The Neurocritic

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

The Neurocritic
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  • December 30, 2012
  • 09:15 PM
  • 1,047 views

More Music, More Empathy

by The Neurocritic in The Neurocritic

Fig. 1 (Molnar-Szakacs & Overy, 2006). Model of the possible involvement of the human mirror neuron system in representing meaning and affective responses to music. ... The shared recruitment of this neural mechanism in both the sender and the perceiver of the musical message allows for co-representation and sharing of the musical experience. Music notes from ‘The Lady Sings the Blues’ by Billie Holiday and Herbie Nichols.The previous post examined the relationship between music and empathy, including the emotional connection that can occur between musician and audience. My thoughts on the issue were originally inspired by a quote in the book Rat Girl, a memoir by musician Kristin Hersh:...We'd play what the audience felt and feel it at the same time and they'd feel it reflected back to them in sound and we'd all care about each other's stories and clouds of feeling and ... good luck with that I think miserably through my stage fright, trudging past the knitters, hippies, junkies, drunks, painters and psychos.-Kristin Hersh, Rat Girl, p. 43Molnar-Szakacs and Overy (2006) suggested that these profound human experiences are mediated by activity in the supercharged mirror neuron system (Fig. 1).2 Although the box and arrow model is lacking in explanatory value, the hypothesis raised two questions: (1) Are musicians more empathetic? and (2) Do they engage the mirror neuron system to a greater extent than those without musical training?Are Musicians More Empathetic?Self-absorbed rock star stereotype aside, it would be difficult to determine causality if this were the case. Do more empathetic people choose to take up music (à la the tortured artist), or does musical training make one more empathetic? The best way to address question #1 is to look at those undergoing musical training. One such study reported that a 9 month-long program of musical group interaction (MGI) increased emotional empathy in 8-11 year old children (Rabinowitch et al., 2012). The MGI program consisted of musical "games" that seemed [to me, at least] designed to increase empathy, rather than musical prowess: entrainment games to be as rhythmically coordinated as possible, imitation games to repeat the musical phrases or gestures of the previous participant, and other games that called on the constructs of shared intentionality and intersubjectivity.Along with a passive control group that received no training, an active control group engaged in a verbal storytelling and drama version of group interaction that didn't involve music, singing, or gesture. It's notable that 33% of all children did not play a musical instrument (which included singing), so the study didn't really ask whether musical training per se can make you more empathetic. Nonetheless, there was a p=.054 level interaction of time (pre- vs. post-training) and group (MGI vs. both controls, who did not differ) on the self-report measure of empathy [which might have resulted from a higher pre-training empathy in controls, along with less improvement].Fig. 3 (Rabinowitch et al., 2012). Index of Empathy scores.However, the MGI and control groups improved to an equivalent extent on an emotional face matching task, also designed to measure emotional empathy. While it's probably beneficial for children to engage in these group activities, we do not yet have a positive answer to question #1.Do Musicians Show More Mirror Neuron Activity?This question has a trivial element to it: of course a trained violinist will have a greater understanding of the movements and sounds involved in Beethoven's Violin Concerto in D major, so you'd expect differences in brain activity somewhere to reflect this. There are at least two studies potentially relevant to question #2 (Chapin et al., 2010; Babiloni et al., 2012). In neither case, however, do we need to invoke the existence of the mirror neuron system.In the first, BOLD signal changes in response to two different versions of the same musical piece (Chopin's Etude in E major) were compared in an fMRI study (Chapin et al., 2010). One version was an expressive piano performance with dynamic stimulus fluctuations, and the other was a synthesized "mechanical" version. In addition, the participants had varying levels of musical training: 7 were experienced (mean 9.2 yrs training) and 7 inexperienced (0.7 yrs training), with 7 more thrown out for various reasons. These are very small groups by modern fMRI standards.3Participants rated their emotional arousal and emotional valence while listening to the pieces before and after scanning, but not during the fMRI experiment. The combined arousal and valence ratings were not consistently correlated across the two time points, so making inferences about what the participants were feeling during the experiment is dicey.The fMRI results showed different activation patterns according to the main effects of performance type and musical experience (shown below). Mirror neuron-ish areas (inferior parietal lobule, inferior frontal gyrus but too anterior) showed greater activation for the expressive piece in both groups (A), but these regions didn't differ as a function of musical experience (B).Fig. 4 (Chapin et al., 2010). fMRI ANOVA results. Brain activations (F-maps) showing a significant main effect of a) performance type (F (1,24) > 7.19, corrected p < .02), SCG = subcallosal gyrus, PHG = parahippocampal gyrus, vACC = ventral anterior cingulate, FPC = frontopolor cortex, DMPFC = dorsal medial prefrontal cortex; and b) main effect of musical experience, BG = basal ganglia, vStri = ventral striatum.But there was an interaction between performance type and musical training, with experienced participants showing greater activation for the expressive piece in the too-anterior-for-mirror neurons IFG and the inferior parietal lobe. Importantly, activation in the mirror neuron-ish areas related to tempo changes in the expressive piece did not differ according to musical training:An unexpected finding of this study was that, for all participants, the tempo fluctuations of the expressive performance correlated with dynamic activation changes in brain regions that are consistent with the human mirror neuron system, including bilateral BA 44/45, superior temporal sulcus, ventral PMC, and inferior parietal cortex, along with other motor-related areas and with insula.Thus, ... Read more »

  • December 26, 2012
  • 11:56 PM
  • 857 views

Music and Empathy

by The Neurocritic in The Neurocritic

I've been reading the book Rat Girl, a memoir by musician Kristin Hersh, who started the band Throwing Muses in 1980, at the age of 14 (along with Tanya Donelly, Leslie Langston, and David Narcizo). The book recounts an eventful year in her life (1985-86) when, among other things, she is diagnosed with bipolar disorder and her band is signed to record label 4AD.Below she describes the intense empathic connection between the band and their music and their audience, which stuck me as a profound (and idealistic) way to live:Our band was started on these two bullshit principles -- well, they're more like bullshit wishes, but here they are:    1. That people should be able to touch one another and feel each other's pain. Physically, like you should be able to touch someone's cheek and feel their toothache; and emotionally, if you move someone, touch them deeply, you have to take responsibility for that depth of feeling and care about them.    So it isn't just pain we should feel in each other -- happiness should seep out of pores, and clouds of jealousy and all the different kinds of love and disappointment should float around us. We could walk in and out of people's clouds and know what they're feeling. That'd be the kindest way to live on planet earth.    2. That maybe our essential selves are drunk -- not wasted, just kinda buzzed enough to let go. If we were always a little tipsy, we'd be light, nonjudgmental, truthful. Our hang-up'd be shaken off, there'd be no second-skin barriers to honesty. Oh, and also no hangovers.    We figure if those two things are true, then it'd be OK for a band to sound like we do: sorta painful and a little out of control. We'd play what the audience felt and feel it at the same time and they'd feel it reflected back to them in sound and we'd all care about each other's stories and clouds of feeling and ... good luck with that I think miserably through my stage fright, trudging past the knitters, hippies, junkies, drunks, painters and psychos.-from Rat Girl, p. 42-43.It's hard to maintain that level of emotional empathy without collapsing from the weight of pain and joy and exhaustion. One would need superpowers to hold up under such unguarded transparency and depth of feeling.I'm wipedI'm so tiredCarry me for a little whileCarry me for a little whileCarry me for a little whileCarry me for a little while-Kristin Hersh, "Your Dirty Answer"from: Superpower WikiMusic and Mirror NeuronsThe mirror neurons, it would seem, dissolve the barrier between self and others. I call them "empathy neurons" or "Dalai Llama neurons".-- MIRROR NEURONS AND THE BRAIN IN THE VAT by V.S. Ramachandran Even the most ardent reductionists might be at a loss when contemplating how to reduce profound human experiences to a map of hemodynamic or electrical changes in the brain. But don't despair! Of course we should all know by now that music's ability to transmit emotion and elicit empathy is mediated by mirror neurons (Molnar-Szakacs & Overy, 2006):It has recently been proposed that music is best understood as a form of communication in which acoustic patterns and their auditory representations elicit a variety of conscious experiences (Bharucha et al., 2006). Here we review some recent evidence on the neural basis of musical processing in relation to two other modes of communication, language and action, both of which have been described as supported by the human mirror neuron system. We hypothesize that the powerful affective responses that can be provoked by apparently abstract musical sounds are supported by this human mirror neuron system, which may subserve similar computations during the processing of music, action and linguistic information. So the magical mirror neuron system is responsible for understanding very diverse types of stimuli (music, action, and language) and for evoking concomitant emotional responses to them. Such accounts always extrapolate from single unit recordings of mirror neurons in ventral premotor area F5 and inferior parietal lobule of monkeys to fMRI results in humans. In monkeys, a mirror neuron increases its firing rate when the animal performs an action, and when the animal watches someone else perform the action (Rizzolatti & Sinigaglia, 2010). As far as I know, no one has recorded mirror neuron activity directly from inferior prefrontal or parietal regions in humans.1 This is not to say that mirror neurons do not exist in humans, just that the scope of the human "mirror neuron system" has expanded beyond recognition into an unfalsifiable theory: 2 "Now wait a minute," said Professor Patricia Churchland [as paraphrased by Prof. Greg Hickok in Talking Brains]. "If mirror neurons are all over the brain then don't they lose their explanatory power? Aren't we now just back to our old friend, the How Does the Brain Work Problem?"A recent post at Brain Myths even suggests that mirror neurons might be The Most Hyped Con... Read more »

Molnar-Szakacs, I., & Overy, K. (2006) Music and mirror neurons: from motion to 'e'motion. Social Cognitive and Affective Neuroscience, 1(3), 235-241. DOI: 10.1093/scan/nsl029  

  • December 17, 2012
  • 02:05 AM
  • 992 views

Want to Be Happier and Avoid Auto Accidents? A TED/BMJ Mashup

by The Neurocritic in The Neurocritic

Are happy people responsible for fewer accidents? Should positive psychology be a mandatory module in high school Driver's Ed classes? Taken together, a new paper in the 2012 Christmas issue of BMJ and a recent TEDx talk tell a potentially interesting story about happiness, car crashes, and mind wandering. Let's see how this dangerous idea holds up to scrutiny.Driving and DaydreamingIt seems rather obvious that distraction is not good for driving, regardless of whether the offending diversion is from external or internal sources. Daydreaming (now known as "mind wandering", its more formal and scientific-sounding name) is a very common state of mind while driving. We'll often travel 10 miles down the road without being aware of our surroundings at all. But does this make us more prone to accidents? Galera et al. (2012) asked this question in a study designed to determine who was responsible for a motor vehicle accident (a "responsibility case-control study"). In other words, was the driver in question responsible for the auto accident? And what were they doing at the time?The authors interviewed 955 patients in the emergency room at Bordeaux University Hospital within 72 hours of a motor vehicle accident. They used a standardized instrument to determine if the patient was at fault (8-12 = responsible; 13-15 = contributory; >15 = not responsible). Notably, eyewitness reports were not considered. The interview protocol is described below (Galera et al., 2012):During the interview, patients were asked to describe their thought content just before the crash. ... Each thought was classified in one of the following categories: thought unrelated to the driving task or to the immediate sensory input, thought related to the driving task, no thought or no memory of any thought. To capture the intensity of the thought when the mind was wandering, the participant filled in a Likert-type scale (0-10) for each thought, answering the question: “How much did the thought disrupt/distract you?” Scores were then categorized into three levels of mind wandering:mind wandering with highly disrupting/distracting content (unrelated to the driving task or to the immediate sensory input)mind wandering with little disrupting/distracting content (unrelated to the driving task or to the immediate sensory input)none reported (no thought or no memory of any thought or thoughts related to the driving task)Also considered were possible confounding variables such as age, sex, season, time of day, vehicle model, amount of sleep (less than 6 hrs was considered sleep deprived), and use of any psychotropic drug in the previous week (sleeping pills, anti-seizure medications, and drugs for various psychiatric disorders).  Blood alcohol level was obtained from the medical record. Sources of external distraction were assessed (e.g., use of a mobile phone, texting, grooming, eating, watching TV, etc.), as was mood or emotional valence at the time of the crash (pleasure-displeasure on a 9-point Likert scale).The major finding was that mind wandering with highly distracting content was associated with a significantly higher likelihood of crash responsibility than if the driver reported no mind wandering. Also significantly related to responsibility were the expected factors of alcohol use and sleep deprivation, as well as the "emerging risk factors" of external distraction [which seemed expected to me], negative affect, and psychotropic medication use (see figure below - click for a larger view).Fig. 1 (Galera et al., 2012). Odds ratios for responsibility for road traffic crashes, adjusted for age, sex, season, time of the day, and location.Thus, internally distracting thoughts were clearly associated with a greater risk of causing an auto accident, with a higher odds ratio than for external distraction and even alcohol use. But what are we to make of the association with negative affect (a "displeased" mood)? Do happy drivers make better drivers??"A Wandering Mind Is an Unhappy Mind." Matt Killingsworth gave a talk at TEDxCambridge (MA) about mind wandering and happiness, based on results obtained from an experience sampling study in thousands of people. An iPhone app and a web-based reporting system (trackyourhappiness.org) were used to record the data, and the findings were published as a short report in Science (Killingsworth & Gilbert, 2010).1Participants were randomly cued by the app to answer questions about their current state of happiness (“How are you feeling right now?” rate from 0-100), their current activities (“What are you doing right now?” report one or more of 22 activities), and whether they were mind wandering (“Are you thinking about something other than what you’re currently doing?” one of four options: no; yes, something pleasant; yes, something neutral; or yes, something unpleasant). Want to be happier? Stay in the moment (Filmed at TEDxCambridge.)Results suggested that the participants were less happy when they were mind wandering, and this difference was significant for neutral topics and (not surprisingly) for unpleasant topics.2Crucially, the authors postulated that mind wandering caused unhappiness, even though the data were correlational in nature.3 In fact, other studies have shown the opposite: that negative affect can lead to mind wandering (Smallwood et al., 2009, 2011). This would make sense, for example, in cases of depression (rumination) and anxiety (excessive worry).... Read more »

Galera, C., Orriols, L., M'Bailara, K., Laborey, M., Contrand, B., Ribereau-Gayon, R., Masson, F., Bakiri, S., Gabaude, C., Fort, A.... (2012) Mind wandering and driving: responsibility case-control study. BMJ, 345(dec13 8). DOI: 10.1136/bmj.e8105  

Killingsworth, M., & Gilbert, D. (2010) A Wandering Mind Is an Unhappy Mind. Science, 330(6006), 932-932. DOI: 10.1126/science.1192439  

  • December 7, 2012
  • 02:06 PM
  • 983 views

The Not So Seductive Allure of Colorful Brain Images

by The Neurocritic in The Neurocritic

We all know that the mere presence of a brain scan image or a neuro-prefix adds instant credibility to any news story, right? And that the public (i.e., undergraduates) is easily swayed into believing in bogus psychological findings if accompanied by pretty colorful brains? Well count me in! But wait...Neuroscience Fiction Fiction?The day after the high-profile Neuroscience Fiction article by Dr. Gary Marcus appeared in The New Yorker, a stealthy blog post in Brain Myths summarized an unpublished paper (Farah & Hook, in press, PDF) that  refutes this notion.1Are Brain Scans Really So Persuasive? New evidence suggests the allure of brain scans is a myth Published on December 3, 2012 by Christian Jarrett, Ph.DA pair of psychologists at The University of Pennsylvania have highlighted a delicious irony. Sceptical neuroscientists and journalists frequently warn about the seductive allure of brain scan images. Yet the idea that these images are so alluring and persuasive may in fact be a myth. Martha Farah and Cayce Hook refer to this as the “seductive allure of ‘seductive allure’” (PDF via author website).Most of their evidence against the "seductive allure" is from unpublished data described in their in press article (which we can't evaluate yet):Two series of as yet unpublished experiments have failed to find evidence for the seductive allure of brain images. Michael, Newman, Vuorre, Cumming, and Garry (2012, under review) reported a series of replication attempts using McCabe & Castel’s Experiment 3 materials. Across nearly 2000 subjects, a meta‐analysis of these studies and McCabe & Castel’s original data produced a miniscule estimated effect size whose plausible range includes a value of zero. Our own work (Hook & Farah, in preparation) has also failed to find evidence that brain images enhance readers’ evaluation of research in three experiments comprising a total of 988 subjects.However, one published paper did fail to find an effect of fMRI images on how participants judged the scientific reasoning and credibility of a fake news story titled, “Scientists Can Reconstruct Our Dreams” (Gruber & Dickerson, 2012).2  The study was designed to replicate the previous study of McCabe and Castell (2008) with some notable exceptions. Rather than using a bar graph or an ugly and cluttered EEG topographic map as the comparison images in separate groups, Gruber and Dickerson used:...a fantastical, artistic image of a human head and a cyberspace-esque background with swirly lines. The final group was given an image from the popular science fiction film Minority Report in which three children’s dreams of the future are projected on a screen and used to prevent crime.Very io9... But both studies did have a no-image condition.The Gruber and Dickerson study also added additional questions to explicitly assess credibility and authoritativeness, in addition to whether the scientific reasoning made sense. Results showed that all cases, ratings did not differ statistically across the conditions, including the fMRI vs. no-image comparison.Hmm... Farah and Hook also debunked the study of Weisberg et al., (2008), which didn't use images at all but added neuroscience-y explanations to 18 actual psychological phenomenon. The problem was that the neuroscience-y paragraphs were longer than the no-neuroscience paragraphs. The author of the excellent but now-defunct Brain In A Vat blog had a similar objection, as explained in I Was a Subject in Deena Weisberg's Study:So how does it feel being held up to the scientific community as an exemplar idiot? Well, it’s a bit embarrassing. One of my coping mechanisms has been to criticize the experimental design. For instance, I think its problematic that the with neuroscience explanations were longer than the without neuroscience explantions. If subjects merely skimmed some of the questions (not that I would ever do such a thing), they might be more likely to endorse lengthier explanations.Neuroskeptic also raised this point in his otherwise [mostly] positive evaluation of the study, Critiquing a Classic: "The Seductive Allure of Neuroscience Explanations":Perhaps the authors should have used three conditions - psychology, "double psychology" (with additional psychological explanations or technical terminology), and neuroscience (with additional neuroscience). As it stands, the authors have strictly shown is that longer, more jargon-filled explanations are rated as better - which is an interesting finding, but is not necessarily specific to neuroscience.He noted that the authors acknowledged this objection, but also that the conclusions we can draw from the study are fairly modest.What does this mean for Neuro Doubt and Neuroscience Fiction and Neurobollocks? The takedowns of overreaching interpretations, misleading press releases, and boutique neuro-fields are still valid, of course, but the critics themselves shouldn't succumb to the seductive allure of seductive allure. But we must also remember that the most thorough critiques of seductive allure still await peer review.3 Footnotes1 And makes me feel a little silly.2 The experiment must have been designed before these actual 2012 headlines: Scientists read dreams (Nature) and Scientists decode contents of dreams (Telegraph).3 I wrote to two of the authors of the original studies (Weisberg and Castel) to get their reactions, but haven't heard back. Very, very tragically, we... Read more »

  • November 28, 2012
  • 07:54 AM
  • 769 views

Bothered by Negative, Unwanted Thoughts? Throwing Them Away Doesn't Help

by The Neurocritic in The Neurocritic

That's my interpretation of a new paper in Psychological Science (Briñol et al., 2012), which differs from the more exciting description given in a press release from APS:Bothered by Negative, Unwanted Thoughts? Just Throw Them Away If you want to get rid of unwanted, negative thoughts, try just ripping them up and tossing them in the trash.In a new study, researchers found that when people wrote down their thoughts on a piece of paper and then threw the paper away, they mentally discarded the thoughts as well.... . .Some types of psychological therapy use variations of this concept by trying to get patients to discard their negative thoughts. But [co-author Richard] Petty said this is the first study he is aware of that has validated that approach.So which interpretation is correct? Let's take a look, then judge for yourself.In Experiment 1, 83 high school students participated in a course designed to prevent eating disorders. They were randomly assigned to one of four conditions in a 2 × 2 factorial design: thought direction (positive vs. negative) × treatment ('thought disposal' vs. control). The students were told they were participating in a study on body image, and asked to write down either positive or negative thoughts about their bodies for 3 min. Then the students read what they had written, followed by instructions to contemplate their thoughts and then to either throw them in the trash ('thought disposal') or check for spelling errors (control). Finally, the participants were asked to rate their attitudes toward their bodies using three different 9-point scales.1 If throwing your negative thoughts away was beneficial, you'd predict a reduction in negative attitudes relative to the control condition (which would result in a higher score, reflecting more favorable attitudes). That is not what was observed, however. A comparison of the two white bars below reveals there was no treatment effect in the negative-thoughts condition.2 In other words, body image scores did not improve in the group that discarded their lists. In contrast, there was a decline in body image for the positive-thoughts group that threw their lists away, relative to those who spell-checked.Fig. 1 (Briñol et al., 2012). Results from Experiment 1: participants’ mean rating of their attitudes toward their own bodies as a function of the type of treatment they received and the direction of their thoughts. Not surprisingly, the authors had an alternate interpretation that hinged on the difference produced by thought-direction in the non-discarding control groups:Consistent with our hypothesis that a thought-disposal treatment can influence judgments by invalidating people’s thoughts, results showed that the attitudes of participants who physically threw their thoughts away showed less impact of the thought-direction induction than did the attitudes of participants who physically retained their thoughts. ... It is important to note that because the treatment was induced after thoughts were already generated, it could not affect the valence or the number of participants’ thoughts. Rather, the treatment decreased the strength of the influence that participants’ thoughts had on their attitudes....and this was because of lower scores in the positive condition, rather than higher scores in the negative condition (or both effects, for that matter). So unless you want to say there were baseline differences in body attitudes between the treatment groups (which is problematic), I'm not buying it.3 Footnotes1 Scores were averaged across the three scales.2 However, these two conditions were not statistically compared; I'm assuming that the difference between 5.6 and 5.4 was not significant. The Thought Direction × Treatment interaction was followed up only by pairwise comparisons between Thought Direction in the different Treatment groups.3 Psychological Science...meet me at camera 3. Reference  Brinol, P., Gasco, M., Petty, R., & Horcajo, J. (2012). Treating Thoughts as Material Objects Can Increase or Decrease Their Impact on Evaluation. Psychological Science DOI: 10.1177/0956797612449176

... Read more »

  • November 19, 2012
  • 01:05 AM
  • 2,328 views

Vicodin for Social Exclusion

by The Neurocritic in The Neurocritic

Cyberball (with apologies to Kipling D. Williams).Cyberball (not the Atari version) is a virtual game designed by social psychologists to be a model for social rejection and ostracism (Williams et al., 2000). The study participant is led to believe they are playing an online ball-tossing game with other people, who then proceed to exclude them from the game. The resultant negative feelings are meant to be a proxy for ostracism based on fundamental attributes such as race, disability, physical appearance, homelessness, etc. This simple game has lead to a burgeoning cottage industry on social pain and its close resemblance to physical pain.Social Pain and Physical Pain Are Not InterchangeableThat statement may sound obvious to you, but an increasing number of neuroimaging studies would have us believe otherwise. Whenever I read an article proclaiming that "the brain bases of social pain are similar to those of physical pain" (Eisenberger et al., 2003), I am reminded of how phenomenologically DIFFERENT they are. Waking up from general anesthesia and feeling undermedicated for surgery that took your body apart and put it back together again feels absolutely nothing like being rejected by your long-term partner. Your anterior insula and anterior cingulate cortex might be very busy in both cases, but they're also activated in many different situations (Yarkoni et al, 2011). Indeed, of the 2238 total papers in the BrainMap neuroimaging database, 735 of them contain the search term 'anterior cingulate' (see also Shackman et al., 2011). Besides pain and emotion, the behavioral domains that activate this brain region include motor learning, language, speech, explicit memory, working memory, bladder control, thirst, sexuality, and perception in all five senses. Sure, the affective components of pain might show some overlap with physical pain (Kross et al., 2011), but distinct networks are likely responsible for the unique aspects of these different qualia.1The Aversive BrainHayes and Northoff (2012) described a core brain network involved in the processing of aversive stimuli (or states) that can be either painful or non-painful in nature. They relied on evidence from both the human and animal literatures. Aversion here refers to more than social and physical pain, and includes avoidance of stimuli that are unpleasant, frightening or disgusting. Meta-analysis of human neuroimaging data showed overlap in some of the structures involved in non-painful aversion and physical pain (shown in green below), which accounted for 35% of Aversion-related voxels and 24% of Pain-related voxels. These overlapping regions included mid-cingulate cortex, posterior cingulate cortex, anterior insula, right ventrolateral prefrontal cortex (PFC), dorsomedial PFC, thalamus, midbrain, secondary motor cortex, and areas related to memory (right hippocampus/parahippocampal gyrus) and even reward (dorsal striatum).2 It is important to note here that some of the social pain darlings (mid-cingulate cortex, anterior insula, right ventrolateral PFC) are also activated by unpleasant pictures, sounds, and smells.- click on image for a larger view - Fig. 2 (Hayes & Northoff, 2012). Overlap of pain- and aversion-related networks in humans. Results of meta-analyses for human pain- (blue) and aversion- (yellow) related studies (top row), overlapping activations (green; top row and isolated in bottom row), and a corresponding table of associated brain regions. All results are family-wise error rate whole-brain corrected at p < 0.05Furthermore, although there was substantial overlap between Aversion and Pain, 65% and 76% of all activations (respectively) were not shared. Structures uniquely activated by Aversion included the amygdala, hypothalamus, more anterior regions of the anterior cingulate, and another reward-related area (ventral striatum). Brain regions uniquely activated by Pain included the cerebellum, rostral pons, somatosensory cortex, posterior insula, and yet another dopamine-rich, reward-related area (ventral tegmental area).3 Dave J Hayes, co-author of the study, wrote about this fruitful cross species network approach to The Aversive Brain in his blog.But Depression Hurts, doesn't it?It sure does according to Lilly, who would also like us to believe that their drug Cymbalta (duloxetine, an SNRI antidepressant) will cure your aches and pains along with your depression. But Duloxetine Does Not Relieve Painful Physical Symptoms in Depression, according to a meta-analysis of five available studies (Spielmans, 2008).How much overlap is there between brain activity associated with physical pain and feelings of sadness? To answer this question, I performed a meta-analysis of my own that made use of the BrainMap database of published neuroimaging experiments. Using GingerALE software, I did two activation likelihood estimate (ALE) meta-analyses to look at brain regions activated by experimental manipulations to induce physical pain and sadness (see Laird et al., 2005 for methodological details of ALE). In brief, the procedure involves three steps to determine the likelihood of activation across experiments:ALE and Testing Significance: Compute the ALE values for each voxel in the brain and performs a test to determine the null distribution of the ALE statistic at each voxel.Thresholding: Take the P values from the previous st... Read more »

  • November 9, 2012
  • 02:12 PM
  • 834 views

The Neuroscience of Speed Dating Choice

by The Neurocritic in The Neurocritic

Can brain activity measured while rating potential dates predict later choices at speed dating events?Haven't you lay awake at night wondering if 36 voxels in your rostromedial prefrontal cortex (RMPFC) can predict your future romantic decisions? If you have, you're in luck. Cooper and colleagues (2012) conducted an fMRI study to answer this burning question in the affirmative. "and then I asked him with my eyes to ask again yes and then he asked me would I yes to say yes my mountain flower and first I put my arms around him yes and drew him down to me so he could feel my breasts all perfume yes and his heart was going like mad and yes I said yes I will Yes."  -James Joyce, UlyssesOK, so maybe nothing that dramatic emerged after your 5 min date at the Campus Rec Center...This might be hard for me, but I'll try to seriously convey the major point of the study: how does the brain form first impressions of potential romantic partners? My immediate retort to the experimental approach is why would you ever think that 36 voxels in one brain area (and 34 in another) can drive such a complicated decision??But that was the finding of this paper, which was published in the Journal of Neuroscience.To describe the methods in brief, 39 single young heterosexual adults participated in a scanning session where they viewed photographs of their potential dates and rated them on on three dimensions:a “first-impression”(FI) rating with the scale “How much would you like to date this person?,” as well as separate ratings of physical attractiveness (Att) and likability (Like).After scanning, the same photos were rated again on scales that assessed potential romantic desirability: “How physically attractive is this person?” and “How much do you think you would like this person?”  Another 112 young adults also participated in the behavioral part of the study, but not the fMRI part.For analysis, the authors estimated four models:Basic decision, two predictors: partners who were later pursued and those who were rejected.Similar but controlled for reaction time (RT) to the FI decision. This will become important, as we'll see below.Regions that correlated with subjective desirability ratings: single predictor for all partners with two parametric modulators: one for subjective physical attractiveness (Att) and one for subjective likeability (Like). Adjustment for partner and relationship effects: single predictor for all partners with two parametric modulators: one for the consensus judgment (hot or not) and one for individual preference (idiosyncratic choice). Let's look at the results for the basic decision (A) and for subjective attractiveness (B) in the figure below.Modified from Fig. 2 (Cooper et al.,  2012). Neural predictors of subsequent decision compared with areas mediating judgments of physical attractiveness. A, Brain regions showing greater responses at the time of first viewing for faces of individuals that are subsequently selected as a potential romantic partner, compared with those who were not. Paracingulate cortex (circled) is the only activated region that significantly independently correlates with subsequent decision in a multiple regression including all activated regions. B, Brain regions positively correlating with subjective ratings of physical attractiveness for each partner. C, Overlap between brain regions related to decision and those related to attractiveness, showing substantial overlap between these variables in the paracingulate cortex. All images thresholded at p < 0.001 voxelwise with extent threshold set to control whole-brain FWE at p < 0.05. Color bars indicate t statistic. The circled area (A) is called paracingulate cortex by these authors and dorsal anterior cingulate cortex (ACC) by many others. The paracingulate is the only region that correlated with subsequent dating decisions. However, the dorsal ACC is activated in a whole host of situations (Botvinick, 2007; Posner et al., 2007). An explanation for this is well beyond the scope of a single blog post. The big blob (B) correlated with physical attractiveness, and (C) shows the overlap between these two.It was important to control for the RT of first impression decisions because activity in the ACC is sensitive to "time on task," or how long it takes to process or respond to a stimulus. This means that the ACC shows greater activity when RTs are long. This is a confound for many studies that examine response conflict, or interference, like the well-known Stroop task (RED, BLUE, etc.).  If you control for longer RTs that are inevitable in tasks like the Stroop, the interference effect in the ACC goes away (Carp et al., 2010). Hence, the paracingulate could merely be responsive to making dating decisions that are sometimes ambiguous or difficult.The table below shows that wasn't entirely the case, but the magnitude of the paracingulate activation was diminished when RT was controlled. This wasn't true of two other brain regions (ventral visual cortex, medial precuneus), which weren't even discussed in the paper. Modified from Table 2 (Cooper et al.,  2012). Activations correlated with subsequent decisions/ratings. [NOTE: compare the two hearts.]As a final comparison, let's look at activations sensitive to universal hotness vs. idiosyncratic choice. Our friend the paracingulate responded to objective attractiveness, as judged by the entire group of participants. In contrast, another region — 36 voxels in the rostromedial prefrontal cortex — responded to whether the potential partner was desirable to a specific participant.... Read more »

  • November 6, 2012
  • 07:05 AM
  • 1,154 views

Cotard's Syndrome: Not Pretending That We're Dead

by The Neurocritic in The Neurocritic

Playing dead game --  A craze called the "playing dead game" has swept this nation where people of all ages stage elaborate death scenes everyplace. Believing That We're DeadCotard's Syndrome is the delusional belief that one is dead or missing internal organs or other body parts (Debruyne et al., 2009). Those who suffer from this "delusion of negation" deny their own existence. The eponymous French neurologist Jules Cotard called it le délire de négation ("negation delirium").Cotard's syndrome has been observed in mentally ill persons with psychotic disorders (such as schizophrenia and psychotic depression), as well as in neurological patients with acquired brain damage. In a review of 100 cases, Berrios and Luque (1995) found that:Depression was reported in 89% of subjects; the most common nihilistic delusions concerned the body (86%) and existence (69%). Anxiety (65%) and guilt (63%) were also common, followed by hypochondriacal delusions (58%) and delusions of immortality (55). An exploratory factor analysis extracted 3 factors: psychotic depression, Cotard type I and Cotard type II. The psychotic depression factor included patients with melancholia and few nihilistic delusions. Cotard type 1 patients, on the other hand, showed no loadings for depression or other disease and are likely to constitute a pure Cotard syndrome whose nosology may be closer to the delusional than the affective disorders. Type II patients showed anxiety, depression and auditory hallucinations and constitute a mixed group. In their overview, Debruyne et al., 2009 presented two cases with distinctively different outcomes:1. An 88-year-old man with mild cognitive impairment was admitted to our hospital for treatment of a severe depressive episode. He was convinced that he was dead and felt very anxious because he was not yet buried. This delusion caused extreme suffering and made outpatient treatment impossible. Treatment with sertraline, 50 mg, and risperidone, 1 mg, resulted in complete remission of the depressive episode and nihilistic delusions...2. A 46-year-old woman with known rapid-cycling bipolar disorder ... presented with a depressive episode with psychotic features. Her nihilistic delusions were compatible with Cotard’s syndrome. She had the constant experience of having no identity or “self” and being only a body without content. In addition, she was convinced that her brain had vanished, her intestines had disappeared, and her whole body was translucent. ... The following pharmacologic treatments previously had been used to treat this patient, without consistent effect: lithium, valproate, carbamazepine, haloperidol, olanzapine, risperidone, clozapine, pimozide, sulpiride, clomipramine, sertraline, paroxetine, fluoxetine, citalopram, mirtazapine, and venlafaxine. Electroconvulsive therapy (ECT) was also used without effect. The nihilistic delusions disappeared in this patient, but a mood switch to a hypomanic episode occurred...In the 46 year old patient, MRI and SPECT findings were negative, but her neuropsychological testing was suggestive of right hemisphere dysfunction.Delusions of Death in a Patient with Right Hemisphere InfarctionDoes the right hemisphere play a unique role in maintaining a sense of self? A new case study by Nishio and Mori (2012) described a 69 year old patient who suffered a stroke affecting portions of the right frontal, temporal, and parietal lobes and right thalamus. A neurological exam a week later revealed severe hemispatial neglect of the left side of space, left sided weakness, motor neglect of his left limbs, and impaired senses of pain, cold, touch, vibration, and position on the left side of his body. These symptoms are typical of such a large right hemisphere lesion (see below).1 FIGURE 1. (Nishio & Mori, 2012). Magnetic resonance images of the patient’s brain, taken just after the onset of the stroke. The right side of the brain appears on the left side of the scans. A, Transverse diffusion-weighted images show fresh infarcts involving the right-frontal, temporal, and parietal lobes and thalamus.What was unusual were other aspects of his behavioral presentation:...He criticized his doctors, nurses, and rehabilitation therapists, and complained bitterly about the hospital’s food and oxygen. He falsely believed that his brother-in-law, previously a director of another hospital, was to blame for this hospital’s flaws. He was treated with mianserin (10 mg/day) and quetiapine (25 mg/day); his irritability and agitation subsided within 2 to 3 weeks. During that time, we became aware that the patient was suffering from several delusional misidentifications. He thought that Kim Jong-il, then the leader of North Korea, was staying on the floor below his own, and that his physical therapist was a grandson of Puyi, the last Emperor of China... A month after the onset of his symptoms, by which time his motor and cognitive symptoms had gradually improved, he began complaining regularly of feelings of unreality, and asked his wife whether he was alive or dead. He said to his doctor, “I guess I am dead. I’d like to ask for your opinion.” Later, his conviction about death became firmer. He said, “My death certificate has been registered. You are walking with a dead man,” and “I am dead. I will receive a death certificate for me from my doctor and have to bring it to the city office early next week.” His discussion of his demise was not associated with a depressed mood or feelings of fear. When his doctor asked him whether a dead man could speak, he understood that his words defied logic, but he could not change his thinking.As time passed, his delusions of death dissipated, yet in retrospect he characterized these delusions as real:His delusion of being dead and his feelings of depersonalization gradually subsided and disappeared 4 months after the stroke. One year after the stroke, however, he still believed in the truth of the memories that he had formed during his delusional state. He said, “Now I am alive. But I was once dead at that time,” and “I saw Kim Jong-il in the hospital where I stayed.”The authors discussed the case in relation to other delusional misidentification syndromes such as Capgras syndrome, where the patient believes their loved ones have been replaced by nearly identical duplicates or impostors. One functional interpretation of Capgras is that a disconnection between facial recognition and affective processes has occurred, such that the person no longer experiences the feelings of familiarity and warmth towards their significant others. In a similar fashion, some cases of Cotard could result from a lack of familiarity with or detachment from one's self, which is then interpreted as being dead or no longer existing.Why did this particular patient show the Cotard delusion, whereas other people with similar right hemisphere strokes have not? Where is the pathology in psychiatric patients with Cotard's, who comprise the bulk of case reports? For that matter, will we be able to develop neuroscientific explanations for these questions and construct something resembling a functional neuroanatomy of the self?Are you really your connectome??... Read more »

Debruyne H, Portzky M, Van den Eynde F, & Audenaert K. (2009) Cotard's syndrome: a review. Current psychiatry reports, 11(3), 197-202. PMID: 19470281  

Nishio Y, & Mori E. (2012) Delusions of Death in a Patient with Right Hemisphere Infarction. Cognitive and behavioral neurology : official journal of the Society for Behavioral and Cognitive Neurology. PMID: 23103861  

  • October 21, 2012
  • 05:43 PM
  • 1,126 views

Savoir Faire or Savant?

by The Neurocritic in The Neurocritic

Is amygdala volume correlated with social network size or with special talents in autism spectrum disorders? Or both??The amygdala is a subcortical structure located within the medial temporal lobes. It consists of a number of different nuclei, or collections of neurons delineated by commonalities in morphology and connectivity. The amygdala is best known for major roles in fear conditioning (Paré et al., 2004) and responding to emotional stimuli more generally (Phelps & LeDoux, 2005), but its functions extend beyond that.A presentation at the recent Society for Neuroscience meeting in New Orleans reported on MRI data obtained from Dr. Temple Grandin, the famous and talented Professor of Animal Science at Colorado State (Cooperrider et al., 2012):Dr. Temple Grandin: A neuropsychological and multimodal neuroimaging case study of a savant with autism. . .Results: Dr. Grandin’s left lateral ventricle showed much more leftward volumetric asymmetry than controls. Her left cerebral white matter volume and bilateral entorhinal cortex thickness were much greater compared to controls. Her fusiform gyrus thickness was much less than the control mean. She had greater left lateral ventricle, intracranial, left cingulate, bilateral amygdala, and bilateral entorhinal cortex volumes. White matter microstructural differences were found for Dr. Grandin in multiple brain regions, including those known to relate to language function and facial information processing. ... The neuropsychological assessment indicated superior visuospatial and nonverbal reasoning abilities... Virginia Hughes wrote a splendid summary of the study, which is not yet published in a peer-reviewed journal.An earlier experiment was conducted with another very talented autistic savant (Corrigan et al., 2012):The subject of this study is a 63-year-old, right-handed male with savant syndrome and a long-standing diagnosis of ASD.1 Institutionalized as a child, he has lived semi-independently as an adult, working for more than 30 years in dishwashing jobs. This individual is gifted with several special skills. One area of considerable talent is in music. He has perfect pitch and plays several musical instruments, of which his favorite is the accordion. He has substantial abilities with languages and can engage in basic conversations in twelve different languages. He also has remarkable abilities with sound imitation. His most exceptional ability, however, is in the area of art. ... He has become a highly regarded and accomplished graphic artist, whose works have been recognized through numerous exhibitions nationally as well as publication in a book. His medium is paper with pencil, marker, and crayon. His interest is in drawing collections, usually quite large, of items such as tools, birds, instruments, trains, flowers, and shoes, among many others. He takes a special interest in categorizing the physical world. The volumes of his amygdala and caudate were both larger than values in the normative literature, and a strong right-sided asymmetry was seen for both structures (Corrigan et al., 2012). Hippocampal volumes did not differ from control values.Although these two single-case studies were of exceptional people who may not be characteristic of the general ASD population, it was notable that both individuals had larger amygdalae than controls. Is this a surprising finding, in light of recent results on the correlations between amygdala volume and social network size in control participants? Surely the average neurotypical college student has a larger Social Network Index of offline contacts (Bickart et al, 2011) and more Facebook friends (Kanai et al., 2012) than the average person with ASD?Grandin says, “the part of other people that has emotional relationships is not part of me” and she has neither married nor had children. ... She describes socializing with others as “boring” and has no interest in reading or watching entertainment about emotional issues or relationships. In an earlier post on the Bickart article (More Friends on Facebook Does NOT Equal a Larger Amygdala), I noted that bigger is not always "better" (see Fig. 2 below):One prominent example is the finding of larger amygdalae in children (and adults) with autism (Howard et al., 2000; Mosconi et al., 2009). However, the literature on this issue is variable (and voluminous)...2 More consistent are observations of increased amygdala volumes in generalized anxiety disorder (Etkin et al., 2009; Schienle et al., 2010). In rats, chronic stress causes hypertrophy (enhanced dendritic arborization) of pyramidal and stellate neurons in the basolateral nucleus of the amygdala (Vyas et al., 2002).Modified from Fig. 2 (Howard et al., 2000). Volume estimation of the amygdala by the stereological point counting method. Section area estimation of posterior, middle, and anterior amygdala sections, using a regular array of test points. Section areas are increased in autism compared to controls.A further interpretive conundrum is presented by the variety of conditions that are associated with increased amygdala volume: first-episode patients with nonschizophrenic psychoses, women high in harm avoidance, learning disabled adolescents at high risk of schizophrenia, adopted Romanian adolescents who experienced severe early institutional deprivation, and political conservatism.3 Most of those things are not especially fantastic for an active social life...Autism is often considered as a disorder of microcircuitry and of long-range connections, so determining the structural and functional connectivity of the amygdala with other brain regions is crucial. One view holds that "underconnectivity" is a characteristic feature of the brains of those with autism, although recently this hypothesis has been called into question.A new study from Bickert and colleagues (2012) followed up on their previous morphometric work and examined the functional connectivity of the amydala in relation to offline social network size in a group of 30 young adults (19 of whom had been in their previous experiment). Two separate groups of subjects, a "discovery sample" (n=89) and a "replication... Read more »

Corrigan, N., Richards, T., Treffert, D., & Dager, S. (2012) Toward a better understanding of the savant brain. Comprehensive Psychiatry, 53(6), 706-717. DOI: 10.1016/j.comppsych.2011.11.006  

  • October 13, 2012
  • 08:02 PM
  • 1,022 views

Surrealistic Imaging Experiment #2

by The Neurocritic in The Neurocritic

Scene from Le sang d'un poète (1930, Jean Cocteau) 1"It is often said that The Blood of a Poet is a surrealist film. However, surrealism did not exist when I first thought of it." -Jean Cocteau 2In our second installment of Surrealistic Imaging Experiments, Marketing Professor Mohamed M. Mostafa of the Gulf University for Science and Technology in Kuwait was interested in how the brain processes Surrealistic imagery used in advertising (Mostafa, 2012). He approached the background to his topic and the fMRI study itself in a very different fashion from Silveira et al. (2012), who performed Surrealistic Imaging Experiment #1.In that study, the authors hypothesized that humans cannot directly relate to surrealistic images because "percepts violating an expected percept cannot be integrated effortlessly into a frame of prior experiences or expectations and therefore also lack the potential for self-reference" (Silveira et al., 2012). Reduced activation in the precuneus to surrealistic relative to naturalistic pictures served as the major support for this contention. However, self-referential processing is also associated with other cortical midline structures (medial prefrontal and posterior cingulate cortices), which were not differentially activated here. Furthermore, there was no mention of top-down input from prefrontal cortex, networks for processing novelty, or lateral temporal regions associated with semantic processing. This seemed odd to me, as I expected that surrealistic paintings would require greater processing resources than realistic paintings.Don't be lost in the weird world of investments. Advertising Agency: Leo Burnett, São Paulo, BrazilThe Persistence of Memory in AdvertisingIn contrast to the restricted frame of reference presented above, Mostafa (2012) provides a historical background of Surrealism and summarizes the major themes and techniques used by iconic painters such as Salvador Dalí, René Magritte, and Giorgio de Chirico (who influenced the Surrealists). He extends the reach of surrealistic imagery to marketing and popular culture: Today, the influence of Surrealism extends to cinema and advertising. Some Surreal advertisements create ambiguity by juxtaposing incongruous visual and verbal elements in a way that deliberately defies reason. It is not surprising that advertisers seek to create unique, unexpected and dreamlike images for use in promotions because advertisers often try to gain consumers' attention to fuel their fantasies and to induce them to view a product in a new light. For this reason, the casually Surrealist image has become, in particular, a stock-in-trade of the advertising industry (Macmillan 2000; Denny 2001). Mostafa then segues into a review of neuromarketing and the brain imaging techniques used to probe the brains of consumers (fMRI, MEG, EEG). The aims of the study are articulated below:...no previous studies have focused solely on investigating how consumers' brains process Surrealistic imagery in advertising. In this study, we aim to fill this void by investigating the neural correlates of Surrealistic imagery in advertising. More specifically, we aim to:1. identify cortical areas that selectively respond to Surrealistic imagery in advertising and2. test whether the elaboration and surprise hypotheses are supported within advertising context.3 Then, the specific hypotheses of the experiment are clearly elaborated after a review of the relevant literature:H1: Surrealistic imagery in advertising will elicit more activation in brain areas associated with novelty detection such as the inferior frontal gyrus (IFG) and the anterior cingulate cortex (ACC).H2: Surrealistic imagery in advertising will elicit more activation in brain areas associated with emotional responses such as the thalamus and the amygdala.H3: Surrealistic imagery in advertising will elicit more activation in brain areas associated with episodic-memory retrieval such as the precuneus and the parietal cortex. As for the methodological details, the participants were 18 right-handed English speakers in their 20s. None were experts in art history. The experimental task (passive picture viewing) used a 2 x 2 factorial design of (1) Surrealistic advertisements (novel, repeated) and (2) congruent advertisements (novel, repeated).novel congruent    repeated congr   novel surrealistic   repeated surrealFigure 1 (Mostafa, 2012). Stimuli and presentation sequence.Thus, the author took into account both stimulus novelty and stimulus repetition (using a modified adaptation design), the latter to examine a form of priming in which a relative reduction in neural activity is observed when a stimulus is repeated. The stimulus set of Silveira et al. (2012) might have been better matched on size, luminance, color saturation, and spatial frequency parameters, but each of their 16 stimuli were repeated 3 times. There could have been differential priming effects for surrealistic vs. naturalistic images, but we don't know. On the other hand, the presentation parameters and number of stimuli in ... Read more »

  • October 9, 2012
  • 04:10 AM
  • 904 views

Surrealistic Imaging Experiment #1

by The Neurocritic in The Neurocritic

"The case against the realist position needs to be considered, after considering the materialist position. The latter, more poetic however than the former, admittedly implies on the part of a Man, a monstrous pride, but not a new and more complete degeneration. It should be seen, above all, as a welcome reaction against certain ridiculous spiritualist tendencies. Ultimately, it is not incompatible with a certain nobility of thought.The realistic position, in contrast, inspired by positivism, from Thomas Aquinas to Anatole France, appears to me to be totally hostile to all intellectual and moral progress. It horrifies me, since it arises from mediocrity, hatred and dull conceit. It is what engenders all the ridiculous books, and insulting plays of our day. It feeds on newspaper articles, and holds back science and art, while applying itself to flattering the lowest tastes of its readers; clarity bordering on stupidity, the life lived by dogs." -from the Surrealist Manifesto, by André Breton (1924) Surrealism was a philosophical movement in art and literature that embraced the unexpected, the impossible, the dream-like elements hidden from waking life. The founder of surrealism was French writer and poet André Breton, who was trained in medicine, psychiatry, and Freudian psychoanalysis. He defined surrealism as "Pure psychic automatism by means of which one intends to express, either verbally, or in writing, or in any other manner, the actual functioning of thought. Dictated by thought, in the absence of any control exercised by reason, free of any aesthetic or moral concern." Breton clearly had no use for the realist position, which he viewed as a pox on society. Eighty-eight years later, he might find it ironic that surrealism itself is the subject of positivist thought and scientific investigation.Does the brain process surrealistic art in a different fashion than realistic art? Why yes, one would expect that to be the case. Undaunted, Silveira and colleagues (2012) asked this question in a recent fMRI study. I would predict that surrealist art is more computationally intensive for the Bayesian brain, so there would be greater activation in regions associated with top-down visual processing in an attempt to construct a coherent meaning from an unusual image.1 There was a precedent for this position in a study that compared the activations produced while viewing possible and impossible objects (Wu et al., 2012). Briefly, regions in both the dorsal and ventral visual streams showed greater activation for impossible than for possible objects.2 The authors of the current study adopted a different perspective (so to speak):While naturalistic paintings present the world in a habitual way, surrealistic paintings violate the expected frame of reference. Surrealistic paintings are characterised by presenting mainly recognisable objects but in constellations that do not exist in real life or that are impossible from a physical point of view. In presenting impossible scenes, these artworks prevent an effortless processing of information to come to a meaningful interpretation of the visual world. ... We hypothesised that percepts violating an expected percept cannot be integrated effortlessly into a frame of prior experiences or expectations and therefore also lack the potential for self-reference. As it has been assumed that cortical midline structures refer to such self-representations (Han and Northoff 2008), we expected naturalistic and surrealistic paintings to have different activations in these areas.The major prediction was that surrealistic images cannot engender self-referential processing, so differences in cortical midline structures (medial prefrontal and posterior cingulate cortices) were expected, with no further mention of dorsal/ventral stream visual regions, top-down input from prefrontal cortex, networks for processing novelty, or lateral temporal regions associated with semantic processing.Figure S2 (Silveira et al., 2012). Reproductions of naturalistic and surrealistic artworks. N = naturalistic, S = surrealistic. N1: Edward Hopper “Sunday”. N2: Edward Hopper “Morning Sun”. N3: Eric Fischl “Japanese Bath”. N4: Francisco de Goya “La Cometa”. N5: Edward Hopper “Chop Suey”. N6: Francisco de Goya “Niños con Mastines”. N7: Edward Hopper “Summer Evening”. N8: Edward Hopper “Cape Cod Morning”. S1: René Magritte “Son of Man”. S2: Vladimir Kush “Pearl”. S3: Salvador Dalí “My Wife Nude”. S4: Max Ernst “Elephant Celebes”. S5: Vladimir Kush “Walnut of Eden”. S6: Giorgio de Chirico “Hector and Andromache”. S7: René Magritte “Le Prêtre Marié”. S8: Vladimir Kush “Departure of the Winged Ship”.The final stimulus set of 8 realistic and 8 surrealistic paintings is shown above. These were selected from a larger set of images rated on valence, arousal, and familiarity by a separate group of participants. Highly familiar pieces were excluded.3 The control stimuli were homogeneous color fields. All pictures were matched in size, luminance, color saturation, and spatial frequency parameters. Each picture was presented 3 times, and the task was to make a binary decision about their reaction to the image: “Are you touched by the painting?” The subjects were equally affected by the realistic and surrealistic paintings, but took longer to decide on the realistic ones.The major neuroimaging result was obtained using a subtraction analysis to compare the BOLD response to naturalistic vs. surrealistic paintings. There was significantly greater activation to the naturalistic pictures bilaterally in the precuneus (Brodmann area/BA 7) and medial occipital cortex (BA 17, 18, 19) and in the right middle temporal gyrus. It seemed that no brain areas showed greater activity while viewing the surrealistic images. In fact, the surrealistic pictures resulted in deactivation of the precuneus, medial occipital, and temporal regions when compared to the color field control condition.Figure 1 (modified from Silveira et al., 2012). Neurometabolic level of processing for naturalistic versus surrealistic images. Sagittal section. Note: Prec = precuneus, MOC = medial occipital cortex.Given some of the hypothesized roles of the precuneus, the authors' interpretation is plausible:As a part of the cortical midline structures, precuneus activity has been suspected to be associated with visuo-spatial imagery, episodic memory retrieval, and even of what has been referred to as the “self ” (Cavanna and Trimble 2006). Episodic memory retrieval is very likely to be associated with top–down processing (Sestieri et al 2010). However, surrealist paintings are not only unfamiliar but also disturb our sense of consistency and coherence and may therefore also hardly be related to our sense of the self. The higher activation of the precuneus in the naturalistic condition supports the hypothesis that percepts matching expectations and therefore confirming specific aspects of reality can be linked both toprior experiences ... Read more »

  • October 3, 2012
  • 01:08 PM
  • 856 views

Law and Order: Psychiatry Unit

by The Neurocritic in The Neurocritic

Crime dramas on American television are known for loosely adapting actual news stories "ripped from the headlines" and calling them fiction. Law and Order: Special Victims Unit is especially known for this pattern. For instance, in one episode last year a much beloved basketball coach who runs a charitable foundation was found guilty of sexually abusing his young players over the course of many years.In another episode, a well-known politician's long-kept secret is finally revealed after 13 years: the child he fathered with the family housekeeper.I thought I would do SVU executive producer Dick Wolf a favor and present a unique psychiatric case study that can be adapted for the small screen.  Since it's unknown to the American viewing public (and most everyone else), it will seem like a more original idea.Patient Presenting with Stockholm Syndrome Ultimately Diagnosed with Münchausen Syndrome and Dissociative Identity Disorder{SPOILER ALERT: it ends badly.}A troika of unusual and spectacular psychiatric disorders was observed in one Dutch patient, as reported by Spuijbroek et al. (2012):A young female of indeterminate age called a crisis hotline several times in the course of a month, giving accounts of severe sexual abuse, kidnapping by her father, and membership in a sect in the recent past. She spoke by preference to male staff members, was difficult to understand, and used a high-pitched, childlike voice. She provided different names and addresses that proved to be wrong. “God,” “men and women,” and “good and evil” were regular topics...After a few weeks, she expressed suicidal feelings, saying she wished to go to God, and she agreed to be admitted to a local psychiatric hospital. She left, however, after 1 day. One month later, she was hospitalized again, using a different family name. She stated that she was 19 years of age and claimed to have been severely abused by her father and other sect members. ... Her isolation from the outside world, the power imbalance, her sympathy for her abusing father, and her unwillingness to escape the life-threatening situation were consistent with the clinical picture of Stockholm syndrome.In cases of Stockholm syndrome, a person held hostage or captive comes to strongly identify and bond with her captor. Here, the patient claimed she was kidnapped into a religious cult and sexually abused, yet she felt sympathy for her abusers (which included her own father). However, it soon became apparent that she was not telling the truth:At first, the personal information provided by the patient could not be verified. After several weeks,  however, her identity was revealed by police detection. The patient turned out to be a 27-year-old woman who had been reported missing 3 weeks earlier by her family. The patient had been receiving mental health care since childhood; she also had financial debts and was at risk of losing her housing. She had wandered about for several years, presenting regularly at various hospitals with a variety of somatic and psychiatric symptoms. She also frequently contacted the police with very detailed and alarming stories that were impossible to verify... The patient at first seemed unaffected by the disclosure of her identity, but after some days she showed concern. She was uncomfortable at the reunion with her parents. Gradually her behavior changed: she answered to her own name now, and she would speak with female staff members. A few weeks later, the patient said that she could not remember anything about the period when she was admitted to the hospital...Thus, paradoxical elements of both Münchausen Syndrome (deliberately fabricating an illness) and a dissociative disorder (involuntary rupture of memory, awareness, identity and/or perception) were observed. The diagnosis of Stockholm Syndrome was withdrawn, and psychotic disorders were ruled out:...The patient did not report hallucinations. While her stories were often improbable, they were never bizarre, and no cognitive impairment was found. Given the many moments of acuity and social responsiveness displayed by the patient, the picture was inconsistent with schizophrenia. The family reported that the patient had fabricated fantastical stories since she was a little girl. Fugue-like states with periods of unexplained peregrination or wandering may have occurred as well. Nevertheless, the patient was regularly able to contact others, continuing her telephone calls to mental health workers and other health care professionals, in a very consistent way. After her identity was disclosed, “Munchausen syndrome,” with imitation of both mental and somatic conditions, turned out to be the most likely description of the patient’s condition.An additional examination of the patient was conducted by specialists from a regional psychological trauma center... their assessment revealed the following cluster of severe dissociative symptoms: derealization, fugue, depersonalization, amnesia, identity confusion, pseudoepileptic seizures, sleep problems, and self-damaging behavior. Although it was recognized that the patient was suffering from pseudologia fantastica [pathological lying], her dissociative symptoms were regarded as serious and authentic...The court ordered the patient to be hospitalized for 6 months. During this time she was prescribed a series of medications (including antidepressants, antipsychotics, and benzodiazepines), none of which were effective. She became suicidal. Although her suicide attempts were characterized as "ambivalent", it was unfortunate that she ultimately succeeded while in hospital:After several months, suicidal tendencies and a desire for euthanasia were a regular topic of conversation for the patient. Several times during her hospitalization, she demonstrated overt suicidal behavior: two medication overdoses, once walking on railroad tracks, and twice putting a plastic bag around her head. These attempts seemed ambivalent, since the chance of detection by staff members was relatively high. The patient was placed in seclusion because of heightened suicidal risk several times, leading to increased fear and tension within the therapeutic relationship. After 7 months, the patient suicided on the ward by suffocation with a plastic bag...The clinical case discussion ends with COMMENTARY by David A. Kahn, MD [imagine a voice-over by Rod Serling]:Why have I been haunted by this case report of a mysterious, unfortunate woman who was never truly knowable? The treating staff was ambivalent in its diagnoses of both Munchausen syndrome, which is the intentional feigning of illness, and DID [dissociative identity disorder], or the unintentional adoption of two or more personalities or identities. These appear to be in contradiction, ironically a most accurate reflection of the emotions evoked by the patient who appeared both manipulative but also helplessly unable to control herself and tell a true story. Who was she? Did she know or not know? Was she putting them on, or was she actually unsure of who she really was? Her final act of suicide was a forceful if equally ambiguous communication, as non-verbal as her others, but the authors suggested that i... Read more »

Spuijbroek EJ, Blom N, Braam AW, & Kahn DA. (2012) Stockholm syndrome manifestation of Munchausen: an eye-catching misnomer. Journal of psychiatric practice, 18(4), 296-303. PMID: 22805905  

  • September 26, 2012
  • 04:28 AM
  • 969 views

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

by The Neurocritic in The Neurocritic

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

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

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

  • September 12, 2012
  • 01:12 AM
  • 921 views

The Electroencephalogram Cocktail Party

by The Neurocritic in The Neurocritic

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

  • August 26, 2012
  • 03:33 AM
  • 1,191 views

The Art of Delicate Sadness

by The Neurocritic in The Neurocritic

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

... Read more »

  • August 18, 2012
  • 05:25 AM
  • 1,070 views

Predicting Brain Age from 231 Neuroanatomical Measures

by The Neurocritic in The Neurocritic

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

  • August 11, 2012
  • 03:51 PM
  • 918 views

Where Are the Clinical Tests for Psychiatric Disorders?

by The Neurocritic in The Neurocritic

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

  • July 27, 2012
  • 04:18 AM
  • 1,295 views

Online Gaming Addiction, Dysfunctional Families, and the Striatum

by The Neurocritic in The Neurocritic

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

  • July 14, 2012
  • 04:48 AM
  • 1,021 views

Brain Responses to Virtual Reality-Induced Hallucinations in Schizophrenia

by The Neurocritic in The Neurocritic

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

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

  • July 8, 2012
  • 08:25 PM
  • 1,122 views

EMPowered to Kill

by The Neurocritic in The Neurocritic

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

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

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

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