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RT @Dostoyevsky Realists do not fear the results of their study."Good God!" he cried, "can it be, can it be, that I shall really take an axe, that I shall strike her on the head, split her skull open... that I shall tread in the sticky warm blood, blood... with the axe... Good God, can it be?"- Fyodor Dostoevsky, Crime and Punishment, Ch. 5A new fMRI paper in Neuron (Buckholtz et al., 2008) claims to have discovered the neural correlates of evaluating another person's crime and deciding on the appropriate sentence, in emulation of judges and juries meting out third-party punishment (Fehr & Fischbacher, 2004).On the other hand, the rotating "freak show" guests on the Jerry Springer Show mete out second-party punishment,1 which is generally harsher (in midget fights and certain economic games, at least).Here’s the great new insight of the paper, according to the Preview by Johannes Haushofer and Ernst Fehr:Thus, the study of Buckholtz makes a valuable contribution in that it illustrates that third-person judgment situations, such as those used in their study, may rely on similar neural mechanisms as two-person economic and social exchanges. While it is difficult to draw reverse inferences about mental states based on brain activation (Poldrack, 2006),2 one might speculate, based on this new study, that the mental processes motivating judicial verdicts involve the suppression of prepotent emotional reactions in favor of impartial and objective verdicts.[NOTE: aren’t you just marveling at this grand new insight from fMRI? Like we didn’t already know that judges and jurors must put aside their emotionally-driven desire for revenge when coming to an impartial verdict.]Thus, this new result might, if confirmed by future studies, elucidate the neural source of judicial impartiality.All right, let's go back to the beginning. Or to the Methods, at least. One of the experimental tasks was to determine whether the perpetrator of a given hypothetical crime was responsible for his actions. There were two versions of the same basic crime scenarios with the details of Responsibility versus Diminished Responsibility counterbalanced across the two sets (e.g., compare #3 and #32 below). Half of the participants read Set 1, the other half read Set 2. Some of the infractions were minor (#7, #22), but some were crimes of the most heinous sort, whether intentional (#3) or unintentional (#27, #32). Thus, the severity of the crimes was matched across the experimental conditions as well. Below are some examples of the stimuli, taken from the Supplementary Materials. Responsibility Scenarios 3) John develops a plan to kill his 60-year-old invalid mother for the inheritance. He drags her to her bed, puts her in, and lights her oxygen mask with a cigarette, hoping to make it look like an accident. His mother screams as her clothes catch fire and she burns to death. 7) John is parking his car in the parking lot of a local football stadium, where he plans to watch a game. In the car next to his, he sees a hat with his team logo in the back seat. Seeing that the door is unlocked, John opens the door, and takes the hat. Diminished Responsibility Scenarios 22) John visits a local bookstore, carrying a large shopping bag with goods from another store. While the store clerk is preoccupied with inventory, another customer, hoping to use John unwittingly in a theft, sneaks a book into John’s shopping bag. Without realizing what has happened, John walks out without paying for the book. 27) A brain tumor is causing increasingly erratic, violent, and callous behavior in John. Soon, he develops an uncontrollable urge to kill. John abducts a boy, puts a broomstick in the boy’s r-----, and lashes him with a whip until he dies. When the tumor is later found and removed, John’s behavior returns to normal. 32) Unbeknownst to John and his doctors, his new prescription interacts with his other medications to induce severe acute psychoses. During that interaction, John returns home to his 60-year old invalid mother, who he has always adored. John lights her oxygen mask with a cigarette, and watches as his mother catches fire, screams, and burns to death. No Crime Scenarios [control condition] 47) The manual to John’s new car states: “The oil must be changed no less frequently than every 4,000 miles.” John reads the manual and is aware of what it says. However, John drives the car for 4,023 miles before taking it to a service station for the car’s first oil change. [gasp!] 48) John and his best friend have played golf together for more than ten years. They used to be evenly matched, but recently John’s friend has consistently outplayed him. Growing frustrated, John responded by taking private golf lessons from the local pro. The next time John played against his friend, he soundly beat him.That was extremely unpleasant and harsh at times, wasn't it? Over the course of the experiment, participants read 50 scenarios (20 Responsibility, 20 Diminished Responsibility, 10 No Crime) three times each: once in the scanner and twice after scanning. The procedures were as follows:Participants rated each scenario on a scale from 0–9, according to how much punishment they thought John deserved, with “0” indicating no punishment and “9” indicating extreme punishment. Punishment was defined for participants as “deserved penalty.”. . .Following the scanning session, participants rated the same scenarios along scales of emotional arousal and valence. They first rated each of the 50 scenarios (presented in random order on a computer screen outside the scanner) on the basis of how emotionally aroused they felt following its presentation (0 = calm, 9 = extremely excited). They then rated each of the scenarios, presented again in random order, on the basis of how positive or negative they felt following its presentation (0 = extremely positive, 9 = extremely negative).The results from these rating tasks are shown below, and it's not surprising that the subjects recommended more severe punishments for the perpetrator in the Responsibility scenarios than in the Diminished Responsibility scenarios.Figure 1 (Buckholtz et al., 2008). Punishment and Arousal Ratings for Each Scenario Type. While punishment and arousal scores were similar in the Responsibility condition, punishment scores were significantly lower than arousal scores in the Diminished-Responsibility condition. Error bars = SEM.As for the neuroimaging results, the authors compared the hemodynamic response in the Responsibility versus the Diminished Responsibility conditions to see what brain areas might be differentially activated. Greater activity in the right dorsolateral prefrontal cortex (rDLPFC) was emphasized (Fig 2). Responses in bilateral anterior intraparietal sulcus were similar, but relegated to the Supplementary Materials.Figure 2 (Buckholtz et al., 2008). Relationship between Responsibility Assessment and rDLPFC Activity. (A) SPM displaying the rDLPFC VOI, based on the contrast of BOLD activity between the Responsibility and Diminished-Responsibility conditions. (B) BOLD activity time courses. BOLD peak amplitude was significantly greater in the Responsibility condition compared with both the Diminished-Responsibility and No-Crime conditions.So now we get to the interpretation that rDLPFC is suppressing emotional reactions in areas such as the amygdala, medial PFC, and posterior cingulate cortex (which were sensitive to the magnitude of punishment) in order to assign a diminished level of criminal responsibility. The problem with that reverse inference is illustrated below.This figure was generated from entering the x, y, z Talairach coordinates from the rDLPFC focus shown above (39, 37, 22)3 into the Sleuth program (available at brainmap.org), which searched the available database of papers for matches. The resulting list of coordinates and experiments was then imported into the GingerALE program, which performed a meta-analysis via the activation likelihood estimation (ALE) method (see this PDF). The figure illustrates that the exact same region of rDLPFC was activated during tasks that assessed attention; execution, inhibition, and observation of actions; various aspects of language and perception; and especially working memory.The authors appear to acknowledge the caveat thatthe brain regions identified in our study are not specifically devoted to legal decision-making. Rather, a more parsimonious explanation is that third-party punishment decisions draw on elementary and domain-general computations supported by the rDLPFC.They also acknowledged the confound of arousal and crime severity. Nonetheless, they concluded by waving their arms around and blabbing about the evolution of the legal system:...on the basis of the convergence between neural circuitry mediating second-party norm enforcement and impartial third-party punishment, we conjecture that our modern legal system may have evolved by building on preexisting cognitive mechanisms that support fairness-related behaviors in dyadic interactions. Though speculative and subject to experimental confirmation, this hypothesis is nevertheless consistent with the relatively recent development of state-administered law enforcement institutions, compared to the much longer existence of human cooperation.What are we to conclude from this? Since it's very late now, I'll let Jerry and Fyodor have the last words.“We can't just have mainstream behavior on television in a free society, we have to make sure we see the whole panorama of human behavior.”- Jerry Springer“Actions are sometimes performed in a masterly and most cunning way, while the direction of the actions is deranged and dependent on various morbid impressions-it's like a dream.”- Fyodor Dostoevsky, Crime and Punishment, Ch. 17But when all is said and done, why don't we let Jerry Fodor have the last word?“It’s a thin line between clarity and pomposity.” — Psychosemantics: The Problem of Meaning in the Philosophy of Mind, p. 17.Footnotes1 But as Wikipedia notes, "there has been continuous debate over the actual authenticity of the fighting."2 "...we won’t let that stop us from rampant speculation" [to paraphrase Haushofer and Fehr]. I feel like a broken record here, but reverse inference is a logical fallacy - one cannot directly infer the participants' cognitive or emotional state from the observed pattern of brain activity. Everyone should know better by now, and there should be a moratorium on such sloppy thinking. Or rather, such sloppy writing and publishing. The high-profile journals are the worst offenders, and they end up promoting the use of totally misleading headlines like this one:Justice may be hard-wired into the human brainCall it the justice instinct. When judging the guilt or innocence of alleged criminals, our brains seem to respond as if we were personally wronged, say researchers.The "justice instinct"?? Spare me. The experiment said absolutely nothing about evolution, genetics, or "hard-wiring."3 According to pages 932 and 938. However, page 936 and Table S1 say the coordinates are slightly different: 39, 38, 18.ReferencesJ BUCKHOLTZ, C ASPLUND, P DUX, D ZALD, J GORE, O JONES, R MAROIS (2008). The Neural Correlates of Third-Party Punishment. Neuron, 60 (5), 930-940 DOI: 10.1016/j.neuron.2008.10.016.Fehr E, Fischbacher U. (2004). Third-party punishment and social norms. Evolution and Human Behavior 25:63–87.Haushofer J, Fehr E (2008). You Shouldn’t Have: Your Brain on Others’ Crimes. Neuron 60:738-740.Ax Murderer FAIL... Read more »
"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
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Dr. Sewall. (1828) CASES OF INJURY OF THE HEAD, ACCOMPANIED BY LOSS OF BRAIN. The Lancet, 10(265), 817. DOI: 10.1016/S0140-6736(02)98130-4
Former U.S. Representative Anthony Weiner served New York's 9th congressional district for 12 years until his online sexual indiscretions forced him to resign on June 16, 2011. We've all been overexposed [so to speak] to the "Weinergate" scandal, so no need to recount all the lurid details. Boxer briefly, he sent lewd photos of himself to young and under-aged girls following him on Twitter. This occurred despite the fact that Huma Abedin, Deputy Chief of Staff for Hillary Rodham Clinton and his wife of 2 years, was newly pregnant. Why would a high profile politician engage in such outrageous behavior?What a silly question! Because he could! Because of his political power and a giant ego that needed massaging from pretty girls less than half his age. And because he thought he could get away with it. Ask Bill, Arnold, John, and Eliot. For more on this phenomenon, I recommend On the biology of sexting, a monograph at the blog Neurological Correlates.Like many other public male figures who have fallen from grace due to their sexual activities, Weiner claimed to have checked into a treatment center to seek professional help for his ill-defined problems:"Congressman Weiner departed this morning to seek professional treatment to focus on becoming a better husband and healthier person," Weiner's spokeswoman, Risa Heller, tells Us Weekly in a statement. "In light of that, he will request a short leave of absence from the House of Representatives so that he can get evaluated and map out a course of treatment to make himself well.This was, of course, before his resignation. The New York Times went on to state:Ms. Heller would not identify the facility or the precise kind of counseling Mr. Weiner, who has admitted having explicit communications with six women he met online, would receive... . . .Ms. Pelosi had hoped that the congressman would reach the decision on his own to go. In addition to her concerns about the political distraction Mr. Weiner had become, Ms. Pelosi concluded that his behavior required medical intervention. “When you are this self-destructive, there is obviously something deeper going on with you,” said a Pelosi adviser who spoke on condition of anonymity for fear of being seen as betraying her confidence.This brings us to the issue of "sexual addiction", or compulsive sexuality, or hypersexuality. Establishing an agreed-upon definition and proper diagnostic critieria for this condition is a minefield (compare Kafka 2010a, 2010b and Levine, 2010). For the present blog post, I will present the view of Reid et al. (2011) from their paper on A Surprising Finding Related to Executive Control in a Patient Sample of Hypersexual Men:The proposed diagnostic criteria for the DSM-V characterize hypersexual disorder (HD) as a repetitive and intense preoccupation with sexual fantasies, urges, and behaviors, leading to adverse consequences and clinically significant distress or impairment in social, occupational, or other important areas of functioning. One defining feature of this proposed disorder includes multiple unsuccessful attempts to control or diminish the amount of time the individual engages in sexual fantasies, urges, and behavior in response to dysphoric mood states or stressful life events. Despite a constellation of studies investigating characteristics of HD (usually defined in the literature as sexual addiction, sexual compulsivity, or hypersexual behavior), little is known about the neuropsychological correlates of this phenomenon, including possible associations with executive functioning.Executive functions are a series of high-level cognitive processes that allow for the flexible control of thought and adaptive behavior. They include processes such as planning, decision making, multitasking, task switching, and impulse control. One might expect that executive functions (or at least some of them) would be impaired in those who show problematic hypersexual behavior. For example, although Weiner may be witty and reasonably intelligent, his apparent narcissism, poor impulse control, and terrible decision making abilities in the sexting realm proved to be his downfall.Anthony Weiner's comedy routine at the Congressional Correspondent's Dinner, March 30, 2011.Highlights:Ambitions to run for mayor of NYWeiner jokesPraises his lovely wife - "opposites attract"Outlines his use of social media, including TwitterFollow me @RepWeiner! (18,000 followers at that time, now over 83,000)Named to Time's 140 Best Twitter FeedsTo jump to the conclusion, the study of Reid et al. (2011) was surprising because the executive function scores of 30 men diagnosed with HD were the same as a group of 30 male volunteers without HD. All participants were administered a series of standardized neuropsychological tests that included the Stroop Color-Word Interference Test (shown above in Weiner's thought bubble), the Wisconsin Card Sorting Test (WCST), the Trail Making Test, and the Verbal Fluency Test. All of these tasks involve planning or overcoming automatic responses.In the Stroop task, the participant is instructed to say the font color and ignore the word. It's much more automatic to read the word than to say the font color, so people are slower to respond when the two dimensions are in conflict:BLUE PURPLEREDGREENTrail Making version B is an attention switching task where the participant connects the dots on the sheet below by alternating between letters and numbers: 1-A-2-B-3-C, etc.Before we examine the authors' interpretation of this interesting null effect, let's take a closer look at some of the defining characteristics of the HD grou... Read more »
Reid, R., Garos, S., Carpenter, B., & Coleman, E. (2011) A Surprising Finding Related to Executive Control in a Patient Sample of Hypersexual Men. The Journal of Sexual Medicine. DOI: 10.1111/j.1743-6109.2011.02314.x
by: crdagainSeasonal affective disorder (SAD) is a cyclical depressive disorder that typically recurs every year during the shorter days and longer nights of late fall-early winter. Much of the research on SAD has focused on changes in the photoperiod and the accompanying effects on circadian rhythms during winter. So it might come as a surprise that in Greenland, the suicide rate peaks during the summer months of continuous sun (especially at the highest latitudes). However, the rate of homicides and the sales of beer do not show the same seasonal variation (Björkstén et al., 2009). Why might this be? Most suicides in Greenland are of the impulsive variety and are committed using violent methods. The authors' previous work observed the summer suicide spike (Björkstén et al., 2005), and now they wanted to determine whether homicides show the same seasonal pattern. They reviewed the evidence on serotonin, impulsivity, and violence, and hypothesized that altered serotonin turnover might be a common factor in both violent suicides and violent homicides (reasoning that increased serotonin turnover in spring and summer might enhance impulsiveness and aggression).How was this assessed? Northern Greenland (obviously) shows the greatest seasonal extremes in the amount of light and darkness. The country maintains good statistics, and the Inuit population is considered to be relatively homogeneous. Thus, Björkstén, Kripke, and Bjerregaard (2009) examined computerized records listing the causes of all deaths in Greenland during the time period of 1968-2002. To determine whether alcohol consumption played a role in the rates of suicides and murders, the pattern of beer purchases at a major chain store from July 2005 to June 2006 were used as a proxy ("Detailed sales data are secret for business reasons").The authors note some extremely tragic statistics:The suicide rate in Greenland increased during the 1970’s from a historically very low level to one of the highest levels in the world, 107 per 100,000 person-years in 1990-1994. The increase has been most pronounced among teenagers and young adults. A rapidly increasing suicide rate has been reported from other areas going through radical changes like in Eastern Europe after the fall of communism and among aboriginal people confronted with modern lifestyle.We have previously demonstrated that the vast majority of suicides in West Greenland are violent and peak in the summer when the Northern half of Greenland has constant day-light and the Southern half has extremely long days. Depression has, however, been reported uncommon and the majority of suicides seem impulsive rather than depressive.The overall homicide rate in Greenland has been reported much higher than that of the other Nordic countries. Homicides are almost exclusively impulsive and committed under the influence of alcohol...Continuing in a depressing vein, there were 1351 suicides (80.5 % were men) and 308 homicides during the 35 year period under study.Persons in upper teens and young adults were heavily over-represented among the suicide cases. Median age was 25 years...In 391 out of the 1351 cases (29%), the death certificate included a psychiatric diagnosis. In 214 cases (15.8%), there was a diagnosis of alcoholism or alcohol intoxication; two cases also had a diagnosis of psychosis. In only 52 cases (3.8%), there was a diagnosis of affective disorder, either unspecified or in the depressive state. In 104 cases, there was a diagnosis of psychosis. In addition to the 104 cases (7.7%), there were two with alcoholism and psychosis.However, affective disorders could have been underdiagnosed in the population... we don't really know for sure. What we do know is that violent methods of suicide were used in 95% of all cases (n=1286), with men using violent methods 97% of the time and women 86% of the time (the latter percentage in stark contrast to the general population outside of Greenland). Figure 3a below shows the seasonal variation in all suicide cases. The annual peak occurred on June 11th and the trough in November-January, and the effect of seasonality was significant (p... Read more »
Bjorksten, K., Kripke, D., & Bjerregaard, P. (2009) Accentuation of suicides but not homicides with rising latitudes of Greenland in the sunny months. BMC Psychiatry, 9(1), 20. DOI: 10.1186/1471-244X-9-20
《Chinese Journal of Drug Dependence》1999-04Does anyone know what aerosol bioelectricity is?? And why it might be used to treat heroin addiction? The entire literature seems to be in Chinese. I came across that particular paper while searching for others, specifically reports on ablative psychosurgery1 for the treatment of opiate addiction in China (Gao et al., 2003 is the first in English). Hence, the title of the present post is a reference to the book by Elliot Valenstein, Great and Desperate Cures: The Rise and Decline of Psychosurgery and Other Radical Treatments for Mental Illness.Are there other "unusual" Chinese treatments for addiction, beyond what might be expected (e.g., acupuncture and traditional medicine)? Tetrodotoxin (TTX), a neurotoxin found in puffer fish, is a worthy runner up to aerosol bioelectricity. TTX inhibits action potentials by blocking voltage-dependent sodium channels. It has been tested as a treatment for severe cancer pain, which motivated Shi and colleagues (2009) to compare low dose TTX to placebo in abstinent addicts. After watching a heroin-related video, the group receiving TTX reported lower levels of craving and anxiety, without alterations in heart rate or blood pressure. However, these acute results were from a single session with no long-term follow up.Although Chinese treatments for internet addiction are getting all the headlines these days, drug addiction is actually a much more serious problem. In their review of the literature, Tang et al. (2006) inform us that:Historically, China has had extraordinarily high rates of opiate dependence. These rates declined drastically following the 1949 revolution; however, opiate abuse has re-emerged in the late 1980's and has spread quickly since then. ... The number of registered addicts in 2004 was 1.14 million (more than 75% of them heroin addicts), but the actual number is probably far higher. Opiate abuse contributes substantially to the spread of HIV/AIDS in China, with intravenous drug use the most prevalent route of transmission (51.2%). Currently, the main treatments for opiate dependence in China include short-term detoxification with opiate agonists or non-opiate agents, such as clonidine or lofexidine [alpha-2 adrenergic drugs that inhibit norepinephrine release]; Chinese herbal medicine and traditional non-medication treatments are also used. Methadone maintenance treatment (MMT) has not been officially approved by the Chinese government for widespread implementation, but some pilot studies are currently underway.Which brings us back to neurosurgery. But before discussing the results of Gao et al., a quick review. In the last post, we learned about a new and less desperate cure, the application of Deep Brain Stimulation for Severe Alcoholism. The target region in this small clinical trial (n=3) was the nucleus accumbens (NAcc), which has been called a "pleasure center" and "hedonic hot spot" that responds to food and pharmaceutical and financial and sexual rewards. The idea behind NAcc DBS was to reduce alcohol craving and "incentive sensitization" in severely impaired patients who had failed multiple treatments (Heinze et al., 2009). The researchers drew upon the experimental and theoretical work of Berridge and colleagues (2009) distinguishing between the "wanting" (incentive salience) and "liking" (hedonic impact) aspects of reward:Usually a brain ‘likes’ the rewards that it ‘wants’. But sometimes it may just ‘want’ them. Research has established that ‘liking’ and ‘wanting’ rewards are dissociable both psychologically and neurobiologically. By ‘wanting’, we mean incentive salience, a type of incentive motivation that promotes approach toward and consumption of rewards, and which has distinct psychological and neurobiological features."Liking" has been strongly linked to endogenous opioid systems in the NAcc and ventral pallidum [part of the globus pallidus] as shown below.2From Fig. 1 (Berridge et al., 2009). Forebrain hedonic hotspots in nucleus accumbens shell and in ventral pallidum where mu opioid agonist microinjections cause amplification of ‘liking’ reactions to sweetness. Red/yellow indicates greatest amplification of ‘liking’ for the sensory pleasure.In contrast, "wanting" has been most strongly associated with dopamine in the NAcc, but in reality......brain substrates for ‘wanting’ are more widely distributed and more easily activated than substrates for ‘liking’. Neurochemical ‘wanting’ mechanisms are more numerous and diverse in both neurochemical and neuroanatomical domains... In addition to opioid systems, dopamine and dopamine interactions with corticolimbic glutamate and other neurochemical systems activate incentive salience ‘wanting’. Pharmacological manipulations of some of those systems can readily alter ‘wanting’ without changing ‘liking’. For example, suppression of endogenous dopamine neurotransmission reduces ‘wanting’ but not ‘liking’.Addiction is conceived as a process by which drugs of abuse produce neural sensitization and compulsive "wanting" even in the absence of "liking". With this literature in mind, Gao et al. (2003) wished to:...explore a new way of treating drug addiction by ablating the NAcc... using stereotactic surgery, blocking the mesocorticolimbic dopamine circuit, alleviating craving for drugs and lowering the relapse rate after detoxification. On the basis of animal experiments, stereotactic surgery was performed in 28 patients by making a lesion in the NAcc bilaterally to treat opiate dr... Read more »
Gao, G., Wang, X., He, S., Li, W., Wang, Q., Liang, Q., Zhao, Y., Hou, F., Chen, L., & Li, A. (2003) Clinical Study for Alleviating Opiate Drug Psychological Dependence by a Method of Ablating the Nucleus accumbens with Stereotactic Surgery. Stereotactic and Functional Neurosurgery, 81(1-4), 96-104. DOI: 10.1159/000075111
Image from All Around The House™We all know that meth is a highly addictive, harmful stimulant drug that rots your teeth and makes you paranoid, stupid, unemployed, and homeless -- thereby ruining your life. So just say NO! to meth. Right, kids?Methamphetamine (meth) and other stimulants are best known for their effects on the dopamine system, and hence for their propensity to be reinforcing and addictive. But meth actually increases the release and blocks the reuptake of all three monoamine neurotransmitters (norepinephrine and serotonin as well as dopamine). Meth addiction can cause alterations in brain function and cognitive performance, according to hundreds of published studies (reviewed in Barr et al., 2006; Baicy & London, 2007). The NIDA website lists a multitude of adverse effects from chronic heavy use:Long-term methamphetamine abuse has many negative health consequences, including extreme weight loss, severe dental problems (“meth mouth”), anxiety, confusion, insomnia, mood disturbances, and violent behavior. Chronic methamphetamine abusers can also display a number of psychotic features, including paranoia, visual and auditory hallucinations, and delusions...However, a new review article by Hart et al. (2011) concludes that prior studies have exaggerated the harmful effects of methamphetamine on brain structure and function, cognition, mental health, and dental health. In my view, one problem with this endeavor arises in the very first sentence of the abstract:The prevailing view is that recreational methamphetamine use causes a broad range of severe cognitive deficits, despite the fact that concerns have been raised about interpretations drawn from the published literature. This article addresses an important gap in our knowledge by providing a critical review of findings from recent research investigating the impact of recreational methamphetamine use on human cognition.Many people can use meth recreationally, in modest doses, without becoming dependent. In fact, the review begins by noting the performance enhancing effects of meth in high-functioning, healthy adults who are occasional users. These laboratory studies are conducted in a very controlled environment, using oral administration of pharmaceutical grade methamphetamine. No one disputes that acutely administered meth can have beneficial effects on cognitive performance (Barr et al., 2006):Numerous studies have confirmed that MA abuse is associated with cognitive impairment. Unlike the acute effects of a single low dose of MA, which can improve cognitive processing speed, attention, concentration and psychomotor performance,77,78 long-term exposure to MA may result in profound neuropsychological deficits (see Nordahl et al2).But how does acute meth affect the performance of meth abusers? Here, the authors cite their own work on the intranasal administration of 3 doses + placebo to 11 meth abusers (Hart et al., 2008). The same computerized battery of 5 cognitive tests was given to the participants during each session. The results in their entirety:Figure 4 shows how methamphetamine altered performance over time on selected measures.1 As can be seen, methamphetamine improved performance on both of the selected tasks. On the DAT [divided attention task, for vigilance], all active methamphetamine doses decreased the mean hit latency and increased the maximum tracking speed (P<0.05). On the DSST [digit-symbol substitution task, for visuospatial processing], only the two intermediate doses (12 and 25 mg) significantly improved performance. Relative to placebo, both doses increased the total number of trial attempts and correct responses (P<0.03). No other significant performance effects were noted.There is no explanation of why these two tasks were "selected" instead of the other three. Nor is there any indication of how this performance compares to "normative data" or to participants who are not meth abusers. This is a bit ironic, because the most annoying critique within the review is the repeated failure to accept the performance of control subjects as valid. Sure, acute meth did speed up performance on "selected" measures of "selected" tasks, but was this generally better or worse than what's observed in those without a history of long-term meth abuse?When evaluating whether meth really isn't that bad for you, my focus is on the chronic effects of meth in long-term abusers of the drug. I'll return to this critical issue in the next post.Footnote1 An intriguing aspect of the data is that a massive performance drop was seen from time 0 to time 15 min in the placebo condition. One could speculate that the participants knew by then that they weren't on meth. The "Good Drug Effects" and "Stimulated" self-report ratings peaked at 15 min post-snort, so there's a disappointment-related decrement on placebo.Figure 4. Selected performance effects as a function of methamphetamine dose and time. Error bars represent one SEM. Overlapping error bars were omitted for clarity.ReferencesBaicy K, London ED. (2007). Corticolimbic dysregulation and chronic methamphetamine abuse. Addiction 102 Suppl 1:5-15.Barr AM, Panenka WJ, MacEwan GW, Thornton AE, Lang DJ, Honer WG, Lecomte T. (2006). The need for speed: an update on methamphetamine addiction. J Psychiatry Neurosci. 31:301-13.... Read more »
Hart, C., Gunderson, E., Perez, A., Kirkpatrick, M., Thurmond, A., Comer, S., & Foltin, R. (2007) Acute Physiological and Behavioral Effects of Intranasal Methamphetamine in Humans. Neuropsychopharmacology, 33(8), 1847-1855. DOI: 10.1038/sj.npp.1301578
Hart, C., Marvin, C., Silver, R., & Smith, E. (2011) Is Cognitive Functioning Impaired in Methamphetamine Users? A Critical Review. Neuropsychopharmacology. DOI: 10.1038/npp.2011.276
As a sequel to the "Trust Your Insula" theme from last time (i.e., Borderline … feels like I'm goin' to lose my mind), The Neurocritic has consulted the BrainMap database, which revealed that the anterior insula is activated in a wide variety of cognitive, perceptual, and motor tasks. But first, a recap.In their recent Science paper entitled The Rupture and Repair of Cooperation in Borderline Personality Disorder, King-Casas et al. (2008) examined how well individuals with borderline personality disorder trusted others in an economic exchange game (called, conveniently enough, the Trust Game). In this game, one player (the Investor) gives a sum of money to the other player (the Trustee). The investment triples, and the Trustee decides how much to give back to the Investor. Relative to the control group, the BPD group was more likely to make a small repayment after receiving a small investment. This reflected a lack of cooperation (or "coaxing" behavior) designed to induce the Investors to trust their partners.For the fMRI portion of the study, the authors bypassed more general analyses comparing BPD and control brains during the point of investment and the point of repayment. Instead, the major neuroimaging result contrasted the receipt of low investment offers vs. high investment offers, as illustrated below. Control brains showed a nearly perfect linear correlation between $ offer and activity in the anterior insula (expressed here as a negative correlation, because low $ offers correlated with high insula activity). Such a relationship was not observed in BPD brains. In fact, no brain region in the BPD group showed a difference between high and low offers.Fig. 3 (King-Casas et al., 2008). Response of 38 healthy trustee brains and 55 BPD trustee brains to level of cooperation. (Top). Results of within-group GLM [general linear model] analyses identified cortical regions with greater response to small investments (less than or equal to $5) relative to large investments (greater than $10). (Bottom). Percent change in hemodynamic signal was averaged from the 115 most significant voxels identified in the group-level GLM during the 4- to 8-s period following the revelation of investment. The means + SE of the resulting signal are plotted in $4 bins.1 Responses in bilateral anterior insula in healthy trustees scale strongly and negatively with the size of investment (r = –0.97; bottom left). In contrast, similar analyses in individuals with BPD showed no such relation.The authors linked the insular activation to the detection of social norm violations in interpersonal contexts, concluding that individuals with BPD are deficient in this regard.2 But what are the participants really thinking about during the 4-8 sec interval following a stingy offer? Do we have yet another example of reverse inference here?Below is a figure generated from entering the x, y, z coordinates from the right insular focus shown above into the Sleuth program (available at brainmap.org), which searched the available database of papers for matches. The resulting list of coordinates and experiments was then imported into the GingerALE program, which performed a meta-analysis via the activation likelihood estimation (ALE) method (see this PDF). The figure illustrates that this exact same region of the right insula was activated during tasks that assessed speech, language, explicit memory, working memory, reasoning, pain, and listening to emotional music.Perhaps the control subjects in the King-Casas et al. study were muttering to themselves about the stingy offer. Maybe they were engaging working memory processes to a greater extent on those trials. Or maybe they were remembering a time when they were shortchanged at the grocery store. Do we conclude, then, that the BPD subjects did not do any of those things? Or that they engaged those types of processes to an equivalent extent after low and high offers?To summarize, the extrapolation about the insula and social norm violations was based on a handful of trials from 38 different control participants. I'll leave you with a few questions to ponder. Can the study can really say anything specific about the insular response on those low $ offers? Do we trust that the rest of the brain is completely silent on the matter? We do know that the BPD group scored lower than controls on a self-report measure of trust (the Interpersonal Trust Scale), but do we know what they were really thinking about during the trust game? At the end of the day, does this finding "give psychiatrists a better diagnostic tool and a brain area to target with therapy or drugs when treating BDP"?What do you think?Footnotes1 Note that these 6 monetary bins were formed from a total of 10 trials per dyad.2 See The Right and The Good and The Insula for discussion of yet another Science paper; this one localized the concept of fairness to the insula.ReferenceB. King-Casas, C. Sharp, L. Lomax-Bream, T. Lohrenz, P. Fonagy, P. R. Montague (2008). The Rupture and Repair of Cooperation in Borderline Personality Disorder Science, 321 (5890), 806-810 DOI: 10.1126/science.1156902... Read more »
B. King-Casas, C. Sharp, L. Lomax-Bream, T. Lohrenz, P. Fonagy, & P. R. Montague. (2008) The Rupture and Repair of Cooperation in Borderline Personality Disorder. Science, 321(5890), 806-810. DOI: 10.1126/science.1156902
Most everything you've read about the Doctors Prescribing 'Tetris Therapy' study is wrong. That ridiculous headline, courtesy of "fair and balanced" Fox News, is the most egregious lie I could find [if you have other favorites, please leave links in the comments]. Press stories frequently distort research findings, but sometimes the authors themselves shoulder the most blame (Holmes et al., 2010). Misuse of the words "trauma" "flashback" "cognitive vaccine" and "PTSD" are at fault here.The experiment in question is interesting as a memory study. It demonstrated that playing a visuospatial video game (Tetris) 30 min after a disturbing film can lessen intrusive visual memories, but playing a verbal trivia game (Pub Quiz) can have the opposite effect (Holmes et al., 2010). According to Baddeley (1992), this occurs because of two modality-specific working memory systems: the visuospatial sketchpad for visual working memory and the phonological loop for verbal working memory. Tetris interferes with the former, while Pub Quiz interferes with the latter.Sixty participants (18–60 yrs old; mean age=27 yrs; 30 females) took part in Experiment 1. They were carefully screened for trauma history, mood, trait anxiety and depression. Potential subjects were excluded if they had ever been treated for mental illness of any kind. So this is a group of healthy controls -- not depressed, not anxious, minimal exposure to trauma, and no PTSD. They were a happy bunch, with mean scores on the Beck Depression Inventory (BDI) of 5.7-6.2.1The participants were divided into three groups for the different treatment conditions, illustrated below.Figure 1 (from Holmes et al., 2010). Experiment 1 study design overview. Participants completed the trauma film paradigm, a well established experimental analog for PTSD. All participants viewed a traumatic film followed by a 30-min structured break. Participants were then allocated to one of three experimental conditions [Tetris vs. no-task control vs. Pub Quiz] which they completed for 10 min. Afterwards participants in the computer game conditions rated their enjoyment of the game. Flashbacks (involuntary memories) were monitored for 1 week using an intrusion diary. After 1 week, diary compliance was checked and a test of voluntary memory (recognition memory test) for the trauma film was administered.What is the "trauma film paradigm"?The 21-min film [previously used in 22] contained 15 clips of traumatic content including fatal road traffic accidents and graphic scenes of human surgery. Following that link leads you to this description (and a series of other studies):Participants were shown a 13 min film of real-life footage of the aftermath of road traffic accidents (compiled by Steil, 1996). This film has been used extensively in studies using the trauma film paradigm (e.g. Brewin and Saunders, 2001, Hagenaars et al., 2008, Halligan et al., 2002, Holmes et al., 2004, Holmes et al., 2006, Holmes and Steel, 2004 and Stuart et al., 2006). It consists of five separate scenes each introduced by a short commentary providing context for the scene.To begin with, actual trauma isn't forewarned or contextualized in advance. It's surprising and shocking. Granted, ethical considerations require informing the participants at the time of recruitment, but this imposes even more limits as a model of real trauma.Going back to the string of references, the first citation (Steil, 1996) indicates the author studied "Posttraumatic intrusions after road traffic accidents" (not merely watching a road traffic accident film). Nonetheless, let's quickly review some of the other papers, with an eye on the terminology used by the respective authors. Brewin and Saunders (2001) looked at "intrusive memories for a stressful film". Hagenaars et al. (2008) reported on "the development of intrusions after an aversive film". In 2004, Holmes et al. studied "intrusive memory development". Notice that "traumatic" and "flashbacks" aren't yet part of the lexicon. As time went on, Holmes et al., 2006 called it a "traumatic film" but hadn't yet transformed "intrusive memories" into "flashbacks". The language used to describe the experimental phenomena shapes the reader's willingness to view the film paradigm as a proxy for real trauma.What is a true flashback? Here's the relevant section of the DSM-IV Criteria for Posttraumatic Stress Disorder, which describes a flashback episode as a complex, multi-sensory experience and not just a visual memory:(3) acting or feeling as if the traumatic event were recurring (includes a sense of reliving the experience, illusions, hallucinations, and dissociative flashback episodes, including those that occur upon awakening or when intoxicated). Another element of these experimental designs can include ratings of how upset the participants were while viewing the gory film (Holmes et al., 2004):Participants rated their distress associated with viewing the film after it had ended. They also rated their level of depression, anger, happiness, and anxiety both pre- and postfilm. Eleven-point scales were used, with anchors of 0 (not at all) and 10 (extremely).In that study, ratings were 5.1 for a "no task" condition that did not involve a secondary task while watching the video. So these participants were not especially distressed. Furthermore, this unvalidated self-rating scale has no clinical relevance to PTSD. Eleven-point scales were also used to rate [non-clinical] levels of depression, anger, happiness, and anxiety both pre- and postfilm.Finally, to illustrate that the "trauma film paradigm" bears no relation to the lasting effects of real trauma that can cause PTSD is this ethical clarification (Holmes et al., 2004):With respect to the ethical issues of showing a film with traumatic content, ... Read more »
Holmes, E., James, E., Kilford, E., & Deeprose, C. (2010) Key Steps in Developing a Cognitive Vaccine against Traumatic Flashbacks: Visuospatial Tetris versus Verbal Pub Quiz. PLoS ONE, 5(11). DOI: 10.1371/journal.pone.0013706
Really? Scantily-clad women are featured in NBC's prime-time coverage of the Summer Olympics? It's true!In the Boston Globe's Uncommon Knowledge feature ("Surprising insights from the social sciences"), Kevin Lewis writes:Fewer clothes = more coverage AS YOU WATCH the Olympics this week, try to put yourself inside the minds of the network executives who get to decide what to broadcast. Given that you've spent billions on licensing and production costs - meaning that you need the most people from the best advertising demographics to watch - which events and athletes do you highlight? A study out of Clemson University analyzed videotapes of all prime-time Summer and Winter Olympic programming since 1996. Although the Summer Olympics covered men's and women's events about the same, the Winter Olympics was significantly biased toward men's events. The author notes that prominent coverage of women in gymnastics, swimming, diving and, lately, beach volleyball is consistent with the notion "that the Summer Games (offering many events that involve women athletes in swimsuits and leotards) will yield higher clock-time totals than the Winter Games (offering many events that involve women athletes in parkas and other less sexually charged apparel)."It's not really a surprising insight, but there you go.In the study, which was published in the journal Television & New Media, Andrew Billings (and 16 students) watched all 348 hours of prime-time TV coverage of the 1998, 2002, and 2006 Winter Olympics and the 1996, 2000, and 2004 Summer Olympics. Why?The objective of providing this longitudinal perspective is to highlight long-term gender trends within this very prominent sportscast by isolating men’s and women’s Olympic clock time in six consecutive Olympics. In doing so, the study underscores how the Olympic telecast itself is changing over time in terms of spotlighting different events.The results demonstrated a slight overall advantage for coverage of male over female athletes in the Summer Games (51.9% vs. 48.1%) which was only significant in 2000. In contrast, coverage of male athletes in the Winter Games was significantly greater in all three years (overall 61.6% male vs. 38.4% female). Note that pairs events (such as pairs figure skating) were excluded.For the Summer Olympics, the big three events for men were gymnastics (28.0% of the total male coverage), track and field (23.9%), and swimming (14.5%). For women, gymnastics (40.1%), track and field (16.9%), and diving (15.0%) had the greatest coverage. Although beach volleyball became an Olympic sport in 1996, the women's competition was only televised in 2004. In that year, the women had 2 hours of prime-time coverage, compared to only 1 minute for men's beach volleyball.Swimsuits have become more modest (and aerodynamic) over time. Has that affected TV time?1996 Olympic Swimming event in AtlantaPossibly, although the article did not place the longitudinal changes in that context:For men, the sports that gained coverage in the Summer Olympics were swimming and track and field (largely the result of network timeslot shifting in which these events moved from earlier time slots to within prime-time coverage).Adapted from Tables 1 and 2 (Billings, 2008).There was no such change in swimsuits in the diving events, however. If anything, men's swimsuits are more skimpy than the women's in this sport. Thus, it was notable that across all three Olympics, women's diving received 7 hrs 47 min coverage (15%) while men's received 4 hrs 34 min (8.2%).These relationships are speculative. Let's read what the author actually said:...the Summer Olympic events in which men were more likely to be shown than women were basketball, cycling, swimming, track and field, and volleyball. While some predictions for these differences could be proffered (i.e., lingering effects of the “Dream Team” in basketball or Lance Armstrong’s effect on the world of men’s cycling), the results only speak to the significant clock time differences rather than the reasons for them.In contrast, women were more likely than men to be shown in beach volleyball (rising from no coverage to a two full hours of clock time in 2004), diving, and gymnastics. While all of these sports could be viewed as the fairly attractive/graceful category that Kane (1988) outlined (with the possible exceptions of basketball and the field sports in track and field), it is interesting to note that all of the sports in which women received the majority of the coverage involved the wearing of swimsuits or leotards. One could presume that the same desire to highlight attractive athletes would result in a desire for attractive male athletes, yet Jones, Murrell, and Jackson’s (1999) analysis found that a very different dichotomy was at work, with sports journalists highlighting “pretty” females but “powerful” males.So yes, sex sells. Or put in more formal terms:While this study does not attempt to interpret the cognitive processes of NBC gatekeepers in determining what to show, three additional propositions can be offered.. . .Second, attractive sports, such as beach volleyball, appear to be on the upswing, specifically for women. While men received more coverage in beach volleyball in 2000 than they did in 2004, women’s coverage increased exponentially. Part of this was likely the result of a highly skilled team, Misty May and Kerri Walsh, who won every match all year en route to a gold medal. Still, one has to note that part of the appeal of showing this event more frequently could reside in showing attractive women in swimsuits. The sexualized male gaze imparts a double standard within clock time differences, as the percentage of men athletes in sexualized situations (i.e., swimsuits/leotards) is not on the upswing nearly as much as for the women athletes.ReferenceBillings, A.C. (2008). Clocking Gender Differences: Televised Olympic Clock Time in the 1996--2006 Summer and Winter Olympics. Television & New Media, 9(5), 429-441. DOI: 10.1177/1527476408315502Analysis of all 348 prime-time hours of the 1996—2006 Olympic telecasts (three Summer, three Winter) pinpointed trends in coverage of men's and women's sports. Results indicate that while men athletes and events received the majority of clock time in all six Olympic telecasts, the Summer Olympic telecasts treated women far more equitably than the Winter Olympic telecast. The longitudinal study does not offer any reason to feel that coverage of women's athletics is improving over time, finding that the proportion of clock time devoted to men's and women's sports is relatively the same in 2006 compared to ten years earlier.... Read more »
A Billings. (2008) Clocking Gender Differences: Televised Olympic Clock Time in the 1996--2006 Summer and Winter Olympics. Television , 9(5), 429-441. DOI: 10.1177/1527476408315502
Fun With Behavior Therapy from the 70s, Part 2In our next installment of food-based behavior therapies to treat phobias in adults, we have a case report of combined exposure/M&M treatment (Kroll, 1975). First is a description of the client's fear of dogs:The client was a 22-yr-old female graduate student with a strong fear and avoidance of dogs. She had been told by her parents that a large brown dog had knocked her over when she was a child, but she did not remember the incident nor did she attribute her fear to it. She could not remember any time in her life when she was not afraid of dogs. The intensity of her fear was unaffected by size or breed of dog. If she was alone and saw a dog approaching her, she became highly anxious and walked away very rapidly or, if possible, crossed the street to avoid an encounter. When leaving her house and seeing a dog, she either exited through the back door or waited until the dog left before walking outside. If she was walking with another person and unavoidably encountered a dog, she became intensely anxious and held onto the other person tightly while attempting to put the person between her and the dog.Next is description of the treatment, which included voluntary food deprivation. Notice, however, that the client did not agree to 24 hrs without food:The client was instructed not to eat anything for 12-hr prior to the treatment session. It was originally planned that she would undergo 24-hr food deprivation, but she did not think she could go without eating longer than 12-hr. Because among her favorite foods M & M's were most preferred, I decided on using them to inhibit anxiety. She was told that they would have greater reward value than any other food and would therefore increase the probability of successfully inhibiting anxiety elicited by a feared object. And here we have evidence of the therapist's condescending attitude:Since I had told her of other cases in which food was used as an anxiety inhibitor, she was receptive to the use of M & M's. (It should be noted that she was unaware of the client populations with whom M & M's are typically used.)So the client bought a large bag of M&M's and went to an animal shelter, accompanied by the therapist. From the very beginning, the therapeutic value of the M&M's is not really clear, given the calming presence of the therapist:Upon entering the room in which the dogs were caged, the client's initial response was fear. She made no attempt, however, to leave the room. Starting at a distance of about seven feet--the farthest away in the room that one could stand from the animals--I walked with the client around the room as far as possible from the cages while feeding her M & M's. ... At the end of the session which lasted approximately 2-hr, she reported feeling relaxed in the presence of the dogs. She expressed confidence that she could encounter dogs without fear or need to avoid them.It's scientifically proven! M&M'S® can cure phobias in a single 2 hr session! However, that laughable conclusion was even questioned by the author at the conclusion of the article:The possibility exists that, instead of the feeding, or perhaps in addition to it, graduated exposure or therapist-client interaction or modeling were responsible, singly or in complex interaction for the client's improvement. As control observations were not made, one cannot rule out the possibility that the feeding was superfluous.To end on a serious note, one application of this approach to behavior therapy is not a laughing matter at all, as noted in a comment on my last post by Michelle Dawson, author of The Autism Crisis blog:Not phobias, but extreme food deprivation has been used as an early autism treatment, with very young children.You can find a 1970s use of extreme food deprivation at UCLA reported in this book. Lovaas' reported recommendation was 36hrs of food and liquid deprivation for a 4yr old. The purpose was to make the child "hungry and desperate enough to do anything for food." Instead the child got very sick, threw up bile, and was too tired and listless to work for his food.Another book reports in passing the use of routine food deprivation as autism treatment by Lovaas at UCLA, within the most famous autism study ever.To my knowledge there has never been any criticism of this kind of practice published in any journal.I highly recommend her three part series on Autism Advocacy and Aversives: part one, part two, part three.ReferenceKroll, H. (1975). Rapid treatment of dog phobia by a feeding procedure Journal of Behavior Therapy and Experimental Psychiatry, 6 (4), 325-326 DOI: 10.1016/0005-7916(75)90071-3
... Read more »
Kroll, H. (1975) Rapid treatment of dog phobia by a feeding procedure. Journal of Behavior Therapy and Experimental Psychiatry, 6(4), 325-326. DOI: 10.1016/0005-7916(75)90071-3
Voodoo no more!The paper everyone loves (or loves to hate) has a new name.1 Through a number of channels [The Chronicle of Higher Education via @vaughanbell, Ed Vul's website, and Neuroskeptic], The Neurocritic has learned that the "Voodoo Correlations" have been downgraded to mere "Puzzlingly High Correlations." The field of social neuroscience has been spared as well, because the full title of the paper is now "Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition" (PDF).By now, most neuroimagers and cognitive neuroscientists have heard about that controversial (some would say inflammatory) paper by Ed Vul and colleagues, summarized in this post.2 In the article, Vul et al. claimed that over half of the fMRI studies that were surveyed used faulty statistical techniques to analyze their data:...using a strategy that computes separate correlations for individual voxels, and reports means of just the subset of voxels exceeding chosen thresholds. We show how this non-independent analysis grossly inflates correlations, while yielding reassuring-looking scattergrams. This analysis technique was used to obtain the vast majority of the implausibly high correlations in our survey sample.Needless to say, authors of the criticized papers were not pleased. Two rebuttals were released online shortly thereafter: one by Jabbi et al. (PDF) -- here's the response to that rebuttal -- and an invited reply by Lieberman et al. (PDF).That was back in January, after the manuscript had been accepted for publication by Perspectives on Psychological Science in late December 2008. Now [finally], the paper has been officially published in the May 2009 issue of the journal, with an introduction (PDF) by Ed Diener, the editor. Also included are six Commentaries by assorted authors and a Reply to the Commentaries by Vul et al. (PDF).I haven't had time to read all the commentaries and rebuttals yet, but the Editor's Introduction is worth a quick mention for the issues it raises about peer review and publication in these modern times.PREPUBLICATION DISSEMINATIONAs soon as I accepted the Vul et al. article, I heard from researchers about it. People around the globe saw the article on the Internet, and replies soon appeared as well. Although my plan was to publish the article with commentary, the appearance of the article on the Internet meant that researchers read the article without the accompanying commentaries and replies that I had planned to publish with it.In some fields such as economics, it is standard practice to widely disseminate articles before they are published, whereas in much of psychology this has been discouraged. An argument in favor of dissemination is that it speeds scientific communication in a fast-paced world where journal publication is often woefully slow. An argument against dissemination of articles before publication is that readers do not have the opportunity to simultaneously see commentary and replies. ... In the Internet age, the issue of prepublication distribution becomes all the more important because an article can reach thousands of readers in a few hours. Given the ability of the Internet to communicate so broadly and quickly, we need greater discussion of this issue.Bloggers have discussed this specific issue months ago. For example, as noted in Mind Hacks,The paper was accepted by a peer-reviewed journal before it was released to the public. The idea that something actually has to appear in print before anyone is allowed to discuss it seems to be a little outdated (in fact, was this ever the case?).And The Neurocritic opined that...[The aggrieved authors] are not keeping up with the way that scientific discourse is evolving. Citing "in press" articles in the normal academic channels is a frequent event; why should bloggers, some of whom are read more widely than the authors' original papers, refrain from such a practice? Is it the "read more widely" part?...and in The Voodoo of Peer Review asked:Are blogs good or bad for the enterprise of scientific peer review? At present, the system relies on anonymous referees to provide "unbiased" opinions of a paper's (or grant's) merits. For today, the discussion will focus on peer review of papers in scientific journals....[An] article [in Seed Magazine] begins:Few endeavors have been affected more by the tools and evolution of the internet than science publishing. Thousands of journals are available online, and an increasing number of science bloggers are acting as translators, often using lay language to convey complex findings previously read only by fellow experts within a discipline. Now, in the wake of a new paper challenging the methodology of a young field, there is a case study for how the internet is changing the way science itself is conducted.Really? Maybe that's true for Biological and Social Sciences, but certainly not for Physics, Mathematics, Computer Science, Quantitative Biology, Quantitative Finance and Statistics (see arXiv.org)...Diener then raises the point that online bloggers and commenters may be discussing various versions of the manuscript:Another problem that has arisen in terms of Internet “publication” of the article and the Internet replies is that different individuals will have read different versions of the article. A single reader is unlikely to read more than one version of the article and will therefore often not see later corrections and changes. Furthermore, the commentaries are to some extent replies to different versions of the article and therefore might not be entirely on-target for the final version. This makes it difficult to fully understand the arguments because comments and replies might not be to the most current versions of articles, and it is impossible to fully correct this because the back-and-forth of revisions could continue indefinitely.So there's never a final version of the article because revisions continue indefinitely?? Or are the accepted and final versions of the manuscript so radically different [why, I might ask] that a discussion of the initially accepted version is misleading? Or instead, is it the online commenters who are "revising" the article ad infinitum? Will Diener's editorial be clarified in a future edition, thus rendering moot my confusion in this particular post?At any rate, Diener also discusses ethical issues surrounding the questionnaire that Vul et al. distributed to the authors. Some believed they were unwitting participants in Human Subjects research and did not give their informed consent (Diener disagreed). Not surprisingly, the "article tone" was another source of contention, and here Diener agreed to change the original "Voodoo" title. Finally, some of the aggrieved authors disputed the accuracy of the entire paper, suggesting that some (if not all) of their research was incorrectly classified. But in the end, the editor defers to the readers, who will judge the article and comments and form their own opinions.I believe that the debate can itself stimulate useful discussions about scientific practices and communication. Further discussion of the issues should now take place in journals that are focused on imaging and neuroscience, so that the readers there can judge and benefit from the ensuing discussions.I believe that further discussion of the issues can also take place on blogs that are focused on imaging and neuroscience. So feel free to discuss at length. Leave your questions and observations in the comments section of this post!Footnotes1 See The Voodoo of Peer Review for a preview of this issue.2 You can also read a quick overview at Scan Scandal Hits Social Neuroscience, and more in-depth commentary in the post Voodoo Schadenfreude. And a comprehensive list of links about the the paper is located here.Ed Diener (2009). Editor's Introduction to Vul et al. (2009) and Comments. Perspectives on Psychological Science, 4 (3).Complete List of References (from PERSPECTIVES ON PSYCHOLOGICAL SCIENCE, Vol. 4, Issue No. 3 · May 2009)Editor's Introduction to Vul et al. (2009) and CommentsEd Diener Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social CognitionEdward Vul, Christine Harris, Piotr Winkielman, and Harold Pashler Commentary on Vul et al.'s (2009) "Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition"Thomas E. Nichols and Jean-Baptist Poline Big Correlations in Little Studies: Inflated fMRI Correlations Reflect Low Statistical Power--Commentary on Vul et al. (2009)Tal Yarkoni Correlations in Social Neuroscience Aren't Voodoo: Commentary on Vul et al. (2009) Matthew D. Lieberman, Elliot T. Berkman, and Tor D. Wager Discussion of "Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition" by Vul et al. (2009)Nicole A. Lazar Correlations and Multiple Comparisons in Functional Imaging: A Statistical Perspective (Commentary on Vul et al., 2009)Martin A. Lindquist and Andrew Gelman Understanding the Mind by Measuring the Brain: Lessons From Measuring Behavior (Commentary on Vul et al., 2009)Lisa Feldman Barrett Reply to Comments on "Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition"Edward Vul, Christine Harris, Piotr Winkielman, and Harold Pashler... Read more »
Ed Diener. (2009) Editor's Introduction to Vul et al. (2009) and Comments. Perspectives on Psychological Science, 4(3).
A study on electrophysiological recordings from single neurons in the dorsolateral prefrontal cortex of two monkeys trained to perform a visual target discrimination task (Lennert & Martinez-Trujillo, 2011) has supposedly given new hope to patients with a diverse array of neurological and psychiatric conditions, according to a press release:Filters That Reduce ‘brain Clutter’ IdentifiedScienceDaily (Apr. 19, 2011) — Until now, it has been assumed that people with conditions like ADHD, Tourette syndrome, obsessive compulsive disorder and schizophrenia -- all of whom characteristically report symptoms of "brain clutter" -- may suffer from anomalies in the brain's prefrontal cortex.Damage to this brain region is often associated with failure to focus on relevant things, loss of inhibitions, impulsivity and various kinds of inappropriate behaviour. So far, exactly what makes the prefrontal cortex so essential to these aspects of behaviour has remained elusive, hampering attempts to develop tools for diagnosing and treating these patients.But new research by Julio Martinez-Trujillo, a professor in McGill University's Department of Physiology and Canada Research Chair in Visual Neuroscience, has brought new hope to these patients. He believes the key to the "brain clutter" and impulsivity shown by individuals with dysfunctional prefrontal cortices lies in a malfunction of a specific type of brain cell. Martinez-Trujilo and his team have identified neurons in the dorsolateral sub-region of the primate prefrontal cortex that selectively filter out important from unimportant visual information. The key to the normal functioning of these "filter neurons" is their ability to, in the presence of visual clutter, selectively and strongly inhibit the unimportant information, giving the rest of the brain access to what is relevant.I am so flabbergasted by the number of misleading statements that I don't know where to begin. Let's take them in the order of occurrence."Until now" - This phrase implies that the study has refuted the assumption that ADHD, Tourette's, OCD, and schizophrenia are all associated with abnormalities in the prefrontal cortex (PFC). In fact, individuals with these disorders (and their PFCs) were not evaluated."brain clutter" - What does this mean? I'm not familiar with it as a technical term, nor how the phenomenon is manifest in all four of the above disorders. This issue is relatively minor."anomalies in the brain's prefrontal cortex" - The human PFC covers a large and diverse area of the brain.Fig. 1 (Fuster, 2002). Three views of the cerebral hemispheres with the areas of the prefrontal cortex numbered in accord with Brodmann’s cytoarcitectonic map.Neuroimaging findings in ADHD, Tourette's, OCD and schizophenia are not uniform, and the implicated subregions of PFC are not the same. For example, OCD has been associated with overactivity in the orbitofrontal cortex (Menzies et al., 2008) while schizophrenia is associated with altered activation of dorsolateral PFC (Volk & Lewis, 2010).1 This is highly relevant because as we'll see, the monkey neurons under investigation were in a specific region analogous to Brodmann area 46 in human dorsolateral PFC."Damage to this brain region" and the subsequent laundry list of altered behaviors - not all associated with damage to BA 46."brought new hope to these patients" - This is by far the most egregious falsehood of the entire press release. I find it to be utterly irresponsible.None of these claims were made in the paper itself, which examined firing rates of neurons in the principal sulcus of two rhesus macaque monkeys trained to perform a color-rank target discrimination task with moving random dot patterns.Figure adapted from the press release. The pinkish highlighted area of the brain is the principal sulcus region where neuron activity was recorded.The authors summarize the results below. You'll notice there's no mention of developing "tools for diagnosing and treating these patients" or bringing "new hope to these patients."Highlights► Interstimulus ordinal distance modulates attentional-filtering strength in monkeys ► Interstimulus ordinal distance modulates target selection by prefrontal neurons ► Varying suppression of distracters by dlPFC neurons determines attentional filtering ► Target enhancement by dlPFC neurons remains invariable with changes in performanceHere's the link for the original press release from McGill University. If you are so inclined:Contact: Katherine Gombay, Media Relations Office, McGill University - Tel.: 514 398-2189 Footnote1 I'm skipping the complexities of multiple fronto-striato-thalamic circuits.ReferencesFuster JM. (2002). Frontal lobe and cognitive development. J Neurocytol. 31:373-85.Lennert, T., & Martinez-Trujillo, J. (2011). Strength of Response Suppression to Distracter Stimuli Determines Attentional-Filtering Performance in Primate Prefrontal Neurons Neuron, 70 (1), 141-152 DOI: 10.1016/j.neuron.2011.02.041Menzies L, Chamberlain SR, Laird AR, Thelen SM, Sahakian BJ, Bullmore ET. (2008). Integrating evidence from neuroimaging and neuropsy... Read more »
Lennert, T., & Martinez-Trujillo, J. (2011) Strength of Response Suppression to Distracter Stimuli Determines Attentional-Filtering Performance in Primate Prefrontal Neurons. Neuron, 70(1), 141-152. DOI: 10.1016/j.neuron.2011.02.041
"Religion is the Xanax of the people" (Inzlicht et al., 2009).The clever quote above is from the latest paper to garner the _______ Are Neurotic and _______ Are Antisocial style of sensationalistic headline, a study that claims to reveal the Neural Markers of Religious Conviction. I was all prepared to hate the paper, but the authors are not unreasonable in their hypotheses and predictions.But first, a little background. A year and a half ago, Amodio et al. (2007) published an eye-catching article in Nature Neuroscience that reported on supposed "hard-wired" differences in the brains of liberals and conservatives. The typical media feeding frenzy ensued, complete with simplistic headlines (and some interpretive stretching on the part of the authors).As we recounted in The Error of Prognosticating Political View by Brain Wave,1 there were:...overblown quotes:Are We Predisposed to Political Beliefs?. . ."In the past, people thought that…[political leanings were]…all environmentally influenced, a combination of biological dispositions as well as cultural shaping," says David Amodio, an assistant professor of psychology at New York University. However, a new study, led by Amodio, indicates that political bent "is not just a choice people have, but it seems to be linked to fundamental differences in the way people process information."And the baseless assertion of innate differences between the brains of liberals and conservatives:brain neurons of liberals and conservatives fire differently [sic] when confronted with tough choices, suggesting that some political divides may be hard-wired, according a study released Sunday.That study is quite relevant here because Inzlicht and colleagues used the same neural measure as Amodio et al. (2007). Both experiments used EEG recordings, specifically event-related potentials. The ERP brain waves reflect electrophysiological activity recorded remotely from the scalp. While it's great for determining the temporal parameters of neural activity, it's not so great at determining where the activity is located in the brain.The brain wave of interest is the error-related negativity (ERN), recorded at the time that people make mistakes in a task:The ERN is evident as a large negative polarity peak in the event-related brain potential waveform that occurs when people make errors in reaction time tasks. It begins at the moment of the error and reaches a maximum about 100 milliseconds later (see Gehring et al., 1993, PDF). It is largest at fronto-central scalp locations and appears to come from an area of the brain called the anterior cingulate cortex...There is some disagreement about what the ERN wave represents: a direct response to the mismatch between the intended action and the actual one, a more generic response to conflict in general, or an emotional response to f***ing up. And because EEG is recorded from the scalp, one cannot say for certain that the anterior cingulate is the sole origin.What does all this have to do with that old time religion? Inzlicht et al. review the neuropsychology of anxiety and how religion serves to quell the angst:XANAX OF THE PEOPLEOne of religion’s primary functions may be to help people cope with existential uncertainty. In the words of St. Ambrose (ca. 390 AD), ‘‘amid the agitations of the world, the Church remains unmoved; the waves cannot shake her. While around her everything is in a horrible chaos, she offers to all the shipwrecked a tranquil port where they will find safety’’ (quoted in Durant, 1950, p. 79). Religion provides people with a meaning system that helps them navigate through and understand an infinitely complex and uncertain world (Peterson, 1999). It meets the fundamental need to comprehend the deepest problems of existence. Scholars of religion, from James (1902/2002) to Durkheim (1912/1954), have noted that religion imbues life with motivation, purpose, and meaning.What does anxiety have to do with the ERN wave?? It's larger in those with anxiety disorders, as Hajcak et al. (2004) have noted. And the hypothesis of the present paper?How is it that religion can bring about both peace of mind and zealous conviction? We suggest that religious conviction buffers against anxiety by providing relief from the experience of uncertainty and error, and in so doing, strengthening convictions and narrowing attention away from inconsistencies. We hypothesize that this muted response to uncertainty and error is evident neurophysiologically such that religious conviction is associated with reduced activity in the anterior cingulate cortex (ACC), a cortical system involved in a form of attention that serves to regulate both cognitive and emotional processing...Although it's simplistic of them to say the ERN reflects only ACC activity, they did avoid some of the pitfalls of Amodio et al.'s paper by taking into account personality factors that can influence this brain wave (hence, the "neurotic" and "antisocial" title).We measured the amplitude of each participant’s ERN during the Stroop task and correlated these values with participants’ self-reported religious zeal (Study 1) and self-reported belief in God (Study 2). In both studies, we also measured other psychological variables to control for their impact on the hypothesized correlation between religious conviction and ACC activity. We expected greater religious conviction to predict lower ERN amplitudes in both studies, even after controlling for important personality traits and cognitive capacities.And that's what they found.Fig. 1C (Inzlicht et al., 2009). The relation between religious zeal and anterior cingulate cortex activity: event-related potentials (ERPs) at electrode Cz for error-related negativities (ERNs) for people high and low in religious zeal.The Religious Zeal scale was used to assess ardent religious conviction. Items included ‘‘I aspire to live and act according to my religious beliefs,’’ ‘‘My religious beliefs are grounded in objective truth,’’ and ‘‘I would support a war that defended my religious beliefs.’’ Behavioral inhibition, behavioral activation, self-esteem, and the need for cognitive closure were also assessed.However, they repeat some of the drawbacks from Amodio's paper by reporting correlations but only showing a median split (presumably) in the figure (and we don't know if this group difference is significant). We also don't know anything about the reaction times, other than the odd finding that greater religious zealotry was associated with a larger Stroop interference effect (slower for BLUE than for RED) but fewer errors.In Experiment 2 with a different group of subjects, the self-report measures were belief in God, political conservatism à la Amodio, and the Big Five personality inventory. Here, too, they found that greater religious belief correlated with smaller ERN responses to errors (and personality did not account for this).Unexplained loose ends? I see at least two of them. First, the estimated localization of the ERN response within the ACC was centimeters apart in the two groups of subjects. Granted, estimated source localization for ERP is tenuous at best (especially with only 32 electrodes), but these two spots are in different functional regions of the ACC.Fig 1D (top) and Fig 2D (bottom) - illustration of the generator for the ERN (in anterior cingulate cortex), as determined by source localization.More critically, this experiment failed to replicate Amodio's finding: there was absolutely no correlation between self-assessed conservatism and the ERN wave! [as in this figure] I don't have a high need for cognitive closure, but it appears to be a glaring omission that this was not even mentioned in the paper. I'm feeling a very large error-related negativity at the moment. Maybe I need a Xanax. Or a religious experience...Footnote1 For more on the same study, see Liberals Are Neurotic and Conservatives Are Antisocial, as well as David Amodio Responds to his neurocritics.ReferencesAmodio DM, Jost JT, Master SL, Yee CM. (2007). Neurocognitive correlates of liberalism and conservatism. Nature Neurosci. 10:1246-1247.Hajcak G, McDonald N, Simons RF. (2004). Error-related psychophysiology and negative affect. Brain Cogn. 56:189-97.Michael Inzlicht, Ian McGregor, Jacob B. Hirsh, Kyle Nash (2009). Neural Markers of Religious Conviction Psychological Science DOI: 10.1111/j.1467-9280.2009.02305.x... Read more »
...is the title of a book by Thea Hillman, in which (according to a review by David S. Hall),She speaks of her experiences as a young child, being diagnosed with Congenital Adrenal Hyperplasia, and what that experience meant to a four year old girl who was growing pubic hairs, a child who was poked and examined by many doctors, and had a total lack of personal privacy of her body. She comes back to this experience many times in the stories she tells of her life as a person who does not really know what gender she is.Congential Adrenal Hyperplasia (CAH) is an autosomal recessive genetic disorder that... is characterized by severe androgen excess beginning in the fetus. In about 95% of patients CAH is caused by a defect in the 21-hydroxylase gene (CYP21), leading to an impaired synthesis of cortisol ["stress hormone" produced by the adrenal gland] and aldosterone [hormone that causes the kidneys to retain sodium and water]. The low cortisol level triggers an increased production of adrenocorticotropic hormone, resulting in hyperplasia of the adrenal glands with increased synthesis of steroid precursors and elevation of androgen levels. The androgen excess is present from early embryogenesis, and causes in girls varying degrees of virilization of the external genitalia, depending on the degree of enzyme deficiency....as summarized in a new paper by Ciumas and colleagues (2008).In Intersex (for lack of a better word),[Hillman] speaks about her "outwardly simple though visually misleading, internally complicated gender."Ciumas et al. wanted to investigate whether fetal testosterone exposure is the major underlying mechanism for sexual dimorphism in the human brain. In particular, sex differences in the anatomy and physiology of the hypothalamus and the amygdala were of interest. Thus, they turned to adult women with CAH, sinceCertain rare conditions, so called experiments of nature, may here potentially offer unique information. A review of the literature suggested that some "sex-atypical" traits and behaviors may occur with CAH, but not all studies have agreed.Normal is a weapon of mass destruction.What is “normal”? Hall's review of Intersex continues:She speaks of her mother's prayers that she would be normal. She speaks of normal this way: "I take the war on terror personally because the war on terror is really a war on difference, because my body strikes terror in the hearts of other Americans. "My body and the bodies of the people I love are the most intimate sites of American imperialism. Because our sex anatomy isn't normal, they operate on us without our consent. Because who we have sex with isn't normal, they won't let us get married. Because our gender isn't normal, they don't give us jobs, health care, or housing. We work, we pay rent, we pay taxes, but because we're not normal, we don't get the same freedoms other Americans enjoy, the same freedoms American soldiers are murdering to protect."The study, which was not conducted in America but in Sweden by Dr. Ivanka Savic Berglund's group1 at the prestigious Karolinska Institute, was a continuation of their work on sex hormones and olfaction. Previously (Savic et al., 2001), they demonstrated that heterosexual men (HeM) and heterosexual women (HeW) showed different hypothalamic responses to smelling the putative pheromones, androstadienone (AND) and estratetraenol (EST). Specifically they used PET (positron emission tomography) to measure changes in cerebral blood flow responses to inhaling various odorants, which included sex steroids, butanol, cedar oil, lavender oil, and eugenol (clove). EST induced activity in the hypothalamus of HeM but in olfactory regions of HeW. Conversely, AND induced activity in the hypothalamus of HeW but in olfactory regions of HeM, which is not too surprising if these substances are, in fact, pheromones. The opposite sex pheromone is not processed like a regular scent, whereas the same sex pheromone is.Furthermore, they also examined hypothalamic responses to these putative pheromones in gay men (Savic et al., 2005) and lesbians (Berglund et al., 2006). In the first experiment, the comparison of gay men, straight men, and straight women was pretty straightforward (so to speak). HeM and HeW scored as 0 on the Kinsey scale (exclusively heterosexual), and the gay male subjects scored as 6 (exclusively homosexual). The results were as expected: the hypothalami of gay men were activated by AND, not EST (which was treated like any other odor). The results from the second experiment were less than straightforward. The lesbian group (between 5 and 6) did not look "just like straight men." Instead,...the lesbian subjects did not show a differentiated pattern of activation with AND and EST; they engaged the amygdala and the piriform and the insular cortices (the classical odor-processing circuits) when smelling both of these compounds.As a consolation prize, however, the lesbians were unlike HeW (since AND didn't turn on their hypothalami) and somewhat like HeM (since EST activated one overlapping region of the hypothalamus at a lower statistical threshold). [For more info on this study, see Sweat, Urine, and Sexual Orientation and The PNAS Word.]Note that I did not say anything about activity in specific hypothalamic nuclei [such as the so-called sexually dimorphic nucleus], because the PET method doesn't have the spatial resolution required to distinguish between them.That brings us to the present experiment. As you might guess, the question was whether CAH women looked more like HeM than HeW when sniffing the steroids.Is that what they found?Despite the genetically verified diagnosis and parental reports about boy-typical play behavior during childhood, the pattern of activation in the presently investigated CAH women was remarkably similar to that of female controls, and different from the pattern of male controls. CAH women and HeW activated the anterior hypothalamus with AND, whereas HeM activated this region with EST. Furthermore, whilst the amygdala connectivity differed between the male and female controls, no difference was observed between control females and CAH females. Thus, both with respect to aspects of functional organization and functional activation of the limbic circuits CAH women showed a pattern congruent with their biological sex, and different from the opposite sex. Our hypothesis that these specific aspects of cerebral dimorphism would have masculine features in CAH women was thereby rejected. So no, it was not what they found.Figure 1 (Ciumas et al., 2008). Illustration of group-specific activations with putative pheromones and odors. The Sokoloff's color scale illustrates Z values reflecting the degree of activation. As the same brain section is chosen, the figures do not always illustrate maximal activation for each condition. Clusters of activated regions are superimposed on the standard brain MRI, midsagittal plane.This failure to show a difference between CAH women and control women was obtained even though the two groups were not particularly well-matched for sexual orientation! [a glaring weakness that could have been rectified by recruiting a few bisexual control women]. Eight of the CAH women rated as Kinsey 0, but three others rated as 2, 4, and 5.2At any rate, these results provide no support for the notion that exposure to high levels of fetal testosterone will result in the "masculinization" of sexually dimorphic limbic circuits. Why? What does this have to say about fetal testosterone and the "male brain" view of development (e.g., Christine Knickmeyer & Baron-Cohen, 2006)? Ciumus et al. were puzzled, but offered the following speculations:Explanations to these discrepancies are not evident from the present data. We can only conclude that intrauterine virilization of genitalia is not necessarily paralleled by a masculinization of the limbic brain, at least not with respect to signal response to AND and EST, and the baseline amygdala connectivity, which are 2 indices of sex-dimorphism. It is theoretically possible that various sex dimorphic features are affected by fetal testosterone in a dose dependent manner. Whilst such a scenario could be attributed for the differences between HeM and HeW (with extremely high testosterone levels in male fetuses), it is less likely to explain the "male" like AND and EST activation and functional connectivity in lesbian women described in our previous studies. None of our lesbian participants in these studies had genital masculinization, which is expected already at moderate elevations of fetal testosterone. An alternative possibility is that various sex dimorphic features may have different etiological factors; in this respect recent studies by Arnolds group at UCLA are of particular interest as they indicate existence of early, and testosterone-independent chromosomal effects on the brain. Finally, several different etiological factors could contribute to a same sexually dimorphic cerebral feature, for example, psychosexual outcome. The 3 alternatives are not mutually exclusive. Although presently speculative, in the view of present results they all seem relevant to address in the near future. So there's no neat conclusion, only ambiguity. The calls for future studies are issued. But where does it all fit, in the grand scientific scheme of things? In the less grandiose human scale of things, to be different and yet not-so-different? When talking about her participation in the Intersex and Transgender communities, Thea Hillman says:"I fear that regardless of the fact that I've been hormonally altered since age six in order to achieve and maintain a mythical gender ideal, I can't safely talk about my concerns about hormones and surgery in our community for fear of being seen as anti-trans and anti-surgery."Footnotes1 In the recent past, The Neurocritic (and other neuropundits) have been critical of Savic's work on cerebral asymmetry and sexual orientation, but we'll put that aside for today.2 Another potential source of variability was the severity of the condition, which ranged from 1 to 5 (least to most severe), with a mean value of 3.18 in the 11 participants. Only four of the CAH women rated a severity of 4 or 5, so this might have obscured potential group differences in the data.ReferencesBerglund H, Lindström P, Savic I. (2006). Brain response to putative pheromones in lesbian women. Proc Natl Acad Sci. 103:8269-74.Christine Knickmeyer R, Baron-Cohen S. (2006). Fetal testosterone and sex differences. Early Hum Dev. 82:755-60.Savic I, Berglund H, Gulyas B, Roland P. (2001). Smelling of odorous sex hormone-like compounds causes sex-differentiated hypothalamic activations in humans. Neuron 31:661-8.Savic I, Berglund H, Lindström P. (2005). Brain response to putative pheromones in homosexual men. Proc Natl Acad Sci. 102:7356-61.C. Ciumas, A. L. Hirschberg, I. Savic (2008). High Fetal Testosterone and Sexually Dimorphic Cerebral Networks in Females. Cerebral Cortex DOI: 10.1093/cercor/bhn160.Active masculinization by fetal testosterone is believed to be a major factor behind sex differentiation of the brain. We tested this hypothesis in a 15O-H2O positron emission tomography study of 11 women with congenital adrenal hyperplasia (CAH), a condition with high fetal testosterone, and 26 controls. Two indices of cerebral dimorphism were measured—functional connectivity and cerebral activation by 2 putative pheromones (androstadienone [AND] and estratetraenol [EST]), previously reported to activate the hypothalamic networks in a sex-differentiated manner. Smelling of unscented air was the baseline condition, also used for measurements of functional connectivity from the amygdala. In CAH women and control women AND activated the anterior hypothalamus, and EST the amygdala, piriform, and anterior insular cortex. The pattern was reciprocal in the male controls. Also the functional connections were similar in CAH women and control women, but different in control men. Women displayed connections with the contralateral amygdala, cingulate, and the hypothalamus, men with the basal ganglia, the insular and the sensorimotor cortex. Furthermore, the connections were in CAH and control women more widespread from the left amygdala, in men from the right amygdala. Thus, we find no evidence for masculinization of the limbic circuits in women with high fetal testosterone."Normal is a weapon of mass destruction.It's just as deadly, and just like those weapons,it'll never be found."-Thea Hillman, writer and intersex activist... Read more »
C. Ciumas, A. L. Hirschberg, & I. Savic. (2008) High Fetal Testosterone and Sexually Dimorphic Cerebral Networks in Females. Cerebral Cortex. DOI: 10.1093/cercor/bhn160
In light of all the sensationalistic press coverage about a journal article that wasn't publicly available last week, it's worth taking a moment to look at the actual experiment. Of course, the savvy skeptics know by now that the paper in question (Immordino-Yang et al., 2009) has absolutely nothing to do with Twitter (see Recommended Reading below for a recap). Instead, the authors conducted a neuroimaging study to examine the brain's response to stories designed to elicit the emotions of admiration and compassion. To do this, the participants (n=13) first watched a series of mini-documentary narratives about real people (who were not celebrities). Each of the 50 narratives was 60-90 sec long, and incorporated audio, video, and still images to convey stories categorized as:1. Admiration for virtue (AV), which involved people performing highly virtuous, morally admirable acts. The narratives emphasized the virtuous and morally admirable nature of the protagonist, such as dedication to an important cause despite difficult obstacles, and did not include displays of notable skill.2. Admiration for skill (AS), which involved people adeptly performing rare and difficult feats, e.g., an athletic or musical performance, with both physical and cognitive components. No physically or socially painful acts were shown, and the skillful feats, although amazing, did not imply a virtuous protagonist or reveal a virtuous act.3. Compassion for social pain (CSP), which involved people in states of grief, despair, social rejection, or other difficult psychological circumstances. No physical pain was evident in these narratives, and the troubling circumstances were discerned from the descriptions, rather than being apparent in the images shown.4. Compassion for physical pain (CPP), which involved people sustaining a physical injury. The injuries were caused by sports and other mishaps and had no moral or social implications. The injuries were not the result of malevolence, and the participants were reassured that the injuries had no long-term implications....5. Control narratives, which involved comparable living, mentally competent people engaged in or discussing how they felt about typical activities under commonplace social circumstances. These circumstances were engaging but not emotion provoking.After each of the narratives, the subjects were asked to discuss how they felt about the protagonist's situation. This part of the study took 2 hrs, and was conducted outside the scanner. For the fMRI portion of the protocol, 5 sec recaps of all 50 scenarios were presented, and the task was to:induce in themselves for each story, as strongly as possible, a similar emotional state to the one they had experienced during the preparation session and to push a button to indicate the strength of the emotion they achieved in the scanner (from 1 to 4...). Participants were asked to report candidly on the strength of their current feelings in the scanner, rather than on the strength of feeling they remembered from the preparation session.OK, so the subjects were first asked to remember how they felt 2 hrs ago, then try to duplicate that feeling, and then report on how they feel now (rather than before). So there's a memory component and a decision component (i.e., to not confuse past feelings with the present). Each trial was sorted post hoc on the strength of the reported emotion, and only the effective trials were included in the analysis.The comparisons of interest were pain (compassion) vs. non-pain (admiration), and emotional responses to other peoples’ social/psychological conditions (AV, CSP) vs. to their physical conditions (AS, CPP). One of the first issues discussed is the recruitment of homeostatic mechanisms when experiencing these social emotions:It is well known that basic emotions such as fear, sadness, and happiness and limited social emotions such as moral indignation engage neural systems concerned with sensing and regulating body function with varying patterns, and it has been hypothesized that among those systems, the insula plays an especially prominent role. It is also known that engagement of social emotions and the consequent feeling for another’s social/psychological situation are described by poets and lay people alike in visceral and bodily terms and in terms of their heightening effect on one’s own self-awareness or consciousness.Basically, people may have visceral responses to the circumstances of others. How do these responses differ across physical vs. psychological situations? For example, admiring a gymnast's skill on the balance beam vs. admiring a student's charity work with Habitat for Humanity? Or feeling compassion for a single mother who loses her job vs. feeling compassion for one who sprains her ankle? Although it's not mentioned in the paper, this idea draws on Antonio Damasio's somatic marker hypothesis (e.g., Damasio, 1996). Perhaps this omission occurred because two of the main regions implicated -- the ventromedial prefrontal cortex (VMPFC) and the amygdala -- were not discussed in the paper [however VMPFC is difficult to image using fMRI because of susceptibility artifacts]. The somatic marker hypothesis is succinctly described by the title of one of Damasio's books: The Feeling of What Happens: Body and Emotion in the Making of Consciousness (1999).Other components in the somatic marker circuit include the insular cortex, a region implicated in interoceptive awareness of bodily states (Craig, 2009), and somatosensory cortices responsive to external stimuli. Because activity in the anterior insula features primarily in the Twitter-warped distortion of the story, I'll start here with the authors' third hypothesis:3. that activation in the anterior insula would peak and dissipate more quickly for CPP than for CSP or varieties of admiration.In a way, this is a trivial prediction, because one can evaluate the sprained ankle narrative more quickly than the job loss scenario. In fact, I will argue below that simple behavioral response time might be a more precise measure of how long it takes to generate the emotion in question than is the hemodynamic response (blood flow changes, measured by the BOLD signal in fMRI) in the insular cortex. One reason for this is because of the significant delay (5-6 sec at least) between initial neural firing and the peak of the hemodynamic response, which is estimated using a procedure that is not trivial for something as complex as an emotional response (for a more detailed discussion of this issue, I recommend this PPT file from Jodi Culham's excellent fMRI 4 Newbies site).Let's start with a simpler example. The figure below shows the averaged hemodynamic response function (HRF) in the primary visual cortex to a series of flashes. The HRF peaks at ~5 sec after the flash, whereas neurons in primary visual cortex fire within 50 msec and drop off shortly thereafter. Thus, the hemodynamic response to even a simple sensory stimulus lags behind neuronal firing by 5 sec.Fig. 2 (Calhoun et al., 1998). Time courses from four regions in the calcarine cortex (Pl-P4) and the averaged response (CIRQ). Amplitude units are normalized to a maximum of one and a baseline of zero.The next example shows the HRFs in occipital regions and the insula while subjects viewed rotating objects. The precise details aren't important here, but note the peak latency for the HRF in the insula is around 6-8 sec, with the later peak for novel objects (compared to repeated objects).Fig 2C (Weigelt et al., 2007). Event-related deconvolved BOLD fMRI responses (GLM parameter estimates averaged across trials and subjects for all voxels in each ROI) reported against time for each of the experimental conditions.That brings us back to Immordino-Yang et al. and the emotional narratives. In the figure below, note that the HRF time course does peak earlier for the CPP condition compared to the others, as predicted. However, the CSP condition rises at the same time, albeit with a later (very broad) peak.Fig. 3 (Immordino-Yang et al., 2009). Event-related averages for the time courses of admiration and compassion in the anterior insula, with standard errors. Units are percentage change in BOLD signal and time in seconds; time courses are not corrected for hemodynamic delay. For display purposes, BOLD data have been linearly interpolated to 1-s resolution. The volume of interest is displayed in pink. Conditions: AV (green): admiration for virtue; AS (yellow): admiration for skill; CSP (blue): compassion for social pain; CPP (red): compassion for physical pain. Note the rapid rise and dissipation of CPP versus the slower and more sustained rise of CSP, AV, and AS.It's critical to note that the onset of a felt emotion is not as easy to determine as the onset of a visual object. Although more detailed methods are in the Supplementary Materials not available as of this writing, it seems that respiration and heart rate data were obtained in 7 of the 13 subjects to help with this. I would say these psychophysiological responses, in concert with the participants' own reaction times for rating their subjective responses, would provide a more accurate measure of how long it takes to feel an emotion than the fMRI data. It's hard to know what an insular HRF of 6 sec vs. 10 sec means when watching a fast-paced movie or reading the CNN news crawl or yes, spending too much time on Twitter. Nonetheless, on the basis of these imprecise latency measures, the authors speculate:If replicated, this finding could have important implications for the role of culture and education in the development and operation of social and moral systems; in order for emotions about the psychological situations of others to be induced and experienced, additional time may be needed for the introspective processing of culturally shaped social knowledge. The rapidity and parallel processing of attention-requiring information, which hallmark the digital age, might reduce the frequency of full experience of such emotions, with potentially negative consequences.And there's your "Twitter is evil" angle.I'll leave you with this final thought: where's the line between admiration and envy, between compassion and schadenfreude? There actually is a recent paper on the Neural Correlates of Envy and Schadenfreude (Takahashi et al., 2009), and for now I'll refer you to this nice summary in Pure Pedantry.Recommended Twitter Reading:Social media threats hyped by science reporting, not science (Ars Technica)Experts say new scientific evidence helpfully justifies massive pre-existing moral prejudice. (Bad Science)For the last time: that "Twitter is Evil" paper is not about Twitter! (Bioephemera)Is Twitter evil? (Cosmic Log at MSNBC - despite the ridiculous headline, it's one of the few popular science articles to talk about the actual study... it even included a figure from the paper)The Neurology of Twitter (The Neurocritic proposes an actual fMRI study of Twitter, complete with predicted results)The Neurology of Twitter, Part 2 (Yet another recap of the media circus, with a time line of certain events)ReferencesCraig AD. How do you feel--now? The anterior insula and human awareness. (2009). Nat Rev Neurosci. 10:59-70.Damasio AR. (1996). The somatic marker hypothesis and the possible functions of the prefrontal cortex. Philos Trans R Soc Lond B Biol Sci. 351:1413-20.Mary Helen Immordino-Yang, Andrea McColl, Hanna Damasio, and Antonio Damasio. (2009). Neural correlates of admiration and compassion. Proceedings of the National Academy of Sciences.... Read more »
Mary Helen Immordino-Yang, Andrea McColl, Hanna Damasio, and Antonio Damasio. (2009) Neural correlates of admiration and compassion. Proceedings of the National Academy of Sciences.
From the authors who first brought you "sexual sweat" (Zhou & Chen, 2008)...Be afraid... be very afraid and prepare yourself for the sequel: "FEARFUL SWEAT" (Zhou & Chen, 2009)!!!In case you didn't know that "sexual sweat" (collected from men watching porn) differs from ordinary sweat, the results of an fMRI experiment suggested that the orbitofrontal cortex and the fusiform region in 20 female participants responded differently when smelling the two substances (Zhou & Chen, 2008). However, we don't know anything specific about the unique chemical composition of sweat obtained from sexually aroused men, and why it resulted in differential brain activity in women who could not identify the odor as "sweaty/human" (see When I Get That Feeling, I Need Sexual Sweating).Nonetheless, in the present study Zhou and Chen (2009) wanted to determine the effects of another putative chemosensory signal on the perception of emotional expressions in faces. Specifically, as they explain below......we conducted two experiments focused on the effect of a fear-related chemosignal (sweat collected from donors viewing horror videos) in an emotion-identification task. We used the same type of olfactory stimuli (emotional sweat collected on gauze pads and gauze pads with no sweat) throughout, but varied the effectiveness of the visual input by varying the ambiguity of the facial emotions (from somewhat happy to ambiguous to somewhat fearful). Our manipulation of ambiguity was achieved through morphing between happy and fearful faces [as shown in Fig. 1a].Fig. 1a (Zhou & Chen, 2009). Examples of the morphed faces of two actors. For each actor, we selected seven morphs, ranging from somewhat happy to somewhat fearful. These faces were judged to be fearful 20% to 80% of the time in our pilot experiment, in the absence of any olfactory stimuli. Specifically, the Level 4 morph for each actor was the most ambiguous, judged to be fearful in the pilot study 45% to 55% of the time. And what about the olfactory stimuli obtained from the male sweat donors?On the day of each session, they wore next to their skin a new T-shirt (provided by the experimenter), to prevent odor contamination by their regular clothes. During each session, they kept a 4- x 4-in. pad (rayon-polyester blend for maximum absorbance) under each armpit while they watched each of three 20-min video segments intended to produce the emotions of fear (horror movies), happiness (slapstick comedies), and neutrality, respectively. Different videos were shown in each session. During the videos, participants’ heart rate was recorded... After watching each video, the donors rated how angry, fearful, happy, neutral, and sad they felt during the video, using a 100-mm visual analog scale. From each donor, we selected the pads worn during the 20-min videos that elicited the highest level of self-reported happy feelings and the highest level of self-reported fearful feelings. So the 48 young female subjects (mean age 19.6 years) viewed the various faces while exposed to different olfactory stimuli, and decided whether they were happy or fearful. Results indicated that on average they were significantly more likely to identify the most ambiguous morph as fearful when smelling the fearful sweat relative to the control condition (which, unfortunately, was a rayon-polyester pad with no sweat). Although the likelihood of identifying an ambiguous face as fearful did not differ between the happy sweat and control conditions, there was no direct statistical comparison between the two sweat conditions, which would seem to be a problem.adapted from Fig. 2b (Zhou & Chen, 2009). Nevertheless, there was some evidence that male horror movie sweat was able to bias the women towards viewing an ambiguous face as fearful, and this was not due to the pleasantness (or lack thereof) or intensity of the olfactory stimulus. I'd be curious to see how the "sweat of neutrality" and the "sweat of sexual arousal" [as identified by Zhou & Chen, 2008) in their earlier study] would influence emotion recognition judgments...ReferencesZhou W, Chen D. (2008). Encoding Human Sexual Chemosensory Cues in the Orbitofrontal and Fusiform Cortices. Journal of Neuroscience, 28 (53), 14416-14421.Zhou, W., & Chen, D. (2009). Fear-Related Chemosignals Modulate Recognition of Fear in Ambiguous Facial Expressions. Psychological Science, 20 (2), 177-183. DOI: 10.1111/j.1467-9280.2009.02263.xIntegrating emotional cues from different senses is critical for adaptive behavior. Much of the evidence on cross-modal perception of emotions has come from studies of vision and audition. This research has shown that an emotion signaled by one sense modulates how the same emotion is perceived in another sense, especially when the input to the latter sense is ambiguous. We tested whether olfaction causes similar sensory modulation of emotion perception. In two experiments, the chemosignal of fearful sweat biased women toward interpreting ambiguous expressions as more fearful, but had no effect when the facial emotion was more discernible. Our findings provide direct behavioral evidence that social chemosignals can communicate emotions and demonstrate that fear-related chemosignals modulate humans’ visual emotion perception in an emotion-specific way—an effect that has been hitherto unsuspected.Bonus! See sensory psychologist and olfactory specialist Avery Gilbert's take on these two studies in Basic Instinct: The Smell of Fear and Sex.TAG body spray for sick cats. "This spray is definitely not for me."... Read more »
Zhou, W., & Chen, D. (2009) Fear-Related Chemosignals Modulate Recognition of Fear in Ambiguous Facial Expressions. Psychological Science, 20(2), 177-183. DOI: 10.1111/j.1467-9280.2009.02263.x
A year ago, Ketamine for Depression: Yay or Neigh? covered acute administration of the club drug (and dissociative anesthetic) ketamine for rapid (albeit transient) relief of major depression. That post was part of a blog focus on hallucinogenic drugs in medicine and mental health, organized by Nature editor Noah Gray following publication of a review article on The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. At the time, I wrote: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 inability to truly blind the ketamine condition due to obvious dissociative effects in many participants.At present, what are the most promising uses for ketamine as a fast-acting antidepressant? Given the disadvantages discussed above, short-term use for immediate relief of life-threatening or end-of-life depressive symptoms seem to be the best indications.For the past few weeks, I've been wanting to do a follow-up post that looks at the ups and downs of the mTOR (mammalian target of rapamycin) protein kinase pathway, which is rapidly activated by ketamine. Although activation of mTOR leads to the beneficial effect of increased synaptogenesis in the medial prefrontal cortex (Li et al., 2010), it can also cause accelerated tumor growth, as recently noted by Yang et al., 2011 ("Be prudent of ketamine in treating resistant depression in patients with cancer"). However, I've been unable to complete this planned post, specifically because the topic of ketamine use in palliative care settings is something I wrote about last year, while watching my father die of cancer.More recently, an open label study in two hospice patients, each with a prognosis of only weeks or months to live, showed beneficial effects of ketamine in the treatment of anxiety and depression (Irwin & Iglewicz, 2010). A single oral dose produced rapid improvement of symptoms and improved end of life quality.To be blunt, the possibility of accelerated tumor growth is not an issue in terminal patients.In terms of medical ethics, it's easier for me to take a different angle and address the unusual case of a grievously and chronically depressed patient (Messer & Haller, 2010). An anonymous reader alerted me to this paper, which isn't indexed in PubMed. The case history is as follows:In January 2008, a 46-year old female with MDD was hospitalized for a course of electroconvulsive therapy (ECT). Successive interventions over 15 years had included trials of 24 psychotropic medications and 273 ECT treatments, 251 of which were bilateral [which can produce significant amnesia]. No intervention had produced remission but only a short-lived response to treatment...ECT during this admission was administered with ketamine as the anesthetic at 2 mg/kg given over 60 seconds. Surgical anesthesia occurred ~30 seconds after the end of intravenous injection and lasted ~10 minutes. There was no significant change in depression symptoms with the ketamine used as an anesthetic during the ECT treatment. Alternative treatments were reviewed for potential use. In addition to no significant recovery from her depression, the long-term use of ECT caused problems with memory loss and focused attention. She was unable to remember much of her history over the previous 15 years. Re-learning the information became futile since each course of ECT would eliminate what had been gained.I'm not going to weigh in here on ECT, beyond saying that it can be beneficial in some intractable patients [with fewer amnestic effects if unilateral]. But here we have an individual with profound ECT-induced amnesia who, although giving informed consent, was then treated with a highly unorthodox regimen of repeated ketamine infusions. The majority of registered clinical trials administer a single dose of ketamine, with one trial administering 5 additional ketamine infusions over a 2-week period. Relapse typically occurs within a week after a single dose.On the other hand Dr. Messer's clinical trial, Ketamine Frequency Treatment for Major Depressive Disorder, was withdrawn prior to enrollment because pilot study determined the trial would not be feasible. The planned regimen was 6 injections every other day for 12 days. But the actual treatment given to the 46 yr old woman was much more extensive: 22 doses over 4 months, followed by 21 doses over 1 yr (approximately):The first ketamine treatment led to a dramatic remission of depressive symptoms: the Beck Depression Inventory (BDI) score decreased from 22 to 6 (Figure). Three additional infusions administered every other day over 5 days produced remission lasting 17 days after the last infusion in this series. Three series of six ketamine infusions given every other day except weekends were repeated over the next 16 weeks (Figure). Each infusion sequence produced remission lasting 16, 28, and 16 days, respectively, followed by a relapse. After three remission/relapse cycles and before relapse could occur after the fourth infusion series, a maintenance ketamine regimen was established on August 27, 2008 using 0.5 mg/kg IBW at a 3-week inter-dose interval. The authors’ estimation for the maintenance dosing interval was based on the time frame between remission and relapse for this patient. Relapse to depression was prevented by treating prior to the onset of a relapse.First, I was struck by the starting BDI score of 22, which falls within the low end of moderate depression, with scores of 29-63 indicating severe depression. I don't want to question Dr. Messer's clinical diagnosis of the patient, but I would guess that a typical BDI II score of 22 might not call for drastic measures. But perhaps the original BDI was used, in which case 19-29 indicates moderate-severe depression (which is still not severe). Second, the number of infusions went well beyond what has been established as safe, particularly in the context of treatment-resistant depression.- click on image for a larger view -What were the cognitive effects? We don't really know, because there was no formal testing:As shown in the Figure, with maintenance infusions the patient has been in remission for >15 months. No concurrent pharmacotherapeutic agents have been administered or required during this time period, no adverse events have emerged, and there has been no cognitive impairment as is typical with ECT, polypharmacy, or from MDD itself.What we do know is that ketamine is cost-effective relative to ECT:The cost and personnel needed for a ketamine treatment are far less than that of... Read more »
Messer M, Haller IV (2010). Maintenance Ketamine Treatment Produces Long-term Recovery from Depression. (2010) Maintenance Ketamine Treatment Produces Long-term Recovery from Depression. Primary Psychiatry, 48-50. info:/
Did you know that male "sexual sweat" differs from ordinary sweat? Apparently so, according to a new paper in the Journal of Neuroscience (Zhou & Chen, 2008). Curiously, the article did not cite any references for this, nor did it specify the chemical composition of sexual sweat. Nonetheless, the results of an fMRI experiment suggested that the orbitofrontal cortex and the fusiform region in 20 female participants responded differently when smelling the two substances. How was such a study conducted, you might ask?And here the fun begins...Sweat collection. From 2 d before the experiment until the end of the experiment, 20 heterosexual male donors in a larger study refrained from using deodorant/antiperspirant/scented products, and used scent-free shampoo/conditioner, soap, and lotion provided by the experimenter. They reported to have experience with watching sexually explicit videos, and signed informed consent before participation. Subjects kept a 4" x 4" pad (rayon/polyester for maximum absorbance) in each armpit while they watched 20-min-long video segments intended to produce the emotions of sexual arousal (sexual intercourse between heterosexual couples) and neutrality (educational documentaries), respectively. ... Over the course of the 20 min video segments, donors experienced greater arousal (measured by skin conductance) while watching erotic videos than while watching neutral videos... Three healthy, male nonsmokers (aged 26, 29, and 29 years) were subsequently selected for the current study mainly because of their higher level of the self-reported sexual arousal.How were the female participants selected?We recruited only women for their superior sense of smell and sensitivity to emotional signals. Twenty right-handed females (mean age = 23.4 years) were selected from a group of 42 women on the basis that they reported to have no rhinal disorders or neurological diseases, and that they showed superior olfactory sensitivity to PSP [the putative sex pheromone androstadienone] and PEA [phenyl ethyl alcohol]. They either were in a heterosexual relationship or had been in one within the previous year. They were not on hormone contraceptives, and were tested during the periovulatory phase of their menstrual cycles. ... Subjects were informed that the study was on brain activations to natural compounds. They were blind to the nature of the smells used in the experiment.The scanning was performed while the women were inhaling......the sweat of sexual arousal in comparison with two other social chemosensory compounds (PSP and the sweat of neutrality) and a nonsocial smell [phenyl ethyl alcohol (PEA)].The sweat of neutrality. The sweat of sexual arousal! [plus the two others.] The subjects rated the four inhalants (presented 10 times each) on intensity and pleasantness, as shown below. And the smell of sexual sweat was not particularly pleasant...Figure 1. Mean intensity and pleasantness ratings. There are four types of olfactory stimuli, and SE bars are shown. For intensity, 1 refers to no smell, 2 little smell, 3 moderate smell, 4 quite a bit smell, and 5 strong smell. For pleasantness, 1 refers to very unpleasant, 2 unpleasant, 3 neutral, 4 pleasant, and 5 very pleasant. Sex, Sexual sweat; Neutral, neutral sweat. Sexual sweat and PSP were perceived to be more intense than neutral sweat; PEA was perceived to be more pleasant than sexual sweat and neutral sweat.At the end of the experiment, the participants gave verbal descriptions of the smells. Only one characterized sexual sweat as "sweaty/human." So the women were not [consciously] aware that the odor was obtained from sexually aroused men.The right hypothalamus showed increased activity to sexual sweat relative to alcohol, but so did androstadienone and neutral sweat. The two brain regions that responded more to sexual sweat than to the other odors are illustrated below. The right orbitofrontal cortex is an olfactory region, but the right fusiform gyrus is a high-level visual region. The authors say their fusiform region1 falls in the vicinity of the fusiform face area (FFA) and fusiform body area (FBA). Hmm.Figure 3. a. Coronal view showing an area in the right orbitofrontal cortex (33, 40, –1) activated in the omnibus ANCOVA F test (svc, p less than 0.005). d. Sagittal view showing a region in the right fusiform gyrus (35, –51, –7) activated in the omnibus ANCOVA F test (uncorrected p less than 0.0005, cluster size = 49 mm3).The authors took a giant leap when speculating about visual imagery of faces and bodies:The Talairach coordinates of the fusiform region identified in our experiment fall in the range of the coordinates for FFA and FBA. Such anatomical location likely reflects a recognition of the human quality in the sexual sweat, whose emotional nature may have also contributed to the activation. Considering its functional connectivity to the right hippocampus/ parahippocampal gyrus, the recognition may arise from implicitly associating the sexual sweat with humans based on past experience. The fact that most subjects did not perceive the sexual sweat as human related suggests that the effects we observed occurred at a subconscious level. Implicit face/body visual processing in response to a sexual chemosensory cue? But nothing specific in the hypothalamus or amygdala? That's a hard one to swallow.Footnote1 The FFA and FBA have been dissociated with scanning at high resolution.ReferenceW. Zhou, D. Chen (2008). Encoding Human Sexual Chemosensory Cues in the Orbitofrontal and Fusiform Cortices Journal of Neuroscience, 28 (53), 14416-14421 DOI: 10.1523/JNEUROSCI.3148-08.2008Chemosensory communication of affect and motivation is ubiquitous among animals. In humans, emotional expressions are naturally associated with faces and voices. Whether chemical signals play a role as well has hardly been addressed. Here, we use functional magnetic resonance imaging to show that the right orbitofrontal cortex, right fusiform cortex, and right hypothalamus respond to airborne natural human sexual sweat, indicating that this particular chemosensory compound is encoded holistically in the brain. Our findings provide neural evidence that socioemotional meanings, including the sexual ones, are conveyed in the human sweat.... Read more »
W. Zhou, & D. Chen. (2008) Encoding Human Sexual Chemosensory Cues in the Orbitofrontal and Fusiform Cortices. Journal of Neuroscience, 28(53), 14416-14421. DOI: 10.1523/JNEUROSCI.3148-08.2008
An article from January is making the rounds again. One in nextgov's exposé-like series on America's Broken Warriors, it highlighted the fact that 20% of U.S. active duty troops are on psychotropic medications. While this may not be a good thing, the article was filled with erroneous information about specific psych meds and general scare-mongering from antipsychiatry "experts" pitching their books. Let's take a look.Military's drug policy threatens troops' health, doctors sayBy Bob Brewin 01/18/2011Army leaders are increasingly concerned about the growing use and abuse of prescription drugs by soldiers, but a Nextgov investigation shows a U.S. Central Command policy that allows troops a 90- or 180-day supply of highly addictive psychotropic drugs before they deploy to combat contributes to the problem. The CENTCOM Central Nervous System Drug formulary includes drugs like Valium and Xanax, used to treat depression, as well as the antipsychotic Seroquel, originally developed to treat schizophrenia, bipolar disorders, mania and depression.1. Valium (diazepam) and Xanax (alprazolam) are not used to treat depression. These sedative-hypnotic benzodiazepine medications are primarily used to treat anxiety disorders.2. The atypical antipsychotic Seroquel (quetiapine) was originally developed to treat schizophrenia, although now it is prescribed for bipolar disorder and major depression. Off-label usage of quetiapine, including as a sleep aid, is controversial and I won't be discussing it further here. That topic could easily take up several posts of its own.The article continues:A June 2010 internal report from the Defense Department's Pharmacoeconomic Center at Fort Sam Houston in San Antonio showed that 213,972, or 20 percent of the 1.1 million active-duty troops surveyed, were taking some form of psychotropic drug: antidepressants, antipsychotics, sedative hypnotics, or other controlled substances. Dr. Grace Jackson, a former Navy psychiatrist, told Nextgov she resigned her commission in 2002 "out of conscience, because I did not want to be a pill pusher." She believes psychotropic drugs have so many inherent dangers that "the CENTCOM CNS formulary is destroying the force," she said.Here we see Dr. Jackson's antipsychiatry agenda first established. All psych drugs are bad. Also note that Dr. Jackson resigned in 2002, before the war in Iraq began on March 20, 2003. So she doesn't have first hand experience with current prescribing practices or the effects of these medications on troops in Iraq and Afghanistan, which is what the article is about.We also have quotes from one of the leading antipsychiatry advocates, Dr. Peter Breggin:Dr. Peter Breggin, an Ithaca, N.Y., psychiatrist who testified before a House Veterans Affairs Committee last September on the relationship between medication and veterans' suicides, said flatly, "You should not send troops into combat on psychotropic drugs." Medications on the CENTCOM CNS formulary can cause loss of judgment and self-control and could result in increased violence and suicidal impulses, Breggin said.Dr. Breggin's credibility as an expert witness has been repeatedly questioned, however. I agree that mentally ill troops should not be sent into combat, but will also point out that untreated and unmedicated psychiatric disorders in a war zone can cause increases in violence and suicidal behavior.Back to Dr. Jackson:Jackson, the former Navy psychiatrist, now has a civilian practice in Greensboro, N.C. She said at least one drug on the CENTCOM formulary -- Depakote, an anticonvulsant, which military doctors prescribe for mood control -- carries serious physical risks for troops.Really? Depakote (valproic acid) is an antiseizure medication also used to treat bipolar disorder. I would like to see statistics on how frequently it's prescribed for "mood control" in soldiers without bipolar disorder.1 Depakote is toxic to certain cells, including hair cells in the ears, and can lead to hearing loss. Troops in a howitzer battery who already run the risk of hearing loss should not take Depakote, she said.3. Depakote is certainly not without its adverse effects, but hearing loss is an extremely rare side effect.2 In a study of 21 patients taking valproic acid (VPA) to control seizures, there were no differences in hearing thresholds between 125 and 16,000 Hz compared to age- and sex-matched controls (Incecik et al., 2007). In addition, there was no relationship between duration or dosage of drug and hearing levels.The medication also can cause what she calls "cognitive toxicity," also known as Depakote dementia, impairing a person's ability to think and make decisions. Jackson said that while Depakote has been investigated as an adjunct therapy for cancer, its use has been limited due to the drug's effects on cognition.4. Contrary to the notion of "Depakote dementia", VPA has been recognized for its potential to treat Alzheimer's disease (Nalivaeva et al., 2009; Zhang et al., 2010). VPA is a histone deacetylase (HDAC) inhibitor that might be able to prevent amyloid-beta aggregation in Alzheimer's disease by increasing the expression of clusterin, or apolipoprotein J (Nuutinen et al., 2010). This would in turn prevent the accumulation of amyloid plaques, a pathological feature in the brains of those with Alzheimer's.While it's possible that VPA could produce impairments in some cognitive domains, proper studies are difficult because you have to control for the length of illness in untreated patients (since cognitive deficits can be caused by the disorder itself). One such report on currently medicated (n=33) and currently unmedicated (n=32) patients with bipolar depression failed to find group difference in visual memory and sustained attention (Holmes et al., 2008). Unfortunately, this study collapsed across patients on lithium and valproic acid. Further, the groups weren't matched on age, sex, and depression scores. Finally, the medicated patients were more depressed, which might be expected to worsen performance on its own.A double-blind cross-over design in healthy controls administered a relatively high dose of VPA for two weeks (800 mg the first week, 1,000 mg the second). There were no changes in memory, concentration, perceptual speed, motor speed, and subjective ratings relative to placebo (Trimble & Thompson, 1981). The drug did, however, slow response times in a category decision task. A review of the literature on cognition and anticonvulsants concluded: "Overall, deficits are subtle, especially in the therapeutic range" for valproic acid (Goldberg & Burdick, 2001). Not exactly a ringing endorsement for cognitive toxicity and Depakote dementia.On to the next drug:The antidepressant Wellbutrin, also on the CENTCOM formulary, likely poses a long-term risk of Parkinson's disease, especially for older troops, said Jackson, author of Drug-Induced Dementia: A Perfect Crime (AuthorHouse, 2009).5. I found no published, peer-reviewed evidence that the antidepressant Wellbutrin (bupropion) increases the long-term risk of developing Parkinson's disease. [Guess we'll have to buy her book ... Read more »
Holmes MK, Erickson K, Luckenbaugh DA, Drevets WC, Bain EE, Cannon DM, Snow J, Sahakian BJ, Manji HK, & Zarate CA Jr. (2008) A comparison of cognitive functioning in medicated and unmedicated subjects with bipolar depression. Bipolar disorders, 10(7), 806-15. PMID: 19032712
Incecik F, Akoglu E, Sangün O, Melek I, & Duman T. (2007) Effects of valproic acid on hearing in epileptic patients. International journal of pediatric otorhinolaryngology, 71(4), 611-4. PMID: 17270285
Thompson PJ, & Trimble MR. (1981) Sodium valproate and cognitive functioning in normal volunteers. British journal of clinical pharmacology, 12(6), 819-24. PMID: 6803819
Deep brain stimulation (DBS) for treatment-refractory psychiatric disorders has been gaining in popularity. The procedure involves neurosurgery to implant stimulating electrodes aimed at a target region inside the brain. It works using the same sort of pacemaker-like device used for DBS in Parkinson's disease, which has been remarkably successful at alleviating symptoms. DBS as a treatment for neurological disorders such as Parkinson's, primary generalised dystonia, atypical tremor syndromes, cluster headache, phantom limb pain, and epilepsy has been mostly unobjectionable.However, the Neurological/Psychiatric Divide makes DBS for mental illnesses such as major depression and obsessive compulsive disorder more ethically problematic. A new paper in the Archives of General Psychiatry (Rabins et al., 2009)1 summarizes a consensus conference held on this and related issues (such as human subjects protection and the design of clinical trials). A list of 16 guidelines was issued, which included the following:2. Deep brain stimulation for disorders of MBT [Mood, Behavior, and Thought] is at an early proof-of-principle stage and must be considered investigational. Currently, no single target has been validated or demonstrated to be superior to others in any disorder of MBT. Therefore, it is premature to rule out the study of new implantation sites that have a good scientific rationale...3. The comparative efficacy and safety of DBS vs other treatments, including ablative surgery, should be studied further. Such studies are ethical and scientifically necessary.4. Given its history, neurosurgical intervention for disorders of MBT is a socially and culturally sensitive area of research and practice. Therefore, DBS for disorders of MBT should be studied in carefully designed trials and should be performed only at expert centers that are participating in such trials and that adhere to the highest scientific, clinical, and ethical standards.. . .12. The consent process should include discussion of what is and is not known about long-term consequences of DBS. Potential adverse outcomes include potentially limiting participation in future research, inability to use certain other treatments, and an inability to undergo certain tests. ... Additionally, the consent process should state explicitly that, even with positive outcomes, DBS for disorders of MBT is unlikely by itself to improve all aspects of the individual's mood, function, and interpersonal relationships: DBS is only one aspect of a comprehensive treatment program.The specific indications mentioned by Rabins and his 18 co-authors were major depression, obsessive-compulsive disorder, and Tourette syndrome. Severe alcohol dependence was not included as one of the disorders. DBS for alcoholism sounds rather drastic, doesn't it? Nonetheless, a German research group led by Hans-Jochen Heinze (et al., 2009) was not deterred. They recently reported results from 3 male patients2 with severe and refractory alcohol dependence as part of a small clinical trial that will ultimately include 10 patients.Inclusion criteria are: male gender, age 25–60 years, finished detoxification and subsequent period of abstinence of at least 2 weeks. Moreover, the patients are required to have demonstrated treatment failures of at least two inpatient programs of at least 6 month duration, failure of anti-craving substances (e.g., acamprosate, naltrexone), failure of community and self-help programs. ... Patients are excluded, if they meet any of the following criteria: seizures during the detoxification phase, high score on neuroticism scales, antisocial personality disorder, clinically significant impairments on a neuropsychological test battery Further exclusion criteria were circumscribed brain damage or marked atrophy on MRI, alcohol-related personality change, and use of additional addictive substances.The target region? The nucleus accumbens (NAcc), the “Universal Addiction Site” -- an oversimplification, they admit, but still, the NAcc is......a central place in orchestrating the events related to the “wanting” [Robinson & Berridge, 2008] of alcohol on the one hand and drug-induced neural sensitization on the other hand. Anatomically, the NAcc receives inputs from the prefrontal cortex on the one hand and limbic structures such as the hippocampus and amygdala on the other. This circuitry allows for the integration of contextual information arising from hippocampus and emotional information coming from the amygdala with cognitive information supplied by the PFC in the selection of goal-directed behaviors in general and behaviors related to drug “wanting” in particular, which is why the NAcc has been called a limbic-motor interface.Since anatomical information was not illustrated in the current paper, a figure from the earlier work of Schlaepfer et al., (2007) is presented below.The topographical location of the nucleus accumbens in relation to other brain structures on a horizontal plane 3 mm below the AC-PC plane (Schlaepfer et al., 2007).That protocol was designed to relieve anhedonia (inability to experience pleasure from normally pleasurable life events) in major depression. Why not stimulate the "pleasure center" when you're feeling blue? Extensive research in animals and humans has demonstrated "hedonic hot spots" (Pecina et al., 2006) [or "liking" of pleasant sensory experiences] in the NAcc that respond to food and pharmaceutical and financial and sexual rewards.But what are the procedures for targeting the same region to reduce reward and pleasure? Well, we don't know from reading Heinze et al. (2009): "Details regarding the stimulation protocols in the different patients can be found elsewhere" [insert citation of an in press paper that is not online yet]. Details on the "clinical aspects" are pretty sparse and the focus is on the "basic science aspects" (electrophysiological recording and cognitive task performance to assess action monitoring and the salience of drug-related cues).Was the DBS treatment effective? All patients had failed multiple detox treatments, withdrawal therapies, and drug trials (acamp... Read more »
Heinze, H. et al. (2009) Counteracting incentive sensitization in severe alcohol dependence using deep brain stimulation of the Nucleus accumbens: clinical and basic science aspects. Frontiers in Human Neuroscience. DOI: 10.3389/neuro.09.022.2009
Rabins, P. et al. (2009) Scientific and Ethical Issues Related to Deep Brain Stimulation for Disorders of Mood, Behavior, and Thought . Archives of General Psychiatry, 66(9), 931-937. info:/
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