attention deficit hyperactivity disorder and bipolar disorder, for which he was prescribed carbemazepine, topiramate,1 and dexmethylphenidate [the d-enantiomer of Ritalin]. Counseling was again attempted briefly without effect.At age 11 B.W. presented to the emergency room of a large tertiary care center with his mother for suicidal ideation. While at a nearby shopping mall he expressed feelings of hopelessness, unworthiness, and wanting “to kill myself… I would cut or burn myself.” The talk of suicide had been ongoing for two months and had been accompanied by suicidal gestures such as jumping from a second story deck onto a trampoline and a superficial laceration to the left hand because “I wanted to kill myself.” Along with the suicidal gestures the parents were alarmed about escalating aggression, destructive behavior, wandering off, and hypersexual behavior that included masturbation, accessing porn sites on the web, and asking younger peers to disrobe in a domineering manner (despite being pre-pubescent at the time). During the admission interview he reported that he had been hearing voices at night from God and the devil motivating him to do good and bad things, respectively.When he was hospitalized, B.W. admitted that he was fabricating the psychotic and suicidal symptoms, along with his self-reported levels of high anxiety and depression. Hospital staff found him manipulative and easily angered. He was given the diagnoses of oppositional defiant disorder, ADHD, and mood disorder not otherwise specified. He was no longer considered bipolar. After discharge his antisocial behavior escalated. He started fires, assaulted the principle, resisted arrest, threatened his mother with a knife, and hit his father over the head with a wrench "in cold blood, without any emotion."Neuropsychological testing revealed his IQ and cognitive functioning to be in the average range, although he had problems with planning and with the Iowa Gambling Task, where he could not learn which decks were safe (vs. risky). He was also given a moral judgment task:On his first attempt, B.W. skipped several questions and scribbled over the entire second sheet and drew a goblin. He completed the task at a later date.He eventually tested at a “relatively immature, preconventional, stage of moral development, in which moral dilemmas were approached primarily from the perspective of avoiding negative consequences for one's self.”On the Antisocial Process Screening Device filled out by his parents, his scores were at the 99-100th percentile for callous-unemotional, narcissism, impulsivity, and total score.Recently (summer 2011), B.W. underwent intracranial mapping of the left ventromedial frontal and anterior temporal regions for monitoring of seizure foci, and subsequent surgical resection of left prefrontal and left temporal regions (including the amygdala). Pathological examination of this tissue revealed dysplastic neurons. Post-surgery, B.W. is on lamotrigine and has remained seizure-free.The authors concluded that B.W.’s bad behavior was caused by the vmPFC abnormality for the following reasons:1) The behavioral and neuropsychological profile described in the results section is strikingly consistent with prior cases of focal vmPFC lesions. … The severity of behavioral problems is more extreme than previously reported following vmPFC damage but this may represent an extension of prior reports of more severe outcomes following early-onset lesions... 2) There is a complete absence of externalizing and antisocial behavioral problems in B.W.’s family, suggesting a lower likelihood of a genetic predisposition. … 3) B.W. has exceptionally few social risk factors. He has intelligent, extraordinarily caring ... Read more »

Boes, A., Hornaday Grafft, A., Joshi, C., Chuang, N., Nopoulos, P., & Anderson, S. (2011) Behavioral effects of congenital ventromedial prefrontal cortex malformation. BMC Neurology, 11(1), 151. DOI: 10.1186/1471-2377-11-151

June 24, 2010
05:03 AM
2,209 views

Suffering from the pain of social rejection? Feel better with TYLENOL®

by The Neurocritic in The Neurocritic

It's not just for headaches anymore! The active ingredient in TYLENOL® (acetaminophen, also known as paracetamol) has been shown to ease the pain of social rejection. Wouldn't it be great if you could pop an over-the-counter medication to lessen the hurt of being excluded from that grad student party? Of being ostracized by all your old friends? Even disowned by your family? The journal article, which was promoted by press release six months ago, has finally appeared online (Dewall et al., 2010). An excerpt from the December 2009 press release is below.A Pill for Psychological Pain?. . .“The idea—that a drug designed to alleviate physical pain should reduce the pain of social rejection—seemed simple and straightforward based on what we know about neural overlap between social and physical pain systems. To my surprise, I couldn’t find anyone who had ever tested this idea,” [psychologist C. Nathan] DeWall said.Perhaps because there's no clear mechanistic basis for such an idea? The authors themselves never proposed one either. One might expect that a psychopharmacological experiment with a drug that can cause serious liver damage would be conducted with a specific hypothesis in mind and some basic knowledge about how the drug is thought to work, but we didn't see that here. Granted, that would not be typical fare for Psych Sci. So instead the rationale given by Dewall et al. (2010) is partially linguistic, partially based on a neuroimaging study (Eisenberger et al., 2003):Studies suggest that the similar linguistic descriptions of social and physical pain extend beyond metaphor, and demonstrate overlap in the neurobiological systems underlying physical pain and social pain (DeWall & Baumeister, 2006; Eisenberger, Lieberman, & Williams, 2003; Way, Taylor, & Eisenberger, 2009). In the present experiments, we examined one functional consequence of the hypothesis that social and physical pain rely on shared neurobiological systems—whether acetaminophen, a common physical pain reliever, also reduces social pain. The "shared neurobiological systems" are thought to be located in the dorsal anterior cingulate cortex (ACC), a brain structure that contains discrete regions responsive to physical pain (Kwan et al., 2000). Interestingly, externally applied vs. self-administered thermal pain activate anatomically distinct areas of the ACC (Mohr et al., 2005). Furthermore, it is not at all clear whether the same regions of ACC represent social pain and the affective components of physical pain. In a study designed to dissociate expectancy violations from social rejection, the dorsal ACC was activated when expectations were violated, while ventral ACC (quite distant from the physical pain regions) was activated by social rejection (Somerville et al., 2006).Figure 2 (Somerville et al., 2006). Differential ACC response to expectancy violation and social feedback. (a) A three-dimensional rendering of the medial surface of the brain illustrates a functional dissociation between dorsal (dACC) and ventral (vACC) anterior cingulate. A whole-brain voxel-by-voxel ANOVA was used to identify voxels that showed a significant main effect (P less than 0.001, uncorrected) of expectancy violation (blue) and a main effect of feedback type (yellow). At any rate, participants in the Eisenberger et al. (2003) study took part in a computerized ball-tossing game while being scanned. Initially, two fictitious players included the scanned subject in the game, but then started to exclude him/her. This was the “social exclusion” condition, which was compared to the inclusion condition. But it happens to be the case that this paper was singled out as one of the worst of the "voodoo correlation" violators by Vul and his colleagues [PDF], since it reported a statistically unlikely value based on a non-independent analysis:Eisenberger, Lieberman, and Williams (2003), writing in Science, described a game they created to expose individuals to social rejection in the laboratory. The authors measured the brain activity in 13 individuals at the same time as the actual rejection took place, and later obtained a self-report measure of how much distress the subject had experienced. Distress was correlated at r=.88 with activity in the anterior cingulate cortex (ACC).A correlation of r=.88 between dACC activity and self-reported distress is implausibly high... But I'll stop here, and point to Lieberman, Berkman, and Wager's (2009) reply to Vul et al.That brings us to the present study by Dewall et al. (2010). In Experiment 1, 30 participants (24 women, 6 men) took one 500 mg acetaminophen pill immediately after waking up and another 500 mg an hour before going to sleep (1,000 mg per day for 3 weeks). The other 32 participants (24 women, 8 men) took the same dosing of placebo for 3 weeks. Each evening, subjects filled out the the Hurt Feelings Scale (the "today" version) to report how much social pain they had experienced that day. Despite the fact that the half life of acetaminophen is 4 hours, it took about 10 days for the drug group to report significantly lower hurt feelings than the placebo group. The difference on day 21 was greatest (p The explanation of the time course for these effects was unclear:Acetaminophen has a relatively short half-life, lasting approximately 4 hr, which means that it is unlikely that acetaminophen had a cumulative effect in our experiments. Our finding that acetaminophen reduced hurt feelings over time could be due to a combination of not feeling hurt and having a greater ability to reappraise the rejection experience.In Experiment 2, the dose was upped to 2,000 mg acetaminophen per day for 3 weeks. Instructions were given to refrain from drinking entirely, since alcohol can potentiate liver damage when taken with acetaminophen. In 2009, an FDA panel made a recommendation to lower the maximum daily dose from 4,000 mg (to an unspecified value). The panel also endorsed limiting the maximum single dose of the drug to 650 mg, down from the current 1,000 mg dose (which was given in E... Read more »

Dewall CN, Macdonald G, Webster GD, Masten CL, Baumeister RF, Powell C, Combs D, Schurtz DR, Stillman TF, Tice DM.... (2010) Acetaminophen Reduces Social Pain: Behavioral and Neural Evidence. Psychological science : a journal of the American Psychological Society / APS. PMID: 20548058

Edward Vul, Christine Harris, Piotr Winkielman, . (2009) Voodoo Correlations in Social Neuroscience. Perspectives on Psychological Science.

March 12, 2010
03:35 AM
2,186 views

Friston is Freudian

by The Neurocritic in The Neurocritic

Professor Karl Friston is one of the most prominent (and prolific) researchers in the field of neuroimaging. His contributions to methodological development in functional magnetic resonance imaging (fMRI) are immense:He invented statistical parametric mapping; SPM is an international standard for analysing imaging data and rests on the general linear model and random field theory (developed with Keith Worsley). In 1994, his group developed voxel-based morphometry. VBM detects differences in neuroanatomy and is used clinically and as a surrogate in genetic studies... In 2003, he invented dynamic causal modelling (DCM), which is used to infer the architecture of distributed systems like the brain. Mathematical contributions include variational filtering and dynamic expectation maximization (DEM) for Bayesian model inversion and time-series analysis. Dr Robin Carhart-Harris and Professor Friston have a new article in the Occasional Papers section of the journal Brain that might raise a few eyebrows. Its title? The default-mode, ego-functions and free-energy: a neurobiological account of Freudian ideas. What might cause the raising of eyebrows? Well, Freudian ideas have been largely rejected by mainstream neuroscience, although there have been some notable exceptions (Turnbull & Solms, 2007):Psychoanalysis has had a turbulent and complex relationship with neuropsychology for the century in which the two fields have existed – largely side by side. Some within the neuroscientific community have found much of value in Freudian ideas – Paul Schilder springs to mind as an early example, with Eric Kandel as the most prominent recent advocate (Kandel, 1999). However, for most neuropsychologists, indeed for most scientists, the obvious response to the mention of psychoanalysis has been one of blanket rejection.The renowned sleep and dreaming expert J. Allan Hobson (2007) has been a particularly harsh critic:With respect to dreams, Sigmund Freud was not only not right. He was dead wrong. And so are Turnbull and Solms (2007) in their desperate effort to save Freudian psychoanalysis from the junk heap of speculative philosophy. Neuroscientists, psychologists, and psychiatrists beware: you are being led down the garden path by this pair of misguided neo-Freudians.It is with this stormy background in mind that one should embark on reading the Brain paper. Mercifully, for those lacking the mathematical background to understand even the most rudimentary quantitative formulation of Friston's free-energy principle (2009, 2006), the paper is free of equations. No matter what you think of the final result, it's an intellectual tour de force with 493 quotes from Freud in 70 pages of Supplementary Data. Essentially, the approach is to take a collection of cutting-edge and trendy ideas in neuroscience and map them onto Freud's id and ego. For your convenience, here is a list of the main neuroscientific concepts:Baysian brainDefault Mode NetworkFree EnergyGamma OscillationsPredictionPrediction ErrorTheta OscillationsTop-Down ControlYou might be saddened by the lack of mirror neurons, social cognition, and empathy in the current conceptualization. But it should be all about sex, right? Well, actually, Carhart-Harris and Friston are much more chaste in their mapping of Freudian ideas onto neurobiology and default mode function. The words sex, sexual, sexuality (and any variants) appear zero times in the Brain article, but 18 times in the collection of Freud quotes. The word libido was mentioned 112 times in the Freud quotes but only 4 times by the present authors [excluding reproduction of Freud quotes in the main text].For "accessibility" cathexis was interpreted in a generic (not specifically sexual) sense to mean activation or energy . But according to Freud, mental energy is the id, the psychic energy that powers the mind:Freud defined Libido as the instinct energy or force. Freud later added the Death drive (also contained in the id) as a second source of mental energy.Next time we'll take a closer look at this ambitious synthesis of psychoanalysis and neuroimaging.Arrangement for psychotherapy fMRI studies using the couch of Sigmund Freud. See Psychodynamic Psychotherapy in the Scanner?ReferencesCarhart-Harris, R., & Friston, K. (2010). The default-mode, ego-functions and free-energy: a neurobiological account of Freudian ideas Brain DOI: 10.1093/brain/awq010Friston K. (2009) The free-energy principle: a rough guide to the brain? Trends Cog Sci. 13:293-301. [PDF]Friston K, Kilner J, Harrison L. (2006). A free energy principle for the brain. J Physiol Paris 100:70-87. [PDF]Kandel ER. (1999). Biology and the future of psychoanalysis: A new intellectual framework for psychiatry revisited. Am J Psychiatry 156: 505-524.Hobson JA. (2007). Wake up or dream on? Six questions for Turnbull and Solms. Cortex 43:1113-5; discussion 1116-21.Turnbull OH, Solms M. (2007). Awareness, desire, and fa... Read more »

Carhart-Harris, R., & Friston, K. (2010) The default-mode, ego-functions and free-energy: a neurobiological account of Freudian ideas. Brain. DOI: 10.1093/brain/awq010

October 23, 2010
08:29 PM
2,114 views

Celebrity Neurostigma

by The Neurocritic in The Neurocritic

Celebrity SPECT scan from rehab patientCelebrity Rehab is an American TV reality show on VH1 that exploits the addictions of the rich and C- or D-List famous.“I thought REAL doctors talked to patients in offices behind closed doors.”-Lindsay Lohan [who reportedly turned down six figures to appear 0n the show]Privacy? Confidentiality? Those rights don't apply to the alcoholic and drug-addicted characters who appear on television and other public media outlets as a form of entertainment. How many of you professional psychology and mental health and cog neuro and pharmaceutical types have taken training courses such as the CITI Course in The Protection of Human Research Subjects? All of you?Medical Ethics do not apply to Dr. Drew, the star and chief physician of the Celebrity Addiction franchise:In 2009 [Dr. Drew] Pinsky drew criticism from experts for publicly offering professional opinions of celebrities he has never met or personally examined, based on media accounts, and has also drawn the ire of some of those celebrities.In contradistinction, proper clinicians who make media appearances take great pains to avoid such unethical outbursts. As explained by Dr Petra Boynton:They tried to make me talk about rehab but I said ‘no, no, no’Yesterday I had over 25 emails and phone messages from journalists wanting me to comment on the mental state of several celebrities currently in the press with various drug/relationships problems. And I’ve said no to all of them.At the risk of sounding like a broken record here’s why psychologists (and other experts working with the media) can’t talk about celebrities.If we know the celeb in person (for example as their therapist or healthcare provider) we are breaking their confidence if we speak about them in public. If we do not know them personally we’re simply speculating about them if we were to comment.The same applies to case studies based on people who are not famous.In Season 3 Episode #6, ('Triggers') Dr. Drew takes former NBA star Dennis Rodman to see our favorite neurohuckster, Dr. Daniel G. Amen, for a SPECT scan. Amen claims he can diagnose all sorts of psychiatric and neurological ailments using SPECT (single photon emission computed tomography)1 procedures performed at his clinics.Drew Pinsky exacerbates the unprofessional circus-like atmosphere by making all sorts of unfounded dire predictions about the state of Rodman's brain.Dr. Drew voiceover: It's day 13, and despite nearly 2 weeks of intense treatment, Dennis has rigidly refused to identify as an alcoholic. It's clear to me there's much more going on here. Probably on an organic basis, both in terms of his personality functioning and possibly damage caused by the alcohol itself. I've arranged for Dennis to receive a brain scan to show him objective evidence of what I suspect is going on.Van arrives at the Amen Clinics in Newport Beach, CA and Rodman is placed in the scanner.Cue colorful images of Mr. Rodman's brain appearing on the monitor. All very scientific. Then Dr. Drew introduces him to Dr. Amen.Amen: "So, we did a study called SPECT that looks at how your brain works. And what we see on your scan here, there's some evidence of alcohol damage. When we see this bumpy appearance, I don't like that. I would worry that you could get something like Alzheimer's disease if you don't do a better job of taking care of your brain. Alcoholic dementia is the second most common cause of dementia in the country. The exciting thing is it can be better but without taking good care of it this is going to deteriorate and get worse."Rodman: "Uh... it doesn't matter. All right." (Gets up and leaves).Amen made some rather outrageous statements here. Even though he used the qualifying words something like, there is absolutely no evidence that alcoholism causes the amyloid plaques and neurofibrillary tangles of Alzheimer's disease. In fact, the pathologies are produced by entirely different mechanisms (Aho et al., 2009):In the present study, no statistically significant influence was observed for alcohol consumption on the extent of neuropathological lesions encountered in the three most common degenerative disorders. Our results indicate that alcohol-related dementia differs from VCI [vascular cognitive impairment], AD [Alzheimer's disease], and DLB [dementia with Lewy bodies]; i.e., it has a different etiology and pathogenesis.One meta-analysis even found that heavy drinkers did not have an increased risk of dementia of any kind,2 and regular drinkers had a reduced risk (Anstey et al., 2009).Then brain imaging non-expert Dr. Drew narrates...Dr. Drew voiceover: Dennis's scans were quite dramatic. In addition to there being an unusual pattern of temporal lobe dysfunction, which confirms my feelings about his personality, he also clearly has damage from alcohol.Dr. Drew (to Amen): "It makes me sad thinking about it... if he doesn't change."I see...Where in the temporal lobe did Dr. Drew find the confirmatory evidence of personality disorder? Anterior temporal lobes (semantic memory)? Posterior/inferior temporal regions, such as the fusiform gyrus (high-level vision)? Superior temporal plane (audition)? Region of the left posterior superior temporal gyrus (Wernicke's area for language comprehension)? Area MT/V5 (perception of motion)? The medial temporal lobe memory system? The amygdala and other portions of the limbic system? Yeah, maybe that, but Amen's "bumpy appearance" was located in ventral visual areas.... Read more »

Adinoff, B., & Devous, M. (2010) Scientifically Unfounded Claims in Diagnosing and Treating Patients. American Journal of Psychiatry, 167(5), 598-598. DOI: 10.1176/appi.ajp.2010.10020157

July 2, 2010
08:43 PM
2,105 views

Living and Forgetting

by The Neurocritic in The Neurocritic

And I'll be easyLike living and forgettingAnd if I pick you upI'll be sure to let you down-Living and Forgetting, Glasstown (mp3)Forgetting Emotional Information Is HardOur memory for emotional events is generally better than our memory of neutral events. This is a key issue in developing treatments for post-traumatic stress disorder. How do we rid ourselves of unpleasant memories? In structured laboratory environments, the best way to forget is intentional inhibition during the encoding phase, when exposed to the material for the first time. In other words, engage in a deliberate strategy to forget while the event is actually occurring, as shown in a recent study by Nowicka and colleagues. This process is effortful, and it engages a larger proportion of the brain when the material is emotionally laden (i.e., negative pictures from the International Affective Picture System, or IAPS), relative to when it is neutral (Nowicka et al., 2010).In the study phase, intention to forget and successful forgetting of emotionally negative images were associated with widespread activations extending from the anterior to posterior regions mainly in the right hemisphere, whereas in the case of neutral images, they were associated with just one cluster of activation in the right lingual gyrus [occipital cortex]. Therefore, forgetting of emotional information seems to be a demanding process that strongly activates a distributed neural network in the right hemisphere. In the test phase, in turn, successfully forgotten images—either neutral or emotionally negative—were associated with virtually no activation... These results suggest that intentional inhibition during encoding may be an efficient strategy to cope with emotionally negative memories.However, "directed forgetting" is usually not a practical strategy when real life events are unfolding. Whether it can effectively occur at all during horrible tragedies is highly controversial (e.g., Terr vs. Loftus). The phenomenon is more often studied when applied to the retrieval of traumatic or unwanted memories (Anderson & Levy, 2009; Geraerts & McNally, 2008; Levy & Anderson, 2008), not during the encoding phase.How to ForgetObviously, it’s unethical to expose people to traumatic events for experimental purposes. Instead, the present study used an item-method directed forgetting task in the lab and measured brain activity with fMRI (Nowicka et al., 2010). Twenty-three participants1 viewed a set of images from the IAPS that were either negative or neutral in content. During the initial encoding phase, participants were instructed to either REMEMBER or FORGET each picture by means of a cue that was presented after the item appeared on the screen. Then in the memory test phase, these previously presented pictures were intermixed with new ones, and the subjects were told to indicate whether they recognized them or not, regardless of the task instruction.Trials were sorted according to task instruction (Remember or Forget) and memory outcome (Remembered or Forgotten). Behavioral data showed that the directed forgetting manipulation was successful. Participants remembered fewer pictures in the To-Be-Forgotten (TBF) condition than in the To-Be-Remembered (TBR) condition. The valence manipulation appeared to be successful as well: recognition was better for emotional pictures, especially in the TBF condition. However, the rate of "false alarms" (incorrect responses to new items) was higher for emotional pictures as well (see figure below). This suggests a bit of a response bias: participants were more likely to say "yes I saw it before" for emotional images than for neutral.Figure 1B (modified from Nowicka et al., 2010). Percentage of correctly recognized TBR and TBF images (TBR_R and TBF_R, respectively) and percentage of false alarms for the group of 16 subjects included in the fMRI analyses. Bars represent SD; E, emotionally negative images; N, neutral images.When corrected for false alarm rate, it appears that recognition accuracy was actually lower for the To-Be-Forgotten emotional pictures, meaning they were easier to forget [unless I'm missing something here]. Hmm.On to the fMRI data. The major analysis was done in relation to the FORGET vs. REMEMBER cue. Was there differential activity when trying to forget an emotional picture compared to a neutral picture? Figure 2A shows the answer: yes, there was greater activity in the bilateral occipital cortex and elsewhere in the right hemisphere for emotional pictures, with only a small occipital focus of activation for the neutral ones.Figure 2 (modified from Nowicka et al., 2010). The study phase. (A) Effect of memory instruction: intention to forget contrasted with intention to remember (F instruction R instruction for all trials). Significant group activations are superimposed on a normalized single subject's T1 image.This indeed suggests that the intention to forget an emotional image (such as a car crash or mutilated body) is more effortful for the brain than trying to forget a neutral landscape scene. During the memory test, however, it didn't matter if you forgot the picture on purpose or by accident -- the neural response to forgotten items was identical to the response produced by entirely new images. Nary a trace [at least as a change in BOLD signal]. Have other investigators found this as well? What does it all mean?In conclusion, the findings of this item-method directed forgetting fMRI study reveal that forgetting of emotional information is supported by a widely distributed neural network, indicating more effort than forgetting of neutral information. These differences were observed in the study phase but not the test phase, which suggests that the directed forgetting effect is mainly based on inhibition at the encoding level rather than at retrieval (but see: Ullsperger et al. 2000; ... Read more »

Nowicka, A., Marchewka, A., Jednorog, K., Tacikowski, P., & Brechmann, A. (2010) Forgetting of Emotional Information Is Hard: An fMRI Study of Directed Forgetting. Cerebral Cortex. DOI: 10.1093/cercor/bhq117

April 29, 2011
08:44 AM
2,100 views

Mental Imagery and the Right Parietal Lobe in OCD

by The Neurocritic in The Neurocritic

Obsessive compulsive disorder (OCD) is a mental illness characterized by unwanted and intrusive thoughts, feelings, or ideas (obsessions), and ritualized behaviors (compulsions) the individual feels driven to perform in order to alleviate the disturbing nature of the obsessions. It is a major anxiety disorder classified in Axis I of the DSM-IV, which can be disabling to those who suffer with it.The specific symptoms of OCD can include fear of contamination (from germs and physical contact with others) and resultant pathological cleaning rituals, fear of causing catastrophic harm to others, disturbing "impure thoughts" often of a sexual nature, and compulsive ordering, organization, and checking.Currently, major treatments for OCD include cognitive behavior therapy (CBT), considered to be......the most effective type of psychotherapy for this disorder. The patient is exposed many times to a situation that triggers the obsessive thoughts, and learns gradually to tolerate the anxiety and resist the urge to perform the compulsion. Medication and CBT together are considered to be better than either treatment alone at reducing symptoms.The most frequently prescribed drugs are the SSRI (selective serotonin reuptake inhibitor) antidepressants such as:Citalopram (Celexa)Fluoxetine (Prozac)Fluvoxamine (Luvox)Paroxetine (Paxil)Sertraline (Zoloft)Neuroanatomical circuit models of the underlying brain dysfunction have implicated fronto-striatal loops that control thoughts and actions. For example, OCD has been associated with overactivity in the orbitofrontal cortex (Menzies et al., 2008), overactive error monitoring processes in the anterior cingulate cortex (Fitzgerald et al., 2005), and reduced activation in dorsal prefrontal-striatal regions during planning (van den Heuvel et al., 2005) and task switching (Gu et al., 2008). In summary, OCD has been conceptualized as an impulse control disorder marked by a breakdown of high-level executive control over behavior.However, a new study by Koçak et al. (2011) has expanded the range of cognitive processes and brain regions that might be implicated in OCD. The authors proposed that since OCD patients are quite impaired at suppressing complex thoughts and intrusive images, they might also show deficits in suppressing very simple, neutral images and shapes.Participants in their fMRI experiment were 12 patients with OCD [eight were cleaners, three were checkers (one of the checkers also had contamination obsessions), and one had harming obsessions] and 12 age-matched controls. The tasks performed in the scanner involved forming a visual mental image of a geometric shape and then manipulating this visual image. Three of the tasks involved cognitive control over visual imagery (imagination, suppression, and erasing) and two were baseline tasks (free imagination, resting). Before the scanning session, participants studied the shape until they were able to draw it from memory.Fig. 1. (Koçak et al., 2011). The shape shown to the participants. The arrow (which did not appear on the paper used in the study) indicates the starting point of the erasing task. The participants were instructed to begin erasing the shape at the point indicated by the arrow and to continue until the shape completely disappeared.The instructions given to the participants for these tasks were as follows: 1. Imagination task: imagine the shape on the paper continuously until another command is given; 2. Suppression task: imagine the paper with the shape on it immediately after the command is given, and then immediately suppress the image of the shape (try to see the paper as blank) until another command is given; 3. Erasing task: imagine the paper with the shape on it, and then erase the shape by tracing its outline it until another command is given; 4. Free-imagination task; imagine whatever comes to mind and change it with any other intrusive image – a type of free-association task of mental images (this task was used as the baseline condition task); 5. Resting condition: rest while in the scanner.Since the tasks involved imagery alone and no overt responding, the only measures of performance were the participants' subjective evaluation of how well they were able to continually perform each task during the 25 sec blocks. The OCD group claimed they performed the suppression task better than controls, but we have no external way to validate this finding.Turning to the neuroimaging results, the major contrasts were the three active imagery tasks, each compared to the free-imagination baseline task. The group comparison across the three active tasks (which did not differ from each other) is shown below.Fig 3 (Koçak et al., 2011). The whole-brain result depicting significant activations related to the main effect of group (control > than OCD). Threshold at P < 0.05 (corrected for the whole brain). L: left; R: right; A: anterior; P: posterior; SFG: superior frontal gyrus; IPL: inferior parietal lobe; PCC: posterior cingulate cortex.Individuals with OCD showed less activation than controls in three regions in the right hemisphere: the superior frontal gyrus,1 the inferior parietal lobe, and the posterior cingulate cortex [part of the default mode network]. The right IPL is very important for visuospatial processing (Verden et al., 2010); OCD patients can exhibit visuospatial impairments. Furthermore, activations in both IPL and PCC have been observed in prior studies of visual imagery (Ganis et al., 2004). If the participants with OCD were less adept at imagining, manipulating and suppressing a geometric shape, perhaps this reflects a deficit in imagery that is much more basic than controlling the contents of thought.Although these results are very preliminary, the idea that obsessive thoughts could be associated with problems in the right parieta... Read more »

Koçak, O., Özpolat, A., Atbaşoğlu, C., & Çiçek, M. (2011) Cognitive control of a simple mental image in patients with obsessive–compulsive disorder. Brain and Cognition. DOI: 10.1016/j.bandc.2011.03.020

April 9, 2011
02:36 AM
2,061 views

Liberals Are Conflicted and Conservatives Are Afraid

by The Neurocritic in The Neurocritic

This sums up the basic conclusion of a new study on political orientation and brain structure by Ryota Kanai, Tom Feilden, Colin Firth and Geraint Rees in the journal Current Biology. Yes, that Colin Firth...Colin Firth's Speech during the 2011 Academy Awards. Firth won Best Actor for The King's Speech.Why are Colin Firth and Tom Feilden, both listed with BBC Radio 4 affiliations, authors on this paper? Let's go back to Tuesday, 28 December 2010 and two pieces that appeared on the BBC website.Politics: Brain or background?Science correspondent Tom Feilden: "What started out as a bit of fun has turned into quite a significant piece of science."Scientific research commissioned by this programme on behalf of our guest editor, Colin Firth, has shown a strong correlation between the structure of a person's brain and their political views. You can also listen to a brief audio clip of Feilden discussing the study at the link above. Firth actually commissioned Professor Geraint Rees at University College London to obtain structural MRI scans from two diametrically opposed politicians: conservative MP Alan Duncan (a member of the Conservative Party) and liberal MP Stephen Pound (a member of the Labour Party).Feilden then asks a question that is unanswerable from studying brain structure in adults: "Are political beliefs learnt, the product of experiences in our environment, or 'hard wired' in the brain?" Since a comparison of n=1 liberal versus n=1 conservative is not scientifically valid, Rees went back to a database of MRI scans from UCL students and asked these participants about their political beliefs. Feilden then discussed the results before the paper had been formally submitted for publication [according to the journal website, the paper was received by Current Biology on 11 January, 2011]. Briefly, he said that the gray matter of the anterior cingulate cortex was thicker among the liberal or left wing participants while the amygdala was much larger in those who identified as conservative or right wing."But is it cause and effect?" asks an interviewer. Rightfully so. Correlation does not equal causation. Then there's the claim that the structural brain variation means the political differences are "hard wired". The observed anatomical differences mean no such thing. Any experience will change the brain in some way, and repeated patterns of behavior, whether it's learning to juggle or voting conservative due to a certain set of core beliefs, can alter the brain. Nonetheless, we have the following headlineAre political beliefs hard-wired?Tom Feilden| 08:10 UK time, Tuesday, 28 December 2010"Give me the child until he's seven and I'll give you the man."It's clear from their motto that the Jesuits are firmly in the acquired camp when it comes to whether our political beliefs and values are learned or hard wired from birth: the product of experience rather than genetics.But is that true? ...along with the eventual admission:Although the results do show that political belief is reflected in the physical structure of the brain it's not clear which comes first. Whether the structure of the brain shapes political belief or political belief leads to the differential development of brain structure.All right, that was a media stunt, you say -- but how about the peer reviewed paper (Kanai et al., 2011)?A total of 90 healthy middle-class to upper-class participants (mean age = 23.5 yrs) underwent MRI scanning and [later?] filled out a very brief questionnaire on their political views:Participants were asked to indicate their political orientation on a five-point scale of very liberal (1), liberal (2), middle-of-the-road (3), conservative (4), and very conservative (5). ... Because none of the participants reported the scale corresponding to very conservative, the analyses were conducted using the scales of 1, 2, 3, and 4.If I'm not mistaken, no special effort was made to recruit very conservative participants, because the study was conceived after the MRIs were obtained.As reported by Feilden, being liberal was associated with a larger anterior cingulate whereas being conservative was associated with a larger right amygdala1 (see Figure 1 below).Figure 1 (Kanai et al., 2011). Individual Differences in Political Attitudes and Brain Structure. (A) Regions of the anterior cingulate where gray matter volume showed a correlation with political attitudes are shown overlaid on a T1-weighted MRI... A statistical threshold of p < 0.05, corrected for multiple comparisons, is used for display purposes. The correlation (left) between political attitudes and gray matter volume (right) averaged across the region of interest (error bars represent 1 standard error of the mean, and the displayed correlation and p values refer to the statistical parametric map presented on the right) is shown. (B) The right amygdala also showed a significant negative correlation between political attitudes and gray matter volume. Display conventions and warnings about overinterpreting the correlational plot (left) are identical to those for (A).The results were based on measurements of gray matter density in these two specific structures. How were they chosen? First, the anterior cingulate was selected based on the finding of Amodio et al. (2007) that......the amplitude of event-related potentials reflecting neural activity associated with conflict monitoring in the anterior cingulate cortex (ACC) is greater for liberals compared to conservatives. Thus, stronger liberalism is associated with increased sensitivity to cues for altering a habitual response pattern and with brain activity in anterior cingulate cortex.I had issues with this interpretation of the Amodio et al. study in 2007, which I will summarize here. One problem was attributing the observed results to political viewpoint and not to other factors. The study used EEG recordings, specifically event-related potentials. The ERP brain waves reflect electrophysiological activity recorded remotely from the scalp. While it's great for determining the temporal parameters of neural activity, it's not so great at determining where the activity is located in the brain.One brain wave of inter... Read more »

Ryota Kanai, Tom Feilden, Colin Firth, Geraint Rees. (2011) Political Orientations Are Correlated with Brain Structure in Young Adults. Current Biology. info:/10.1016/j.cub.2011.03.017

April 11, 2010
10:27 PM
2,057 views

"Sleeping Beauty Paraphilia" and Body Image Disturbance After Brain Injury

by The Neurocritic in The Neurocritic

Brain injuries caused by strokes, tumors or head trauma can, on occasion, result in Unusual Changes in Sexuality, as discussed in an earlier blog post. A new case report by Bianchi-Demicheli et al. (2010) describes a unique paraphilia1 in a married 34 year old man. The authors called it Sleeping Beauty paraphilia:This [man] felt sexually aroused from seeing sleeping women as well as from taking care of their hands and nails while they were asleep.The patient came to the attention of the authors when he was brought to the emergency psychiatric unit after assaulting his wife with pepper spray while wearing a latex mask.2 More details of the case are as follows:His marriage had been in crisis for several years because over the time the patient developed a particular and progressive sexual deviant behaviour. He felt sexually aroused from seeing sleeping women as well as from taking care of their hands and nails while they were asleep, beginning mostly with the right hand. In the first time of his marriage he could control these fantasies, but over the years he lost the control of his sexual urges and he must irresistibly act his deviant behaviour. In order to realize his uncontrollable impulse, he was used to provide his wife sleeping pills to satisfy his paraphilia. In the first time his wife used to agree to take sleeping pills, but later she refused to bend to man’s freakish will. The man began secretly to administer benzodiazepines since the dosage of 23 mg of Bromazepam.In September 2006, his wife discovered this practice and refused to take sleeping pills and the couple entered in a very strong conflict.The assault occurred because the woman refused to comply with her husband's "freakish will":Because of the extremely powerful obsession with sleeping women and painting their nails, the patient disguised himself with a latex mask an attacked his wife, as she returned from work, with an Olerosin Capsicum (OC) spray, to anaesthetize her. During this episode, his wife succeeded in taking off his mask, escaped and called the police who brought him to the psychiatric emergencies.The psychiatric exam and laboratory tests all came out as normal. The patient reported no family history of mental illness. However, he sustained a head injury at the age of 10 which resulted in a four day coma.3 He was given a neurological exam, including an MRI, which showed "moderate atrophy in the fronto-parietal region with a diffuse and severe white matter injury compatible with his previous head trauma (Figure 1)." I don't know that I would characterize the white matter damage as severe, but then again I'm not a neuroradiologist.Figure 1 (Bianchi-Demicheli et al., 2010). On the T2 images (A–C) one notes atrophy in the parietal and frontal lobes as well as subcortical lesions in the frontal white matter (arrows B,C); FLAIR also shows multiple subcortical white matter lesions (arrows: D); DTI [dffusion tensor imaging] demonstrates a decrease of the fractional anisotropy in the areas seen on the right (E: arrow) and on the left (F: arrow).Bianchi-Demicheli et al. (2010) linked the fronto-parietal damage to behavioral disinhibition and a specific disturbance in body image, which was revealed by neuropsychological testing:The patient was diagnosed with a moderate dysexecutive syndrome and a very specific body image disorder characterized by an incomplete mental image of his hands, mostly the right (i.e., personal representational hemineglect), as ascertained by his graphical representation of his body parts.The clinical hypothesis was that the paraphilia might be related to his post-traumatic disturbed body image and more specifically to the incomplete hands representation.One puzzling aspect of this case is why the "Sleeping beauty paraphilia" became uncontrollable only in adulthood, showing a progressive escalation during his marriage. This might be suggestive of a neurodegenerative disorder, but that was not part of his diagnosis. And I'm not sure why an old traumatic brain injury would have lead to "moderate" atrophy in the fronto-parietal region. I might have expected more involvement of the orbitofrontal cortex (e.g. Burns & Swerdlow, 2003), given the nature of the patient's behavioral changes. However, many other examples of impulsive sexual offenses (Langevin, 2006) are even less obviously related to neurological status (e.g. after head injuries when the damage might not be visible on an MRI scan, and of course the population of offenders who have never sustained a TBI). Since the lesions were distributed and not focal, a final mystery is why the body image disturbance was confined to the right hand (implying a left hemisphere origin). This type of personal representational hemineglect (neglect for a mental representation of one side of the body) is most often associated with lesions in the right hemisphere (Ortigue et al., 2006).A final comment concerns the sort of urges or behaviors that are categorized as paraphilias. What is considered acceptable can vary widely across cultures and subcultures (Bhugra et al., 2010) and across individuals. If the patient of Bianchi-Demicheli et al. found a partner willing to have her fingernails done while sedated with sleeping pills, perhaps the classification would change from paraphilic disorder (see Footnote 1 below) to something that might be considered strange and paraphilic to most people, but causing no distress to the two willing participants.Footnotes1 According to DSM-IV, paraphilias are defined as recurrent, and intense sexual urges, fantasies, or behaviors that involve unusual objects, activities, or situations and cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. Changes in this set of diagnoses are being discussed for the new DSM-5 (currently under development):The Paraphilias Subworkgroup is proposing two broad changes that affect all or several of the paraphilia diagnoses, in addition to various amendments to specific diagnoses. The first broad change follows from our consensus that paraphilias are not ipso facto psychiatric disorders. We are proposing that the DSM-V make a distinction between paraphilias and paraphilic disorders. A paraphilia by itself would not automatically justify or require psychiatric intervention. A paraphilic disorder is a paraphilia that causes distress or impairment to the individual or harm to others. One would ascertain a paraphilia (according to the nature of the urges, fantasies, or behaviors) but diagnose a paraphilic disorder (on the basis of distress and impairment). In this conception, having a paraphilia would be a necessary but not a sufficient condition for having a paraphilic disorder. 2 No mention of whether or not it was a Prince Charming mask.3 The authors did not speculate too much on the Freudian im... Read more »

Bianchi-Demicheli F, Rollini C, Lovblad K, & Ortigue S. (2010) "Sleeping Beauty paraphilia": deviant desire in the context of bodily self-image disturbance in a patient with a fronto-parietal traumatic brain injury. Medical science monitor : international medical journal of experimental and clinical research, 16(2). PMID: 20110923

July 19, 2010
07:57 AM
2,037 views

Tales of Passion and Disgust

by The Neurocritic in The Neurocritic

Robert Mapplethorpe - St. SebastianThe previous post (Pleasure or Pain?) described the visual stimuli and behavioral results (subjective emotional ratings) from an experiment examining brain activity in response to pictures from four categories: neutral, disgust-inducing, erotic, and sadomasochistic (Stark et al., 2005). The participants were 24 adults, 12 of whom identified as having sadomasochistic sexual preferences (SM) and 12 without (non-SM).Some of the results were of no surprise to anyone. The emotion ratings for neutral and disgust-inducing stimuli did not differ between the two groups. As expected, however, ratings for the other two stimulus classes were divergent:The erotic pictures revealed more positive affect, more arousal, and more sexual arousal for the nonSM group in comparison to the SM group. SM subjects indicated to have felt more positive, more dominant, less disgusted, and more sexually aroused during the presentation of the pictures with sadomasochistic content than the nonSM subjects.Why conduct this study in the first place, you ask? One reason given by the authors is to examine the neural correlates of two motivational systems, the approach and withdrawal systems (Cacioppo & Gardner, 1999). The withdrawal (or avoidance) system is triggered by threats in the environment, including those inducing fear and disgust, while the approach (or appetitive) system promotes feeding, sexual activity, and social behavior. Everyone in Stark et al.'s experiment wanted to avoid rotting hamburgers, but only the non-SM participants wanted to avoid sadomasochistic images. Thus, the same exact stimulus class induced different approach and avoidance responses in two groups of people with divergent sexual preferences.I would add that a broader societal function of such a study might be to educate and to reduce stigma. A greater understanding of people different from ourselves makes for a more accepting and tolerant populace.What about the possibility of viewing similar images in different contexts? A painting of St. Sebastian in a cathedral vs. Mapplethorpe's Sebastian in a retrospective at the Whitney? A flogging scene from The Passion of the Christ vs. a flogging scene in a dungeon? Interestingly, some of the most fervent supporters of the former are the most rabid critics of the latter (Frank Rich provides examples in The Good News About Mel Gibson).Disgust and MoralityThis brings us back to the possible evolutionary basis of disgust. Since this emotion is a response to things that are physically distasteful or morally repugnant, disgust has been examined in a specific evolutionary framework: "from oral to moral" (Rozin et al., 2009) -- from the rejection of bitter tastes to being grossed out by bugs to being repelled by certain social groups or sexual acts (Haidt & Hersh, 2001). Are there identical brain systems underlying these emotional responses? To answer this question, the most important comparison is the one between sadomasochistic and disgust-inducing images in the non-SM group.Several T-contrasts were calculated for each subject: the emotional conditions versus the neutral condition (Disgust Neutral, Erotic Neutral, Sm Neutral), and for the positive emotion versus negative emotion (Erotic Disgust, Sm Disgust, Sm Erotic).For each of the six contrasts above, there were two within-group comparisons and one between-group comparison for 20 regions of interest (ROIs), which were selected from a meta-analysis on neuroimaging studies of emotion (Phan et al., 2002). Exploratory analyses were performed as well. That's an awful lot of comparisons! [requiring stringent correction, of course]. The power to detect differences was reduced further by small group sizes (n=12 for each), rather diverse subject groups, and the use of stimuli that weren't terribly potent at eliciting some of the desired effects. Compare the relatively tame images used here (no explicit presentation of the genitals) to the 3 minute porn films of Zhang et al. (see Erotic or Disgusting?).With all these caveats in mind, what were the results? For the Disgust vs. Neutral comparison, there were no significant differences between the groups, which matches their behavioral ratings. For Erotic vs. Neutral, there was greater activation for non-SM participants in the ventral striatum (known as a reward-related area), the hypothalamus, (controls many metabolic and endocrine functions) and the thalamus (a sensory and motor "relay station"). Ratings for the erotic pictures were similar in the two groups for dominance and disgust but higher in valence, arousal, and sexual arousal for the non-SM group. For Sm vs. Neutral, the SM group showed extensive activations in a number of frontal, temporal, and subcortical regions, including (most bizarrely) the insula, which has been associated with disgust. The only significant between-group difference, however, was in the ventral striatum. And the non-SM group didn't seem to activate any "disgust-related" regions, perhaps because many of them weren't actually disgusted by those images -- rated only 4.25 on a 9-point scale (1=very low and 9=very high). The variability was large, though, which prevented a statistically significant difference between Sm and disgust-inducing pictures (the latter rated 6.67 on disgust).I think this level of variability in disgust reactions to the Sm images compromises the all-important Sm Disgust contrast in the non-SM group. But for what it's worth, right anterior cingulate showed greater activation to disgust pictures, whereas left posterior cingulate showed greater activation to sadomasochistic pictures. In the SM participants, the same contrast revealed greater activity in frontal, temporal/occipital, and subcortical structures (ventral striatum, thalamus, and brainstem). The between-group comparison again demonstrated the obvious: Sm pictures were more rewarding for the SM participants than for their non-SM counterparts.I'm not sure how to interpret the cingulate findings, so I'll let the authors speak for themselves... Oh, wait, they didn't say anything about that, either. Ultimately, this study needed more potent sti... Read more »

STARK, R., SCHIENLE, A., GIROD, C., WALTER, B., KIRSCH, P., BLECKER, C., OTT, U., SCHAFER, A., SAMMER, G., & ZIMMERMANN, M. (2005) Erotic and disgust-inducing pictures—Differences in the hemodynamic responses of the brain. Biological Psychology, 70(1), 19-29. DOI: 10.1016/j.biopsycho.2004.11.014

May 8, 2010
06:53 PM
2,030 views

Motivating a Cumulative Cognitive Neuroscience

by The Neurocritic in The Neurocritic

Why are large-scale structured databases and meta-analyses important to advance the field of human brain mapping? One reason is that individual functional magnetic resonance imaging (fMRI) studies can be notoriously unreliable and underpowered (Bennett & Miller, 2010; Fliessbach et al., 2010; Kriegeskorte et al., 2009; Vul et al., 2009). At the recent CNS 2010 Annual Meeting, symposium organizer Dr. Tal Yarkoni gave the first talk in a session on the value of a cumulative cognitive neuroscience.---------------Symposium Session 1Sunday, April 18, 10:00 am - 12:00 pm, Westmount et al BallroomTowards a cumulative science of human brain function. . .Talk 1: Motivating a cumulative cognitive neuroscienceTal Yarkoni; Columbia University and University of Colorado at BoulderThousands of functional neuroimaging studies are published every year. Only a small fraction of these studies explicitly attempt a formal synthesis of previous findings. In this talk, I argue for an increased emphasis on cumulative approaches to the study of brain function that aim to synthesize and distill the results of previous studies. Three different motives for such an approach are discussed, including (a) the need to distinguish real findings from false alarms; (b) the desire to organize both cognitive tasks and brain activations into coherent ontologies; and (c) the high likelihood that many fMRI studies are underpowered and consequently produce distorted results. I focus primarily on the last of these points, using simulations and empirical analyses to demonstrate that the results of many individual fMRI studies are likely to appear considerably stronger and more selective than they actually are. I conclude by arguing that these limitations are difficult or impossible to overcome in individual studies, necessitating a stronger focus on consensus building at the disciplinary level.---------------What are the motivations for consensus building? Here are four major reasons:The value of a cumulative scienceMake the literature manageableDistinguish true positives from false positivesDevelop overarching frameworksMinimize the effects of low powerYarkoni's talk focused on the last point. The problem with most individual fMRI studies is a lack of statistical power. Yarkoni (2009) argued that:the primary cause of grossly inflated correlations in whole-brain fMRI analyses is not nonindependence, but the pernicious combination of small sample sizes and stringent alpha-correction levels. Far from defusing Vul et al.'s conclusions [from their notorious 2009 paper], the simulations presented suggest that the level of inflation may be even worse than Vul et al.'s empirical analysis would suggest. Fig. 2 (Yarkoni, 2009). Inflation of significant r values as a function of sample size (x axis) and population effect size (lines). Each point represents the result of 10,000 simulated correlation tests, each conducted at a threshold of p Simply put, small n's result in massively inflated brain-behavior correlations. What can be done about this problem? Include more participants in your studies! And make use of the tools that were described by the subsequent speakers (Van Essen, Wager, Poldrack) for synthesis of mega-databases.For more information, the slides from Tal's talk are available online (PDF).ReferencesBennett CM, Miller MB. (2010). How reliable are the results from functional magnetic resonance imaging? Ann NY Acad Sci. 1191:133-55.Fliessbach K, Rohe T, Linder NS, Trautner P, Elger CE, Weber B. (2010). Retest reliability of reward-related BOLD signals. Neuroimage 50:1168-76.Kriegeskorte N, Simmons WK, Bellgowan PS, Baker CI. (2009). Circular analysis in systems neuroscience: the dangers of double dipping. Nat Neurosci. 12:535-40.Vul E, Harris C, Winkielman P, Pashler H (2009). Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition. Perspectives on Psychological Science 4:274-290.Yarkoni, T. (2009). Big Correlations in Little Studies: Inflated fMRI Correlations Reflect Low Statistical Power-Commentary on Vul et al. (2009). Perspectives on Psychological Science, 4 (3), 294-298. DOI: 10.1111/j.1745-6924.2009.01127.x
... Read more »

Yarkoni, T. (2009) Big Correlations in Little Studies: Inflated fMRI Correlations Reflect Low Statistical Power-Commentary on Vul et al. (2009). Perspectives on Psychological Science, 4(3), 294-298. DOI: 10.1111/j.1745-6924.2009.01127.x

May 19, 2010
05:35 AM
2,018 views

Towards a Focal Consensus in Cognitive Neuroscience: Databases and Meta-Analyses

by The Neurocritic in The Neurocritic

Moving right along with our timely, fast-paced, cutting edge blog coverage from the CNS 2010 Annual Meeting [held last month], the first symposium urged the field to advance beyond the current piecemeal single-study approach to neuroimaging by moving Towards a cumulative science of human brain function.1 Building comprehensive, structured, and searchable databases (Van Essen, 2009) and using meta-analytic tools (Wager et al., 2009) were proposed to be key methods aimed at achieving this goal.In his talk, prolific neuroanatomist Dr. David Van Essen (of primate visual cortex wiring diagram fame)2 discussed SumsDB (Surface Management System Database), "a repository of brain-mapping data (surfaces & volumes; structural & functional data) from many laboratories."---------------Talk 2: Lost in Localization – But Found with Foci!David Van Essen; Washington University in St. LouisMore than 50,000 studies related to functional imaging of the human brain have been published in recent decades. Of these, more than 10,000 report key experimental data (centers of fMRI activation foci, etc.) in tables of stereotaxic coordinates (‘foci’) in one or another standardized atlas space. To aid in mining this extensive literature, we developed the SumsDB database, which supports storage, visualization, and searching of many types of neuroimaging data. SumsDB includes a Foci Library that currently contains 40,000 foci from ~1,400 published studies. This includes comprehensive coverage of five major journals and almost 15% of the relevant literature. Foci searches can be based on many criteria (e.g., cortical area or region, spatial coordinates, functional criteria, or disease condition). Search results can be viewed online (WebCaret) or downloaded for offline visualization and analysis using Caret sofware. As the Foci Library continues to expand, through contributions from curators and volunteers alike, it will become increasingly valuable as a way to efficiently access the burgeoning neuroimaging literature.---------------Van Essen emphasized the importance of maintaining a central repository of neuroimaging foci, the 3D localization of peak activations in x, y, z coordinates (Fox et al., 1985). He and his lab have established SumsDB, which currently contains 50,000 foci from 1,700 studies, a relatively small fraction of the literature (see figure below).Fig. 1 (Derrfuss & Mar, 2009). Total number of published fMRI studies reporting coordinates by year and number of studies included in current coordinate databases. One impediment to having more complete coverage of the literature is how labor intensive it is to add new articles to the database (30-60 min per paper after 5-10 hr training), as lamented by Derrfuss and Mar (2009) in their Comments and Controversies article in NeuroImage. Because of the effort involved, many in the neuroimaging community haven't been particularly motivated to participate in the project. In in his reply (2009) to Derrfuss and Mar, Van Essen listed the benefits of voluntary data entry duties:submitting foci from publications of your own lab will increase their visibility, through data mining initiated in SumsDB or NIF [Neuroscience Information Framework];submitting relevant studies from your research subfield will facilitate cross-study comparisons and promote broader awareness of research in that area;individual contributors are recognized by ‘provenance’ assignments for each study (or version) entered into SumsDB.SumsDB libraries can also be used to store foci and study collections for ongoing projects that are not yet published. (Data in these libraries are not made public until requested by the submitter and then vetted by a curator in the Van Essen lab to insure conformance to basic metadata description standards.)And what a great classroom project for graduate students and highly motivated undergraduates! (suggested Van Essen, 2009). Greater participation is essential, however. But who wants to do all that work for free?An attractive and feasible model is for one or two individuals (students, postdocs, or knowledgeable technicians) from each of many laboratories to enter data published by their own laboratory plus selected topics related to that lab's research interests. For example, if 50 volunteers each added ~20 studies per year (15–30 h per volunteer, including training), the current rate of submission would approximately double, and about half of the relevant literature would be covered in ~5 years.But even more appealing, a semi-automated data entry system for SumsDB is under development...What does one do with all that data? In the next talk, Dr. Tor Wager discussed meta-analysis, a statistical technique for summarizing quantitative research. Why is it important to combine results across multiple studies (Wager et al. 2007)?Meta-analysis is an increasingly popular and valuable tool for summarizing results across many neuroimaging studies. It can be used to establish consensus on the locations of functional regions, test hypotheses developed from patient and animal studies and develop new hypotheses on structure–function correspondence. It is particularly valuable in neuroimaging because most studies do not adequately correct for multiple comparisons; based on statistical thresholds used, we estimate that roughly 10–20% of reported activations in published studies are false positives. The 'Quick-Search' function in SumsDB can be used to retrieve foci of interest from all papers in the database. For example, one can search by anatomical area (Fig. 1B) or by research topic (Fig. 1C). Searches can also be performed by task, function, disorder, etc.Adapted from Fig. 1 (Van Essen, 2009). ... Read more »

Van Essen, D. (2009) Lost in localization — But found with foci?!. NeuroImage, 48(1), 14-17. DOI: 10.1016/j.neuroimage.2009.05.050

Wager, T., Lindquist, M., Nichols, T., Kober, H., & Van Snellenberg, J. (2009) Evaluating the consistency and specificity of neuroimaging data using meta-analysis. NeuroImage, 45(1). DOI: 10.1016/j.neuroimage.2008.10.061

August 7, 2010
11:14 PM
2,011 views

Bad News for the Genetics of Personality

by The Neurocritic in The Neurocritic

CREDIT: RYAN SNOOK (from Holden, 2008).The latest search for genetic variants that underlie differences in personality traits has drawn a blank (Verweij et al., 2010). The researchers conducted a genome-wide association study using personality ratings from Cloninger's temperament scales in a population of 5,117 Australian individuals:Participants' scores on Harm Avoidance, Novelty Seeking, Reward Dependence, and Persistence were tested for association with 1,252,387 genetic markers. We also performed gene-based association tests and biological pathway analyses. No genetic variants that significantly contribute to personality variation were identified, while our sample provides over 90% power to detect variants that explain only 1% of the trait variance. This indicates that individual common genetic variants of this size or greater do not contribute to personality trait variation, which has important implications regarding the genetic architecture of personality and the evolutionary mechanisms by which heritable variation is maintained.But it's still fun and popular for some science writers to assert that personality traits are "hard wired" into our brains, like there's really A Brain Circuit for Bungee Jumping? [thanks for the exciting new info, ScienceNOW.] In reality, some of the major early findings in personality genetics, such as an association between Novelty Seeking and the Dopamine D4 Receptor gene (Benjamin et al., 1996; Ebstein et al., 1996), have failed to replicate (Gelernter et al., 1997; Paterson et al. 1999; Strobel et al., 2002). Fortunately, others writers have pointed out the increasingly obvious difficulties of this endeavor, as did Constance Holden in Parsing the Genetics of Behavior:For some of us, it's satisfying to attribute social awkwardness to anxiety genes or to think that the driver who cuts off other cars as he zips across lanes is pumped up by the "warrior" gene. Was it a bad dopamine receptor gene that made author Ernest Hemingway prone to depression? Can variations in a vasopressin receptor gene--a key to monogamy in voles--help explain adulterous behavior? But as scientists are discovering, nailing down the genes that underlie our unique personalities has proven exceedingly difficult. That genes strongly influence how we act is beyond question. Several decades of twin, family, and adoption studies have demonstrated that roughly half of the variation in most behavioral traits can be chalked up to genetics. But identifying the causal chain in single-gene disorders such as Huntington's disease is child's play compared with the challenges of tracking genes contributing to, say, verbal fluency, outgoingness, or spiritual leanings. In fact, says Wendy Johnson, a psychologist at the University of Edinburgh, U.K., understanding genetic mechanisms for personality traits "is one of the biggest mysteries facing the behavioral sciences."Nonetheless, unscrupulous businesses like My Gene Profile (which offers the "Inborn Talent Genetic Test" for the low low price of $1,397) have capitalized on the public's desire for simple explanations. Now you can find out whether your child has the Split Personality Gene! The Propensity for Teenage Romance Gene! The Self Detoxifying Gene!Returning to the current study, the authors cast a genome-wide net to find genetic variants related to the four dimensions of temperament identified by Cloninger in his Temperament and Character Inventory (TCI), a 240 item self-report questionnaire. As described by Verweij et al., (2010):Novelty Seeking reflects the tendency to respond strongly to novelty and cues for reward as well as relief from punishment, and is thought to play a role in the activation or initiation of behaviours. Harm Avoidance reflects the tendency to respond strongly to aversive stimuli, which leads to learned inhibition of behaviour, and is thought to play a role in the inhibition or ceasing of behaviours. Reward Dependence reflects the tendency to react strongly to rewards and to maintain behaviours previously associated with reward or relief of punishment, and is thought to play a role in the maintenance or continuation of behaviour. Persistence reflects the tendency to persevere despite frustration and fatigue.The participants completed a short form of Cloninger's (1986) original Tridimensional Personality Questionnaire (TPQ).1 The fourth dimension of temperament -- Persistence -- was constructed using a small subset of the Reward Dependence questions. The 1986 version of Cloninger's biosocial theory of personality associated Novelty Seeking with low dopamine activity, Harm Avoidance with high serotonin activity, and Reward Dependence with low noradrenaline activity. These were thought to be independent and heritable aspects of personality that influence responses to reward, punishment, and novelty. The TPQ was later revised to include Persistence and also three character dimensions (Self-Directedness, Cooperativeness, and Self-Transcendence) to form the basis of the TCI (Cloninger et al., 1993).Cloninger's theory of personality is not without its critics. In 2008, Farmer and Goldberg challenged the psychometric validity of the TCI in a target article and in a wonderfully titled reply to Cloninger. A trenchant quote from the latter (Farmer & Goldberg, 2008) is below:Overall, several core theoretical assumptions and predictions associated with the psychobiological model and TCI-R assessment are either non-falsifiable, in conflict with each other, or not supported by empirical evidence. So the question arises, are we dealing with a flawed set of personality constructs to begin with? No matter. The scales are widely used, so we'll go on.For genotyping, single nucleotide polymorphisms (SNPs) across the entire genome were tested for association with each of the four traits. The Illumina and Affymetrix platforms were used. [Those technical and statistical methods are beyond the scope of this blog, so I will leave it to someone else to describe and critique the genotyping aspects of the paper.] Stated succinctly, the results showed that:No SNPs reached genome wide significance (α = 7.2*10-8) and the SNP with the lowest p-value for each personality scale explains less than 0.5% of the total variance.None of the previously identified candidate genes (e.g., serotonin receptor gene, D4 receptor gene) were close to showing a significant relationship with any trait, nor were any of the SNPs with the lowest p val... Read more »

Verweij, K., Zietsch, B., Medland, S., Gordon, S., Benyamin, B., Nyholt, D., McEvoy, B., Sullivan, P., Heath, A., & Madden, P. (2010) A genome-wide association study of Cloninger's Temperament scales: Implications for the evolutionary genetics of personality. Biological Psychology. DOI: 10.1016/j.biopsycho.2010.07.018

January 28, 2011
07:23 PM
1,837 views

White Matter Differences in Pre-Op Transsexuals Should NOT be the Basis for Childhood Interventions

by The Neurocritic in The Neurocritic

Diagram showing principal systems of association fibers in the human brain. The superior longitudinal fasciculus (SLF) is labeled at the center top (marked by purple arrows).New Scientist covered two journal articles by Rametti and colleagues (2010, 2011), a group of Spanish researchers and clinicians affiliated with Unidad Trastorno Identidad de Género [Gender Identity Disorder Unit]. Using the diffusion tensor imaging (DTI) method, they initially wanted to identify any sex differences in the white mater of the brains of non-transgendered male and female heterosexuals. Then the next step was a prediction that FTM (Female-to-Male) transsexuals would be more like males, while MTF (Male-to-Female) transsexuals would be more like females.Transsexual differences caught on brain scan12:16 26 January 2011 by Jessica HamzelouDifferences in the brain's white matter that clash with a person's genetic sex may hold the key to identifying transsexual people before puberty. Doctors could use this information to make a case for delaying puberty to improve the success of a sex change later.In 5 years of writing this blog, I have come across a multitude of news stories and press releases that make outrageous claims. Here's another one to add to the list. On the basis of two highly variable DTI studies in 36 pre-operative, pre-hormone treatment transgender individuals, now we're supposed to screen children for gender variant behavior and scan them at a young age, so their hormones can be altered before puberty?Returning to the structural imaging experiments, were there any hypotheses at the outset, or were these completely exploratory studies? The authors cite the work of Zhou et al. (1995) on postmortem staining of the bed nucleus of the stria terminalis (BST). This subcortical nucleus connects the amygdala to the septal nuclei, hypothalamus, and thalamus. BST has been shown to play a role in the sexual behavior of male rats. The size of this nucleus in MTF brains was similar to that in female controls, both being smaller than male controls.However, it's not possible to visualize the BST in living humans, so the authors went with DTI to look for cortical white matter changes. The participants in the first study were 18 FTM transgendered persons (before undergoing hormonal treatment), along with 24 male and 19 female heterosexual controls. The major findings in terms of sex differences between groups were located mainly in 3 fiber tracts:anterior and posterior parts of the right superior longitudinal fasciculus - contains connections between the frontal, parietal, occipital, and temporal lobes including language-related areas (Mori et al., 2008).forceps minor (anterior forceps) - fiber bundle connecting the lateral and medial surfaces of the frontal lobes, crossing the midline via the genu of the corpus callosum.corticospinal tract - connects the cerebral cortex and the spinal cord, contains mostly motor axons.In all 3 tracts, males showed higher fractional anisotropy (FA) than females. FA is a measure of local tissue properties including density, coherence, diameter, and myelination.Fig. 1 (Rametti et al., 2010). Sex differences in fractional anisotropy (FA). FA is lower in female than in male controls in the superior longitudinal fasciculus with a posterior (A) and anterior (B) predominance. Control females also show lower than control male FA values in the forceps minor (C) and the corticospinal tract (D). The group skeleton used for the between group contrast study is green. The red color shows the clusters of significantly decreased FA in female compared to male controls. The threshold for significance was set at p < 0.05 corrected for multiple comparisons.FTM individuals showed greater FA values in all 3 tracts than did the control females. They were similar to control males for anterior and posterior SLF and forceps minor, and in between control male and female FA values for the corticospinal tract.What does this mean? Basically, at this point, it's like reading tea leaves. We have no indication of other potential differences between the groups in cognitive, emotional, personality, or motor measures, in alcohol use, or in other psychiatric diagnoses. We do know that testosterone levels of the FTM participants were like those of control females, because they had yet to undergo hormone treatment.Moving right along to the second experiment, which compared MTF individuals to controls (Rametti et al., 2011)... The participants were 18 untreated MTF transsexuals (mean age = 25 yrs), 19 female (mean = 33 yrs) and 19 male controls (mean age = 32 yrs). Yes, the MTF individuals were significantly younger than controls [the human frontal lobe in particular is known to continue maturation processes into the 20's]. Procedures were similar to those used previously. Results in this study showed a greater number of differences in the white matter of male vs. female controls (again, with larger FA values for males): left and the right SLFforceps minorright inferior front-occipital fasciculus (IFOF)corticospinal tract left cingulumSo what's new in this list? Left SLF, Right IFOF, Left cingulum. This finding indicates that individual differences were observed between two groups of male and female control subjects [or else there were unreported methodological differences]. If normal sex differences in DTI studies include IFOF and cingulum here but not there, that presents a problem for comparison to the transgendered populations.Nonetheless, what did that comparison show? The MTF individuals showed FA values between those of male and female controls for all tracts (except for IFOF, where they did not differ from males).Fig. 2 (Rametti et al., 2011). Histograms showing the FA... Read more »

Rametti, G., Carrillo, B., Gómez-Gil, E., Junque, C., Segovia, S., Gomez, �., & Guillamon, A. (2011) White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. Journal of Psychiatric Research, 45(2), 199-204. DOI: 10.1016/j.jpsychires.2010.05.006

Rametti, G., Carrillo, B., Gómez-Gil, E., Junque, C., Zubiarre-Elorza, L., Segovia, S., Gomez, �., & Guillamon, A. (2010) The microstructure of white matter in male to female transsexuals before cross-sex hormonal treatment. A DTI study. Journal of Psychiatric Research. DOI: 10.1016/j.jpsychires.2010.11.007

September 6, 2008
10:32 PM
1,295 views

Pain & Paintings: Beholding Beauty Reduces Pain Perception and Laser Evoked Potentials

by The Neurocritic in The Neurocritic

-Marcel Duchamp, Nude Descending a Staircase, No. 2Neuroesthetics, a term coined by Semir Zeki, is "the attempt to use neuroscience to understand art and aesthetic behaviour" (as defined in an excellent overview by BRAINETHICS). Some would say the venture is anathema, that reductionistic explanations of the sublime are misguided at best and destructive at worst. Others hold that since all qualia emanate from the brain, a neuroscientific approach is the only true way to understand aesthetic experience.Here's an early manifesto on neuroesthetics and visual art:Credo (manifesto of physiological facts)All visual art must obey the laws of the visual system.The first law is that an image of the visual world is not impressed upon the retina, but assembled together in the visual cortex. Consequently, many of the visual phenomena traditionally attributed to the eye actually occur in the cortex. Among these is visual motion.The second law is that of the functional specialization of the visual cortex, by which we mean that separate attributes of the visual scene are processed in geographically separate parts of the visual cortex, before being combined to give a unified and coherent picture of the visual world.The third law is that the attributes that are separated, and separately processed, in the cerebral cortex are those which have primacy in vision. These are colour, form, motion and, possibly, depth. It follows that motion is an autonomous visual attribute, separately processed and therefore capable of being separately compromised after brain lesions. It is also one of the visual attributes that have primacy, just like form or colour or depth.We conclude that it is this separate visual attribute which those involved in kinetic art have tried to exploit, instinctively and physiologically, from which it follows that in their explorations artists are unknowingly exploring the organization of the visual brain though with techniques unique to them.-S. Zeki and M. Lamb (1994), The Neurology of Kinetic Art (PDF).The above passage serves as background to an exploration of how visual art can literally affect our bodies. A new paper by Tommaso et al. (2008) used the methods of neuroesthetics to examine whether the act of viewing beautiful art (as individually defined by each participant) would reduce the perception of pain as well as its physiological manifestations.An earlier paper by Kawabata and Zeki (2004) studied the neural correlates of beauty. Prior to getting scanned,each subject viewed 300 paintings for each painting category that were reproductions viewed on a computer monitor. Each painting was given a score, on a scale from 1 to 10. Scores of 1–4 were classified as "ugly," 5–6 "neutral," and 7–10 "beautiful." Each subject thus arrived at an independent assessment of beautiful, ugly, and neutral paintings. Paintings classified as beautiful by some were classified as ugly by others and vice versa with the consequence that any individual painting did not necessarily belong in the same category for different subjects. Based on these psychophysical tests, a total of 16 stimuli in each category (abstract, still life, landscape, or portrait) were viewed by subjects in the scanner... However, in the ugly and beautiful categories, only paintings classified as 1–2 and 9–10, respectively, were viewed in the scanner, whereas for paintings classified as neutral, paintings belonging to both categories 5 and 6 were viewed. In the scanner, the participants performed the same aesthetic rating task. Paintings rated as beautiful were associated with greater activity in the medial orbitofrontal cortex (when compared to ugly or neutral paintings). Additional activations were observed in anterior cingulate cortex and left parietal cortex for the beautiful vs. neutral contrast.Adapted from Fig. 3 (Kawabata & Zeki, 2004). Statistical parametric maps rendered onto a standard brain showing judgment-specific activity in comparisons of (A) beautiful vs. ugly, and (B) beautiful vs. neutral. (A) shows medial orbito-frontal cortex only (Talairach coordinates –2, 36, –22). (B) medial orbito-frontal cortex (–2, 50, –20), anterior cingulate gyrus (–4, 48, 14) and left parietal cortex (–54, –68, 26). In their study on beauty and pain, Tammaso and colleagues used the aesthetic rating methods of Kawabata and Zeki (2004) to classify the set of paintings for each participant. Several days after the rating task, the 12 subjects participated in an EEG experiment. Brain waves were recorded while they not only viewed the paintings, but also while a laser delivered unpleasantly hot stimuli to their hands.Cutaneous heat stimuli were delivered on the dorsum of the left hand. ... The location of impact on the skin was adjusted slightly between two successive stimuli to avoid nociceptor sensitization and fatigue. A laser (7.5 W) was used in each case, with a duration of 25 ms. The subjects were requested to rate the quality of sensation (pain rating: PR) after each series of stimuli on a visual analogue scale (VAS) where 0 indicated no pain in white, increasing in a gradual scale of reds to 100, which indicated the worst possible pain.So the subjects rated their level of pain on a visual analogue scale while looking at the various paintings and getting fried with a laser. Presentation of the painful stimuli evoked a specific type of EEG response, called laser evoked potentials (LEPs). A sequence of three LEPs were recorded in rapid succession, within the first 400 milliseconds after laser stimulation. These responses are called the N1, N2 and P2 potentials.The first LEP component commonly identified is the N1, a negativity that is seen in temporal EEG-leads at about 150 ms following the laser stimulus (or later, depending on the type of laser). Its generator has been localized in the operculo–insular cortex, and this component has been demonstrated to be involved in focussed attention or spatial discrimination. The second is a large positive-negative complex named N2–P2 with its maximum amplitude at the vertex, generating from the posterior zone of the anterior cingulate cortex and expressing the variations in arousal and emotive reaction against pain.Remarkably, the P2 potential was smaller when participants were viewing beautiful paintings, and their subjective pain ratings were lower than in the other conditions (baseline, neutral, ugly). The figure below shows LEPs from electrodes placed on the scalp over frontal, central, and parietal midline regions, and over the right temporal lobe.Fig. 3 (Tommaso et al., 2008). Grand average of LEPs obtained by stimulation of the left hand in the different experimental phases. The Fz, Cz, Pz and contralateral temporal (T4) recordings are shown. Compared with the baseline condition, the amplitude of the vertex N2–P2 component is smaller while viewing beautiful pictures. No changes were observed in the middle-latency N1 amplitude throughout the experiment.The authors concluded thataesthetic perception can affect subjective sensation and pain-related cortical responses. It is generally accepted that distraction produces analgesia (Johnson, 2005). The present study revealed that there is a different effect of distraction on pain depending on the type of distracting stimulus used. The vision of beautiful images seemed to have the maximum distractive effect from pain, as is shown by the lower subjective pain rating and the inhibition of pain-related evoked responses. Beauty is not only in the eye of the beholder, it modulates pain-related activity in the anterior cingulate cortex.1Footnote1 Although the activity of the ACC was increased in the beautiful vs. neutral contrast of Kawabata and Zeki but reduced by beauty during painful laser stimulation, the precise regions might be different in the two studies.ReferencesKawabata H, Zeki S. (2004 ). Neural correlates of beauty. J Neurophysiol. 91:1699-705.M TOMMASO, M SARDARO, P LIVREA (2008). Aesthetic value of paintings affects pain thresholds. Consciousness and Cognition DOI: 10.1016/j.concog.2008.07.002Zeki S, Lamb M. (1994). The neurology of kinetic art. Brain 117:607-36.... Read more »

M TOMMASO, M SARDARO, & P LIVREA. (2008) Aesthetic value of paintings affects pain thresholds☆. Consciousness and Cognition. DOI: 10.1016/j.concog.2008.07.002

August 25, 2008
04:08 AM
1,240 views

Borderline … feels like I'm goin' to lose my mind

by The Neurocritic in The Neurocritic

No, the 80s Madonna song isn't really about Borderline Personality Disorder. But a new study in Science (King-Casas et al., 2008) makes me feel like I'm goin' to lose my mind. Or more precisely, makes me exhibit two of nine DSM-IV-TR criteria:6. Affective instability due to a marked reactivity of mood (e.g., intense episodic dysphoria, irritability, or anxiety usually lasting a few hours and only rarely more than a few days). 8. Inappropriate anger or difficulty controlling anger (e.g., frequent displays of temper, constant anger, recurrent physical fights, getting mad over something small).All right all right, a stigmatizing label is no laughing matter.Roth and Fonagy (1996) defined BPD thusly:The essential feature of this disorder is a pervasive pattern of instability of self-image, interpersonal relationships and mood. The person’s sense of identity is profoundly uncertain. Interpersonal relationships are unstable and intense, fluctuating between the extremes of idealisation and devaluation. There is often a terror of being alone, with great efforts made to avoid real or imagined abandonment. Affect is extremely unstable, with marked shifts from baseline mood to depression and anxiety usually lasting a few hours. Inappropriate anger and impulsive behaviour are common, and often this behaviour is self-harming. Suicidal threats and self-mutilation are common in more severe forms of this disorder.So it's a very serious personality disorder. However, the diagnostic label is a controversial one, coming under fire from feminists (Shaw & Proctor, 2005) and from my favorite psychiatry blog, Shrink Rap. Here's why Dinah doesn't like the label:Over The Border Line...I'm going to talk about why I hate the term, why I rarely place it in writing, why I wish it would go away.. . . [read the nine diagnostic criteria for BORDERLINE PERSONALITY DISORDER at Wikipedia] I mean, okay, these symptoms cluster in some people, so why don't I like them? Here goes, with no particular rhyme or reason:The diagnosis (unlike, say, Trichotillomania or Major Depression) is pejorative. Clinicians are sloppy with the diagnosis and it's not uncommon for a doc to refer to a patient as "a borderline" as a defense--- the patient is difficult to deal with, he's angry or demanding--it's gotta be him, not the doc.It's what clinicians label patients they don't like.Actually, men are almost never called "borderline"....they get to be narcissistic or antisocial.Treatment-wise, many docs avoid these patients and hope runs dry quickly. The prognostic implications are generally not great, these patient don't have rapid and dramatic improvements.The diagnosis ends up being it's own endpoint, it doesn't leave room for alternate explanations and sometimes patients with Bipolar Disorder look a lot like patients with borderline personality disorder. Oh, while I'm there, patients with Borderline Personality Disorder often have co-morbid Bipolar Disorder (and hey, how about some substance abuse issues thrown in) and if the clinician can get focused on treating the Mood Disorder, sometimes the other noise fades into the background.It doesn't seem to me that every patient who has these symptoms has them forever in an inflexible way. They come, they go, they change, they get better, they get worse.With all those caveats in mind, let's look at the lucky 08/08/08 Science paper entitled "The Rupture and Repair of Cooperation in Borderline Personality Disorder." It examines how well individuals with BPD play along with others in an economic exchange game (see also King-Casas et al., 2005, the first of their three Science papers on the topic).The key participants were 38 controls and 55 people with BPD.1 The vast majority of these participants were female (37 controls, 51 BPD). The two groups were also matched for age and verbal IQ. Each person was paired with another individual (all controls) to play the game, to form a total of 93 dyads.Who can you trust?Distrust of others is a cardinal feature of BPD. A history of childhood abuse and neglect is very common in this disorder -- leading to an early rupture of trust that is not easily repaired. A recent paper by Bhar, Brown, and Beck (2008) examined the factor structure of the Personality Beliefs Questionnaire (BPD subscale) and found three major factors: dependency, distrust, and the belief in acting preemptively to avoid threat. All three factors were associated with depression. Dependency and distrust were associated with hopelessness. Distrust, however, was the only factor that was significantly correlated with suicidal ideation.Thus, assessing trust in BPD patients is a worthwhile endeavor. King-Casas et al. (2008) measured it using the trust game (reviewed in Camerer, 2003).How does the "trust" game work? (see Read Montague give a brief explanation in Real Player). One player (the Investor) gives a sum of money to the other player (the Trustee). The investment triples, and the Trustee decides how much to give back to the Investor.You can also read The Neurocritic's previous post on The Trust Game, which discussed the paper by Tomlin, Kayali, King-Casas, et al. (2006).2I give the authors credit for developing the nifty "hyperscanning" methodology, which involves two subjects who interact with each other while their brains are scanned simultaneously (in adjoining or distant magnets). The task is illustrated below. Brain images are taken at three critical "reveal" points:The comparison groups in the current experiment played the Trustee role in 10 rounds of the game. The results indicated that in the early rounds, Investors gave BPD and control Trustees similar amounts of money. In the latter 5 rounds of the game, however, there was a decline in the investments given to BPD Trustees but not to control Trustees, because the former weren't as generous with their returns overall. Specifically, the BPD subjects were less likely to use a "coaxing" strategy:Healthy trustees are twice as likely as BPD trustees to coax when cooperation between players is low. Specifically, healthy trustees are more likely to make a large repayment (greater than or equal to investment amount) after having received a small investment (less than or equal to $5). Conversely, BPD trustees are more likely to make a small repayment (less than the investment amount) after receiving a small investment.In general, players do not always behave rationally. To maintain higher investments in later rounds, however, coaxing is a beneficial strategy for the Trustee. Maybe levels of the natural "trust drug" oxytocin are low in BPD (ask Paul Zak, or read this PDF), or maybe they just aren't as good at mental arithmetic. Perhaps the BPD propensity to punish low investments could be viewed as analogous to what is seen in the Ultimatum Game (Sanfey et al., 2003) where players reject unfair offers (to their own detriment).So why do I feel like I'm goin' to lose my mind?3 As suggested by a colleague, the present paper 1) makes liberal use of reverse inference and 2) reeks of fishing.4 In my view, the real trouble arises when the authors try to explain what bits of the brain might be implicated in the lack of trust shown by players with BPD. It's the insula! [and only the insula]. Why is that problematic? We shall return to that question in a moment.In the study of Sanfey et al., unfair offers were associated with greater activity in bilateral anterior insula, dorsolateral prefrontal cortex, and anterior cingulate cortex, with the degree of insular activity related to the stinginess of the offer. A similar relationship was observed here in the controls, but not in the BPD patients. Taking a step back for a moment, we see differences between control and BPD participants (for the contrast low vs. high investment) in quite a number of places, as illustrated in the table below.Table S3 (King-Casas et al., 2008). General linear model of Trustee brain regions with greater response to the revelation of small investments (less than or equal to $5) relative to large investments (greater than $10) in healthy Trustees relative to Trustees with BPD. (p less than .05, FDR corrected; min 5 voxels)However, the within-group analysis in controls yielded a "small investment" effect only in bilateral anterior insula (12 voxels and 15 voxels, respectively, at p less than .10). The same analysis in the BPD group yielded absolutely no significant differences anywhere in the brain! BPD participants react to small stingy investments with differential behavior (by returning a very low percentage of the investment), yet there is no area in the brain telling them to do this. Perhaps something is going on in the delay period between the investment and repayment phases, but if so we don't find out. The authors' interpretation of the null brain effect is that BPD subjects have a social perception problem (as Montague explains here), and do not respond correctly to social norm violations.The association of the insula with a representation of outcome variance suggests that the insula may encode the distribution of likely outcomes in social interactions; that is, responses in the anterior insula may indicate social norm violations within interpersonal contexts.When dishing out small returns in the repayment phase, both control and BPD groups show the inverse correlation between insular activity and monetary amount. ...in BPD, the apparent insensitivity of the insula only to offer level size, and not their own repayment, suggests two possibilities: (i) Monetary reward is not reinforcing to individuals with BPD; or, (ii) low offers are not perceived to be a violation of social norms to individuals with BPD. They rule out the first possibility and go with the second.But what about the role of dorsal striatum (King-Casas et al., 2005) and ventral tegmental area (Krueger et al., 2007) in the development of trust, or the importance of medial prefrontal cortex and theory of mind [see Mentalizing Mentalizing ]? We do not find out about these, either. Guess we'll have to wait for the next Science paper.Finally, there's the wildly overblown quotes on the significance of the findings in the popular press:Mind games reveal people who are 'blind' to trustThe finding ... could give psychiatrists a better diagnostic tool and a brain area to target with therapy or drugs when treating BDP, says project leader Read Montague, a neuroscientist at Baylor College of Medicine in Houston.And this quote, which heralds the dawn of a golden new age of psychiatry:Peter Bossaerts, a neuroeconomist at Caltech in Pasadena, says that since the games are scored and have a predicted outcome, they may help diagnose mental illnesses."This could really revolutionise the way people think about and treat psychiatric illnesses," he says.Who can you trust?Footnotes1 Why those particular numbers? We don't know for sure, but it could be due to the fact that supplementary analyses were run with subgroups of the BPD patients to control for income level and medication status.2 Oddly (or not), the present King-Casas paper did not even cite their earlier work (Tomlin et al., 2006). The authors appear to have taken the approach of "one brain region, one Science paper." Today it's the insula, in 2006 it was the anterior cingulate cortex, and in 2005 it was the dorsal striatum. How do these brain regions work together to produce the complex behavior in question? Are the three papers even consistent with each other? These issues are not important, apparently.3 Other than the fact that I am not knowledgeable in behavioral game theory (see Camerer et al., 2003 for that, PDF).4 They also reported significance (corrected using FDR procedures) at the p... Read more »

B King-Casas, C Sharp, L Lomax-Bream, T Lohrenz, P Fonagy, & P Montague. (2008) The Rupture and Repair of Cooperation in Borderline Personality Disorder. Science, 321(5890), 806-810. DOI: 10.1126/science.1156902

March 29, 2009
03:32 AM
1,173 views

One pill makes you larger and one pill makes you small

by The Neurocritic in The Neurocritic

And the ones that mother gives you Don't do anything at all Go ask Alice When she's ten feet tallWhite Rabbit ---Jefferson AirplaneNo, we're not really discussing hallucinogenic drugs today (despite the psychedelic reference). The real question for today is this: Does the wakefulness drug modafinil (Provigil) lessen the weight gain caused by atypical antipsychotics? Not really (Roerig et al., 2009), despite what the Elsevier press release tells us:Combating Weight Gain Caused by Antipsychotic TreatmentsPhiladelphia, PA, March 26, 2009 – Antipsychotic drugs, such as olanzapine (Zyprexa), risperidone (Risperdal), and quetiapine (Seroquel) are commonly used to treat psychotic disorders like schizophrenia, but also bipolar disorder and even behavioral problems related to dementia. Unfortunately, the weight gain commonly experienced with antipsychotic treatment is an important side effect for many patients, and causes many patients to discontinue their use leading to even further problems. Biological Psychiatry, in its April 1st issue, is now publishing a new study that has evaluated an add-on treatment to potentially reduce treatment-associated weight gain.In a randomized, double-blind, placebo-controlled trial, Dr. James Roerig and colleagues evaluated the effect of modafinil on olanzapine-associated weight gain in normal volunteer subjects. Modafinil is a drug currently used to increase wakefulness in individuals with sleep disorders, such as narcolepsy. All of the subjects received olanzapine, and half also received modafinil treatment while the other half instead received placebo. After three weeks, although the body mass index was increased in both groups, those receiving olanzapine/placebo showed significantly greater weight increase than those receiving olanzapine/modafinil.The April 1st issue, hmm... You'll notice the study was conducted in normal volunteer participants and only for a 3 week period. What you didn't see in the press release is that during the 3 week period, 10 of the 50 original subjects withdrew from the trial (2 in modafinil + olanzapine group, and 8 in placebo + olanzapine group).Zyprexa has rightfully received some bad press lately (so has Seroquel, but that story is more colorful). Although olanzapine is quite effective in treating schizophrenia and bipolar mania, it is notorious for causing very large weight gains in those taking it ("you'll gain five pounds just by filling the prescription" or 1.5 pounds per month according to a recent meta-analysis by Parsons et al., 2009). A 1999 article by Allison et al. was even worse: a gain of nearly a pound per week for 10 weeks (4.45 kg total!).1 One mechanism for this might involve increases in ghrelin, a hormone that stimulates appetite (see Brain Health Hacks).Enter modafinil, which has been touted as a cognitive enhancing drug taken by some shifty academics. A recent paper on the Effects of Modafinil on Dopamine and Dopamine Transporters in the Male Human Brain (Volkow et al., 2009) caused some to ask whether modafinil might be addictive. But the answer is that it's probably not, even though it increases the level of dopamine (the "reward" neurotransmitter) by blocking the dopamine transporter. In addition to its effects on dopamine, modafinil also affects the norepinephrine neurotransmitter system, as shown in a technically difficult neuroimaging study (Minzenberg et al., 2008) of the human locus coeruleus, a small nucleus in the brainstem. Also on the plus side for modafinil is its potential usefulness in psychiatric practice: for improving attention and executive control function in schizophrenia (Morein-Zamir et al., 2007), and as an add-on medication in treating bipolar depression (Belmaker, 2007).But the paper of today (Roerig et al., 2009) did none of that, instead enrolling healthy control participants2 and seeing whether modafinil attenuated the olanzapine-induced weight gain. A previous experiment by this group (Roerig et al., 2005) observed a 5 lb. increase over a 2 week period, significantly greater than both risperadone and placebo (Table 2). The number of calories consumed was numerically greater, but did not reach significance.Table 2 (Roerig et al., 2005). Weight Change (in kilograms). Calorie Change (in kilocalories).What about the current study?In the completer analysis, the primary outcome variable, BMI [body mass index] change from baseline, was significantly different between groups with the olanzapine/placebo group experiencing a greater increase in BMI than the olanzapine/modafinil group (.89 + .59 vs. .47 + .50 kg/m2, p... Read more »

Roerig, J., Steffen, K., Mitchell, J., Crosby, R., & Gosnell, B. (2009) An Exploration of the Effect of Modafinil on Olanzapine Associated Weight Gain in Normal Human Subjects. Biological Psychiatry, 65(7), 607-613. DOI: 10.1016/j.biopsych.2008.10.037

November 12, 2008
05:04 AM
1,168 views

Superior Auditory Signal Detection Abilities in Late-Stage Huntington's Disease

by The Neurocritic in The Neurocritic

Figure 1 (Ruocco et al., 2006). Samples of coronal and sagittal magnetic resonance imaging from a patient with Huntington's disease (top row) and a normal control (bottom row) showing the outlines of caudate and putamen (left), cerebral (center) and cerebellar volumes (right).Huntington's disease is an inherited, autosomal dominant, neurodegenerative disorder. Although primarily viewed as a movement disorder characterized by uncontrollable body movements (chorea), there is also a marked decline in cognitive abilities, often accompanied by psychiatric issues as well.

It's a terrible disease that typically onsets in middle age. A heartbreaking New York Times article, Facing Life With a Lethal Gene, follows a 23 year old woman who decides to get tested and finds out she carries the gene. Her grandfather had the disease, meaning that her mother, who did not know her own genetic status, was doomed to develop HD.As stated in this Lancet review article (Walker, 2007),The mutant protein in Huntington’s disease—huntingtin—results from an expanded CAG repeat leading to a polyglutamine strand of variable length at the N-terminus. Evidence suggests that this tail confers a toxic gain of function.The defective protein causes cell death in various brain regions, particularly in the striatum (caudate and putamen), perhaps due to an excitotoxic mechanism (Sánchez et al., 2008). As Beste et al. (2008) explain in their new J Neurosci paper,Excitotoxicity describes cell death that results from the activation of excitatory amino acid receptors. In HD, voltage-dependent NMDA receptors are assumed to be more receptive to endogenous levels of glutamate; thus glutamatergic neurotransmission is increased, leading to excitotoxic cell death. The medium spiny neurons in the striatum are especially affected. Given all this neurodegeneration and the concomitant decline in motor function and cognition, it was surprising to see a paper reporting an enhanced perceptual/cognitive ability. But that's what Beste et al. (2008) observed. In their study, patients with HD, pre-symptomatic carriers, and controls participated in an auditory processing experiment while EEG data were recorded. The task consisted of categorizing the duration of pure tones as either long (400 ms) or short (200 ms). The tones were of different frequencies and different probabilities, but this was irrelevant to the task. This difference in probability, however, results in different patterns of brain waves to the common ("standard") and rare ("deviant") tones. Specifically, the authors looked at the mismatch negativity (MMN) component associated with auditory sensory memory, and the P3a component associated with attention. These waves were derived by averaging together many trials of the task, which produces event-related potentials (ERPs).Behaviorally speaking, the participants with HD were faster and more accurate on the auditory task.Figure 1 (Beste et al., 2008). Behavioral data. A, Mean reaction time (error bars indicate SEM) of the control, the presymptomatic (pHD), and the symptomatic (HD) group for the standard and deviant stimuli. B, Mean error rates (error bars indicate SEM) of the control, the presymptomatic (pHD), and the symptomatic (HD) group for the standard and deviant stimuli.For the ERPs, responses to the standard tones were subtracted from responses to the deviant tones, producing a so-called "difference wave." The MMN can be seen between 100-250 ms after stimulus presentation and the P3a can be seen between 300 and 500 ms post-stimulus. A later wave (the reorienting negativity, or "RON") was seen between 400 and 600 ms.adapted from Figure 2 (Beste et al., 2008). Neurophysiological data (difference waves). For all electrodes shown, the time course from 200 ms before tone onset until 1100 ms beyond tone presentation is given. Red lines denote the ERP time course of the HD group, orange lines of the pHD group, and green lines of the control group. The HD group showed a significant increase in MMN compared to the pHD and control groups. On the other hand, although the P3a looked smaller in HD participants, the difference was not significant. The later RON wave was enhanced in the HD group, however. The authors suggest:The results show that specific cognitive functions, namely auditory sensory memory (reflected by the MMN) and reorientation of attention (reflected by the RON) are not deteriorated and can even be enhanced in late stage HD. Moreover, the results suggest that superiority in these functions emerge primal in the late stage of this disease, because pHDs performed worse. I should point out that on nearly every other neuropsychological test (i.e., word fluency, digit span, Stroop interference, immediate and delayed memory), the subjects with HD were extremely impaired. Then what is the mechanism for the enhancement of auditory abilities?...the specific dependence of the MMN on the corticostriatal NMDA system underlies this dissociation of performance in HD as well as the enhancement and acceleration of the MMN. The NMDA-receptor system has been found to modulate the MMN (Javitt et al., 1996).. . .The observation that the reorientation of attention (reflected by the RON) was also increased in the HD group accords with the enhanced behavioral performance in the relevant task... Although the primary effects of neurodegenerative diseases like HD might be largely confined to certain cell populations in restricted areas of the brain, these changes can affect cognitive and motor systems at multiple levels of the brain. In most cases, the pathological alterations of neural systems result in a deterioration of cognitive functions. However, as shown in the present study, a pathogenic increase in responsiveness of a transmitter system can increase cognitive functions if these functions selectively depend on this neural system, whereas other cognitive functions are deteriorated. What is the clinical relevance of this finding? It's not clear. But the results revealed an unexpected and striking dissociation of cognitive abilities in patients with Huntington's disease.ReferencesC. Beste, C. Saft, O. Gunturkun, M. Falkenstein (2008). Increased Cognitive Functioning in Symptomatic Huntington's Disease As Revealed by Behavioral and Event-Related Potential Indices of Auditory Sensory Memory and Attention. Journal of Neuroscience, 28 (45), 11695-11702 DOI: 10.1523/JNEUROSCI.2659-08.2008Estrada Sánchez AM, Mejía-Toiber J, Massieu L. (2008). Excitotoxic neuronal death and the pathogenesis of Huntington's disease. Arch Med Res. 39:265-76.Javitt DC, Steinschneider M, Schroeder CE, Arezzo JC. (1996). Role of cortical N-methyl-D-aspartate receptors in auditory sensory memory and mismatch negativity generation: Implications for schizophrenia. Proc Natl Acad Sci. 93:11962–11967.H.H. Ruocco, I. Lopes-Cendes, L.M. Li, M. Santos-Silva, F. Cendes. (2006). Striatal and extrastriatal atrophy in Huntington’s disease and its relationship with length of the CAG repeat. Braz J Med Biol Res. 39: 1129-1136.Walker FO. (2007). Huntington's disease. Lancet 369:218-28.... Read more »

C. Beste, C. Saft, O. Gunturkun, & M. Falkenstein. (2008) Increased Cognitive Functioning in Symptomatic Huntington's Disease As Revealed by Behavioral and Event-Related Potential Indices of Auditory Sensory Memory and Attention. Journal of Neuroscience, 28(45), 11695-11702. DOI: 10.1523/JNEUROSCI.2659-08.2008

January 5, 2009
08:49 AM
1,126 views

Voodoo Correlations in Social Neuroscience

by The Neurocritic in The Neurocritic

The end of 2008 brought us the tabloid headline, Scan Scandal Hits Social Neuroscience. As initially reported by Mind Hacks, a new "bombshell of a paper" (Vul et al., 2009) questioned the implausibly high correlations observed in some fMRI studies in Social Neuroscience. A new look at the analytic methods revealed that over half of the sampled papers used faulty techniques to obtain their results.Edward Vul, the first author, deserves a tremendous amount of credit (and a round of applause) for writing and publishing such a critical paper under his own name [unlike all those cowardly pseudonymous bloggers who shall go unnamed here]. He's a graduate student in Nancy Kanwisher's Lab at MIT. Dr. Kanwisher1 is best known for her work on the fusiform face area.Credit (of course) is also due to the other authors of the paper (Christine Harris, Piotr Winkielman, and Harold Pashler), who are at the University of California, San Diego. So without further ado, let us begin.A Puzzle: Remarkably High Correlations in Social NeuroscienceVul et al. start with the observation that the new field of Social Neuroscience (or Social Cognitive Neuroscience) has garnered a great deal of attention and funding in its brief existence. Many high-profile neuroimaging articles have been published in Science, Nature, and Neuron, and have received widespread coverage in the popular press. However, all may not be rosy in paradise:2Eisenberger, Lieberman, and Williams (2003), writing in Science, described a game they created to expose individuals to social rejection in the laboratory. The authors measured the brain activity in 13 individuals at the same time as the actual rejection took place, and later obtained a self-report measure of how much distress the subject had experienced. Distress was correlated at r=.88 with activity in the anterior cingulate cortex (ACC).In another Science paper, Singer et al. (2004) found that the magnitude of differential activation within the ACC and left insula induced by an empathy-related manipulation was correlated between .52 and .72 with two scales of emotional empathy (the Empathic Concern Scale of Davis, and the Balanced Emotional Empathy Scale of Mehrabian).Why is a correlation of r=.88 with 13 subjects considered "remarkably high"? For starters, it exceeds the reliability of the hemodynamic and behavioral (social, emotional, personality) measurements:The problem is this: It is a statistical fact... that the strength of the correlation observed between measures A and B reflects not only the strength of the relationship between the traits underlying A and B), but also the reliability of the measures of A and B.Evidence from the existing literature suggests the test-retest reliability of personality rating scales to be .7-.8 at best, and a reliability no higher than .7 for the BOLD (Blood-Oxygen-Level Dependent) signal. If each of these measures was [impossibly] perfect, then the highest possible correlation would be sqrt(.8 * .7), or .74.This observation prompted the authors to conduct a meta-analysis of the literature. They identified 54 papers that met their criteria for fMRI studies reporting correlations between the BOLD response in a particular brain region and some social/emotional/personality measure. In most cases, the Methods sections did not provide enough detail about the statistical procedures used to obtain these correlations. Therefore, a questionnaire was devised and sent to the corresponding authors of all 54 papers:APPENDIX 1: fMRI Survey Question TextWould you please be so kind as to answer a few very quick questions about the analysis that produced, i.e., the correlations on page XX. We expect this will just take you a minute or two at most.To make this as quick as possible, we have framed these as multiple choice questions and listed the more common analysis procedures as options, but if you did something different, we'd be obliged if you would describe what you actually did.The data plotted reflect the percent signal change or difference in parameter estimates (according to some contrast) of...1. ...the average of a number of voxels.2. ...one peak voxel that was most significant according to some functional measure.3. ...something else?etc.....Thank you very much for giving us this information so that we can describe your study accurately in our review.They received 51 replies. Did these authors suspect the final product could put some of their publications in such a negative light?SpongeBob: What if Squidward’s right? What if the award is a phony? Does this mean my whole body of work is meaningless?After providing a nice overview of fMRI analysis procedures (beginning on page 6 of the preprint), Vul et al. present the results of the survey, and then explain the problems associated with the use of non-independent analysis methods....23 [papers] reported a correlation between behavior and one peak voxel; 29 reported the mean of a number of voxels. ... Of the 45 studies that used functional constraints to choose voxels (either for averaging, or for finding the ‘peak’ voxel), 10 said they used functional measures defined within a given subject, 28 used the across-subject correlation to find voxels, and 7 did something else. All of the studies using functional constraints used the same data to select voxels, and then to measure the correlation. Notably, 54% of the surveyed studies selected voxels based on a correlation with the behavioral individual-differences measure, and then used those same data to compute a correlation within that subset of voxels.Therefore, for these 28 papers, voxels were selected because they correlated highly with the behavioral measure of interest. Using simulations, Vul et al. demonstrate that this glaring "non-independence error" can produce significant correlations out of noise!This analysis distorts the results by selecting noise exhibiting the effect being searched for, and any measures obtained from such a non-independent analysis are biased and untrustworthy (for a formal discussion see Vul & Kanwisher, in press, PDF).And the problem is magnified in correlations that used activity in one peak voxel (out of a grand total of between 40,000 and 500,000 voxels in the entire brain) instead of a cluster of voxels that passed a statistical threshold. Papers that used non-independent analyses were much more likely to report implausibly high correlations, as illustrated in the figure below.Figure 5 (Vul et al., 2009). The histogram of the correlations values from the studies we surveyed, color-coded by whether or not the article used non-independent analyses. Correlations coded in green correspond to those that were achieved with independent analyses, avoiding the bias described in this paper. However, those in red correspond to the 54% of articles surveyed that reported conducting non-independent analyses – these correlation values are certain to be inflated. Entries in orange arise from papers whose authors chose not to respond to our survey.Not so coincidentally, some of these same papers have been flagged (or flogged) in this very blog. The Neurocritic's very first post 2.94 yrs ago, Men are Torturers, Women are Nurturers..., complained about the overblown conclusions and misleading press coverage of a particular paper (Singer et al., 2006), as well as its methodology:And don't get me started on their methodology -- a priori regions of interest (ROIs) for pain-related empathy in fronto-insular cortex and anterior cingulate cortex (like the relationship between those brain regions and "pain-related empathy" are well-established!) -- and on their pink-and-blue color-coded tables!Not necessarily the most sophisticated deconstruction of analytic techniques, but it was the first...and it did question how the regions of interest were selected. And of course how the data were interpreted and presented in the press.SUMMARY from The Neurocritic : Ummm, it's nice they can generalize from 16 male undergrads to the evolution of sex differences that are universally valid in all societies.As you can tell, this one really bothers me...And what are the conclusions of Vul et al.?To sum up, then, we are led to conclude that a disturbingly large, and quite prominent, segment of social neuroscience research is using seriously defective research methods and producing a profusion of numbers that should not be believed.Finally, they call upon the authors to re-analyze their data and correct the scientific record.Footnotes1 Kanwisher was elected to the prestigious National Academy of Sciences in 2005.2 The authors note that the problems are probably not unique to neuroimaging papers in this particular subfield, however.ReferencesEisenberger NI, Lieberman MD, Williams KD. (2003). Does rejection hurt? An FMRI study of social exclusion. Science 302:290-2.Singer T, Seymour B, O'Doherty J, Kaube H, Dolan RJ, Frith CD. (2004). Empathy for pain involves the affective but not sensory components of pain. Science 303:1157-62.Singer T, Seymour B, O'doherty JP, Stephan KE, Dolan RJ, Frith CD. (2006) Empathic neural responses are modulated by the perceived fairness of others. Nature 439:466-9.Edward Vul, Christine Harris, Piotr Winkielman, & Harold Pashler (2009). Voodoo Correlations in Social Neuroscience. Perspectives on Psychological Science, in press. PDFVul E, Kanwisher N. (in press). Begging the question: The non-independence error in fMRI data analysis. To appear in Hanson, S. & Bunzl, M (Eds.), Foundations and Philosophy for Neuroimaging. PDF... Read more »

Edward Vul, Christine Harris, Piotr Winkielman, . (2009) Voodoo Correlations in Social Neuroscience. Perspectives on Psychological Science.

November 27, 2009
04:24 PM
1,111 views

Does "Internet Addiction" Really Shrink Your Brain?

by The Neurocritic in The Neurocritic

Internet addiction is a murky and controversial disorder that is the subject of intense debate over whether it should be included in the new DSM-V. Here are the proposed diagnostic criteria as developed by Dr. Kimberly Young:Do you feel preoccupied with the Internet (think about previous online activity or anticipate next online session)?Do you feel the need to use the Internet with increasing amounts of time in order to achieve satisfaction?Have you repeatedly made unsuccessful efforts to control, cut back, or stop Internet use?Do you feel restless, moody, depressed, or irritable when attempting to cut down or stop Internet use?Do you stay on-line longer than originally intended?Have you jeopardized or risked the loss of significant relationship, job, educational or career opportunity because of the Internet?Have you lied to family members, therapist, or others to conceal the extent of involvement with the Internet?Do you use the Internet as a way of escaping from problems or of relieving a dysphoric mood (e.g., feelings of helplessness, guilt, anxiety, depression)? Answering "yes" to five or more questions may mean you suffer from Internet addiction over a six month period and when not better accounted for by a manic episode.You can rate your own level of addiction by taking the Internet Addiction Test (sponsored by The Center for Internet Addiction, of course).Dr. Young was featured in a recent article, along with Dr. Vaughan Bell (of Mind Hacks fame) taking the contrary position:Internet addiction: New-age diagnosis or symptom of age-old problem?. . .Kimberly Young, director of the online resource The Center for Internet Addiction, says that internet addiction may not yet be clearly defined, but you know it when you see it.. . .Young: “The internet has inherent value and utility, and there are many good things about it, but there is this dark side.”Or is there? Not according to Vaughan Bell, a visiting research fellow with the Department of Clinical Neuroscience, Institute of Psychiatry at King's College London in the United Kingdom. Bell has argued that the internet is not an activity, and therefore internet addiction is a flawed idea (J Ment Health 2007;16[4]:445-57).“Fundamentally, the internet is a medium of communication,” says Bell, who claims that one can no more be addicted to the internet than to radio waves. “The concept itself doesn’t make sense.”Bell acknowledges that some people use the internet and other technologies to excess, but believes they do so to avoid dealing with underlying problems, such as depression or social anxiety disorder, which have well-established treatments.Other prolific bloggers who are noted opponents of the IA diagnosis include Dr. Shock and Dr. John Grohol.1 On the other hand, internet addiction is accepted as a major a problem in several Asian countries, including China and South Korea. Some of you might be familiar with the stories of [alleged] abusive and illegal clinics in China. With this as background, it was inevitable that someone would do a neuroimaging study of individuals with IA, and it was a group in Shanghai that was the first to do so (Zhou et al., 2009).In their study, 18 teenagers (2 females and 16 males, mean age = 17.23 ± 2.6) with IA were compared to 15 age-matched control participants. Structural MRIs were performed and quantified using voxel-based morphometry (VBM):VBM is a neuroimaging analysis technique that allows investigation of focal differences in brain anatomy, using the statistical approach of so-called statistical parametric mapping. ... VBM registers every brain to a template, which gets rid of most of the large differences in brain anatomy among people. Then the brain images are smoothed so that each voxel represents the average of itself and its neighbors. Finally, the image volume is compared across brains at every voxel.The paper was very light on analytic methods and mum on important details about possible co-morbid psychiatric diagnoses in the kids with IA. As noted by Vaughan, depression and social phobia -- along with bipolar disorder, obsessive-compulsive disorder, various addictions, and other impulse control disorders -- could compel one to spend more time on the internet for gambling, gaming, chatting, porn-watching, etc.With all these caveats in mind, the results are shown below....the VBM of the MRI data illustrated that the IA group had lower GMD [gray matter density] in the left anterior cingulate cortex (ACC), left posterior cingulate cortex (PCC), left insula, and left lingulate gyrus. No significant difference was found in the white matter change between the two groups.Fig. 1 (Zhou et al., 2009). Regions of decreased GM shown on the template in the left anterior cingulate cortex (A), left posterior cingulate cortex (B), left insula (C), and left lingual gyrus (D) in IA subjects compared with the controls.Most of the changes look pretty small, so it's hard to know what to make of them. On top of that, some of the regions seem mislabeled (the posterior cingulate in particular looks way off). And the findings only demonstrate correlation, not causation.So in the end we have no idea if "internet addiction" shrinks tiny bits of your brain...Footnote1 Blogging and social media are not addictive at all. Right?ReferenceZhou, Y., Lin, F., Du, Y., Qin, L., Zhao, Z., Xu, J., & Lei, H. (2009). Gray matter abnormalities in Internet addiction: A voxel-based morphometry study. ... Read more »

Zhou, Y., Lin, F., Du, Y., Qin, L., Zhao, Z., Xu, J., & Lei, H. (2009) Gray matter abnormalities in Internet addiction: A voxel-based morphometry study. European Journal of Radiology. DOI: 10.1016/j.ejrad.2009.10.025

< Prev
1
2
3
4
5
6
7
8
9
10
11
12
Next >

login

The Neurocritic

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

Why is this post inappropriate?

search

topics

dates

View

Language

Languages to Display

join us!

News