The Neurocritic

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

The Neurocritic
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  • September 15, 2010
  • 06:51 AM

Modern Tract-Tracing for Historical Psychosurgery

by The Neurocritic in The Neurocritic

Figure 3 (Schoene-Bake et al., 2010). Intersection of connectivity maps of Anterior Capsulotomy (red), Anterior Cingulotomy (blue), and Subcaudate Tractotomy (green) tracking results. Overlap of AC and ACT shown with magenta, AC and SCT in yellow, and ACT and SCT in cyan. The white area shows overlapping of AC, ACT, and SCT mean probability-tracking maps in axial (a), coronal (b), and sagittal (c) slices. Acg, anterior cingulate gyrus; ATR, anterior thalamic radiation; CST, corticospinal tract; FM, forceps minor; FP, frontal pole; Nacc, accumbens nucleus; PAG, periaqueductal grey matter; slMFB, superolateral branch of medial forebrain bundle; Thal, thalamus.When I first saw a journal article titled Tractographic Analysis of Historical Lesion Surgery for Depression, I assumed the authors (Schoene-Bake et al., 2010) located some elderly patients who had received psychosurgery in the 1960s, then scanned them using diffusion tensor imaging to trace the white matter tracts affected by the surgeries. This was not the case, however. Instead, the paper is a lesion simulation study that used MRIs from a large sample of control participants.Although this revelation was initially disappointing, the results included the pretty colorized DTI figure shown above.1 And it reviewed the four historical surgical approaches and their anatomical targets, shown in the table below.Jumping ahead to the punchline, what were the conclusions?Shared connectivities between the four surgical approaches mapped onto the most mediobasal aspects of bilateral frontal lobe fibers, including the forceps minor and the anterior thalamic radiations that contacted subgenual cingulate regions [Brodmann area 25]. Anatomically, convergence of these shared connectivities may derive from the superolateral branch of the medial forebrain bundle (MFB), a structure that connects these frontal areas to the origin of the mesolimbic dopaminergic ‘reward’ system in the midbrain ventral tegmental area [VTA]. Thus, all four surgical anti-depressant approaches may be promoting positive affect by converging influences onto the MFB.Putting aside for a moment the actual efficacy of these surgeries, the claim is that disconnection of the "sad cingulate" from the VTA was at least partly responsible for improved mood. In modern times, the subgenual cingulate has been a target for deep brain stimulation (DBS) trials for intractable major depression (Mayberg et al., 2005; Lozano et al., 2008). In contrast to creating a permanent lesion, in DBS a stimulating electrode is stereotaxically implanted in the targeted region. Dr. Helen Mayberg and her colleagues at Emory University are still recruiting patients with treatment resistant depression to participate in a clinical trial using chronic, high frequency stimulation of the subgenual cingulate white matter.To determine the anatomical connectivity of the subgenual cingulate region, these researchers performed tractography (using diffusion-weighted MRI) to trace the pathways mediating treatment response with DBS (Johansen-Berg et al., 2007). The authors compared the connections of the subgenual ACC (sACC, blue/cyan) and the perigenual ACC (pACC, red/yellow).Figure 3 (Johansen-Berg et al., 2007). Connectivity-based parcellation of ACC and location of electrode contacts. (A, B) Population probability maps of connectivity-defined sACC and pACC. Color scales represent the population probability of a voxel belonging to sACC (from 50% [dark blue] to 80% [light blue] probability) or pACC (from 50% [red] to 80% [yellow] probability). Also shown are the locations of effective electrode contacts from 9 patients overlaid in black. Effective electrode locations are mainly localized within the sACC subregion.Resting metabolic activity in subgenual cingulate was shown to be increased in the patients with treatment-resistant depression (Mayberg et al., 2005):The baseline pattern of subgenual cingulate hyperactivity in combination with frontal hypoactivity described here in this TRD patient group is a finding that is in contrast to the hypoactivity reported in a more rostral region of subgenual medial prefrontal cortex in familial bipolar and unipolar depressed patients (Drevets et al., 1997). This distinction suggests important differences across subtypes of depression that are potentially relevant to the pathophysiology of major depressive disorders and perhaps their treatment.Reflecting further on the historical lesion data, one might infer that a hyperactive subgenual cingulate ultimately inhibited activity in the VTA, a dopamine "reward center". The idealized lesions for all four surgical approaches are shown in the simulation below.Figure 1 (Schoene-Bake et al., 2010). Mean probability maps of simulated lesions. (a) Anterior capsulotomy (AC); (b) anterior cingulotomy (ACT), I - sagittal, II - coronal, III - axial; (c) subcaudate tractotomy (SCT); and (d) stereotactic limbic leucotomy (SLL).I would like to see how these simulated lesions compare to the actual surgical lesions from days of yore. Schoene-Bake et al. (2010) hope that a look back at the past will enhance the future of depression treatment:DTI probabilistic connectivity analysis is a useful tool to explore and to simulate the structural and functional impact of past stereotactic lesion surgery app... Read more »

Schoene-Bake, J., Parpaley, Y., Weber, B., Panksepp, J., Hurwitz, T., & Coenen, V. (2010) Tractographic Analysis of Historical Lesion Surgery for Depression. Neuropsychopharmacology. DOI: 10.1038/npp.2010.132  

  • September 6, 2010
  • 04:23 AM

Limbaugh/Palin "death panels" extend the lives of terminally ill patients

by The Neurocritic in The Neurocritic

What is palliative care? Until quite recently, it's something I haven't given much thought. Although there was a highly regarded article on hospice and palliative care by Atul Gawande in last month's New Yorker, I didn't read it or think it applied to my life. All that changed less than two weeks ago, when my father was hospitalized in critical condition after collapsing. First he went to the ER, then the transitional ICU, and finally he was placed in the palliative care unit by the time I arrived. You see, my father has metastatic lung cancer, for which he had refused treatment for more than a year. Instead, he decided to stay home with my mother, watch DVDs, go out to eat, and do yard work.1A recent paper in the New England Journal of Medicine demonstrated that the introduction of palliative care shortly after the diagnosis of metastatic lung cancer not only improved the patients' quality of life, but also extended median survival from 8.9 months to 11.6 months (Temel et al., 2010). According to the American Academy of Hospice and Palliative Medicine:The goal of palliative care is to prevent and relieve suffering and to support the best possible quality of life for patients and their families, regardless of the stage of the disease or the need for other therapies. Palliative care is both a philosophy of care and an organized, highly structured system for delivering care. Palliative care expands traditional disease-model medical treatments to include the goals of enhancing quality of life for patient and family, optimizing function, helping with decision-making and providing opportunities for personal growth. As such, it can be delivered concurrently with life-prolonging care or as the main focus of care.This finding is critically important for providers of medical care for terminally ill cancer patients as well as for health policy, because it provides categorical, scientific proof that the notion of "death panels" is false. As stated in the New York Times:“It shows that palliative care is the opposite of all that rhetoric about ‘death panels,’ ” said Dr. Diane E. Meier [@DianeEMeier], director of the Center to Advance Palliative Care at Mount Sinai School of Medicine and co-author of an editorial in the journal accompanying the study. “It’s not about killing Granny; it’s about keeping Granny alive as long as possible — with the best quality of life.”A straw man in the 2009 health care debate, "death panels" invoked the specter of rationing medical procedures provided for the sick and the elderly. In the name of cost cutting, blared the phony rhetoric on talk radio and Sarah Palin's Facebook page, the Obama administration would sanction euthanasia for elders and the terminally ill under provisions of the health care bill. This would save on expensive treatments that prolong patients' lives but increase the deficit, claimed the conservative crew. However, these scare tactics were an outright lie, as we learn from the Wall Street Journal:Palin’s “Death Panels” Charge Named “Lie of the Year”...“Of all the falsehoods and distortions in the political discourse this year, one stood out from the rest,” writes, the non-partisan, Pulitzer Prize-winning site run by the St. Petersburg Times. Palin’s “assertion — that the government would set up boards to determine whether seniors and the disabled were worthy of care — spread through newscasts, talk shows, blogs and town hall meetings.”“Opponents of health-care legislation said it revealed the real goals of the Democratic proposals. Advocates for health reform said it showed the depths to which their opponents would sink,” says.The NEJM study enrolled 151 patients with newly diagnosed metastatic non–small-cell lung cancer. Seventy-four received standard care and 77 patients received palliative care, which included meetings with a member of the palliative care team (board-certified palliative care physicians and advanced-practice nurses). The first meeting was within 3 weeks of enrollment, and subsequent meetings were held on a monthly basis, with additional sessions at the discretion of the patient and the clinical treatment team. Patients assigned to standard care did not meet with the palliative care team (unless requested). All patients continued to receive standard oncology care for the duration of the study.These meetings are the so-called "death panels" that would have been covered by Medicare, as mentioned by the NYT in Palliative Care Extends Life, Study Finds:During the debate over President Obama’s 2009 health care bill, provisions to have Medicare and insurers pay for optional consultations with doctors on palliative and hospice care led to rumors, spread by talk-show hosts like Rush Limbaugh and Glenn Beck and by the former vice-presidential candidate Sarah Palin, that the bill empowered “death panels” that would “euthanize” elderly Americans. [emphasis mine]The primary outcome measure of the study was quality of life at 12 weeks (compared to baseline), as assessed by the Functional Assessment of Cancer Therapy–Lung (FACT-L) scale. Mood was assessed using the Hospital Anxiety and Depression Scale (HADS) and the Patient Health Questionnaire 9 (PHQ-9).Results indicated that patients in the palliative care group had a significantly higher quality of life at 12 weeks (see Table 2) and a lower incidence of depression (but similar levels of anxiety).[click on Table for larger image]Table 2 (Temel et al., 2010). Plus–minus values are means ±SD. Quality of life was assessed with the use of three scales: the FACT-L scale, on which scores range from 0 to 136, with higher scores indicating better quality of life; the lung-cancer subscale (LCS) of the FACT-L scale, on which scores range from 0 to 28, with higher scores indicating fewer symptoms; and the Trial Outcome Index (TOI), which is the sum of the scores on the LCS and the physical well-being and functional well-being subscales of the FACT-L scale (scores range from 0 to 84, with higher scores indicating better quality of life).In addition, patients in the palliative care group lived longer:Despite receiving less aggressive end-of-life care,2 patients in the palliative care group had significantly longer survival than those in the standard care group (median survival, 11.6 vs. 8.9 months; P=0.02).The study has its limitations, however, as noted by Dr. Meier in Palliative Care: We Still Have a Lot to Learn:...The patients (and doctors) were not blinded to their treatment group, that is, they knew which group they were in, which could have affected their outcomes. Also, there was no “attention-control” group—a group that got the same amount of human time and attention that the palliative care group got but without the palliative care skill and expertise.Nonetheless, the purpose and goals of palliative care cannot be understated. As I mentioned in my previous post... Read more »

J.S. Temel et al. (2010) Early Palliative Care for Patients with Metastatic Non–Small-Cell Lung Cancer. N Engl J Med, 733-742. info:/10.1056/NEJMoa1000678

  • August 30, 2010
  • 12:58 PM

Ketamine for Depression: Yay or Neigh?

by The Neurocritic in The Neurocritic

Venn diagram of psychoactive drugs [click for larger image]This post is part of a Nature Blog Focus on hallucinogenic drugs in medicine and mental health, inspired by a recent Nature Reviews Neuroscience paper, The neurobiology of psychedelic drugs: implications for the treatment of mood disorders, by Franz Vollenweider & Michael Kometer. This article will be available, open-access, until September 23. For more information on this Blog Focus, including a Table of Contents, please visit The Great Beyond.The secret history of psychedelic psychiatry is discussed over at Neurophilosophy. Neuroskeptic covers Serotonin, Psychedelics and Depression while Mind Hacks provides a personal look at yagé in Visions of a psychedelic future.Veterinary Anesthetic, Club Drug, or Antidepressant?Club drug "Special K" (aka ketamine) is stepping out of the laser light into the broad daylight of mainstream psychiatry with the publication of a new review article by Vollenweider and Kometer (2010). Long used to anesthetize animals (and children), ketamine was classified as a "dissociative anesthetic" by Domino et al. (1965) for its combined effects of sedation/analgesia and hallucinations. Domino (2010) recently revisited his classic paper, which reported on a study in 20 volunteers incarcerated at the Jackson Prison in Michigan:The first human was given ketamine in an intravenous subanesthetic dose on August 3, 1964. Guenter [Corssen, M.D.] and I gradually increased the dose from no effect, to conscious but “spaced out,” and finally to enough for general anesthesia. Our findings were remarkable! The overall incidence of side effects was about one out of three volunteers. Frank emergence delirium was minimal. Most of our subjects described strange experiences like a feeling of floating in outer space and having no feeling in their arms or legs. The ego death of the "K hole" can be a terrifying experience for some ("I ceased to exist") or transformative for others ("I witnessed myself as a part of the universal collective of strange energy")1. In their Nature Reviews Neuroscience opinion piece, Vollenweider and Kometer considered ketamine a psychedelic, along with the traditional hallucinogens such as LSD, psilocybin, and mescaline. They noted that both classes of drugs may have psychotherapeutic effects through actions on the excitatory glutamate neurotransmitter system.Ketamine is an antagonist of the glutamate NMDA receptor and is thought to work by blocking NMDA receptors on inhibitory GABA-containing interneurons, ultimately promoting glutamate release. In a scientific tour de force, Li and colleagues (2010) demonstrated that the mTOR (mammalian target of rapamycin) protein kinase pathway is rapidly activated by ketamine. This sets off a cascade of events including the formation of new synapses on dendritic spines. Using a combination of cellular, molecular, electrophysiological, behavioral, and phamacological techniques, ketamine was shown to exhibit antidepressant properties in animal models of depression and anxiety, perhaps via rapid induction of synaptic plasticity in the medial prefrontal cortex (PFC). Regions of the medial PFC in humans, particularly the ventral anterior cingulate cortex, have been implicated in the pathophysiology of major depression.Human clinical trials of ketamine as a rapidly acting antidepressant aren't especially new. A randomized, double-blind study in 2000 involved administration of saline or a single subanesthetic dose of ketamine (0.5 mg/kg intraveneously) to nine depressed patients, seven of whom completed the trial (Berman et al., 2000). Within 72 hrs, amelioration of depressive symptoms was observed. Half of the treated patients showed a 50% or greater improvement in depression scores. However, these therapeutic effects weren't very long-lasting, returning to baseline levels in 1-2 weeks. In a larger study, 18 patients with major depression participated in a similar double-blind cross-over design where they received the 0.5 mg/kg dose of ketamine and placebo one week apart (Zarate et al., 2006). The patients were rated at baseline and at 40, 80, 110, and 230 minutes and 1, 2, 3, and 7 days post-infusion on a number of clinical scales, including the Hamilton Depression Rating Scale (HDRS), the Brief Psychiatric Rating Scale (BPRS) positive symptoms subscale, and the Young Mania Rating Scale (YMRS).The primary outcome measure was change in HDRS score, shown in Figure 2 below (top graph). Significant improvements began at the 110 min time point. Scores declined further from 1-3 days and remained below placebo levels for 7 days. However, unusual experiences were noted at 40 min, with substantial increases in scores for psychosis-like and mania-like symptoms. Other adverse events associated with ketamine included......perceptual disturbances, confusion, elevations in blood pressure, euphoria, dizziness, and increased libido. ... The majority of these adverse effects ceased within 80 minutes after the infusion. In no case did euphoria [YMRS] or derealization/depersonalization [BPRS] persist beyond 110 minutes (Figure 2, middle and bottom graphs).Figure 2 (Zarate et al., 2006). Change in the 21-item HDRS, BPRS positive symptoms subscale, and YMRS scores over 1 week (n=18). Values are expressed as generalized least squares means and standard errors for the completer analysis. * indicates PSo here we have several research groups that say yay! to ketamine as an antidepressant. Are there any naysayers?Although the immediate onset of symptom amelioration gives ketamine a substantial advantage over traditional antidepressants (which take 4-6 weeks to work), there are definite limitations (Tsai, 2007). Drawbacks include the possibility of ketamine-induced psychosis (Javitt, 2010), limited duration of effectiveness (aan het Rot et al., 2010), potential long-term deleterious effects such as white matter abnormalities (Liao et al., 2010), and an inab... Read more »

  • August 15, 2010
  • 06:47 PM

Airplane Headache

by The Neurocritic in The Neurocritic

Cartoon Reenactment of JetBlue Flight Attendant’s Dramatic ExitNo, the term "airplane headache" does not refer to disgruntled JetBlue flight attendant Steven Slater (or to being a passenger on that flight). Instead, it refers to a recently characterized 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.A new case study of a man with airplane headaches has been reported by Domitrz (2010). Clinical details are as follows:A 29-year-old healthy man, who works as a psychologist, reported that during his last airplane journey, he developed a very severe and sudden jabbing headache located in the left frontal region with radiation into the left eye. It started during take-off, diminished during the 2-h flight, a very mild pain was present during the flight and increased during plane’s descent and lasted until a few minutes after landing. Then, the pain completely and spontaneously subsided. The same situation took place 3 days later when the patient was returning. He remembers that he had similar, but milder headaches during previous flights. However, they occurred only during airplane flights and did not develop during jumbo jet flights. Similar headache did not appear in other altitude variation moments, e.g. in mountain trips.The pain was always located in the left frontal region with radiation into the left eye without any autonomic symptoms and neurological focal problems. He could not move until the headache disappeared. The patient has no medical history of sinus problems and using any medications. The family history has shown only tension type headache in patient’s 4 years older sister. General (including blood pressure and heart rate), neurological, otolaryngological and ophthalmological examinations were normal. Brain magnetic resonance imaging also with angiography excluded any structural lesions and arterial malformations. Domitrz (2010) further notes that most reported cases have been in young males, as is her patient. She is also puzzled by why he gets these headaches only on airplanes that are not jumbo jets -- perhaps it is connected with differences in air pressure, she speculates.What causes this specific type of headache? One view is that barotrauma is involved, with pressure changes affecting the trigeminovascular system (Berilgen & Müngen, 2006):We think that barotrauma caused by pressure changes in the cabin during take-off and landing could affect ethmoidal nerves (branching from the ophthalmic branch of the trigeminal nerve) that carry the senses of the mucosa on the inner surface of the paranasal sinuses, and/or nociceptors in ethmoidal arteries, thereby activating the trigeminovascular system and leading to headache.It's enough to make someone attempt an emergency exit!ReferencesAtkonson V, Lee L. (2004). An unusual case of an airplane headache. Headache 44:438–439Berilgen MS, Müngen B. (2006). Headache associated with airplane travel: report of six cases. Cephalalgia 26:707-11.Domitrz, I. (2010). Airplane headache: a further case report of a young man. The Journal of Headache and Pain DOI: 10.1007/s10194-010-0245-9

... Read more »

  • August 7, 2010
  • 11:14 PM

Bad News for the Genetics of Personality

by The Neurocritic in The Neurocritic

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

  • July 25, 2010
  • 07:25 PM

What Color Is Your Cuneus?

by The Neurocritic in The Neurocritic

Career counseling via voxel-based morphometry? With the U.S. unemployment rate at 9.5% as of June 2010, job seekers might be willing to try anything to gain an edge. As part of the Trends in Phrenology craze sweeping the field, the Johnson O’Connor Research Foundation appears to be capitalizing on the new cultural neurophilia:The Johnson O'Connor Research Foundation is a nonprofit scientific research and educational organization with two primary commitments: to study human abilities and to provide people with a knowledge of their aptitudes that will help them in making decisions about school and work. Since 1922, hundreds of thousands of people have used our aptitude testing service to learn more about themselves and to derive more satisfaction from their lives. Sounds noble, right? Although they are a nonprofit, JOCRF charges $675 ($750 in New York)1 for a proprietary assessment battery. And a very preliminary morphometric analysis by Haier et al. (2010) features prominently on their homepage. The genesis of this structural MRI study is helpfully described on their website.Relationships Between Aptitudes and Brain Areas...In late 2006 at a professional research conference, David Ransom, exploring how our founder’s vision could be pursued by funding an outside researcher through the Johnson O’Connor Research Support Corporation, discussed with Dr. Richard Haier, a leading researcher on brain imaging and intelligence, the possibility of relating the volumes of defined brain areas measured with structural magnetic resonance imaging (sMRI) to performance on Johnson O’Connor aptitude tests. In the spring of 2007 Dr. Haier agreed to work on such a study, and in conjunction with Mt. Sinai Medical Center in New York, to conduct sMRI scans of 40 Foundation examinees, under the supervision of Dr. Cheuk Tang.In the summer of 2007 a sample of Foundation clients aged 18 to 35 was recruited to participate in the study by having scans completed at Mt. Sinai. These examinees were selected in two ways. First, a solicitation letter was sent to former clients tested in New York in the previous year and a half. Second, new examinees were recruited in person when they came in for testing.In January 2008 the goal of 40 examinees with completed sMRI scans and Johnson O’Connor test scores was met. Dr. Tang sent the brain-scan data for the examinees to Dr. Haier, and Chris Condon sent along the corresponding aptitude test data. Working with the sMRI scans, Dr. Haier used recently-developed technology called “voxel-based morphometry” to identify various brain areas and measure the volume of gray and white matter in each area.In addition to the structural MRI, each participant received the following cognitive tests:The eight tests in the JOCRF battery were: Inductive Speed (IS), Analytical Reasoning (AR), Number Series (NS), Number Facility (NF), Wiggly Block (WB), Paper Folding (PF), Verbal-associative Memory (VM), and Number Memory (NM). Each is described in Additional file 1: supplemental table S1 [.DOC]. These tests have been used in research on various aspects of cognition and intelligence [e.g., Schroeder & Salthouse, 2004]. A confirmatory factor analysis was performed using the entire psychometric database from 2002-2003, consisting of 6,889 people who had visited JOCRF for vocational guidance and aptitude tests. Combining this group with the 40 MRI subjects, the analysis revealed loadings for g (general intelligence) and four other factors: Speed of Reasoning (IS, AR), Numerical (NS, NF), Spatial (WB, PF), and Memory (VM, NM). Using standard voxel-based morphometry methods (Ashburner & Friston, 2000), the authors correlated gray matter volumes with each of these independent factors.However, with n=40 the study was underpowered to produce much in the way of significant results, which accounts for why it was published in BMC Research Notes. I have no problem with that, once we're clear on the scope of the journal:The aim of BMC Research Notes is to reduce the loss suffered by the research community when results remain unpublished because they do not form a sufficiently complete story to justify the publication of a full research article. A key objective of the journal is to ensure that associated data sets are published in standard, reusable formats whenever possible. Data sets published in the journal will be made searchable and easy to harvest for reuse.Press releases and news stores were not very clear on this point, however:Brain Scans Could Guide Career ChoicesBy Jeanna Bryner, LiveScience Managing EditorBrain scans may guide a person toward the optimal career, new research suggests.The results show people's cognitive strengths and weaknesses are linked to differences in the volume of gray matter in certain parts of the brain.And this!MRI challenges Myers-BriggsBy Rebekah MoanGood news radiologists! There’s a new place to set up that MRI machine: the guidance counselor’s office. Researchers are starting to use MRI to document an individual’s ability to perform on vocational guidance tests. I see.There should be some sort of prominent disclaimer when the popular press reports on such preliminary findings, but we find nothing of the sort. Instead we'll have pushy overbearing parents clamoring for that MRI to give their kid the advantage needed to get into Harvard.Let's return to the actual methods and results reported in the article (which is open access for all you science writers out there):Given the limited statistical power of 40 subjects, we detail results at puncorrected, in all the tables...; figures are shown consistently for all analyses at puncorrected, to allow straightforward comparisons. Findings corrected using the False Discovery Rate (FDR) pTable 1 gives the full list of brain areas that showed non-significant positive correlations between gray matter volume and the factors of g, Speed of Reasoning, Numerical, and Spatial. The Memory factor did show significant negative correlations with some regions, as shown below [note that a higher memory score was associated with smaller gray matter volumes]:... Read more »

  • July 19, 2010
  • 07:57 AM

Tales of Passion and Disgust

by The Neurocritic in The Neurocritic

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

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

  • July 17, 2010
  • 04:46 AM

Pleasure or Pain?

by The Neurocritic in The Neurocritic

Robert Mapplethorpe - Untitled (Self Portrait)The previous post (Erotic or Disgusting?) covered a functional MRI experiment on the neural responses to erotic films in heterosexual and homosexual males (Zhang et al., 2010). Specifically, the study examined sexual arousal and disgust while the participants viewed various types of porn. Neuroimaging results were reported only for the stimuli deemed distasteful by each group, wherein the left ventromedial prefrontal cortex was more active for gay men, and the left cuneus [visual cortex] was more active for straight men. It was unclear why this particular outcome was obtained. Other problems with the paper included the comparison condition (passive rest, rather than viewing neutral film clips) and the analysis strategy.An earlier study, however, took a more comprehensive look at arousal and disgust in a different sexual minority group: those with sadomasochistic preferences, who were compared to those without (Stark et al., 2005). Here, the stimuli were pictures from four categories: neutral, disgust-inducing, erotic, and sadomasochistic:The erotic pictures included either pictures of single naked subjects or pictures of couples in an intimate situation. The pictures with sadomasochistic content either had a submission/dominance theme (e.g. a naked man pulling a coach with a dressed woman), or showed sadomasochistic techniques (e.g. hurting someone with hot wax, pictures of bound subjects). The scenes depicted single subjects (male and female), couples, and groups of subjects.The disgust-inducing pictures showed a broad range of different disgust elicitors: unusual food (e.g. man eating a grasshopper, man biting into a monkey head), disgusting animals (e.g. snails, maggots), poor hygiene (e.g. dirty toilet, garbage piles, and body products (e.g. excrements, vomit). Neutral pictures showed household articles, geometric figures, and nature scenes.This allowed within-subject and between-subject approaches in the same experiment. Presumably, rotting garbage would be disgusting to everyone, while the groups would differ in their reactions to images with erotic or sadomasochistic content.Participants were 24 adults, 12 of whom identified as having sadomasochistic sexual preferences (SM)1 and 12 without sadomasochistic preferences (non-SM). Each group was comprised of 6 men and 6 women. Subjects were initially classified by asking, “Are you interested in sadomasochistic sexual activities?” This was followed by an 8 item questionnaire asking about sexual orientation, identity, and experiences, with each item rated on a 5-point scale (e.g., “I describe myself as a sadomasochist”, “I describe myself as sadistic/dominant”, etc.).All pictures were rated in advance by separate groups of SM and non-SM participants on the dimensions of disgust and sexual arousal using 9-point visual analog scales, and on valence, arousal, and dominance using the self-assessment manikin (also on a scale from 1 to 9). The scanned subjects also rated the pictures after the fMRI experiment was over. The emotional ratings for neutral and disgust-inducing stimuli did not differ between the two groups. As expected, however, ratings for the other two stimulus classes were divergent:The erotic pictures revealed more positive affect, more arousal, and more sexual arousal for the nonSM group in comparison to the SM group. SM subjects indicated to have felt more positive, more dominant, less disgusted, and more sexually aroused during the presentation of the pictures with sadomasochistic content than the nonSM subjects.Statistically speaking, emotion ratings for the disgust-inducing and sadomasochistic images did not differ in the non-SM group.2 On the other hand, ratings for the sadomasochistic pictures in the SM participants were similar to those for erotic pictures in the non-SM group. These findings were important for the between-subjects comparison of disgust and sexual arousal.During the fMRI experiment, each category of pictures was presented in separate blocks. Subjects were instructed to “let the pictures affect you”. For data analysis purposes, a number of different comparisons were performed:Several T-contrasts were calculated for each subject: the emotional conditions versus the neutral condition (Disgust Neutral, Erotic Neutral, Sm Neutral), and for the positive emotion versus negative emotion (Erotic Disgust, Sm Disgust, Sm Erotic). For a random effect analysis the individual contrast images (first level) were used in a second level analysis.As you can imagine, the amount of data reported in this paper is voluminous. Brain regions of interest (ROIs) were selected from the meta-analysis of Phan et al. (2002) on neuroimaging studies of emotion. Exploratory analyses were performed as well.The Erotic or Disgusting? Pleasure or Pain? series will conclude next time with the functional neuroanatomy associated with states of disgust and sexual arousal in those with vanilla and BDSM preferences.Footnotes1 Specific orientations were as follows:In the SM group three subjects reported a bisexual orientation (two male, one female). Furthermore, the SM group could be separated into eight masochists (four female), one sadist (female) and three switchers (one female).2 Numerically speaking, however, disgust ratings were higher for the former than for the latter (6.67 vs. 4.25).ReferencesPhan KL, Wager T, Taylor SF, Liberzon I. (2002). Functional neuroanatomy of emotion: a meta-analysis of emotion activation studies in PET and fMRI. Neuroimage 16:331-48.STARK, R., SCHIENLE, A., GIROD, C., WALTER, B., KIRSCH, P., BLECKER, C., OTT, U., SCHAFER, A., SAMMER, G., & ZIMMERMANN, M. (2005). Erotic and disgust-inducing pictures—Differences in the hemodynamic responses of the brain. Biological Psychology, 70 (1), 19-29 DOI: 10.1016/j.biopsycho.2004.11.014
... Read more »

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

  • July 8, 2010
  • 07:11 AM

Erotic or Disgusting?

by The Neurocritic in The Neurocritic

What's hot? What's not? What do you consider unappealing?A greater understanding of people different from ourselves makes for a more accepting and tolerant populace. Are attempts to deliberately evoke disgust by the sexual practices of "others" an important and worthy step towards achieving this goal? Or does it further stigmatize the minority "outgroup"? What if the "outgroup" is disgusted by the practices of the majority?Different strokes for different folksAnd so on and so on and scooby dooby doobyEveryday People------Sly & The Family StoneBrain Responses to Erotic FilmsWhat are the neural correlates of sexual arousal and disgust in heterosexual men and homosexual men viewing various types of porn (Zhang et al., 2010)? "Where can I sign up?" you say, both as a participant and a researcher. Or maybe you're horrified that such an experiment would be conducted by the scientific establishment. Pornography is a hot-button topic, and a discussion of its potential harms and merits is well beyond the scope of this post.1Disgust is considered to be one of the six basic emotions (Ekman, 1992). Given that disgust is a response to things that are physically distasteful or morally repugnant, this emotion has been examined in a specific evolutionary framework: "from oral to moral" (Rozin et al., 2009):According to the principle of preadaptation, a system that evolves for one purpose is later used for another purpose. From this viewpoint, disgust originates in the mammalian bitter taste rejection system, which directly activates a disgust output system. This primal route (e.g., bitter and some other tastes) evokes only the output program, without a disgust evaluation phase. During human evolution, the disgust output system was harnessed to a disgust evaluation system that responded not to simple sensory inputs (such as bitter tastes) but to more cognitively elaborated appraisals (e.g., a cockroach). ... Later, through some combination of biological and cultural evolution, the eliciting category was enlarged to include reminders of our animal nature, as wel [sic] as some people or social groups.In a rationale that is simple yet puzzling, Zhang et al. wished to see if the brains of gay men process disgust in a different manner from those of straight men.2To our knowledge, there have been few studies concerning the [sic] disgust in homosexual men. Whether the patterns of disgust differ between homosexual and heterosexual men is unknown. The participants were 16 heterosexual and 16 homosexual men (as identified by self-report). Bisexuals were excluded. The stimuli were 3 minute long film clips depicting explicit sexual activity between two men (M-M), two women (F-F), or a woman and a man (F-M). "Each type of erotic film was montaged with attractive short films." Subjects passively watched the films during scanning, then rated their levels of sexual arousal and sexual disgust after the fMRI portion had finished (shown below).Fig 1 (Zhang et al., 2010). Mean scores of the sexual films showing F–F, F–M and M–M in the two groups. F–F and M–M stimuli induce sexual disgust, respectively. Results of two independent samples test comparisons (homosexual versus heterosexual) are displayed. Blue indicates homosexual men; green, heterosexual men; the asterisk, p less than 0.01. Error bars equal 1 SD. NOTE: the level of sexual disgust was assessed by scores from 1 (extremely high) to 4 (extremely low), and the level of sexual arousal was rated from 6 (extremely low) to 9 (extremely high).It was no surprise to anyone that straight men were most turned on by F-M film clips and turned off by the M-M films. Straight guys were also a bit turned on by F-F (also not surprising given the popularity of girl-on-girl p0rn), although there was a great deal of variability. Also as expected, gay men were most aroused by M-M films. They rated their disgust as highest for F-F clips but were close to neutral for heterosexual p0rn (interestingly).3The neuroimaging data were analyzed using Disgust versus Rest as the comparison of interest.In the homosexual group, the F–F stimulus identified great activity in a large number of brain regions, including the left superior frontal gyrus, right and left medial frontal gyrus, left and right cerebellum, left middle occipital gyrus (BA 19), right lingual gyrus (BA 18), left precuneus, right middle temporal gyrus, left superior temporal gyrus (BA 38), left thalamus, and left supplementary motor area.In the heterosexual group, M–M stimuli elicited great activations in the left middle frontal gyrus, right middle frontal gyrus (BA 6), left inferior frontal gyrus (BA 45), right inferior frontal gyrus (BA 47), left middle temporal gyrus, right middle temporal gyrus (BA 37, BA 39), left superior temporal gyrus (BA 13), right superior temporal gyrus (BA 38), left inferior occipital gyrus (BA 18), bilateral caudate, bilateral thalamus, bilateral insula, left putamen, right parahippocampal gyrus, right cerebellum, right anterior cingulate (BA 42), and right amygdala.OK, so that's a bunch of areas that are activated relative to doing nothing (instead of relative to watching a neutral film). I won't try to interpret those results. How about comparing the Disgust vs. Rest responses of the gay and straight men? There was one region of the brain more active in each of the groups: left ventromedial prefrontal cortex for gay men (Fig. 4), and left cuneus [visual cortex] for straight men (Fig. 5).Fig. 4 (modified from Zhang et al., 2010). Aversive sexual stimuli compared to rest: stronger brain activation in homosexual men compared to heterosexual men in the left medial frontal gyrus (maximum at −1, 39, −12).... Read more »

  • July 2, 2010
  • 08:43 PM

Living and Forgetting

by The Neurocritic in The Neurocritic

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

  • June 24, 2010
  • 05:03 AM

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

by The Neurocritic in The Neurocritic

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

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

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

  • June 13, 2010
  • 11:21 PM

The Unique Case of “50 First Dates” Amnesia

by The Neurocritic in The Neurocritic

Scene from 50 First Dates with Drew Barrymore and Adam Sandler.50 First Dates maintains a venerable movie tradition of portraying an amnesiac syndrome that bears no relation to any known neurological or psychiatric condition (Baxendale, 2004).That isn't true anymore...Smith et al. (2010) have recently reported an unusual case of functional, or psychogenic amnesia in which FL, a 51 year old woman with 15 years of education and average intelligence, cannot remember what happened to her from one day to the next. Her case history is summarized below.In May 2005, FL was involved in a motor vehicle accident in which her car was struck from behind. She hit the left side of her head and briefly lost consciousness. She was treated and released from the emergency room, but upon awakening the next morning, she had no memory for the previous day and believed that the accident had just occurred. Every morning since has been similar. She awakens with anxiety, believes it to be the day of the accident, and states that she has no memory for anything that has occurred since the accident. Each morning her husband orients her to time and place and provides her with her journal where she has recorded salient events from previous days and weeks. During the course of the day, she describes her memory as normal, but states that memory for each day is lost at night during sleep. The plot summary for 50 First Dates, taken from Wikipedia, is as follows:One morning, Henry (Sandler) meets Lucy Whitmore (Barrymore), a local art teacher, in a café. They hit it off and agree to meet the next day, but when Henry returns, Lucy has no memory of him or their previous meeting. Pulling him aside to where Lucy can't hear them, the café owner explains to Henry that, as a result of a car accident a year earlier, Lucy suffers from Goldfield Syndrome, a fictional form of anterograde amnesia in which each day's events disappear from her memory overnight. FL reported she did not see the movie before her accident, but noted that Drew Barrymore was her favorite actress. Smith et al. (2010) speculated that FL could have known the plot of the film, which could have influenced her unusual manifestation of memory loss after the auto accident. Her husband mentioned that she had seen the movie several times since her accident.FL underwent a series of imaging and neuropsychological tests in Dr. Larry Squire's Memory Research Laboratory. Her MRI was read as normal by the neuroradiologist, and quantatitive analysis revealed the volumes of her medial temporal lobe structures [critical for forming new memories] to be quite well matched with a small group of control participants.Fig. 1 (Smith et al., 2010). (A) A T1-weighted coronal MRI image from FL. The left side of the brain is on the left side of the image. (B) The volume of bilateral hippocampus (HIP) and parahippocampal gyrus (PHG) were similar for FL and controls (n = 4). The volumes are expressed as a percentage of the whole-brain volume for each participant. FL's neurological exam was normal. She had no previous history of psychiatric disorder. On the basis of these negative neurological and MRI findings, combined with her neuropsychological profile, the psychiatrist diagnosed psychogenic [i.e. functional] amnesia, with one unusual difference: she did not have retrograde amnesia [memory loss for remote events].Although functional amnesia is not associated with structural brain damage, there is evidence of hypometabolism, especially in the frontal lobe as measured by neuroimaging. Similar findings have also been observed in other psychiatric and neurological conditions (i.e., transient global amnesia, bipolar and major depressive disorder, schizophrenia).The pattern of impairment in functional amnesia is variable, though it typically presents as severe retrograde amnesia (sometimes including loss of personal identity) in the absence of anterograde amnesia [problems encoding new memories].However, FL was impaired on some standardized neuropsychological measures of memory when tested the same day, which belied her claim of intact memory for events occurring within a day. But as expected, she was at chance performance for material tested 24 hrs later, after she had slept.The authors constructed a tricky memory test of their own to see whether FL could retain some memory for items she had learned 24 hrs ago but believed to be presented on the same day. This did work to some extent, as shown in the black bars for FL on the left (Next-day Covert).Fig. 2 (Smith et al., 2010). Recognition memory for color photographs of scenes. One presentation: FL, Controls (n = 3), and Simulators (n = 2) [asked to fake an amnesia like FL's] saw 160 scenes once each and then took recognition memory tests later on the same day (Same day) as well as on the morning of the next day (Next day). After the Next-day test, participants studied 160 new scenes and then took recognition memory tests later on the same day. In this case, unbeknownst to the participants, the retention tests included scenes that had been studied and tested on the previous day (Next-day Covert). Multiple Presentations: the same scenes that had been studied and tested during the first 2 days were studied an additional time. As above, testing was done in three ways (Same day, Next day, and Next-day Covert). FL exhibited evidence of day-to-day memory in the Next-day covert tests (black bars) and in her improved performance when the same scenes had been viewed across multiple days (compare the two white bars and the two black bars in the left panel).In an interesting twist to the story, an intensive training program at Johns Hopkins University taught FL to sleep for 3.5 hrs at a time, at which point she could still retain the day's memories.Initially, she was placed on a sleep deprivation protocol and remained awake for 36 h. There was no loss of memory during this period. The following day the treatment team initiated a regimen in which she was awakened after longer and longer periods of sleep each night. After 1, 2, 3, or 4 h of sleep... Read more »

Smith, C., Frascino, J., Kripke, D., McHugh, P., Treisman, G., & Squire, L. (2010) Losing memories overnight: A unique form of human amnesia. Neuropsychologia. DOI: 10.1016/j.neuropsychologia.2010.05.025  

  • June 1, 2010
  • 07:28 AM

Amygdala Vegetariana

by The Neurocritic in The Neurocritic

In Short Cuts, the "vegetarians and vegans are more empathetic" neuroimaging article was mentioned in passing, but I didn't actually blog about it. However, there has been one thing [OK, more than one thing] bothering me about this paper... But first, a quick summary of the Methods which were rather straightforward.Filippi and colleagues (2010) recruited 20 omnivores, 19 vegetarians, and 20 vegans to participate in a study that examined their brain responses to images of human and animal suffering. They were naïve as to the goals of the experiment. Before entering the scanner, all participants completed the Empathy Quotient, a 40 item questionnaire [plus 20 filler questions] that rates one's level of empathy (Baron-Cohen & Wheelwright, 2004). And the omnivores did indeed have lower EQ scores (38.8) than the vegetarians (49.5) and the vegans (44.6), who did not differ from each other.The fMRI experiment used an......event-related design during observation of negative affective pictures of human beings and animals (showing mutilations, murdered people, human/animal threat, tortures, wounds, etc.). Participants saw negative-valence scenes related to humans and animals, alternating with natural landscapes. So what were the neuroimaging findings? To no one's surprise, results indicated differences between the groups, as shown below.Figure 3. Results of the between-group comparisons of emotional (human and animal) negative valence picture views. Results are superimposed on a high resolution T1-weighted image in the standard MNI space, at a threshold of p less than 0.05 corrected for multiple comparisons. Areas activated during human picture view in vegetarians and vegans vs. omnivores are shown in yellow. Activations specific for vegetarians are shown in blue. Activations specific for vegans are shown in red. A: human picture view; B: animal picture view. [NOTE: I've labeled the corpus callosum.]Also to no one's surprise, differences between the groups were more pronounced for animal pictures (Fig. 3B) than for human pictures (Fig. 3A).Some of the results were interpreted in Rorschach inkblot fashion: the authors saw want they wanted to see in them. Since when are the specific regions of the anterior cingulate cortex (ACC) and the inferior frontal gyrus (IFG) shown above primarily known as "empathy-related regions"? They're not.2...vegetarians and vegans have constantly an higher engagement of empathy related areas while observing negative scenes, independently of the species of the individuals involved, which is characterized by an increased recruitment of the ACC and the IFG. Increased activation in the ACC and left IFG in vegetarians and vegans during human and animal suffering view is likely to reflect a stronger empathic response in the first two groups.Curiously enough, the amygdala (a limbic structure important for emotion) was not activated by animal suffering in either the vegetarians or the vegans. Although the amygdala (LeDoux, 2007) is predominantly known for its role in fear conditioning, it is also activated by other emotional responses including disgust (e.g., Kober et al., 2008).Remarkably, the within-group analysis during animal picture view, showed the absence of signal changes (in terms of activations and deactivations) within the amygdala in vegetarians and vegans, suggesting a down-regulation of amygdala response from areas located in the frontal lobes, in an attempt to regulate emotion through cortical processes in these subjects.Why would the vegetarians and vegans attempt to downregulate their emotional responses to animal suffering? And why would the vegans show greater amygdala responses to human suffering than did the omnivores and vegetarians??Figure 4. Interactions between stimuli (animal/human) and groups (omnivore/vegetarian/vegan). (A) An interaction was found in the right amygdala, indicating greater increase to animal negative valence picture view in omnivores and to human negative valence picture view in vegans. An interaction between “human pictures” and “vegan group” was also found in the left amygdala.Previously, NeuroKüz mentioned some objections to the study design in a post on The empathetic vegetarian brain.1 I won't detail his critique here other than to summarize:The control condition consisted of “neutral” scenes that did not include living beings, faces, or suffering of any kind.Participants passively viewed the photos, they did not have to respond by indicating their emotional reactions.Participants could be desensitized to human suffering by watching the news. One of the greatest issues, in my view, is with the mode of stimulus presentation. The event-related design (which is usually preferable) may not have allowed adequate time between pictures to "recover" from the shock of seeing a mutilated human or animal. If this were especially true for vegetarians and vegans viewing images of animal suffering, it could explain the curious silence of the amygdala. In such scenario, a blocked design (presenting all stimuli of one category in blocks, rather than intermixed) might have been a better idea.The vegetarians and vegans in this study all made their dietary choices for ethical reasons. It is quite conceivable that they differed from the omnivores on any number of other dimensions. For example, evolutionary psychology extremist Satoshi Kanazawa recently blogged about Why Vegetarians Are More Intelligent than Meat Eaters, but this only held for a UK sample born in 1958, but not for a US sample born b... Read more »

  • May 27, 2010
  • 02:08 AM

Short Cuts

by The Neurocritic in The Neurocritic

There is way too much to blog about these days. I can't decide among these 3 new papers:Sometimes, Categorical Statements about Prefrontal Neurons Are Just Wrong(1) Earl K. Miller (2007) in The Prefrontal Cortex: Categories, Concepts, and Cognitive Control (PDF):There was virtually no category effect across the ITC [inferior temporal cortex] population and no examples of neurons whose activity showed the sharp across-distinction/within-category generalization that is the behavioral signature of categorization. Rather, ITC neurons were sensitive to the physical appearance of the individual stimuli; its neurons did not “throw away” information about individuals in favor of the category groupings, like PFC [prefrontal cortex] neurons did. This finding suggests that learned visual categories are abstracted at the level of the PFC, not in visual cortex.No, not really. Monkeys were able to easily learn visual categories when their lateral prefrontal cortices were ablated bilaterally, IF they were tested using an incentive value task (Minamimoto et al., 2010). Earlier single-unit recording studies (reviewed in the Miller 2007 chapter) required maintenance of a set of two stimulus-response mappings. Thus PFC might be necessary for rule-based response selection, but not for visual categorization.Minamimoto T, Saunders RC, Richmond BJ (2010). Monkeys Quickly Learn and Generalize Visual Categories without Lateral Prefrontal Cortex. Neuron 66:501-507.Categorization is a basic mental process that helps individuals distinguish among groups of negative and positive objects, e.g., poisons and nutrients, or predators and prey. Monkey experiments have suggested that lateral prefrontal cortex (LPFC) participates in learning and processing visual categories. However, in humans category specific visual agnosia follows inferior temporal cortex but not LPFC damage. Here, we use a new behavioral approach to show that both normal monkeys and those with bilateral removal of LPFC learn and generalize perceptual categories of related visual stimuli rapidly without explicit instruction. These results strongly indicate that visual categorization occurs at some earlier stage of feed-forward processing, presumably in temporal cortex, without top-down information from LPFC.Minamimoto et al.'s incentive value task is shown below.Figure 1 (A) Sequence of events during a trial of the reward-delay task. A visual cue (Cue) indicates size and delay interval for the reward after successful behavioral reaction (bar release within 200–3000 ms after green target appears).You Are What You Eat, or Don't Eat(2) Empathy and Diet? Are vegetarians too sensitive, or more empathetic? And those vegans, they're out of control!Filippi M, Riccitelli G, Falini A, Di Salle F, Vuilleumier P, Comi G, Rocca MA (2010). The Brain Functional Networks Associated to Human and Animal Suffering Differ among Omnivores, Vegetarians and Vegans. PLoS ONE 5(5): e10847.Empathy and affective appraisals for conspecifics are among the hallmarks of social interaction. Using functional MRI, we hypothesized that vegetarians and vegans, who made their feeding choice for ethical reasons, might show brain responses to conditions of suffering involving humans or animals different from omnivores. We recruited 20 omnivore subjects, 19 vegetarians, and 21 vegans. The groups were matched for sex and age. Brain activation was investigated using fMRI and an event-related design during observation of negative affective pictures of human beings and animals (showing mutilations, murdered people, human/animal threat, tortures, wounds, etc.). Participants saw negative-valence scenes related to humans and animals, alternating with natural landscapes. During human negative valence scenes, compared with omnivores, vegetarians and vegans had an increased recruitment of the anterior cingulate cortex (ACC) and inferior frontal gyrus (IFG). More critically, during animal negative valence scenes, they had decreased amygdala activation and increased activation of the lingual gyri, the left cuneus, the posterior cingulate cortex and several areas mainly located in the frontal lobes, including the ACC, the IFG and the middle frontal gyrus. Nonetheless, also substantial differences between vegetarians and vegans have been found responding to negative scenes. Vegetarians showed a selective recruitment of the right inferior parietal lobule during human negative scenes, and a prevailing activation of the ACC during animal negative scenes. Conversely, during animal negative scenes an increased activation of the inferior prefrontal cortex was observed in vegans. These results suggest that empathy toward non conspecifics has different neural representation among individuals with different feeding habits, perhaps reflecting different motivational factors and beliefs.How did the authors get the idea for this experiment??How Dare You! I Feel So Guilty! This Is an Outrage!(3) Oh no! The neural correlates of "moral sentiments"? Smells like phrenology to me...Green S, Ralph MA, Moll J, Stamatakis EA, Grafman J, Zahn R. Selective functional integration between anterior temporal and distinct fronto-mesolimbic regions during guilt and indignation. Neuroimage 2010 May 19. [Epub ahead of print].It has been hypothesized that the experience of different moral sentiments such as guilt and indignation is underpinned by activation in temporal and fronto-mesolimbic regions and that functional integration between these regions is necessary for the differentiated experience of these moral sentiments. A recent fMRI study revealed that the right superior anterior temporal lobe (ATL) was activated irrespective of the context of moral feelings (guilt or indignation). This region has been associated with context-independent conceptual social knowledge which allows us to make fine-grained differentiations between qualities of social behaviours (e.g. "critical" and "faultfinding"). This knowledge is required to make emotional evaluations of social behaviour. In contrast to the context-independent activation of the ATL, there were context-dependent activations within different fronto-mesolimbic regions for guilt and indignation. However, it is unknown whether functional integration occurs between these regions and whether regional patterns of integration are distinctive for the experience of different moral sentiments. Here, we used fMRI and psychophysiological interaction analysis, an established measure of functional integration to investigate this issue. We found selective functional integration between the right superior ATL and a subgenual cingulate region during the experience of guilt and between the right superior ATL and the lateral orbitofrontal cortex for indignation. Our data provide the first evidence for functional integration of conceptual social knowledge representations in the right superior ATL with representations of different feeling contexts in fronto-mesolimbic regions. We speculate that this functional architecture allows for the conceptually differentiated experience of moral sentiments in healthy individuals. ... Read more »

Minamimoto T, Saunders RC, Richmond BJ. (2010) Monkeys Quickly Learn and Generalize Visual Categories without Lateral Prefrontal Cortex. Neuron, 66(4), 501-507. info:/10.1016/j.neuron.2010.04.010

  • May 21, 2010
  • 06:27 AM

Attentional bias and "gaydar"

by The Neurocritic in The Neurocritic

Global or Local? Gay or Eurotrash? Navon figure flanked by two game pieces from Gay or EUROtrash? the ultimate gaydar game!Believe it or not, there's an article in the new journal Frontiers in Cognition1 entitled "Sexual orientation biases attentional control: a possible gaydar mechanism" (Colzato et al., 2010). What is "gaydar"? And why on earth would one think of studying the allocation of attention to global and local visual perceptual features in relation to gaydar? Here's why:Individuals with a homosexual orientation are often believed to have a “telepathic sixth sense” (Reuter, 2002) for recognizing each other, an ability that is often referred to as gaydar (Shelp, 2002) – a portmanteau of gay and radar. Even though perceivable differences between homosexuals and heterosexuals may not be salient to everyone, some studies revealed subtle but distinctive features that homosexuals tend to share, such as coiffure (Rule et al., 2008), body-movement and gesturing style (Ambady et al., 1999), speech patterns (Linville, 1998), and penile size (Bogaert and Hershberger, 1999).2 Hence, there is a rich perceptual basis for people to develop a reliable gaydar, and homosexuals are apparently better trained in making use of it.To test the possible perceptual basis of gaydar, the authors made use of Navon figures (1977), which are comprised of small letters that form a larger letter. The characters can be the same or different, as shown below.Navon (1977) demonstrated that global visual features take precedence over the local ones ("forest before trees"). When in conflict, the large letter (global) interferes with the ability to identify the smaller letters (local), but local features do not hinder the ability to identify global features. Colzato et al. (2010) reasoned that gay individuals might need to focus on specific and local perceptual cues in order to correctly identify others with the same (or different) sexual orientation. Hence, the global precedence effect was predicted to be smaller in gay people than in straight people.To test this hypothesis, 42 Dutch participants (25 male and 17 female) were recruited for the study. On a multidimensional Kinsey-like scale (with seven variables each scored from 1-7), half were self-identified as straight (1.0) and the other half as gay (6.5). The stimuli were composed of large and small rectangles and/or triangles. Participants made button press responses to stimulus shape, based on the stimulus dimension (global or local) that was cued on each trial. The results demonstrated that the gay group did indeed show a smaller global precedence effect than the straight folk (see below).Figure 1 (Colzato et al., 2010). Mean global precedence effect for homosexuals and heterosexuals. Vertical capped lines atop bars indicate standard error of the mean.Heterosexuals were 68 msec faster to respond to global than to local features, but homosexuals were only 40 msec faster. The groups differed for this main effect of global/local dimension... but we don't know about the interaction with congruity. Nor do we know anything about potential male/female differences, because those weren't reported either. Nonetheless, results are consistent with the interpretation that gay men and women might have a relative bias towards detail-oriented processing when compared to heterosexuals.Now sexual orientation can join the other studies of group identity and attention to global vs. local features. These same authors previously showed that Dutch Calvinists (who have an independent view of the self) show a smaller global precedence effect than Dutch atheists (Colzato et al., 2008). Other research has demonstrated that participants raised in collectivist Asian cultures tend to be more globally-oriented than individualistic North American participants (Masuda & Nisbett, 2001). What might all this mean?From a more general perspective, our findings add to previous observations that being a member of a particular social group seems to shape cognitive-control operations in specific ways – whether this group is defined by shared culture, religious practice or, as the present study suggests, shared sexual orientation. Footnotes1 The bar for article titles in this journal has been set pretty high, since the other two papers are DOOM'd to switch: superior cognitive flexibility in players of first person shooter games and Games with(out) Frontiers: toward an integrated science of human cognition.2 Yes, the mean size is larger in gay men. On all five measures of penile length and circumference from Kinsey's original protocol (Bogaert & Hershberger, 1999).ReferencesColzato LS, van den Wildenberg WP, Hommel B. (2008). Losing the big picture: how religion may control visual attention. PLoS One 3:e3679.Colzato, L., van Hooidonk, L., van den Wildenberg, W., Harinck, F., & Hommel, B. (2010). Sexual orientation biases attentional control: a possible gaydar mechanism. Frontiers in Psychology DOI: 10.3389/fpsyg.2010.00013Masuda T, Nisbett RE. (2001). ... Read more »

Colzato, L., van Hooidonk, L., van den Wildenberg, W., Harinck, F., & Hommel, B. (2010) Sexual orientation biases attentional control: a possible gaydar mechanism. Frontiers in Psychology. DOI: 10.3389/fpsyg.2010.00013  

  • May 19, 2010
  • 05:35 AM

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

by The Neurocritic in The Neurocritic

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

  • May 12, 2010
  • 08:10 AM


by The Neurocritic in The Neurocritic

"Head-wound Hank", from Geek Orthodox.The 19th century archive of The Lancet1 is filled with simply delightful case reports. Who can resist the allure of early plastic surgery failures, such as RHINOPLASTIC OPERATION, PERFORMED BY M. LISFRANC, FOLLOWED BY DEATH? Or how about a Case of Local Tubercular Deposit on the Surface of the Brain, presented by Robert Dunn, Esq.? Finally, the tragic History of a Case of Hydrophobia, treated at the Hotel Dieu at Paris, by an injection of water into the veins did not end well (through no fault of R. Magendie, of course):2 It results from the history of this case, that a disease, which exhibited all the characters of hydrophobia, ceased by the introduction of a pint* of warm water into the veins; that the patient survived this introduction eight days: that no accident appeared to follow from it; and that the death of the patient appears to have been caused by a local disease, which was wholly unconnected with the hydrophobia, and the new mode of treatment.* The pint of Paris contains 48 cubic inches. -ED.In 1828, Dr. Sewall (Professor of Anatomy in the Colombian College, D.C.) reported on two of his cases. They are not for the faint of heart. A warning for political incorrectness is also warranted here.CASE 1. In February 1827, W. Brown, a coloured man, aged fifty years, in encountering with another individual, received a severe blow on the right side of the head with a sharp spade. When Dr. Sewall arrived, which was only a few minutes after the accident, he found him bleeding profusely, and much exhausted from the loss of blood. Though not insensible, he had lost his reason, and did not know how he came by the injury. There was a deep wound dividing the integuments, the whole of the temporal muscle, penetrating the cavity of the cranium, and extending horizontally, from an inch above the external angular process of the frontal bone, through the parietal bone just above the squamous suture, forming a fissure of three inches in length. The lower portion of bone was considerably depressed, and the two edges separated about half an inch. Two branches of the temporal artery were taken up; when, on a more critical examination, it was ascertained that the dura mater was divided for an inch in extent...OK, so the patient really did have a 3 inch crack in his skull with brain matter oozing out. Mr. Brown was treated by Dr. Sewall ("dressings were applied"). When pus was coming from the gaping wound, there was swelling followed by sloughing (apparently). Then bits of brain were scooped away with a spatula. Lovely.Although he suffered from severe headaches, Mr. Brown was declared none the worse for the wear:For about ten days after the accident, the patient complained of constant, and sometimes of severe, pain in the head; and on one occasion was affected with a slight spasm of the muscles of the face, neck, and extremities. The wound healed, and in six weeks the patient was quite well. He subsequently followed his occupation, that of scavenger, and did not manifest any deviation in the functions either of body or mind from their ordinary healthy condition.The bar was probably set pretty low for what was considered an "ordinary healthy condition" for a "coloured" man who worked as a scavenger in 1827...The second case was of a five year old boy who was kicked in the head by a horse. No race was specified, so we'll assume he was white. More oozing and scooping of brain:CASE 2. September 18th, 1827, Lewis Poole, aged five years, while playing in the street, was kicked by a horse, and taken up in a state of insensibility. Dr. Sewall arrived a quarter of an hour after the accident, and found a semicircular wound in the integuments of the head, and, corresponding with this, a large fissure in the frontal and parietal bones, about three inches above the external angle of the right eye. Through this fissure a portion of brain protruded, somewhat larger than a walnut, and was composed both of cortical [gray] and medullary [white] matter, which were easily distinguished. This was so far separated from the parts beneath, as to be removed without any violence.Once again we're informed of the patient's full recovery, but only after much unpleasantness. He was bled to the point of unconsciousness initially and then given a powerful and toxic emetic for two weeks straight:Particular circumstances prevented the subsequent use of the lancet; but he was purged actively and daily for two weeks, and the pulse kept down by nauseating doses of the tartate of antimony. Extensive suppuration came on, with a copious discharge of pus; the wound gradually healed, and in about five weeks the child was quite well. He has since remained in perfect health.I wonder for how long that lasted, since Antimony Potassium Tartate is considered a dangerous good (.doc). Inhalation can cause irritation, sore throat, coughing, and shortness of breath. Eye or skin contact causes irritation, redness, and pain. Ironically, the recommended treatment after swallowing this compound is to induce vomiting immediately. The long-term consequences of antimony poisoning are not likely to be conducive to perfect health. Neurosurgical care has certainly come a long way since 1827.Footnotes1 Now on Facebook and Twitter! Keeping up with the 21st century.2 It probably wasn't his fault if the patient was really infected with the rabies virus (aka hydrophobia).ReferenceDr. Sewall (1828). CASES OF INJURY OF THE HEAD, ACCOMPANIED BY LOSS OF BRAIN. The Lancet, 10 (265) DOI: 10.1016/S0140-6736(02)98130-4
... Read more »

  • May 8, 2010
  • 06:53 PM

Motivating a Cumulative Cognitive Neuroscience

by The Neurocritic in The Neurocritic

Why are large-scale structured databases and meta-analyses important to advance the field of human brain mapping? One reason is that individual functional magnetic resonance imaging (fMRI) studies can be notoriously unreliable and underpowered (Bennett & Miller, 2010; Fliessbach et al., 2010; Kriegeskorte et al., 2009; Vul et al., 2009). At the recent CNS 2010 Annual Meeting, symposium organizer Dr. Tal Yarkoni gave the first talk in a session on the value of a cumulative cognitive neuroscience.---------------Symposium Session 1Sunday, April 18, 10:00 am - 12:00 pm, Westmount et al BallroomTowards a cumulative science of human brain function. . .Talk 1: Motivating a cumulative cognitive neuroscienceTal Yarkoni; Columbia University and University of Colorado at BoulderThousands of functional neuroimaging studies are published every year. Only a small fraction of these studies explicitly attempt a formal synthesis of previous findings. In this talk, I argue for an increased emphasis on cumulative approaches to the study of brain function that aim to synthesize and distill the results of previous studies. Three different motives for such an approach are discussed, including (a) the need to distinguish real findings from false alarms; (b) the desire to organize both cognitive tasks and brain activations into coherent ontologies; and (c) the high likelihood that many fMRI studies are underpowered and consequently produce distorted results. I focus primarily on the last of these points, using simulations and empirical analyses to demonstrate that the results of many individual fMRI studies are likely to appear considerably stronger and more selective than they actually are. I conclude by arguing that these limitations are difficult or impossible to overcome in individual studies, necessitating a stronger focus on consensus building at the disciplinary level.---------------What are the motivations for consensus building? Here are four major reasons:The value of a cumulative scienceMake the literature manageableDistinguish true positives from false positivesDevelop overarching frameworksMinimize the effects of low powerYarkoni's talk focused on the last point. The problem with most individual fMRI studies is a lack of statistical power. Yarkoni (2009) argued that:the primary cause of grossly inflated correlations in whole-brain fMRI analyses is not nonindependence, but the pernicious combination of small sample sizes and stringent alpha-correction levels. Far from defusing Vul et al.'s conclusions [from their notorious 2009 paper], the simulations presented suggest that the level of inflation may be even worse than Vul et al.'s empirical analysis would suggest. Fig. 2 (Yarkoni, 2009). Inflation of significant r values as a function of sample size (x axis) and population effect size (lines). Each point represents the result of 10,000 simulated correlation tests, each conducted at a threshold of p Simply put, small n's result in massively inflated brain-behavior correlations. What can be done about this problem? Include more participants in your studies! And make use of the tools that were described by the subsequent speakers (Van Essen, Wager, Poldrack) for synthesis of mega-databases.For more information, the slides from Tal's talk are available online (PDF).ReferencesBennett CM, Miller MB. (2010). How reliable are the results from functional magnetic resonance imaging? Ann NY Acad Sci. 1191:133-55.Fliessbach K, Rohe T, Linder NS, Trautner P, Elger CE, Weber B. (2010). Retest reliability of reward-related BOLD signals. Neuroimage 50:1168-76.Kriegeskorte N, Simmons WK, Bellgowan PS, Baker CI. (2009). Circular analysis in systems neuroscience: the dangers of double dipping. Nat Neurosci. 12:535-40.Vul E, Harris C, Winkielman P, Pashler H (2009). Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition. Perspectives on Psychological Science 4:274-290.Yarkoni, T. (2009). Big Correlations in Little Studies: Inflated fMRI Correlations Reflect Low Statistical Power-Commentary on Vul et al. (2009). Perspectives on Psychological Science, 4 (3), 294-298. DOI: 10.1111/j.1745-6924.2009.01127.x
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  • May 5, 2010
  • 05:36 AM

Mindscape explains life, mind, consciousness and happiness

by The Neurocritic in The Neurocritic

Conflict of interest: ABN, NJS and DRS are scientific co-founders of Mindscape Diagnostics, Inc.Special review article!AbstractWhat are mind, consciousness and happiness, in the fundamental context of life? We propose a convergent perspective (coupling evolutionary biology, genomics, neurobiology and clinical medicine) that could help us better understand what life, mind, consciousness and happiness are, as well as provides empirically testable practical implications.Well. So a speculative, flaky, and pretentious journal article1 (Niculesc et al., 2010) proposed a grandiose theoretical framework for understanding "life" et cetera, et cetera. I was amused.We propose that the mind can be viewed as a composite of mechanisms that have evolved to achieve GuU [genes (G), proximal umbrella (u), general umbrella (U)] objectives. The latest genetic, neurobiological and clinical evidence suggest that normal mental functioning and psychiatric disorders can be classified in three broad and overlapping domains: the anxiety domain, the mood domain and the cognitive domain (Niculescu, 2006), somewhat paralleling the archaic Freudian constructs of id, ego and super-ego.Each section of the paper (n=8) is introduced by a scientific quote or aphorism, such as...“It is always advisable to perceive clearly our ignorance”.-Charles Darwinand...“For a scientist, it is a unique experience to live through a period in which his field of endeavour comes to bloom — to be witness to those rare moments when the dawn of understanding finally descends upon what appeared to be confusion only a while ago — to listen to the sound of darkness crumbling.”- George E. PaladeHere are the main bullet points, followed by a Venn diagram lacking in explanatory value:Anxiety is about reactivity in the face of uncertainty and potential dangerMood is about trophicityCognition is about connectivity and congruence—within the organism, and with the environment Consciousness is about monitoring the environment through the mind (anxiety, mood and cognition)Happiness is about achieving GuU objectivesFig. 1 (Niculesc et al., 2010). Overlap and interdependence: Venn diagram.In my view this general framework is comparable to horoscopes and fortune telling: so vague that almost anything could fit. However, the authors do get more specific when they speculate on the testable therapeutic implications of "whole organism effects" (see Table 1 below, in the Appendix). Some are radical (anti-cancer medications to treat mood disorders; mood meds to treat cancer); others are mundane (anti-hypertensive medication to treat anxiety [yeah, beta blockers, how novel]; anti-anxiety meds to treat hypertension).But it gets better!The above ideas and paradigms can be modeled using a three-dimensional spatial representation of the life landscape–Lifescape, and of the mental landscape–Mindscape. The three dimensions for the Lifescape are G, u, U. The three dimensions for the Mindscape are mood, cognition and anxiety. The axes are not orthogonal, to reflect the interdependence of the three domains. Thus, changes in one dimension translate into changes in the other two dimensions.Fig. 2 (Niculesc et al., 2010). Mindscape 3D modelling of anxiety, mood and cognition. At each moment in time, an individual is represented by a point with (x, y, and z) coordinates in this tri-dimensional space. The sum of points over time is distributed as a cloud, unique to each individual.What a coincidence that the name of the authors' company is Mindscape Diagnostics! Hence we have Mindscape psychiatry, Mindscape therapeutics, Mindscape addictions, et cetera, et cetera. Looks like they're really on cloud 9...Footnote1 No, the article was not in Medical Hypotheses. Presumably the Journal of Affective Disorders requires some sort of peer review for special review articles.ReferencesNiculescu AB 3rd (2006). Polypharmacy in oligopopulations: what psychiatric genetics can teach biological psychiatry. Psychiatr Genet. 16:241-4.Niculescu AB 3rd, Schork N, Salomon D. (2010). Mindscape: A convergent perspective on life, mind, consciousness and happiness. Journal of Affective Disorders, 123 (1-3), 1-8 DOI: 10.1016/j.jad.2009.06.022Appendix (click on image fo... Read more »

  • April 27, 2010
  • 02:55 PM

Training of Executive Control Functions: Negative Transfer and Far Transfer

by The Neurocritic in The Neurocritic

The Cognitive Neuroscience Society 2010 Annual Meeting was held last week in Montreal, Québec. Unfortunately, many European registrants were unable to attend because of the Eyjafjallajokull volcano. The meeting website has links to the PDFs for 67 of these "Volcano Posters".One of those unable to attend was Dr. Jonas Persson of Stockholm University. He was scheduled to speak in the final symposium of the conference, which was on control of executive control, or who controls the "controller" in the brain (without resorting to a homunculus or an infinite regress of Mini-Me's). His co-author, Dr. Patricia Reuter-Lorenz of the University of Michigan, gave an interesting presentation about their work on the ups and downs of cognitive training: gains that transfer to other tasks across sessions and fatigue that transfers to other tasks within a session. The abstract is reprinted below.---------------Symposium Session 5Tuesday, April 20, 1:00 - 3:00 pm, Westmount et al BallroomWhat Controls Executive Control? The Influence of 'Control Context'Chair: Amishi Jha, University of Pennsylvania. . .Talk 3: Training and Depletion of Executive Functions: The Case of Interference ControlJonas Persson1, Patricia Reuter-Lorenz2; 1Stockholm University, 2University of MichiganBrain imaging reveals overlapping sites of prefrontal activation for different cognitive tasks suggesting they may share core executive processes. We tested this hypothesis by measuring behavioral interactions between memory tasks presumed to require interference control - a putative executive process that mediates selection from competing representations. Behavioral data show that different training regimens produce either negative or positive transfer from working memory to semantic and episodic memory task performance. We show that eight days of training on high interference versions of three different working memory tasks increased the efficiency of interference control on the training tasks and on untrained tasks in new memory domains. In contrast we have also demonstrated negative transfer and process-specific “fatigue” effects indicating that control efficiency in a second task is diminished by high control demands in a prior task immediately preceding it in time. This suggests that interference control is a finite resource that can be temporarily depleted. Functional magnetic resonance imaging (fMRI) was used to elucidate the mechanisms associated with decreasing efficiency or resource depletion of the interference control process. Along with reduced performance, fMRI indicates negative transfer is associated with reduced process-specific activation, and increased homologous activation that may be compensatory. In sum, this suggests that interference control is an executive function that is both resource limited and plastic making it possible for training to alter its efficiency.---------------These findings became extremely relevant (albeit ignored) in light of the ultra-high impact paper by Adrian Owen et al. (2010) published in BBC/Nature on April 20, informing us there was "No gain from brain training" in a massive group of 11,430 volunteers. The research volunteers participated in online training exercises that tapped (1) reasoning, planning, problem solving; (2) short-term memory, attention, visuospatial processing, mathematics; or (3) ability to answer obscure questions using the internet.Numerous other outlets have already summarized these results, so I won't attempt to do so here. The main issue was whether the gains obtained through simple practice effects transferred to tasks that weren't in the training set. The short answer is no.Brain training doesn't boost brain power, work suggests (BBC)Brain-training games don't work (Guardian)Brain training games don't work (BPS Research Digest)Brain-training games get a D at brain-training tests (Not Exactly Rocket Science)Brain Test Britain - Results in-depth (BBC - Lab UK)I am not a proponent of brain training games that make unsound claims lacking credible scientific evidence to back them up. But in light of the spectacularly negative findings of Owen et al., the question arises of whether their training regimen (10 min 3 times a week for 6 weeks) was adequate to produce significant effects. Predictably, those with a stake in the matter said no, the training was neither sufficient in duration nor applicable to other commercially available products.BBC “Brain Training” Experiment: the Good, the Bad, the UglyPosit Science Disputes Results of the BBC Brain Training StudyA final issue concerns the population under study, a presumably "normal" group of 18-60 year olds without cognitive impairments or cognitive decline. Would the same training exercises help an older population at risk for dementia? On the other hand, seniors might be especially vulnerable to persuasive false claims from unscrupulous brain training vendors. Thus it's important to have scientifically valid and accessible research on whether cognitive training might help an aging population (Lustig et al., 2009). Coincidentally, the NIH is currently trying to reach a consensus on:NIH State-of-the-Science ConferencePreventing Alzheimer’s Disease and Cognitive DeclineApril 26–28, 2010Bethesda, MarylandLive webcast, also information on archived video and publicly available consensus statement.Let us now return to the studies of Persson and Reuter Lorenz (2008). This work examined wheth... Read more »

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