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

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  • May 5, 2012
  • 06:30 PM

Neurophysiological Explanation for the Perception of Poltergeists

by The Neurocritic in The Neurocritic

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

  • April 29, 2012
  • 09:26 PM

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

by The Neurocritic in The Neurocritic

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

  • April 23, 2012
  • 12:42 PM

Magic Buttons, Silver Linings, and Two-Edged Swords

by The Neurocritic in The Neurocritic

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

  • April 13, 2012
  • 05:06 AM

Suffering for art is still suffering

by The Neurocritic in The Neurocritic

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

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

  • April 8, 2012
  • 09:25 AM

tDCS Symposium Stimulates Giant Brain in Chicago

by The Neurocritic in The Neurocritic

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

  • April 1, 2012
  • 09:59 AM

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

by The Neurocritic in The Neurocritic

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

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

  • March 23, 2012
  • 11:50 AM

I Feel Your Pain... and I Enjoy It

by The Neurocritic in The Neurocritic

Dennis Rader - the BTK KillerCourt Transcript of BTK's Confession. . .The Court: -- you were engaged in some kind of fantasy during this period of time?The Defendant: Yes, sir.The Court: All right. Now, where you use the term “fantasy,” is this something you were doing for your personal pleasure? The Defendant: Sexual fantasy, sir.The Archives of General Psychiatry has published a neuroimaging study of nonconsensual sexual sadism in a forensic setting (Harenski et al., 2012), sure to be controversial among BDSM practitioners, DSM-5 critics, and Christian fundamentalists alike.Here's a brief background and rationale for the study:Context Sexual sadism is a psychiatric disorder in which sexual pleasure is derived from inflicting pain, suffering, or humiliation on others. While the psychological and forensic aspects of sexual sadism have been well characterized, little is known about the neurocognitive circuitry associated with the disorder. Sexual sadists show increased peripheral sexual arousal when observing other individuals in pain. The neural mechanisms underlying this unusual response are not well understood. We predicted that sadists relative to nonsadists would show increased responses in brain regions associated with sexual arousal (amygdala, hypothalamus, and ventral striatum) and affective pain processing (anterior cingulate and anterior insula) during pain observation.The participants were 15 violent sexual offenders housed at Sand Ridge Secure Treatment Center: 8 sadists and 7 nonsadists, as rated on the Severe Sexual Sadism Scale.1 One additional participant with an ambiguous score was excluded. The groups were fairly well-matched for age (about 50 yrs), education (12 yrs), IQ (92-97), substance use, and level of psychopathy.The subtitle of the paper is Preliminary Findings and one must keep this in mind, given the small n in the groups.The experimental design involved presenting a set of three images depicting (a) one person inflicting pain upon another ("Pain"), and (b) control images with two people but no pain inflicted ("No Pain"). The participants rated the severity of pain inflicted for each stimulus set on a 0-4 scale. A third condition depicted one person causing damage to an object, but those results were not presented in the paper.Figure 1 (Harenski et al., 2012). Example of pain and no-pain picture sets, along with the pain severity rating scale.By definition, sexual sadists obtain pleasure and gratification via the suffering of others. Here are the DSM-IV-TR diagnostic criteria (APA, 2000) for Sexual Sadism (see Krueger, 2010; PDF):A. Over a period of at least 6 months, recurrent, intense sexually arousing fantasies, sexual urges, or behaviors involving acts (real, not simulated) in which the psychological or physical suffering (including humiliation) of the victim is sexually exciting to the person.B. The person has acted on these sexual urges with a nonconsenting person, or the sexual urges or fantasies cause marked distress or interpersonal difficulty.2 So it comes as no surprise that brain regions associated with sexual arousal were predicted to show greater activity to Pain in the sadists. What are the "sexual arousal areas"? According to the authors, these include the amygdala, hypothalamus, and ventral striatum. The problem is that none of these areas is selectively involved in sexual arousal [with the possible exception of specific hypothalamic nuclei]. In fact, the amygdala is more often related to fear, so greater activity might also be expected in those who take the perspective of the victim.The other major prediction was that activity in the "affective pain areas" (anterior cingulate cortex and anterior insula)3 would be greater to Pain images in the sadists, because they are actually more sensitive to the suffering of others. This might seem counterintuitive in such callous individuals, but...In any scenario where pain is imminent, sadists may pay closer attention than nonsadists to the thoughts and feelings of the victim because this enhances their sexual arousal when pain is inflicted. In other words, whereas sadists lack sympathy for their victims, they may exhibit empathy (simulating their victims' feelings) when consistent with their goals.In support of this view, the sadists rated Pain pictures as higher in severity than the nonsadists did. The two groups did not differ in their ratings of No-Pain pictures. In the future, comparison to a control population of nonviolent offenders would be helpful.Since Sand Ridge does not have its own scanning facility [gasp!], running the fMRI experiment involved use of a mobile unit.Kent Kiehl outside the mobile scanner he has used to look at the brains of inmates at a New Mexico prison. Credit: Nature News.What were the results of the imaging study? The sadists showed greater activity to Pain (vs. No-Pain) in the left amygdala, but the nonsadists did not. The right ventral striatum showed a main effect of group (greater activation in the sadists) which did not differentiate between Pain and No-Pain pictures. No significant effects were observed in the hypothalamus.... Read more »

  • March 19, 2012
  • 01:16 PM

Does the Human Dorsal Stream Really Process Elongated Vegetables?

by The Neurocritic in The Neurocritic

What do zucchini and hammers have in common? Both might be processed by the dorsal stream.The primate visual system is divided into ventral ("what") and dorsal ("where") visual streams that are specialized for object recognition and spatial localization, respectively (Mishkin et al., 1983; Haxby et al., 1991).Goodale and Milner (1992) conceptualized the two pathways as "vision for perception" and "vision for action":We propose that the ventral stream of projections from the striate cortex to the inferotemporal cortex plays the major role in the perceptual identification of objects, while the dorsal stream projecting from the striate cortex to the posterior parietal region mediates the required sensorimotor transformations for visually guided actions directed at such objects.Other researchers have extended the degree of specialization shown by the visual and semantic systems. Some studies have suggested there might be category-specific processing of living and non-living things (e.g., animals and tools), although the reasons for this specialization are a matter of debate (Caramazza & Shelton, 1998; Thompson-Schill et al., 1999). Chao and Martin (2000) found that pictures of tools activated the left posterior parietal cortex in the dorsal stream to a greater extent than pictures of animals, houses, and faces. The idea is that objects with salient motor-based properties (hammers) should recruit "vision for action" cortical regions to a greater extent than objects without such affordances (zucchini).More recently, Almeida and colleagues (2008) used two different visual masking techniques in a priming study designed to isolate the influence of the dorsal stream:We used two techniques to render prime pictures invisible: continuous flash suppression (CFS), which obliterates input into ventral temporal regions, but leaves dorsal stream processes largely unaffected, and backward masking (BM), which allows suppressed information to reach both ventral and dorsal stream structures. Their results suggested that categorically related primes suppressed under CFS still facilitated reaction times to tool targets, but not to animal targets. In other words, participants were faster to classify tools when preceded by a picture of a tool than when preceded by a picture of an animal, and this priming effect held up when the ventral stream was unavailable.A new study by Sakuraba et al. (2012) wanted to clarify which specific attributes of tools are processed by the dorsal stream, so they used a greater variety of categorically related and unrelated prime stimuli suppressed under CFS, as shown below.Fig. 1 (Sakuraba et al., 2012). Procedure using CFS. Different images were presented into the subject's left and right eyes by using anaglyphs. Dynamic high-contrast random-noise patterns (10 Hz) were presented to the dominant eye, while low-luminance, low-contrast prime stimuli were presented to the nondominant eye. Subjects could report the dynamic noise but not the static image. Each trial started with a fixation cross for 500 ms, followed for 200 ms by a prime stimulus suppressed by CFS. Finally, a target stimulus masked by 70% additive noise was presented until the subject responded (maximum duration: 3 s) by pressing a key to indicate the category of the target stimulus. One of the manipulated attributes was shape. Non-elongated ("stubby") tools, elongated vegetables, and stubby vegetables1 were used as primes for elongated tools (e.g., hammer, ax, fork, etc.). Other conditions used geometric shapes as primes.In Experiment 2, we used tool pictures without elongated shape components, namely stubby tools (e.g., a punch, a squeezer, a mouse, and so on). ... In Experiment 3, elongated stick figures were used as prime stimuli. In Experiment 4, elongated and stubby vegetable pictures were presented as prime stimuli. Because the elongated shapes involve an orientation component, we could not exclude the possibility that orientation, rather than shape attribute, explained the results. Therefore, we conducted Experiment 5 to clarify this. We used elongated stick figures, diamond shapes, and cut circles that were rotated in 45° increments as prime stimuli.Interestingly, membership in the category of tools per se was irrelevant; it was the shape of the prime that mattered.Fig. 4 (Sakuraba et al., 2012). Priming effect in Experiment 4 and 5.2 Light and dark gray bars represent mean priming effects to tool targets and animal targets, respectively. Error bars indicate SEM. The pictures represent examples of the prime stimuli we used. This throws a wrench (so to speak) into the dorsal stream as the vision for action pathway, unless you normally use a zucchini to pound your nails into the wall. The less dramatic interpretation is that the categorical information obtained by viewing pictures of tools isn't neatly respected by the dorsal stream, but visually-guided reaching and grasping remain unscathed.Footnote1 The "stubby vegetables" were my favorite part of the paper.2 You might want to quibble with the size and functional significance of the priming effect. Although statistically significant, it was rather small.ReferencesAlmeida J, Mahon BZ, Nakayama K, Caramazza A. (2008). Unconscious processing dissociates along categorical lines. Proc Natl Acad Sci. 105:15214-18.Caramazza A, Shelton JR. (1998). Domain-specific knowledge systems in the brain: the animate-inanimate distinction. J Cogn Neurosci. 10:1-34.Chao LL, Martin A. (2000). Representation of manipulable man-made objects in the dorsal stream. Neuroimage 12:478-84.Goodale MA, Milner AD. (1992). Separate visual pathways for perception and action. Trends Neurosci. 15:20-5.Haxby JV, Grady CL, Horwitz B, Ungerleider LG, Mishkin M, Carson RE, Herscovitch P, Schapiro MB, Rapoport SI. (1991). ... Read more »

Sakuraba S, Sakai S, Yamanaka M, Yokosawa K, & Hirayama K. (2012) Does the human dorsal stream really process a category for tools?. The Journal of neuroscience : the official journal of the Society for Neuroscience, 32(11), 3949-53. PMID: 22423115  

  • February 19, 2012
  • 04:21 AM

That's Impossible! How the Brain Processes Impossible Objects

by The Neurocritic in The Neurocritic

Relativity, by M.C. Escher.The artwork of M.C. Escher is famous for its visual trickery. The human visual system tries to project the two dimensional image onto a three dimensional scene, but the perspective is contradictory: it cannot exist in the real world. These impossible constructions violate the laws of geometry and fascinate consumers of t-shirts, posters, and Apple products.How does the brain represent these illusory staircases and towers? While a fascinating topic of study in the field of object perception (Levy et al., 2004), Escher prints can make for overly complicated stimuli in neuroimaging experiments. Simpler 2D figures, such as the impossible objects drawn by Swedish artist Oscar Reutersvärd, have been used in fMRI experiments (Soldan et al., 2008).An extensive collection of 810 impossible objects is available from Impossible World, which is a fantastic resource1 maintained by Vlad Alexeev.Previous neuroimaging experiments have used the possible/impossible object decision task to study the neural correlates of perceptual priming, an implicit form of memory. Behaviorally, repeated presentation of possible objects results in faster decision times, and this priming effect is smaller (Soldan et al., 2008) or non-existent (Schacter et al., 1995) for impossible objects. Neurally, the phenomenon of repetition suppression, or the reduction in neural activity seen upon repeated stimulus presentation, is thought to reflect facilitated perceptual processing (and perhaps behavioral priming).2 Repetition suppression predicts behavioral priming for possible objects (Habeck et al., 2006):A set of occipital, parietal, and temporal brain regions decreased their activation across presentations, including bilateral middle occipital gyrus, left precuneus, right supramarginal gyrus, as well as some frontal and thalamic areas, such as right inferior frontal gyrus, left cingulate gyrus, and right thalamus. However, no such relationship was observed for impossible objects.The previous studies focused on varieties of repetition priming and whether there is a "structural description system" that facilitates the identification of perceptually coherent objects. A recently published article was specifically interested in the neural basis of impossible figures and how they are represented in the visual cortex (Wu et al., 2012). The stimuli were impossible and possible exemplars of the two-pronged trident (Fig. 1 below), shown at four different angles.Fig. 1 (Wu et al., 2012). Examples of stimulus figures used in impossible condition and possible condition. (a) Is an impossible figure and (b) is a possible figure [that] resembles the former.The paper started by reviewing the basic neuroanatomy of the visual system and its division into dorsal ("where") and ventral ("what") visual streams. Objects are primarily represented in the ventral stream, and the lateral occipital complex (LOC) is one area that seems to be specialized for object recognition. The authors predicted that impossible objects would be difficult for the LOC to process; therefore, additional regions would be recruited:In the present study, we thought that the 3D structures of impossible figures might be difficult to be represented by object-selective regions (such as the LOC), and the impossible perceptions might be derived from detecting the contradiction in interpretation of the 3D structure. Therefore, we postulated that both the brain regions in the dorsal visual pathway, such as the SPC [superior parietal cortex] related to the perceptual ambiguities resolving and perceptual content modifying, and the brain areas related to the object-selective regions in the ventral pathway would be involved in the impossible figures processing.Nineteen participants performed the possible/impossible object decision task (30 trials of each condition) while their brains were scanned. Four participants showed repetition priming in the task (first 15 trials of each condition slower than the last 15) and were excluded. The remaining subjects did not show priming.3 Personally, I would have used 30 unique possible and impossible figures to avoid priming effects entirely.What were the results? As predicted, regions in both dorsal and ventral visual streams showed greater activation for impossible than for possible figures: right superior parietal in the former and right fusiform and inferior temporal gyri in the latter.The right SPG in the dorsal visual pathway might be related to spatial information processing and the right LOC (FG and ITG) in the ventral visual pathway (the object-selective regions) might be related to the representation of the impossible 3D structure. Therefore, our results indicated that the impossible 3D structure might be difficult to be represented by human visual system, and the impossible perception might be derived from the detecting and resolving the contradiction in the subjects’ interpretations according to different perceptions triggered by 3D cues.Fig. 2 (Wu et al., 2012). Brain regions showing significant difference between impossible condition and possible condition [FEW-corrected threshold of P < 0.05 at the cluster level (P < 0.001, 10 contiguous voxels cutoff at the voxel level)].There were no brain regions that showed greater activation for possible objects.... Read more »

  • February 13, 2012
  • 01:35 AM

21st Century Treatments for Insomnia

by The Neurocritic in The Neurocritic

Are you having trouble sleeping? But you're not feeling that 19th century retro hipster insomniac vibe? Try some of these behavioral remedies recommended by the finest scientific and medical journals of today.What a Difference a Day MakesIs Intensive Sleep Retraining (ISR) a new overnight treatment for chronic insomnia (Harris et al., 2012)? ISR is conducted in one 25 hr session at a sleep lab, where the insomniac sleeps a maximum of 3 min every 30 min for a period of 25 hrs. Instant cure! (supposedly). The basic idea is that the person will learn they can fall asleep fairly quickly and easily, and this will translate directly to real life sleeping patterns.In a commentary accompanying the main article in Sleep, Spielman and Glovinsky (2012) describe it as:...a novel insomnia treatment that while radical in procedure is grounded in learning theory, a long-established conceptual framework for understanding insomnia. ISR combines two familiar components of sleep research—sleep deprivation and the polysomnographic recording of sleep onset—to yield an entirely new therapeutic procedure: repeated practice in falling asleep quickly. Massed practice in achieving sleep is here shown to possess a therapeutic value rivaling that of stimulus control therapy (SCT), that mainstay of behavioral sleep medicine, as well as offering a possible additive effect when administered in conjunction with SCT.ISR employs sleep laboratory technology to measure the speed of sleep onset, limit the duration of sleep, and allow immediate feedback to subjects as to whether objectively recorded sleep has occurred. It typically provides dozens of successful entries to sleep over the course of a single night and day. Then it is over, handing off responsibility for good sleep management to sleep hygiene recommendations.In contrast to ISR, there is already strong research support for stimulus control therapy (SCT), which is designed to:...reduce the anxiety or conditioned arousal individuals may feel when attempting to go to bed. Specifically, a set of instructions designed to reassociate the bed/bedroom with sleep and to re-establish a consistent sleep schedule are implimented. These include: 1) Going to bed only when sleepy; 2) Getting out of bed when unable to sleep; 3) Using the bed/bedroom only for sleep and sex (i.e., no reading, watching TV, etc); 4) Arising at the same time every morning; and 5) Avoiding naps.One question, then, is whether ISR is better than SCT, an accepted behavioral therapy for insomnia. Eighty participants in the study of Harris et al. were randomized into one of four groups: (1) ISR + sleep hygeine instruction (SH); (2) SCT + SH; (3) ISR + SCT; (4) SH alone, which served as the control condition. All participants kept a sleep diary, answered questionnaires, and wore an actigraph to measure motor activity. Those in the ISR groups slept no more than 5 hrs the night before they came to the lab.The highly intrusive ISR procedure involved arriving at 21:00.Following an explanation, the signing of an informed consent form, electrode application, and a quiet settling period, treatment began at 22:30. Treatment trials were conducted every half hour, finishing after 23:00 on night 2. Thereby, the ISR treatment routine allowed a series of 50 half-hourly sleep onset opportunities. ... Within each treatment trial, the opportunity for sleep onset was limited to a 20-min period, with the trial stopping if sleep onset had not occurred by this time. For those trials in which sleep was initiated, 3 consecutive minutes of sleep were permitted, prior to being awoken [the method of awakening was not described]. Upon awakening, treatment participants first rated their perception of whether sleep onset had occurred (on a Likert scale of 1 “No, definitely not” to 7 “Yes, definitely”). Following this response, participants were provided with information as to whether sleep onset had or had not occurred.Then they got out of bed to read or watch DVDs. After 10 trials of this nonsense, people were falling asleep in 5 min or less.Ultimately, did this punitive procedure work? Yes. But it wasn't significantly better than SCT for most of the subjective sleep measures used. All three active treatment conditions produced improvements in self-reported duration and efficiency of sleep, relative to the SH control. Of the 16 or so analyses at 2 of 7 selected time points (which did not seem to be corrected for multiple comparisons), there were some instances where ISR or the combined ISR + SCT treatment was better than stimulus control therapy (see below), but nothing earth shattering.In another graph (Fig. 5 - Mean sleep diary wake time after sleep onset), the SCT groups were superior to ISR at Week 1 and Post-Treatment.What about the objective sleep measures obtained by actigraphy?The actigraphy data failed to support significant changes in sleep, despite using an adjusted manual scoring method and a sensitivity setting in the scoring algorithm that calibrated actigraphy TST [total sleep time] to PSG [polysomnography] TST. Actigraphy has similarly failed to mirror subjective sleep changes in other treatment studies in insomnia, and objective measures (i.e., EEG) fail to replicate the extent of subjective sleep changes in clinical insomnia treatment studies.The authors concluded that actigraphy is useless and that subjective sleep report is the only thing that matters (basically).So what's next? Intensive Sleep Retraining is costly and available only from highly specialized centers.1 But the possibility of self-administered ISR is on the horizon, using portable EEG headsets, actigraphs, and vibrating alarms. Is there an app for that?Footnote1 I'm not sure that it's even being offered as a clinical treatment. The RCT was conducted in Australia.References... Read more »

  • January 28, 2012
  • 04:53 AM


by The Neurocritic in The Neurocritic

Today was the sixth anniversary of this blog. I'm not much for meta-blogging or general chattiness, but I thought I would highlight the nine posts (out of 700) with the most comments. Thank you for your support over the years, and keep the comments coming.9. Friston Is Freudian - Friday, March 12, 2010Neuropsychoanalysis is in the news again because of the recent publication of Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. In 2010, first author Carhart-Harris published an expansionist mega-opus (with Karl Friston) on The default-mode, ego-functions and free-energy: a neurobiological account of Freudian ideas, the basis for the present post and its follow-up.8. Is CBT Worthless? - July 03, 2009According to a meta-analysis by Lynch, Laws and McKenna, Cognitive Behavioral Therapy (CBT) is not helpful for those with schizophrenia and bipolar disorder, and any improvements seen in major depression are rather small.7. White Matter Differences in Pre-Op Transsexuals Should NOT be the Basis for Childhood Interventions - January 28, 2011 Contains a number of comments by transgendered individuals who took exception with various aspects of this post.6. The Precuneus and Recovery from a Minimally Conscious State - July 05, 2006 Includes a number of comments, over a two year period, from a father caring for his son.5. Voodoo Correlations in Social Neuroscience - January 05, 2009 On the infamous paper by Edward Vul, Christine Harris, Piotr Winkielman and Harold Pashler, ultimately retitled Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition.4. Glossolalia - November 04, 2006 Includes personal statements from many individuals who feel they speak in tongues.3. Bad News for the Genetics of Personality - August 07, 2010 A recent search for genetic variants that underlie differences in personality traits came up empty (Verweij et al., 2010).2. The Pseudoscience of Anti-Psychiatry in PLoS Medicine - August 01, 2006 Antipsychiatry is always a hot-button topic, and this early post attracted 44 comments.1. Airplane Headache - August 15, 2010 The winner by a mile, with 72 comments, is on a supposedly rare type of headache that occurs during take-off and landing (Atkonson & Lee, 2004). The pain appears to be unique to plane travel and not associated with other conditions. Neurological exam and brain imaging results in all published cases (n=14) have been normal. Clearly, there are more than 14 people who suffer from these excruciating headaches on airplanes. Triptan drugs (used to treat migraines and cluster headaches) may be effective in preventing airplane headaches (Ipekdal et al., 2011).Thank you for reading!

... Read more »

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

  • January 19, 2012
  • 07:27 PM

Deep Brain Stimulation for Bipolar Depression

by The Neurocritic in The Neurocritic

The Melancholia of Kirsten Dunst and Lars von Trier“Gray wool, clinging to my legs, it's heavy to carry along” The disastrous wedding reception of the severely depressed Justine precedes the end of the world, depicted as a highly stylized and artistic event feared by some but welcomed by others. Kirsten Dunst plays the role of von Trier's own melancholia, which was the inspiration for his film. The image above occurred out of context, at the very beginning, during the bombastic Wagnerian apocalyptic prelude to Part One, "Justine" and Part 2, "Claire." We don't hear Justine say those words until later, when she had lost the ability to care for herself. "She should be hospitalized," I thought at the time, and wondered why no one was getting her psychiatric help. But then we wouldn't have a movie that deals with internal struggle and suffering.Deep Brain Stimulation for Treatment-Resistant DepressionSevere depression that is refractory to treatment, i.e. unresponsive to psychotherapy, multiple trials of antidepressant drugs (often combined with atypical antipsychotics, mood stabilizers, benzodiazepines, etc.) and electroconvulsive therapy (ECT), takes a tremendous toll on the long-suffering patients and their families. An alternative treatment modality, deep brain stimulation (DBS), has been in clinical trials for intractable depression for nearly 10 yrs. It works using the same sort of device used in DBS for Parkinson's disease, which has been remarkably successful in alleviating symptoms. Electrodes are implanted deep in the brain, targeting the ventral portion of the anterior cingulate cortex, in Brodmann's area 25.Other brain regions have been targeted for DBS in major depressive disorder, including the nucleus accumbens, but today we'll focus on the work of Dr. Helen Mayberg and her colleagues at Emory University in Atlanta, Georgia.Figure 1 (Holtzheimer et al., 2012). Surgical targeting. Preoperative MRI shows the sagittal (A) and coronal (B) views of the planned optimal subcallosal cingulate (SCC) white matter target (red circle). The dotted black line indicates the subcallosal plane of interest, parallel to the anterior-posterior commissural line; the dotted white line indicates the rostral limit of the subcallosal plane; and the dotted red line indicates the midsubcallosal plane. The red circle indicates demarcation of the SCC white matter target and surrounding gray matter. C and D, Postoperative computed tomography scan merged with preoperative MRI showing a typical case with the deep brain stimulation electrodes in situ. Note that the contacts span the SCC gray and white matter in the vertical plane proximal to the split of the cingulum bundle and rostral medial frontal white matter tracts (C, red arrows, sagittal view). Contacts are numbered by convention (1-4 on the left, 5-8 on the right), inferior to superior. Contacts 2 and 3 are directly in the SCC white matter, and contacts 1 and 4 are in the inferior and superior gray matter, respectively. Why stimulate subcallosal cingulate/area 25 1 in depression? Previous neuroimaging studies by Mayberg and colleagues (2000) showed that resting glucose metabolism in this region is overly active in depressed people, and a reduction in activity was associated with antidepressant treatment response. Another key observation was made using a mood induction paradigm in healthy volunteers (Mayberg et al., 1999). After the participants remembered a sad autobiographical memory, their SCCs showed greater blood flow relative to a neutral mood state. Thus, the "sad cingulate" was implicated in normal sadness as well as in depression.The most recent DBS report, published in the Archives of General Psychiatry (Holtzheimer et al., 2012), is a follow-up after two years of chronic, high frequency stimulation of the subgenual cingulate white matter. The basic findings have been summarized elsewhere, including Providentia, with a review of possible mechanisms at The Scicurious Brain.The aspect of the study that I'd like to focus on today is the inclusion of patients with Bipolar-Type II (BP-II) for the first time, in addition to those with unipolar depression. Just as with the unipolar patients, those with BP-II had to be in a depressive episode for at least 1 yr.The specific DSM-IV diagnostic criteria for Bipolar II Disorder are:A. Presence (or history) of one or more Major Depressive Episodes. B. Presence (or history) of at least one Hypomanic Episode. C. There has never been a Manic Episode or a Mixed Episode. D. The mood symptoms in Criteria A and B are not better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified. E. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.Are the same neural circuits implicated in treatment-resistant depression also involved in BP-II? Remarkably, there is nothing in the literature that presents a rationale for using DBS for bipolar depression specifically, nor about why the subgenual cingulate white matter should be the target. A 2010 review by Lipsman, Lozano, and others from the Toronto neurosurgical group stated: "There are currently no trials or reports in the literature on the use of DBS for the exclusive treatment of bipolar diseas... 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  • January 14, 2012
  • 04:10 AM

Remembering and Forgetting in Traumatized Ugandan Refugees

by The Neurocritic in The Neurocritic

Gulu, Uganda (vis photography)Most of us have memories from the past that we'd rather forget. When those memories are of a traumatic nature, they can more difficult to expel from our minds. Unwanted memories can be rejected by means of active inhibitory processes (Anderson & Levy, 2009), but these mechanisms are impaired in individuals with post-traumatic stress disorder, or PTSD (Zwissler et al., 2011): Essentially, PTSD patients have trouble remembering what they are supposed to remember and forgetting what they would rather not remember. They appear to have impaired memory control.A group of German investigators conducted a study on memory and forgetting in one of the more unsettling regions of the world: northern Uganda. The Lord's Resistance Army (LRA), a terrorist organization, has waged a long and brutal campaign to overthrow the government of Uganda:Rape, torture, and murder have become the group's hallmarks in the almost fifteen [twenty or twenty-five] years that they have terrorized the citizens of Northern Uganda. The ranks of the LRA are filled in large part (approximately 80%) by children, who are kidnapped and brainwashed into service with the group. Human rights NGOs place the number of children currently fighting with LRA at around 3,000. LRA members also kidnap children, particularly girls, to serve as sex slaves; some have even been given as "gifts" to arms dealers in Sudan.Zwissler and colleagues (2011) recruited severely traumatized participants for a study on directed forgetting, a memory task where instructions are given to remember some items but to forget others during the encoding phase. The participants were 51 young people (mean age=20.8 yrs, range 16–30) living in Internally Displaced Persons (IDP) camps near the city of Gulu in Northern Uganda. All were equally exposed to traumatic events such as abduction, but only 26 were diagnosed with PTSD, an anxiety disorder marked by intrusive memories and flashbacks.The participants had two years of education on average, and many were functionally illiterate. For this reason, pictures were used as the stimuli (instead of words, which are commonly used in this type of study). The pictures were neutral in valence to examine whether memory issues in this population would extend to non-emotional material.In the experiment, 28 pictures (Set A) were presented during an initial encoding phase. Each picture was followed by a symbol that signaled whether the preceding picture should be remembered or forgotten. During the test phase, all 28 pictures were presented, along with new pictures that served as "lures" that were similar to the initial set (Set B; see below).Fig. 1 (Zwissler et al., 2011). Illustration of the picture sets showing three representative target-distractor pairs: (a) set A; (b) Set B. (Original photographs were shown in colour.)For each stimulus, participants were told to indicate whether they had seen it before, regardless of the prior instruction to remember or forget. Overall accuracy in the task is shown in the figure below. The non-PTSD group had better memories for the pictures they were told to remember, compared to those they were told to forget. In contrast, the PTSD group showed no difference in accuracy for the to-be-remembered vs. the to-be-forgotten pictures.Fig 2 (Zwissler et al., 2011). A comparison of the effect of directed forgetting on discrimination accuracy in the two groups. PTSD, post-traumatic stress disorder. *Indicates significant differences.One way to view these results is that the participants with PTSD performed worse than controls for items they were supposed to remember, and were unable to invoke inhibitory processes to suppress memory for the to-be-forgotten items ("trouble remembering what they are supposed to remember and forgetting what they would rather not remember"). Breaking down task performance a little further, the PTSD group was more inclined to make "false alarm" errors to the lures related to pictures they were supposed to remember. This suggests that the details of the to-be-remembered pictures weren't encoded as well, and were more easily confused with related pictures they didn't see.The authors concluded that......traumatized individuals with (but not without) PTSD are impaired in their ability to selectively control episodic memory encoding. This impairment may contribute to clinical features of the disorder such as intrusions and flashbacks.However, "directed forgetting" is usually not a practical strategy when real life events are unfolding. Do these results this imply that the non-PTSD group was better able to dissociate themselves from traumatic events as they were occurring (or shortly thereafter)? Whether such a process can effectively occur at all during horrible tragedies is highly controversial (e.g., Terr vs. Loftus). The phenomenon is more often studied when applied to the retrieval of traumatic or unwanted memories (Anderson & Levy, 2009), not during the encoding phase.Tragically, there appears to be No End to LRA Killings and Abductions in central Africa, according to Human Rights Watch. These ongoing atrocities should not be ignored.So watch the video Dear Obama: A Message from Victims of the LRA.Further Reading on Forgetting:Forgetting is Key to a Healthy MindLetting go of memories supports a sound state of mind, a sharp intellect--and superior recallLiving and ForgettingI Forget...I Forgot......and it's Memory Week at the Guardian.ReferencesAnderson MC, Levy BJ. (2009). Suppressing unwanted memories. Curr Dir Psychol Sci. 18:184-194.... Read more »

  • January 6, 2012
  • 06:34 AM

Subjects Wanted to Drink Bourbon and Watch Erotic Films

by The Neurocritic in The Neurocritic

Our fun New Year's Eve post reviewed the suspected brain mechanisms of an alcohol blackout, or an episode of amnesia after a bout of heavy drinking (Rose & Grant, 2010). Alcohol-induced alterations of hippocampal circuits are thought to disrupt memory encoding, which can lead to two different types of blackout: en bloc, a complete loss of memory for the affected time period; and fragmentary, where bits and pieces of memories remain. The en bloc blackout is more likely to occur when a large quantity of alcohol is ingested in a short period of time.In 1970, less was known about the causes and mechanisms of alcohol blackouts. A study by Goodwin and colleagues set out to learn more:Some psychiatrists believe blackouts to be a functional disturbance, related to guilt or anxiety. Others believe they reflect a toxic effect of alcohol on the brain. There are few data to support either concept. Blackouts usually occur erratically; comparable amounts of alcohol do not always produce memory loss, and it has not been possible to predict when an intoxicated person will suffer amnesia. During the amnesic interval, the person may function reasonably well and perform complicated acts, suggesting that the amnesia is retrograde. To confirm this, however, memory must be observed systematically during drinking periods followed by amnesia, which heretofore has not been done.Human subjects protection programs were less stringent (or non-existent) 40 years ago, so it was no problem to enlist unemployed alcoholic day laborers to drink a pint of bourbon and undergo memory testing of an unusual sort.The subjects were recruited from individuals seeking daily employment at the Casual Labor Division of the Missouri Employment Office in St. Louis. Previous experience with this source had shown that a sizable proportion of the job applicants are alcoholic. Individuals were eligible for the study if they met two criteria; (1) willingness and ability to drink more than a pint of whiskey in a few hours , and (b) good physical health.Ten men (mean age 41 yrs) were recruited as participants. Eight of them were alcoholics, and five experienced frequent blackouts. After fasting for 5 hrs, the experimental procedure was to drink 16-18 ounces of 86 proof bourbon on the rocks in 4 hrs. Cognitive testing began after the first hour of drinking to assess immediate, short-term, and remote memory as well as calculation abilities. In brief, the drunk participants looked at toys and watched porn and were asked to recall these items after a delay (Goodwin et al., 1970):The tests were as follows. (a) Every 30 min the subject was shown a toy for 1 min, after which it was removed from sight. Two minutes later the subject was asked to recall the toy. If recalled correctly immediate memory was considered intact. Thirty minutes later he as asked again to recall the toy to measure short term memory...(b) Every 30 min the subject was shown for 1 min a scene from an erotic movie. He was asked to describe and discuss the scene. If he could recall the scene 2 min later, this was considered a reflexion of intact immediate memory. Thirty minutes later he was again asked to recall the scene to measure short term memory.(c) Remote memory was tested by asking questions about early upbringing (name of schools, teachers, and so on) and events that occurred during the previous 2 days.(d) Ability to perform calculations was tested by asking the subject to do simple multiplication and subtraction tasks.Other than wanting to create a highly desirable means of employment for the target population, why did the authors use erotic movies as stimuli?? (1) So that memory for arousing, emotional material could be compared to memory for the [presumably] more neutral toys; (2) Because very drunk men would be unwilling or unable to cooperate if more boring tests were used; and (3) Toys and porn were highly memorable to sober male subjects 24 hrs later.The results indicated that all 10 subjects performed well when tested at the 2 min retention interval, but half of them showed impaired memory when tested 30 min and 24 hrs later. These same 5 participants were the ones with histories of blackouts. The authors speculated that the faster rise in blood alcohol levels (BAL) in the blackout subjects could be a reason for their amnesia. However, this explanation is implausible because the blackout group had poor memories at the earliest 30 min time point, when there was no difference in BAL between the groups.So what have we learned? Retrieval of remote memories and simple calculation abilities are not impaired by heavy drinking, is possible to predict amnesia during a drinking bout: on formal testing individuals who are later to experience amnesia will have a specific loss of short therm memory correlated in time with the period of amnesia, while other types of memory are intact.A final lesson is that it was much easier to publish in Nature in 1970. Group comparisons with n=5? Fine and dandy. Pesky statistics and error bars on figures? Who needs them? Those were the days my friend...ReferencesGOODWIN, D., OTHMER, E., HALIKAS, J., & FREEMON, F. (1970). Loss of Short Term Memory as a Predictor of the Alcoholic “Blackout” Nature, 227 (5254), 201-202. DOI: 10.1038/227201a0Rose, M. & Grant, J. (2010). Alcohol-Induced Blackout. Journal of Addiction Medicine, 4 (2), 61-73.
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  • December 31, 2011
  • 11:21 PM

Alcohol Blackout

by The Neurocritic in The Neurocritic

This post is for all you New Year's Eve party goers who don't remember where you were or what you did. If that's the case, then you experienced an alcohol-induced blackout. Haven't you always wondered about the clinical manifestations and neurobiological mechanisms of alcohol-induced blackouts? Maybe you have, but you can't remember.A definitive review of the phenomenon by Rose and Grant (2010) explains that there are two different types of blackout: en bloc, a complete loss of memory for the affected time period; and fragmentary, where bits and pieces of memories remain. The en bloc blackout is more likely to occur when a large quantity of alcohol is ingested within a small time period.What causes an alcohol blackout? A good source of information on the topic is the NIAAA website: What Happened? Alcohol, Memory Blackouts, and the Brain:Alcohol primarily interferes with the ability to form new long–term memories, leaving intact previously established long–term memories and the ability to keep new information active in memory for brief periods. ... Blackouts are much more common among social drinkers—including college drinkers—than was previously assumed, and have been found to encompass events ranging from conversations to intercourse. Mechanisms underlying alcohol–induced memory impairments include disruption of activity in the hippocampus, a brain region that plays a central role in the formation of new autobiographical memories.Rose and Grant (2010) summarize the suspected hippocampal mechanisms as follows:Blackouts are caused by breakdown in the transfer of short-term memory into long-term storage and subsequent retrieval primarily through dose-dependent disruption of hippocampal CA1 pyramidal cell activity. The exact mechanism is believed to involve potentiation of gamma-aminobutyric acid-alpha [GABA-A]-mediated inhibition and interference with excitatory hippocampal N-methyl-d-aspartate [NMDA] receptor activation, resulting in decreased long-term potentiation [LTP].In addition...Another possible mechanism involves disrupted septohippocampal theta rhythm activity because of enhanced medial septal area gamma-aminobutyric acid [GABA]-ergic neurotransmission. Women are more susceptible to alcohol blackouts than men (and recover more slowly) because of their generally less muscular body composition, and gender differences in pharmacokinetics.Cheers to knowing what's happening in your brain after downing a few too many Jell-O shots. If you can remember tomorrow...ReferenceRose, M., & Grant, J. (2010). Alcohol-Induced Blackout Journal of Addiction Medicine, 4 (2), 61-73 DOI: 10.1097/ADM.0b013e3181e1299d

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Rose, M., & Grant, J. (2010) Alcohol-Induced Blackout. Journal of Addiction Medicine, 4(2), 61-73. DOI: 10.1097/ADM.0b013e3181e1299d  

  • December 24, 2011
  • 09:07 PM

Orthopedic Surgeons vs. Anesthesiologists

by The Neurocritic in The Neurocritic

from Subramanian et al. 2011 [Image: Clive Featherstone]Every year, BMJ [British Medical Journal] has a special Christmas issue with spoof articles and silly studies. Favorites from the past include:Sword Swallowing And Its Side EffectsSex, aggression, and humour: responses to unicyclingRage Against the Machine Syncope and the Texting SignWhy are the letters "z" and "x" so popular in drug names?The clear winner this year is a revenge piece by a group of orthopaedic surgeons and trainees (Subramanian et al., 2011) that convincingly demonstrates they are stronger and smarter [?] than their colleagues the anesthesiologists (anaesthetists in the UK). The motivation for such a study is as follows:A humorous anaesthetic colleague recently repeated the following popular saying while an operating table was being repaired with a mallet: “typical orthopaedic surgeon—as strong as an ox but half as bright.” Making fun of orthopaedic surgeons is a popular pastime in operating theatres throughout the country. This pursuit has recently spread to the internet; a humorous animation entitled “orthopedia vs anesthesia” had received more than half a million hits at the time of writing.1 Several comparisons of orthopaedic surgeons to primates have been published, and the medical literature contains suggestions that orthopaedic surgery requires brute force and ignorance.2 3 4The stereotypical image of the strong but stupid orthopaedic surgeon has not been subject to scientific scrutiny. Previous studies have shown that the average hand size of orthopaedic surgeons is larger than that of general surgeons.2 3 However, a search of the worldwide scientific literature found no studies assessing the strength or intelligence of orthopaedic surgeons. In the absence of a cohort of willing oxen as a control group, and given that the phrase is popular with anaesthetists, we designed this study to compare the mean grip strength of the dominant hand and the intelligence test score of orthopaedic surgeons and anaesthetists.The participants in the study were 36 male orthopaedic surgeons (there were no female OS's available) and 40 male anaesthetists (the six women who volunteered were excluded). They were recruited from three hospitals over a 2 week period. Grip strength was tested with a hand dynamometer. The proxy for IQ was rather unacceptable however - the Mensa Brain Test version 1.1.0 administered on an iPhone 4. The validity of the IQ measure was apparently irrelevant and the results were actually laughable, befitting the spoof study format.Fig 3 (Subramanian et al. 2011). Box plot of intelligence test score by specialty. Upper and lower whiskers represent 1.5 times and −1.5 times interquartile range; upper and lower hinges represent 25% and 75% quartiles; middle represents median or 50% quartileThe means for IQ were 98.38 for the anaesthetists vs. 105.19 for the orthopaedists, which squeaked in as a significant difference at p=0.0489 (although there was quite a bit of overlap between the groups). A few more things are notable about this result:(1) mean IQ for the entire population is 100, and it would be surprising if licensed professionals who are graduates of medical schools and residency programs were of entirely average intelligence. A 2002 paper {PDF} on male high school graduates in Wisconsin (class of 1957)1 found that doctors had the highest IQ (120) of all professions.(2) One anaesthetist tested in the mentally retarded range: below 70, which is over two standard deviations from the average IQ of 100. This would make him a very unique savant anesthesiologist. At any rate, if you threw out his score, the difference between groups would no longer be significant.(3) Test results from two more anaesthetists suggested borderline intellectual functioning (between 70–84). A couple more doctors from each category were right on the edge of this borderline, which again would be highly improbable.The authors did acknowledge some of these weaknesses:The intelligence scores were lower than anticipated for IQ in the medical profession. This is likely to be a reflection of the way in which intelligence was tested, and the scores derived from the rather difficult Mensa brain test may not be directly comparable to IQ scores. We selected the abbreviated Mensa test carried out by touch screen for speed and convenience. Full formal IQ testing is more time consuming and cumbersome and would have affected doctors’ willingness to participate in this study.Moving on to the other major finding, it was no surprise that the orthopaedic surgeons had greater grip strength than the anaesthetists (p=0.0274). But a quick peak at Fig 2 shows that one exceptionally strong OS helped drive this small difference.But who am I to be a scrooge and spoil the fun of the orthopaedic surgeons, who think they finally have intellectual bragging rights over the anesthesiologists?ConclusionThe stereotypical image of male orthopaedic surgeons as strong but stupid is unjustified in comparison with their male anaesthetist counterparts. The comedic repertoire of the average anaesthetist needs to be revised in the light of these data. However, we would recommend caution in making fun of orthopaedic surgeons, as unwary anaesthetists may find themselves on the receiving end of a sharp and quick witted retort from their intellectually sharper friends or may be greeted with a crushing handshake at their next encounter.Footnote1 Obviously, that study (Hauser, 2002) was based on very old data from one US state. Results may differ in the contemporary UK, as described in this authoritative report in the Daily Mail: Why doctors are not as clever as they used to be.Reference... Read more »

  • December 19, 2011
  • 12:56 AM

The Disconnection of Psychopaths

by The Neurocritic in The Neurocritic

Functional connectivity between the right amygdala and anterior vmPFC is reduced in psychopaths. From Fig. 2 of Motzkin et al., (2011).The last post discussed the case of a 14 yr old boy with congenital brain abnormalities and severe antisocial behavior said to be "consistent with" psychopathy. This label is quite stigmatizing and the diagnosis is a controversial one (Skeem et al., 2011),1 particularly in children. What is psychopathy, exactly? According to Ermer and colleagues (2011),Psychopathy is a serious personality disorder marked by affective and interpersonal deficiencies, as well as behavioral problems and antisocial tendencies (Cleckley, 1976). Affective and interpersonal traits (termed Factor 1) include callousness and a profound inability to experience remorse, guilt, and empathy; antisocial and behavioral problems (termed Factor 2) include impulsivity, stimulation seeking, and irresponsibility. These symptoms tend to manifest at an early age, continue throughout adulthood, and pervade numerous aspects of psychopaths’ daily functioning.As for the brain regions implicated in psychopathy, dysfunction in the amygdala and ventromedial prefrontal cortex (vmPFC) have been suspected for quite some time (Abbott, 2001; Blair, 2007; Koenigs et al., 2011). From this perspective, a recent study on the structural and functional connectivity of these two regions (Motzkin et al., 2011) isn't entirely groundbreaking. However, the logistics of conducting those experiments were anything but simple: the participants were male inmates of a medium security prison in Wisconsin.Kent Kiehl outside the mobile scanner he has used to look at the brains of inmates at a New Mexico prison. Credit: Nature News.Dr. Kiehl's work with criminal psychopaths has been featured in the New Yorker. In the present study, diffusion tensor imaging (DTI) and resting state fMRI were used to examine the structural and functional connectivity of the vmPFC (Motzkin et al., 2011), which has been associated with decision making and the regulation of emotional behavior. The Psychopathy Checklist-Revised (PCL-R) (Hare, 2003)2 was administered to the participants. Those with scores >30 were classified as psychopaths, while the non-psychopaths scored <20.In the DTI study of structural connectivity, 13 non-psychopaths were compared to 14 psychopaths, 7 of whom were low-anxious or primary psychopaths and 7 were high-anxious/secondary psychopaths.3 The uncinate fasciculus (UF) is the main pathway connecting the vmPFC and the anterior temporal lobe (including the amygdala). Fractional anisotropy (FA), a measure of white matter structural integrity, was compared between the groups for regions of interest (after scaling for overall whole brain FA, which was reduced in the psychopaths). For comparison, FA in other frontal-temporal tracts was examined. Results indicated that FA was indeed reduced in the right UF, which replicates an earlier study (Craig et al., 2009).Fig. 1 (modified from Motzkin et al., 2011). DTI results: reduced white matter integrity is specific to the right UF in psychopaths. b, The UF ROI (red) superimposed on an entire UF tract, as computed with tractography. f, Bar plots of mean scaled FA values in the UF. Psychopaths exhibited significantly lower scaled FA values only in right UF. Error bars indicate SEM. *p < 0.05. Resting state fMRI, which measures spontaneous, low-frequency fluctuations in BOLD signal, was used to examine functional connectivity. In this experiment, 20 prisoners who were not psychopaths were compared to 20 prisoners who were considered psychopaths. Based on the DTI study, the right amygdala was used as a "seed region" to examine functional connectivity with vmPFC. In addition, the medial parietal cortex (precuneus and posterior cingulate) was used as a seed region, because this area is also reciprocally interconnected with vmPFC. If the amygdala-vmPFC and medial parietal-vmPFC circuits are not functioning properly, it was expected that correlated activity between regions would be lower. And indeed, that's what was observed in the psychopaths: resting vmPFC BOLD signal was less correlated with amygdala and medial parietal activity.Fig. 3 (modified from Motzkin et al., 2011). Functional connectivity between medial parietal cortex and vmPFC is reduced in psychopaths. [...] The group difference map indicates two separate clusters within vmPFC where non-psychopaths have significantly greater connectivity with the precuneus/PCC seed than psychopaths (vmPFC and rACC). b, Group differences in connectivity were assessed in the vmPF... Read more »

Sundt Gullhaugen A, & Aage Nøttestad J. (2011) Looking for the hannibal behind the cannibal: current status of case research. International journal of offender therapy and comparative criminology, 55(3), 350-69. PMID: 20413645  

Motzkin JC, Newman JP, Kiehl KA, & Koenigs M. (2011) Reduced prefrontal connectivity in psychopathy. The Journal of neuroscience : the official journal of the Society for Neuroscience, 31(48), 17348-57. PMID: 22131397  

  • December 15, 2011
  • 12:51 AM

Born This Way?

by The Neurocritic in The Neurocritic

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

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

  • December 2, 2011
  • 12:31 AM

Meth Really Isn't That Bad for You? (Part 2)

by The Neurocritic in The Neurocritic

Methamphetamine Use and Risk for HIV/AIDS... Methamphetamine is very addictive, it can be injected, and it can increase sexual arousal while reducing inhibitions. Because of these attributes, public health officials are concerned that users may be putting themselves at increased risk of acquiring or transmitting HIV infection―a valid concern, considering that methamphetamine use has been linked with increased numbers of HIV infections in some populations [1]. 1 Meth addiction can cause alterations in brain function and cognitive performance, according to hundreds of published studies (reviewed in Barr et al., 2006; Baicy & London, 2007). However, a new paper concludes that prior studies have exaggerated the harmful effects of methamphetamine on brain structure and function, cognition, mental health, and dental health (Hart et al., 2011).So who's right? The previous post (Meth Really Isn't That Bad for You... Or is it?) covered the acute effects of meth on cognitive performance. This post will focus on the cognitive consequences of chronic meth abuse. The bulk of the literature suggests that long-term use "leads to neurocognitive deficits in a dose-dependent manner, with deficits relating to both the frequency and severity of METH dependence" (McCann et al., 2008). In that study, chronic meth users performed worse than controls on some tests of memory and attention, with intact performance on other tests. Another paper found similar differences between controls and former meth users (abstinent anywhere from 3 months to over 1o yrs) on some tests but not others (Johanson et al. , 2006). Those authors were cautious in interpreting their findings:In the present study, MA users showed deficits in the DSST [Digit Symbol Substitution Test] of the WAIS-III relative to the controls. However, neither the mean standard score (9.63) nor individual scores were greater than one SD (3) below the age-controlled norm (10.0). This finding suggests that although MA may produce long-term, possibly irreversible deficits in speed and accuracy of information manipulation, these deficits are relatively small and for some may not reach clinical significance. ...and...In the present investigation, MA users showed significantly poorer performance on several of the subtests of the CVLT [California Verbal Learning Test] including both cued and noncued short and long delayed recall. However, despite this statistically significant difference compared to controls, their performance was not outside the normal range for their age group. Thus, the functional significance of these differences in memory function is questionable. Nevertheless, it seems likely that these deficits are permanent because they were not correlated with duration of abstinence. It is obvious that the possibility remains that these deficits predated drug use but the present study cannot address this possibility.These statements were much appreciated in the review article, which repeatedly downplayed observations of poorer performance as having any functional significance whatsoever. However, I will draw your attention to Johanson et al. 's inclusionary criteria and their table below:To qualify for the study, MA participants had to report at least one 3-month period when they experienced MA-induced toxic symptoms (agitation, sleeplessness, paranoia, or tremors). Table 5 (Johanson et al. , 2006). Other self-reported symptomsClearly, every symptom listed above is of functional significance. Meth use was detrimental to many areas of their lives when they were using. However, those participants were given the cognitive tests a mean of 3.4 yrs after they stopped using. We'll return to the issue of recovery a bit later.Returning now to the comparison of acute low dose meth vs. chronic abuse, in the abstract Hart et al. (2011) stated:In general, the data on acute effects show that methamphetamine improves cognitive performance in selected domains, that is, visuospatial perception, attention, and inhibition. Regarding long-term effects on cognitive performance and brain-imaging measures, statistically significant differences between methamphetamine users and control participants have been observed on a minority of measures.Let’s take a closer look. Of the 16 studies on the acute effects of meth shown in Table 1 of Hart et al., five of them (by the authors) tested inhibitory control. Meth had no effect on inhibition performance in any of those studies.Am I just being persnickety? Well, if the authors are going to say that long-term meth abuse results in “poorer performance on a minority of cognitive tasks” [which appears to be true in many cases], they should be more precise when describing their own data. Perhaps something like this: "Acute meth sometimes improves the performance of infrequent users on a minority of cognitive tasks, but these results are inconsistent (see Table 1)."Again, what about the specific cognitive impairments observed in chronic abusers? There was a didactic paragraph on the use on the word “impairment”:The literature on methamphetamine use is focused on ‘impairment,’ and seems to conflate two different meanings of this term. One meaning is captured by the canonical situation in which one group of participants performs statistically significantly less well on a task than does a control group. Although there is a statistically significant difference, its clinical relevance, or everyday import, is rarely specified. A second meaning of ‘impairment’ is that of a substantial loss of function, a dysfunction, in which performance may even fall outside of normal range and bears clinical significance. (The two meanings probably represent end points on a continuum of meanings of ‘impairment’ that appears in the general literature on group differences.) The problem in the literature on methamphetamine use is that in many studies the results support only the first or difference interpretation, but the results are discussed in terms of the ‘dysfunctional’ interpretation. In essence, the English word ‘impairment’ (or ‘deficit’) is ambiguous, and researchers in this field often switch meanings in moving from actual findings to discussion of the implications of these findings.One reason for avoiding use of the word “impairment” is to reduce the stigma attached to meth abuse, which is an important goal. To that end, it’s puzzling that the authors failed to cite some of the literature on recovery.GREEN RED BLUEOne such paper (Salo et al., 2009) compared 38 recently-abstinent meth abusers (3 weeks to 6 months), 27 longer-abstinent meth abusers (at least 1 yr), and 33 controls on the Stro... Read more »

Salo, R., Nordahl, T., Galloway, G., Moore, C., Waters, C., & Leamon, M. (2009) Drug abstinence and cognitive control in methamphetamine-dependent individuals. Journal of Substance Abuse Treatment, 37(3), 292-297. DOI: 10.1016/j.jsat.2009.03.004  

  • November 29, 2011
  • 06:28 AM

Meth Really Isn't That Bad for You... Or is it?

by The Neurocritic in The Neurocritic

Image from All Around The House™We all know that meth is a highly addictive, harmful stimulant drug that rots your teeth and makes you paranoid, stupid, unemployed, and homeless -- thereby ruining your life. So just say NO! to meth. Right, kids?Methamphetamine (meth) and other stimulants are best known for their effects on the dopamine system, and hence for their propensity to be reinforcing and addictive. But meth actually increases the release and blocks the reuptake of all three monoamine neurotransmitters (norepinephrine and serotonin as well as dopamine). Meth addiction can cause alterations in brain function and cognitive performance, according to hundreds of published studies (reviewed in Barr et al., 2006; Baicy & London, 2007). The NIDA website lists a multitude of adverse effects from chronic heavy use:Long-term methamphetamine abuse has many negative health consequences, including extreme weight loss, severe dental problems (“meth mouth”), anxiety, confusion, insomnia, mood disturbances, and violent behavior. Chronic methamphetamine abusers can also display a number of psychotic features, including paranoia, visual and auditory hallucinations, and delusions...However, a new review article by Hart et al. (2011) concludes that prior studies have exaggerated the harmful effects of methamphetamine on brain structure and function, cognition, mental health, and dental health. In my view, one problem with this endeavor arises in the very first sentence of the abstract:The prevailing view is that recreational methamphetamine use causes a broad range of severe cognitive deficits, despite the fact that concerns have been raised about interpretations drawn from the published literature. This article addresses an important gap in our knowledge by providing a critical review of findings from recent research investigating the impact of recreational methamphetamine use on human cognition.Many people can use meth recreationally, in modest doses, without becoming dependent. In fact, the review begins by noting the performance enhancing effects of meth in high-functioning, healthy adults who are occasional users. These laboratory studies are conducted in a very controlled environment, using oral administration of pharmaceutical grade methamphetamine. No one disputes that acutely administered meth can have beneficial effects on cognitive performance (Barr et al., 2006):Numerous studies have confirmed that MA abuse is associated with cognitive impairment. Unlike the acute effects of a single low dose of MA, which can improve cognitive processing speed, attention, concentration and psychomotor performance,77,78 long-term exposure to MA may result in profound neuropsychological deficits (see Nordahl et al2).But how does acute meth affect the performance of meth abusers? Here, the authors cite their own work on the intranasal administration of 3 doses + placebo to 11 meth abusers (Hart et al., 2008). The same computerized battery of 5 cognitive tests was given to the participants during each session. The results in their entirety:Figure 4 shows how methamphetamine altered performance over time on selected measures.1 As can be seen, methamphetamine improved performance on both of the selected tasks. On the DAT [divided attention task, for vigilance], all active methamphetamine doses decreased the mean hit latency and increased the maximum tracking speed (P<0.05). On the DSST [digit-symbol substitution task, for visuospatial processing], only the two intermediate doses (12 and 25 mg) significantly improved performance. Relative to placebo, both doses increased the total number of trial attempts and correct responses (P<0.03). No other significant performance effects were noted.There is no explanation of why these two tasks were "selected" instead of the other three. Nor is there any indication of how this performance compares to "normative data" or to participants who are not meth abusers. This is a bit ironic, because the most annoying critique within the review is the repeated failure to accept the performance of control subjects as valid. Sure, acute meth did speed up performance on "selected" measures of "selected" tasks, but was this generally better or worse than what's observed in those without a history of long-term meth abuse?When evaluating whether meth really isn't that bad for you, my focus is on the chronic effects of meth in long-term abusers of the drug. I'll return to this critical issue in the next post.Footnote1 An intriguing aspect of the data is that a massive performance drop was seen from time 0 to time 15 min in the placebo condition. One could speculate that the participants knew by then that they weren't on meth. The "Good Drug Effects" and "Stimulated" self-report ratings peaked at 15 min post-snort, so there's a disappointment-related decrement on placebo.Figure 4. Selected performance effects as a function of methamphetamine dose and time. Error bars represent one SEM. Overlapping error bars were omitted for clarity.ReferencesBaicy K, London ED. (2007). Corticolimbic dysregulation and chronic methamphetamine abuse. Addiction 102 Suppl 1:5-15.Barr AM, Panenka WJ, MacEwan GW, Thornton AE, Lang DJ, Honer WG, Lecomte T. (2006). The need for speed: an update on methamphetamine addiction. J Psychiatry Neurosci. 31:301-13.... Read more »

Hart, C., Gunderson, E., Perez, A., Kirkpatrick, M., Thurmond, A., Comer, S., & Foltin, R. (2007) Acute Physiological and Behavioral Effects of Intranasal Methamphetamine in Humans. Neuropsychopharmacology, 33(8), 1847-1855. DOI: 10.1038/sj.npp.1301578  

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