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

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  • November 30, 2008
  • 09:59 PM
  • 1,173 views

Intersex (for lack of a better word)...

by The Neurocritic in The Neurocritic

...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 »

  • December 17, 2008
  • 10:46 PM
  • 1,173 views

Crime, Punishment, and Jerry Springer

by The Neurocritic in The Neurocritic

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 »

J 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  

  • March 19, 2009
  • 02:25 PM
  • 1,173 views

Lie To Me on the Autobiographical Implicit Association Test

by The Neurocritic in The Neurocritic

Lie to Me - Season 1 - "Moral Waiver" - Monica Raymund as Ria Torrescourtesy Adam Taylor/FoxLie detection is all the rage with the new TV show based on Paul Ekman's work1 that uses "microexpressions" to detect deception.The use of brain imaging technologies as lie detectors, and the admissibility of data obtained in this fashion as evidence in a court of law, has a high media profile as well - most recently (and notoriously) because of a juvenile-sex-abuse case in San Diego, recounted by Wired Science. The Stanford Center for Law & the Biosciences Blog has sounded the alarm in their post, No Lie MRI being offered as evidence in court:The case is a child protection hearing being conducted in the juvenile court. In brief, and because the details of the case are sealed and of a sensitive nature, the issue is whether a minor has suffered sexual abuse at the hands of a custodial parent and should remain removed from the home. The parent has contracted No Lie MRI and apparently undergone a brain scan... The defense plans to claim the fMRI-based lie detection (or “truth verification”) technology is accurate and generally accepted within the relevant scientific community in part by narrowly defining the relevant community as only those who research and develop fMRI-based lie detection.The Neurocritic weighed in on the overblown nature of these claims three years ago, with Brain Scans and Lie Detection: True or False?, Would I Lie to You?, and More Lies... Damn Lies... But even better, check out the excellent Deception Blog for an updated overview of the field.Given the high cost and dubious accuracy of fMRI technologies -- as well as the questionable accuracy of older EEG and polygraph methods -- there has been some interest in developing faster, easier, more reliable lie detection methods. Ian Sample at the Guardian's Science Blog went with this futuristic headline about the potential use of pupillometry as a routine security screening measure:Homeland Security seeks Bladerunner-style lie detectorDo our eyes betray us when we lie? The US government hopes to find out. . .Under the Small Business Innovation Research programme, the department has asked tech companies to bid for contracts to kick-start research in the area. Such a system, if it works, would undoubtedly be useful at airports and other high-security points.Here's the original SBIR solicitation for applications, which were due in February 2008:TITLE: Assess Ability to use Eye Tracking and Pupil Dilation to Determine Intent to DeceiveDESCRIPTION: Recent government sponsored research is working to produce a new line of flexible physiological and behavioral sensor technologies that are to be available for homeland security applications. These sensors, which must be non-invasive in nature and protect the privacy of the individual(s) involved, will be used to support human centered/behavioral screening processes in a variety of high and low volume venues. Security screening is conducted to evaluate the risk of individuals entering transportation and other critical infrastructure and requires efficient, rapid and accurate examination of a person. Persons involved in or planning to be involved in possible malicious or deceitful acts will show various behavioral or physiological abnormalities. Much of the technology and publications to date have focused on detection of guilty individuals using electrodermal measures. Research into other psychophysiological measures or the mechanisms underlying deception is still in its early stages. Early research has shown that pupil size varies with changes in a person's cognitive processing load. Current but unproven studies suggest that a cognitive decision to deceive or practice deception will result in a increased pupil size due to the greater cognitive processing required in comparison to truthful recall. An assessment study to determine the correlation between Pupillometry (dilation and contraction of the pupil relative to observed stimulus or emotion) and intent to deceive is required.For the ultimate in low-cost methods for lie detection, computerized reaction time tasks take the cake. An article about one of these appeared last year in Psychological Science (Sartori et al., 2008). The task they used is a variant of the Implicit Association Test (IAT) franchise that pits competing response tendencies against each other. Without getting into a lengthy discussion of the IAT, and the debates between its proponents and detractors,2 the autobiographical IAT (aIAT) employed by Sartori et al. ......allows one to evaluate which of two contrasting autobiographical events is true for a given individual. This is accomplished by requiring the respondent to complete two critical blocks of categorization trials, each of which pairs a different potentially autobiographical event with true events. Because pairing of a truly autobiographical event with true events should facilitate responses, the specific pattern of response times (RTs) in the two blocks indicates which autobiographical event is true and which is false.The participants saw different types of sentences and had to classify them as true/false or guilty/innocent. Examples of the different stimuli are listed below.adapted from Table 2 (Sartori et al., 2008).The real trick was in the way these sentence types were matched to response keys. In a series of five blocks of trials, the subjects were told to respond to each sentence as rapidly as possible. Across five experiments (each of which had a different kind of "guilty knowledge"), the order was Block 1: logical discrimination (true/false) - Block 2: initial autobiographical information (guilty/innocent) - Block 3: initial double categorization (false/innocent and true/guilty) - Block 4: reversed autobiographical discrimination (false/true) - Block 5: reversed double categorization (true/innocent and false/guilty). The order of the critical blocks 3 and 5 was counterbalanced across participants (as was the order of 2 and 4, which counterbalanced the response mapping for autobiographical trials accordingly). The key measure was the comparison between RTs to the double categorization trials in Blocks 3 and 5 -- innocent participants were expected to be slower on the "conflict" trials in which true/guilty and false/innocent were matched to the same response key, while guilty participants (who always denied their crimes) were expected to show the opposite pattern, which would reveal they were lying about their innocence.For the mock crime of stealing a CD for example, the results looked like this for the pairings of true/guilty and true/innocent:Fig. 1C (Sartori et al., 2008). For Experiment 2, results are shown for the critical block associating true sentences with guilty sentences and for the critical block associating true sentences with innocent sentences.Because the tests were able to discriminate between true and false events with 91% accuracy, the authors concluded that "the aIAT is an accurate method of detecting concealed knowledge that outperforms currently available lie-detection techniques." However, a brand new paper by Verschuere et al. (2009) has demonstrated that it's easy to fake your results in this aIAT! Oops. What Verschurere and colleagues did was provide the participants with instructions on how to beat the test. Before performing the aIAT a second time, they were told to slow down their responses in the true/guilty mapping condition. And the results for the faking version of the aIAT classified the majority of guilty liars as innocent. Imposing a response deadline, so the subjects had to respond within 1200 msec, did not alter the results.So there you have it. An extremely easy method for faking your results on the aIAT. In the past, The Neurocritic has taken the Human or Alien? test and the Dead or Alive? test. Turns out I'm neither human nor alien, and neither dead nor alive. Read those posts, and then try the tests yourselves.Footnotes1 However, as noted recently by World of Psychology, a paper by Bond (2008) questioned whether Ekman et al. (1991, 1999) omitted data unfavorable to their previously reported lie detection success rate of 73% in some federal agents. 2 The sadly defunct blog Mixing Memory was particularly critical of the IAT:The IAT isn't the only test of implicit "attitudes." . . . However, the IAT is the most popular, and has received a great deal of attention in the popular press, due in large part to a public relations campaign by its authors and the NSF and NIMH. In my mind, giving the IAT so much publicity is the most irresponsible thing I've seen in psychology since I began studying it... While the IAT has been publicized (by its authors!) as a measure of implicit attitudes, and even more, as a measure of implicit prejudice, there is no real evidence that it measures attitudes, much less prejudices. In fact, it's not at all clear what it measures, though the fact that its psychometric properties are pretty well defined at least implies that it measures something. On top of that, the IAT (like all of the other implicit tests) has serious methodological flaws that are currently being discussed in the literature. It's just irresponsible to publicize work, and claim that it does something very particular, when the work is still in the early stages and it's not at all clear what it's actually doing (read paper, or this one, for discussions of some of the problems with the IAT and other measures, including whether they actually measure "attitudes").ReferencesSartori, G., Agosta, S., Zogmaister, C., Ferrara, S.D., & Castiello, U. (2008). How to accurately assess autobiographical events. Psychological Science 19:772–780.Verschuere, B., Prati, V., & Houwer, J. (2009). Cheating the Lie Detector: Faking in the Autobiographical Implicit Association Test. Psychological Science DOI: 10.1111/j.1467-9280.2009.02308.x.Lie to Me - Season 1 - "Moral Waiver" - Kelli Williams as Gillian Foster and Tim Roth as Cal Lightmancourtesy Adam Taylor/Fox... Read more »

  • April 20, 2009
  • 09:06 AM
  • 1,170 views

Neural Correlates of Admiration and Compassion and Envy and Schadenfreude

by The Neurocritic in The Neurocritic

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.

  • March 15, 2009
  • 12:52 AM
  • 1,166 views

I Know What You Sweated Last Summer

by The Neurocritic in The Neurocritic

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 »

  • February 20, 2011
  • 10:30 PM
  • 1,159 views

Is Romantic Love a Western, Heterosexual Construct?

by The Neurocritic in The Neurocritic

ROMANTIC LOVE WAS INVENTED TO MANIPULATE WOMEN-Jenny Holzer, TruismsDoes romantic love manipulate women into providing free domestic labor and sexual favors for men? Some feminist views of romantic love [and the institution of marriage] portray it as controlling and oppressive (Burns, 2000):‘STOP HUMAN SACRIFICE. END MARRIAGE NOW.’ ‘IT STARTS WHEN YOU SINK IN HIS ARMS AND ENDS WITH YOUR ARMS IN HIS SINK.’ From a feminist perspective, romantic love was, and is, seen to obscure or disguise gender inequality and women’s oppression in intimate heterosexual relationships.But some in the men's movement see romantic love as dangerous for men as well as women, because it prevents men from being vulnerable (Bloodwood, 2003):...historically, romantic love has been a highly gendered but workable deal in which men provide women with social status and material goods while women provide men with sex/affective labour. Thus romantic relationships not only reinforce women’s second class status but also reinforce men’s lack of sex/affective autonomy, so that romantic love is equally dangerous for women and for men.Furthermore, romantic love is often portrayed as a relatively recent construct that is specific to Western societies. A cross-cultural study by Jankowiak and Fischer (1992) claimed that:The anthropological study of romantic (or passionate) love is virtually nonexistent due to the widespread belief that romantic love is unique to Euro-American culture. This belief is by no means confined to anthropology. The historian Philippe Aries (1962), for example, argues that affection was of secondary importance to more utilitarian ambitions throughout much of European history.However, their own analysis of the ethnographic literature found that romantic love (however ill-defined) could be observed in 147 out of 166 societies, including 77% in Sub-Saharan Africa and 94% in East Eurasia (Jankowiak & Fischer, 1992). Likewise, evolutionary anthropologist Helen Fisher and colleagues suggest that romantic love evolved as one of three motivational brain systems for mating, reproduction, and parenting (Fisher et al., 2002).The biological concept that romantic love (or attraction) is an emotional/motivational system in the human brain has prompted some neuroimaging investigators to search for its elusive neural correlates. How do you measure long-term intense romantic love in an fMRI experiment? Researchers have adopted the practical (yet flawed) strategy of examining the hemodynamic response to viewing pictures of a partner with whom participants were "madly in love".Previous studies on the "neural correlates of romantic love" have focused on recently attached heterosexuals from the UK (Bartels & Zeki, 2000) or US (Aron et al., 2005). One of the main findings from these studies is that the expected dopamine/reward areas [including ventral tegmental area (VTA), substantia nigra (SN), and caudate nucleus] showed greater activation when looking at the pictures of the partner, compared to pictures of a close friend or neutral acquaintance. And in the previous post on Posterior Hippocampus and Sexual Frequency, we saw a similar response in a specifically recruited group of participants still "madly in love" after 21 years of marriage (Acevedo et al., 2011).So are the "neural correlates of romantic love" the same in non-Western, non-heterosexual participants? Two recent papers attempted to spread the love to include diverse "others" (Xu et al., 2010; Zeki & Romaya, 2010). Is the simple act of asking if the Chinese and teh gays are "just like us" when it comes to love offensive? I'll let you be the judge.Although the original study of Bartels and Zeki (2000) recruited an ethnically and culturally diverse group of subjects, all were heterosexual. Zeki and Romaya (2010) wanted to extend this work to include romantically involved gay participants. This time, they included 12 females (6 in straight and 6 in lesbian relationships) and 12 males (6 in straight and 6 in gay relationships) in their fMRI experiment. I won't belabor the methods [and the critiques thereof] here, but will refer the reader to Posterior Hippocampus and Sexual Frequency.1Fig. 2 (Zeki & Romaya, 2010). Illustration of the t statistic for the contrast Loved > Neutral showing selected activations superimposed over averaged anatomical sections. Random effects analysis with 24 subjects. Background threshold p uncorrected < 0.001. (A) Medial sagittal plane (x = 0) showing activations in the tegmentum [VTA], hypothalamus and [cerebellar] vermis. (B) Sagittal plane x = −12 (LH) showing activation in the caudate head, anterior cingulate and parietal cortex. (C) Horizontal plane z = −30; right cerebellum. (D) Horizontal plane z = −9; mid insula, left hemisphere. As for differences between the groups, there were none: no main or interactive effects of gender or sexual orientation. The results were the same for gay and straight, male and female participants [but remember that the numbers were very low, n=6 for each of the four cells]. So this particular [underpowered] study suggests that "the romantic love brain circuit" (i.e., familiarity, attention, memory, reward, etc. activity associated with looking at your partner's face) is not restricted to heterosexuals. Did they really expect anything different? Actually not, Zeki and Romaya predicted a null effect.However, the authors themselves note the difficulties inherent in their entire endeavor:We begin by emphasizing that any study of so complex and overpowering a sentiment as love is fraught with difficulties. Chief among these is that the sentiment itself involves many components – erotic, emotional, and cognitive – that are almost impossible to isolate from the overall sentiment of love. ... While acknowledging this difficulty, we tried as best we could to circumvent it, by applying a uniform criterion – that of a loved face – for studying the brain's love system. Another problem is the difficulty of controlling the mental processes that occur when subjects view their lovers' faces. The only way to address this is through the statistical methods we have used to analyze our results. We have employed a random effects analysis using the summary st... Read more »

  • March 20, 2011
  • 06:30 PM
  • 1,147 views

On M&M'S® and Dog Phobia

by The Neurocritic in The Neurocritic

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  

  • May 11, 2011
  • 02:59 PM
  • 1,144 views

Revisiting Depression's Cognitive Downside

by The Neurocritic in The Neurocritic

Depression, by h.koppdelaneyIs depression actually good for you?Experts now believe that mild to moderate depression may be good for us – and even help us live longer. Rebecca Hardy explains how to reap the benefitsWe constantly hear how depression is blighting our lives, but some experts have an interesting, if controversial, theory: depression can be "good for us", or at least a force for good in our lives.Is this the start of a new Negative Psychology1 movement? Let's all seek out personal tragedy, sadness, insomnia, and a profound sense of failure and hopelessness, because it's good for us!!Last year, author and blogger Jonah Lehrer had a lengthy (and controversial) essay in the New York Times Magazine on Depression's Upside. The main idea, that depression has cognitive and evolutionary advantages, was largely based on a review paper by Andrews and Thomson (2009). In it, they put forth the analytical rumination hypothesis: depression is an evolved response to complex problems, and focusing on them to the exclusion of everything else is beneficial.In response, The Neurocritic was motivated to write about Depression's Cognitive Downside:On the contrary, numerous papers have shown that impairments in cognitive processes such as executive control, attention, and memory persist after a depressed person has recovered (Andersson et al., 2010; Baune et al., 2010; Hammar et al., 2009). In actively depressed patients, Baune and colleagues (2010) found impairments in all domains tested: immediate memory, visuospatial construction, language, attention, and delayed memory. These deficits can contribute to lower social and occupational functioning and a diminished quality of life. In addition, depression can be associated with declines in problem solving abilities on neuropsychological tests such as the Wisconsin Card Sorting Test and the Tower of London test.Now, a new paper by von Helversen et al. (2011) has claimed that depression is good for decision making. Lehrer wrote about this study as support for the analytical rumination hypothesis in Does Depression Help Us Think Better?Here’s where things get interesting: depressed patients approximated the optimal strategy [for hiring the best applicant in a simulated job search] much more closely than non-depressed participants did. The main problem with healthy subjects is that they proved lazy, unwilling to search through enough applicants. Those with depression, on the other hand, were much more willing to keep on considering alternatives, which is why they performed far better on the task. While this study comes with many caveats, it remains an interesting demonstration that depression, at least in specific situations, seems to enhance our analytical skills, making us better at focusing on social dilemmas.Participants in the study were 37 inpatients diagnosed with major depression upon admission to the hospital (10 of whom were omitted "due to technical difficulties with the choice task"). The 27 remaining patients were classified as either "depressed" (n=15) or "recovered" (n=12) based on improved scores on the Patient Health Questionnaire (PHQ-D) between admission and testing (which was a mean of 6.25 days -- that seems like an incredibly rapid remission, which makes one wonder about the actual severity and why they were admitted in the first place). Only half of the patients, both depressed and recovered, were on antidepressants (none were on other medications), which seems unusual for patients who may have been suicidal. Perhaps the criteria for admission to the psych ward in Germany are different than they are in the U.S. and Canada. The still-depressed patients were in hospital an average of 4.20 days when they were tested (which was not significantly different from the recovered patients). It wasn't completely clear if any of the patients were already on antidepressants, or whether the pharmacological treatment started during hospitalization for those on meds.2 The paper did not state whether any of the depressed patients had another diagnosis, such as an anxiety disorder of any sort (co-morbidity is common).Mean scores on the Beck Depression Inventory (BDI) were higher in the Depressed group (29.13) than in the Recovered group (16.67) or the Control participants (6.63), who also differed from each other. BDI scores of 14–19 are considered mildly depressed, 20–28 moderately depressed, and 29–63 severely depressed. So patients in the Depressed group scored at the low end of severely depressed, the Recovered participants were mildly depressed, and the Controls (n=27) were not depressed at all.The task administered to all participants is called the "Secretary Problem":The sequential decision-making task consisted of playing 30 games of a secretary-type problem. Each game challenged participants to find the best candidate for a job out of a sequence of 40 applicants. The 40 applicants were presented one after another, in a random sequence. After an applicant was presented, participants needed to decide whether they would accept the applicant or not. If they accepted the applicant, the game concluded and the next game started. If they rejected the applicant, the next applicant was presented. Rejected applicants could not be chosen later in that game. Information about the current candidate included their relative ranking compared to the candidates that came before, but not their absolute ranking. Points were awarded based on the absolute ranking of the candidate chosen on each round. If a participant didn't make a choice until the end of the sequence, they were forced to accept the final candidate. So it seems that an indecisive person would be more likely to continue the search for a longer time...Results showed there was a trend in that direction (p=.08): search length was 23.37 for Depressed, 16.87 for Recovered, and 17.96 for Controls. Performance goals for each round (how good a candidate would have to be in order to be chosen) and the relative rank of candidates did not differ between groups. However, the number of points awarded for each game did differ (p=.02): 37.67 for Depressed, 35.50 for Recovered, and 35.17 for Controls. A computational model suggested that the Depressed group had higher internal thresholds for the first and second, but not the third threshold. A caveat from the authors:However, although we found that depressed participants had higher thresholds than did nondepressed participants, we did not find significant differences in the self-reported goals of participants. This suggests that differences in behavior may not result from participants’ conscious effort to perform well. Thus, increases in thresholds could be an artifact stemming from greater persistence and the inability to disengage from a task.What does this mean? That severely depressed inpatients should be given the task of selecting job candidates for Fortune 500 companies, while they are so impaired otherwise that they are unable to work or function socially? Is a very modest performance benefit in a laboratory sequential decision making task worth the pain and suffering of severe depression, along with its concomitant deficits in other cognitive domains?... Read more »

  • December 21, 2010
  • 02:07 PM
  • 1,135 views

Neuroradiology as Art

by The Neurocritic in The Neurocritic

Crucifixion, by Francis Bacon (1933).Crucifixion (1933) (oil on canvas) was subsequently purchased by Sir Michael Sadler (who, other than friends or relations, was the first to buy a painting), and who also commissioned a second version, Crucifixion (1933) (chalk, gouache and pencil), and sent Bacon an x-ray photograph of his own skull, with a request that he paint a portrait from it. Bacon duly incorporated the x-ray directly into The Crucifixion (1933).A paper by an interdisciplinary team of Serbian radiologists, anatomists, artists, and pathologists examined how neuroradiological images have been used as a form of artistic expression (Marinković et al., 2010). They started by describing skull x-rays incorporated into the paintings of Francis Bacon and Diego Rivera, then gave examples of contemporary artists who transform computerized tomography (CT) and magnetic resonance images (MRI) into art. These works include Wooden Brain (The 3D MRI Cubes) by Neil Fraser and "Art and Science #1" by Marjorie Taylor, which can be seen at the The Museum of Scientifically Accurate Fabric Brain Art.I would add to the list any number of works by Damien Hirst, including this self-portrait:...which he incorporated into this album cover for See the Light by The Hours.Marinković and colleagues (2010) mentioned the commercialization of neuroradiology and colorized pictures of the brain by companies such as shutterstock, where you can subscribe for $249 a month and download stock photos of a "female doctor examining a brain cat scan" and "colorful brain model isolated on dark background" (much like this one).The authors also surveyed 12,673 artworks in books and Google images. They found that neuroradiological images were used in 29 works (1.01%) created by 31 artists (1.58% of 1,964 total).They wished to make their own contributions to this collection, and they did so with three pieces presented in the paper. In one of these, they...performed an x-ray of four post mortem hemispheres following the injuction of a radiopaque substance into their sulci and insertion of the copper wires around the corpus callosum and along the calcarine and parieto-occipital sulci. The radiograph of one of the hemispheres was then superimposed in Phototshop with the photograph of the subsequently made cast of the cerebral arteries.Radiological Image, by Marinković et al. (2010).Finally, they......made an inverse image of a colorized brain in a front view. this image was then superimposed with a photograph of illuminated optic fibers in the background.Cognitive Radiation, by Marinković et al. (2010).Anatomy and art intersect in a number of places, at the Mütter Museum in Philadelphia, the Morbid Anatomy website, the Bioephemera website by Jessica Parker, and Gunther von Hagens' BODY WORLDS (the Bioethics of which is discussed here), among many others. Portraits of the Mind: Visualizing the Brain from Antiquity to the 21st Century by Carl E. Schoonover is a popular new book that's currently out of stock at Amazon.Neuroradiology, and especially the development of beautiful colorized diffusion tensor images, has captured the minds of artists, designers, and the public.From the Human Connectome Project, an effort to map the white matter connectivity of the human brain.ReferenceMarinkovic, S., Stošic-Opincal, T., Štrbac, M., Tomic, I., Tomic, O., & Djordjevic, D. (2010). Neuroradiology and Art: A Review and Personal Contribution The Tohoku Journal of Experimental Medicine, 222 (4), 297-302. DOI: 10.1620/tjem.222.297"I think one of the things is that, if you are going to be a painter, you have got to decide that you are not going to be afraid of making a fool of ... Read more »

Marinkovic, S., Stošic-Opincal, T., Štrbac, M., Tomic, I., Tomic, O., & Djordjevic, D. (2010) Neuroradiology and Art: A Review and Personal Contribution. The Tohoku Journal of Experimental Medicine, 222(4), 297-302. DOI: 10.1620/tjem.222.297  

  • August 11, 2009
  • 12:06 AM
  • 1,134 views

A New Clitoral Homunculus?

by The Neurocritic in The Neurocritic

Homunculus image from Reinhard Blutner.OK kids, let's start today's lesson by viewing the G-Rated [i.e., genital-less] flash explanation of homunculus.The neuroanatomical definition of homunculus is a "distorted" representation of the sensorimotor body map (and its respective parts) overlaid upon primary somatosensory and primary motor cortices. The above figure illustrates the sensory homunculus, where each body part is placed onto the region of cortex that represents it, and the size of the body part is proportional to its cortical representation (and sensitivity). It's rare to see the genitals represented at all. And if they are present, they are inevitably male genitals. To remedy this puritanical and androcentric situation, Swiss scientists at University Hospital in Zurich conducted a highly stimulating study in 15 healthy women to map the somatosensory representation of the clitoris (Michels et al., 2009).The authors begin by reviewing the work of Wilder Penfield et al.:During the last 70 years the description of the sensory homunculus has been virtually a standard reference for various somatotopical studies (Penfield and Boldrey 1937; PDF). This map consists of a detailed description of the functional cortical representation of different body parts obtained via electrical stimulation during open brain surgery. In their findings they relied on reported sensations of different body parts after electrical stimulation of the cortex. Assessment of the exact location was generally difficult and sometimes led to conflicting results. The genital region was especially hard to assess due to difficulties with sense of shame.Recent studies have tried to map the somatosensory represenation of the human penis using neuroimaging methods, but there has been disagreement over whether it shows the classic medial representation seen in the figure above, or a more laterally located representation in the postcentral gyrus. For example, Kell et al. (2005) noted that......classical and [some] modern findings appear to be at odds with the principle of somatotopy, often assigning it to the cortex on the mesial wall. Using functional neuroimaging, we established a mediolateral sequence of somatosensory foot, penis, and lower abdominal wall representation on the contralateral postcentral gyrus in primary sensory cortex and a bilateral secondary somatosensory representation in the parietal operculum.But there are no comparable fMRI studies of female genitalia. So how is such a study conducted, methodologically speaking? Electrical stimulation of the dorsal clitoral nerve was compared to electrical stimulation of the hallux (big toe). It was all very clinical, no sexual arousal involved. Here's the experimental protocol:Prior to the imaging session, two self-attaching surface disc electrodes (1 × 1 cm) were placed bilaterally next to the clitoris of the subjects so that we were able to stimulate the fibers of the dorsal clitoral nerve. Before the start of the experiment, electrical test stimulation was performed to ensure that subjects could feel the stimulation directly at the clitoris. In addition, the strength of electrical stimulation was adjusted to a subject-specific level, i.e. that stimulation was neither felt [as] painful nor elicited – in case of clitoris stimulation – any sexual arousal (see below). Functional imaging was performed in a block design with alternating rest and stimulation conditions, starting with a rest condition. ... In addition to the clitoris stimulation, we performed in eight of the recorded subjects a second experimental session, in which we applied electrical stimulation of the right hallux using the same type of electrodes, stimulation and scan paradigm.If you "see below" in the Methods you'll discover that after the fMRI session, participants rated their level of sexual arousal and discomfort on a visual analogue scale that ranged from -10 (unbearable pain or strong sexual arousal) to 10 (pleasure or no arousal at all/sleepiness). The median score for sexual arousal was zero with some variability [range: −7.5 to 8; −2 (25% percentile) and 2.5 (75% percentile)]. The median score for comfortableness was −2 [range: −7 to 9; −2.5 (25% percentile) and 0 (75% percentile)]. C'est la vie.The neuroimaging results revealed that compared to the rest blocks,Electrical clitoral stimulation produced significant activations predominantly in bilaterally prefrontal areas (BA 6, 8 and 45), the precentral, parietal and postcentral gyri, including S1 (BA 2 and 3; 40–70% probability) and S2 (BA 43 and ventral BA 40, 30–60% probability). In addition, distributed activations were also seen in the anterior and posterior parts of the insula and the putamen.Fig. 3 (Michels et al., 2009). Illustration of the random-effect group-activation pattern for the contrast ‘electrical clitoral stimulation versus rest’ (orange–yellow color code; p less than 0.02 uncorrected for multiple comparisons) and for the contrast ‘electrical hallux stimulation versus rest’ (green–blue color code; p less than 0.001 uncorrected for multiple comparisons) on a group average brain. A cluster extent threshold of p less than 0.05 is applied for both contrasts. Electrical clitoral stimulation elicited bilateral activations of lateral surface of S1 as indicated by the white circles.The major result was similar to the penile homuculus findings of Kell et al. (2005): a failure to replicate the original 1937 studies of Penfield and Boldrey. Although the statistical thresholds here for the clitoral stimulation were not stringent enough, the authors use this to their advantage:We found no evidence of clitoral representation in the mesial wall, even when using unconventionally low statistical thresholds. This finding is further substantiated by other recent cytoarchitectonic studies revealing that BA 2 does not reach the inter-hemispheric fissure and BA 3 and BA 1 reach the postcentral mesial wall with a probability of only 30% . Our results are also in good agreement with [neuroanatomical] studies on nonhuman primates. In conclusion, it appears that Michels et al. (2009) have indeed mapped out a new clitoral homunculus, to go along with the new penile homunculus. The standard somatosensory images should be revised accordingly.... Read more »

  • May 26, 2008
  • 05:01 PM
  • 1,124 views

You're My Favorite Person...

by The Neurocritic in The Neurocritic

Japanese actress and singer Ryoko Hirosue...and watching your movies boosts my peripheral levels of dopamine and circulating natural killer cells, and activates my medial prefrontal cortex, thalamus, hypothalamus, subcallosal gyrus, posterior cingulate cortex, superior temporal gyrus, and cerebellum.Fig. 3 (Matsunaga et al., 2008). Statistical parametric maps (SPM99) showing significant increases in the rCBF in the positive condition minus those in the control condition. (a) Activations of the MPFC and thalamus (TH). (b) Activations of the hypothalamus (HYP)... Read more »

  • October 26, 2009
  • 06:37 AM
  • 1,124 views

Unusual Changes in Sexuality: Case Studies in Neurology

by The Neurocritic in The Neurocritic

Fig. 1 (Currier et al., 1971). Scalp EEG showing sharp wave activity from left anterior temporal region.In the last post we learned a bit about hypergraphia, a compulsion to write that sometimes occurs in those with temporal lobe epilepsy (TLE). According to the late behavioral neurologist Norman Geschwind (reprinted in 2009; also see Devinsky & Schachter, 2009), hypergraphia is one in a cluster of interictal [between seizure] personality traits in some TLE patients1 which can also include religiosity, hypermorality, aggressiveness, clinginess, increased emotionality, and sexual changes (mostly hyposexuality but also other alterations):Hyposexuality is the most common, but other kinds of sexual changes do occur. ... In England, Davies and Morgenstern went out and found, among the temporal lobe epileptics, several other patients who were transvestites. ... I’m sure that the great majority of transvestites don’t have temporal lobe epilepsy, but it’s interesting that for whatever reason it can cause this. Although I’ve seen many women with temporal lobe epilepsy, someone called to my attention a phenomenon that I hadn’t observed before. The last four women I have seen have all been bisexual, which again is a rather striking finding.Sexual behavior preceding (auras) or during (automatisms) seizures is another story. The EEG traces in Fig. 1 above are from an epilepsy patient who experienced "sexual seizures" during which she engaged in somewhat purposeless "pseudointercourse" behavior, with no memory for the event afterward. Although the general consensus is that sexual automatisms are usually associated with seizure foci in the temporal lobes (Mascia et al., 2005), an influential earlier paper insisted the origin of "sexual seizures" was in the frontal lobes (Spencer et al., 1983).Changes in sexuality can also occur after strokes or due to brain tumors. Neurophilosopher Patricia Churchland drew attention to one of these case reports in a New Scientist article on free will and criminal responsibility:In 2003, the Archives of Neurology carried a startling clinical report [Burns & Swerdlow, 2003]. A middle-aged Virginian man with no history of any misdemeanour began to stash child pornography and sexually molest his 8-year-old stepdaughter. Placed in the court system, his sexual behaviour became increasingly compulsive. Eventually, after repeatedly complaining of headaches and vertigo, he was sent for a brain scan. It showed a large but benign tumour in the frontal area of his brain, invading the septum and hypothalmus - regions known to regulate sexual behaviour.After removal of the tumour, his sexual interests returned to normal. Months later, his sexual focus on young girls rekindled, and a new scan revealed that bits of tissue missed in the surgery had grown into a sizeable tumour. Surgery once again restored his behavioural profile to "normal".Figure 1 (Burns & Swerdlow, 2003). MRI scans at the time of initial neurologic evaluation: T1 sagittal (A), contrast-enhanced coronal (B), and contrast-enhanced axial (C) views. In A and B, the tumor mass extends superiorly from the olfactory groove, displacing the right orbitofrontal cortex and distorting the dorsolateral prefrontal cortex.This case raises the issues of diminished capacity and criminal responsibility. The man knew what he was doing was wrong -- intact capacity and moral knowledge -- but he could not inhibit his inappropriate sexual behavior. It's hard to argue against the finding of diminished responsibility when staring at a gigantic brain tumor. But many other examples of impulsive sexual offenses (Langevin, 2006) aren't nearly as obvious (e.g. after head injuries when the damage might not be visible on an MRI scan). How does society deal with them?A key factor is a change in behavior...Multidirectional disorders of sexual drive in a case of brain tumourThe next report is from Poland (Lesniak et al., 1972 -- before the days of MRI or even CT scans). This case history is even more disturbing and involves greater criminal offenses than the patient of Burns and Swerdlow (2003).A description and analysis of various disorders of sexual impulse are presented. They occurred gradually between the ages of 56 and 60 years in a man previously in good health. The disorders were as follows: harlotry, incestuous intercourse with his under-age daughter [used physical violence and threatened to kill her if she told], sodomy, hetero- and homosexual pedophilia, masochism [he demanded that his wife beat him with a club] with some symptoms of sadism, coprolalia and exhibitionism. [Also bestiality with cows and calves.] Pedophilia and exhibitionism [he fancied wearing a red ribbon around his exposed penis] were the counts of the man’s indictment. After twice-repeated forensic and psychiatric examination and observation, sexual psychopathy and male climacteric were also recognized; and the defendant was acknowledged to be responsible. In the course of further examination, the psychoorganic syndrome with symptoms of moria was recognized clinically. Further specialist examinations, especially by X-ray (pneumoencephalography) showed the presence of neoplasm (probably benign glioma or meningioma) situated at the basal paracentral part of the right forehead lobe [right orbitofrontal cortex again]. Its presence being acknowledged, the defendant was found irresponsible; due precautions and eventual neurosurgical treatment were proposed. It has been stressed that the appearance of the above disorders, especially in view of the age of the subject, must lead one to suspect an organic origin.During the trial (reminiscent of the proceedings against serial child killer and cannibal Albert Fish), expert witnesses for the prosecution found nothing organically wrong, and declared the defendant “at the moment of committing the criminal acts he was charged with, had retained the ability to recognize the significance of these acts, whereas his ability to control his acts had been slightly restricted”. The defendant was found guilty, the defense appealed and a retrial was granted. He was placed under observation for 2 months at the Psychiatric Clinic in Cracow, when the authors became involved in his case:The neurological examination revealed a considerable bilateral impairment of smell [a tell-tale sign of bilateral orbitofrontal damage] and a marked inequality of the reflexes of... Read more »

  • March 26, 2011
  • 07:04 PM
  • 1,121 views

Pharmacological Misinformation Foisted on Unsuspecting Public

by The Neurocritic in The Neurocritic

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  

  • September 9, 2009
  • 01:55 PM
  • 1,116 views

Deep Brain Stimulation for Severe Alcoholism

by The Neurocritic in The Neurocritic

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 »

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:/

  • May 12, 2010
  • 08:10 AM
  • 1,116 views

CASES OF INJURY OF THE HEAD, ACCOMPANIED BY LOSS OF BRAIN (oozing from the skull)

by The Neurocritic in The Neurocritic

"Head-wound Hank", from Geek Orthodox.The 19th century archive of The Lancet1 is filled with simply delightful case reports. Who can resist the allure of early plastic surgery failures, such as RHINOPLASTIC OPERATION, PERFORMED BY M. LISFRANC, FOLLOWED BY DEATH? Or how about a Case of Local Tubercular Deposit on the Surface of the Brain, presented by Robert Dunn, Esq.? Finally, the tragic History of a Case of Hydrophobia, treated at the Hotel Dieu at Paris, by an injection of water into the veins did not end well (through no fault of R. Magendie, of course):2 It results from the history of this case, that a disease, which exhibited all the characters of hydrophobia, ceased by the introduction of a pint* of warm water into the veins; that the patient survived this introduction eight days: that no accident appeared to follow from it; and that the death of the patient appears to have been caused by a local disease, which was wholly unconnected with the hydrophobia, and the new mode of treatment.* The pint of Paris contains 48 cubic inches. -ED.In 1828, Dr. Sewall (Professor of Anatomy in the Colombian College, D.C.) reported on two of his cases. They are not for the faint of heart. A warning for political incorrectness is also warranted here.CASE 1. In February 1827, W. Brown, a coloured man, aged fifty years, in encountering with another individual, received a severe blow on the right side of the head with a sharp spade. When Dr. Sewall arrived, which was only a few minutes after the accident, he found him bleeding profusely, and much exhausted from the loss of blood. Though not insensible, he had lost his reason, and did not know how he came by the injury. There was a deep wound dividing the integuments, the whole of the temporal muscle, penetrating the cavity of the cranium, and extending horizontally, from an inch above the external angular process of the frontal bone, through the parietal bone just above the squamous suture, forming a fissure of three inches in length. The lower portion of bone was considerably depressed, and the two edges separated about half an inch. Two branches of the temporal artery were taken up; when, on a more critical examination, it was ascertained that the dura mater was divided for an inch in extent...OK, so the patient really did have a 3 inch crack in his skull with brain matter oozing out. Mr. Brown was treated by Dr. Sewall ("dressings were applied"). When pus was coming from the gaping wound, there was swelling followed by sloughing (apparently). Then bits of brain were scooped away with a spatula. Lovely.Although he suffered from severe headaches, Mr. Brown was declared none the worse for the wear:For about ten days after the accident, the patient complained of constant, and sometimes of severe, pain in the head; and on one occasion was affected with a slight spasm of the muscles of the face, neck, and extremities. The wound healed, and in six weeks the patient was quite well. He subsequently followed his occupation, that of scavenger, and did not manifest any deviation in the functions either of body or mind from their ordinary healthy condition.The bar was probably set pretty low for what was considered an "ordinary healthy condition" for a "coloured" man who worked as a scavenger in 1827...The second case was of a five year old boy who was kicked in the head by a horse. No race was specified, so we'll assume he was white. More oozing and scooping of brain:CASE 2. September 18th, 1827, Lewis Poole, aged five years, while playing in the street, was kicked by a horse, and taken up in a state of insensibility. Dr. Sewall arrived a quarter of an hour after the accident, and found a semicircular wound in the integuments of the head, and, corresponding with this, a large fissure in the frontal and parietal bones, about three inches above the external angle of the right eye. Through this fissure a portion of brain protruded, somewhat larger than a walnut, and was composed both of cortical [gray] and medullary [white] matter, which were easily distinguished. This was so far separated from the parts beneath, as to be removed without any violence.Once again we're informed of the patient's full recovery, but only after much unpleasantness. He was bled to the point of unconsciousness initially and then given a powerful and toxic emetic for two weeks straight:Particular circumstances prevented the subsequent use of the lancet; but he was purged actively and daily for two weeks, and the pulse kept down by nauseating doses of the tartate of antimony. Extensive suppuration came on, with a copious discharge of pus; the wound gradually healed, and in about five weeks the child was quite well. He has since remained in perfect health.I wonder for how long that lasted, since Antimony Potassium Tartate is considered a dangerous good (.doc). Inhalation can cause irritation, sore throat, coughing, and shortness of breath. Eye or skin contact causes irritation, redness, and pain. Ironically, the recommended treatment after swallowing this compound is to induce vomiting immediately. The long-term consequences of antimony poisoning are not likely to be conducive to perfect health. Neurosurgical care has certainly come a long way since 1827.Footnotes1 Now on Facebook and Twitter! Keeping up with the 21st century.2 It probably wasn't his fault if the patient was really infected with the rabies virus (aka hydrophobia).ReferenceDr. Sewall (1828). CASES OF INJURY OF THE HEAD, ACCOMPANIED BY LOSS OF BRAIN. The Lancet, 10 (265) DOI: 10.1016/S0140-6736(02)98130-4
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  • May 10, 2012
  • 08:22 AM
  • 1,102 views

Spindle Neurons in Macaques?

by The Neurocritic in The Neurocritic

Spindle neurons, or Von Economo neurons (VENs), are a unique type of large, bipolar neuron found primarily in layer Vb in the anterior cingulate cortex and the frontoinsular cortex of humans.1 In 1999, Nimchinsky and colleagues discovered that among the 28 nonhuman primate species they examined, only great apes had VENs [see Spindle Neurons: The Next New Thing?].Spindle neurons are also seen in humpback, fin, sperm, and killer whales (Hof & Van der Gucht, 2007), elephants (Hakeem et al., 2009), and cetaceans such as the bottlenose dolphin, Risso’s dolphin, and the beluga whale (Butti et al., 2009).Because VENs are only found in large-brained, highly evolved social species, and are potentially implicated in certain neurological and psychiatric disorders, their hypothesized functions include empathy, conscious awareness, and self-referential processing. A 2011 review by Allman and colleagues reiterated that only great apes (bonobos, chimpanzees, gorillas, orangutans) have VENs and suggested they......may be a specialization related to very large brain size. The large size and simple dendritic structure of these projection neurons suggest that they rapidly send basic information from FI [frontoinsular cortex] and LA [limbic anterior area] to other parts of the brain, while slower neighboring pyramids send more detailed information. Selective destruction of VENs in early stages of frontotemporal dementia (FTD) implies that they are involved in empathy, social awareness, and self-control, consistent with evidence from functional imaging.VENs: Not Only for Great Apes Any More!But now, a new study has identified these special neurons in the insular cortex of macaque monkeys (Evrard et al., 2012).Figure 1 (Evrard et al., 2012). The Von Economo Neuron Is Present in Layer 5b in a Restricted Portion of the Agranular Anterior Insula in the Macaque Monkey (A) High-magnification photomicrographs demonstrating the identical morphology of the macaque and human VENs. Scale bar represents 25 μm.Why weren't they found in the earlier studies that looked for them?Three reasons: (1) they're a lot smaller in monkeys; (2) they're more fragile in monkeys; and (3) they're confined to a more limited anatomical region.First, the large human VENs unambiguously stand out at low microscope magnifications. Searching for relatively smaller VENs among the densely packed cell population in layer 5 in the monkey required the highest microscope magnification, which would be unusual for anyone accustomed to examining the more obvious VENs in hominids. Second, the cytoskeletal matrix of the small monkey VENs might be more fragile during histological processing than that of the larger human VENs. ... Third, in the major prior study, the number of VENs in humans and great apes was counted in consecutive sections that were apparently spaced at 1 mm intervals ... such a sampling paradigm would likely have been inadequate for the identification of VENs within the small VEN-containing region of the ventral AAI that measures ∼2 × 2 × 1 mm3 in macaques.The authors pointed out a major advantage of their new discovery, namely that more invasive studies are now possible (i.e., you can't do single cell neurophysiology in dolphins or bonobos).But wait... are they really VENs?The morphology, size, laminar distribution, and proportional distribution of the monkey VEN suggest that it is at least a primal anatomical homolog of the human VEN. Allman, Hof, and colleagues might have something more to say on the matter, based on their earlier findings (e.g., Allman et al., 2011):The VENs are illustrated at higher magnification in Figure 3, which shows that they have very similar morphology in the great apes and humans. In primates, the VENs are present in FI only in great apes and humans. This is the same taxonomic distribution as was found for the VENs in LA, which suggests that the VENs emerged as a specialized neuron type in the common ancestor of great apes and humans. Figure 3 (Allman et al., 2011). VENs in area FI of humans and great apes.The new paper concedes that:The presence of VENs in the macaque does not discredit prior evidence for a crucial role of the VENs and AIC in the emergence of self-awareness and social cognition in humans (Craig, 2009; Allman et al., 2011). VENs in humans appear to be disproportionally slightly larger than in macaques (see above); they may also have an enhanced immunopositivity (and perhaps gene expression) for proteins that are typically involved in homeostasis, which perhaps favors higher interoceptive sensitivity. Are they confined to the anterior insula in macaques? No, VENs were also found in the ACC, but that will be reported separately (a lesson for all you junior scientists).Now that they've been found in monkeys [and can be studied physiologically], will spindle neurons finally catch up with their more glamorous elder cousins, the mirror neurons? Are they really the next new thing? Six years ago, I pondered these points:Somehow, the "spindle neuron" meme hasn't caught on like the "mirror neuron" meme. Is it because spindle neurons have been only been described anatomically (not physiologically), while the reverse is true for mirror neurons? Anatomically speaking, do we know much about mirror neurons? Evrard, Forro, and Logothetis are all over it:...invasive studies of their organization, hodology, and physiology could provide significant insights into the evolutionary basis for self-awareness and empathy in humans. Regarding the latter, it would be particularly interesting to examine whether the VENs share functional similarities with the “mirror” neurons of the ventral premotor cortex (Gallese et al., 2004).Finally, a commentary in Neuron by Critchley and Seth (2012) wonders if studies of the macaque insula will reveal the neural mechanisms of self-referen... Read more »

  • September 7, 2011
  • 07:07 AM
  • 1,101 views

Chronic Ketamine for Depression: An Unethical Case Study?

by The Neurocritic in The Neurocritic

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:/

  • February 14, 2011
  • 07:09 PM
  • 1,099 views

Posterior Hippocampus and Sexual Frequency

by The Neurocritic in The Neurocritic

Fig. 2D (Acevedo et al., 2011). Image and scatter plot illustrating greater response to the Partner (vs. a highly familiar acquaintance) in the region of the posterior hippocampus is associated with higher sexual frequency.Now there's an unexpected correlation suitable for Valentine's Day. How romantic! Actually, it is romantic because the neuroimaging study by Acevedo et al. (2011) is entitled "Neural correlates of long-term intense romantic love." How do you quantify long-term intense romantic love in an fMRI experiment?Well, what the study really examined is the brain's hemodynamic response to viewing pictures of a spouse with whom participants were still "madly in love" after an average of 21 years. Over the course of the experiment, subjects repeatedly viewed four different digital photos: Partner, Close Friend (CF), Highly Familiar "Neutral" acquaintance (HFN), and a Low-Familiar Neutral acquaintance (LFN). Specifically,The protocol implemented a block design of two 12-min sessions each consisting of six sets of four 30-s tasks in an alternating fashion, followed by stimulus ratings. Each session included two alternating images (starting image counterbalanced), interspersed with a count-back task. Duplicating procedures of Aron et al. (2005), Session 1 displayed Partner and HFN images. For the additional control comparisons, Session 2 displayed CF and LFN images. Participants were instructed to think about experiences with each stimulus person, nonsexual in nature.Yeah, it might be a problem if the participants remembered bouts of sex when they viewed their partners... Fig. 2D shows that activation in a tiny area of the left posterior hippocampus correlated with sexual frequency. The two outliers who had sex every day (or nearly every day)1 could be driving the correlation -- they certainly had a greater number of memories to choose from, and to suppress. In humans, activity in the posterior hippocampus is sensitive to the familiarity of stimuli that have behavioral relevance (Strange et al., 1999), and is associated with memory for repeated stimuli (Poppenk et al., 2010).How do Acevedo et al. (2011) interpret this correlation?Although little is known about the posterior hippocampal region [NOTE: untrue], some studies have shown increased activation in this area in association with hunger and food craving (LaBar et al., 2001; Pelchat et al., 2004), with particularly greater activity shown in obese individuals (Bragulat et al., 2010).Craving, eh? Not memory? Although the authors would like to think they controlled for familiarity with the Close Friend contrast, it seems to me nearly impossible that a co-worker, sibling, cousin, or friend could fulfill all familiarity criteria except romantic relationship. Furthermore, most of the analyses focused on comparisons between Partner vs. Highly Familiar Neutral 2 to match their previous paper (Aron et al., 2005) on the early stages of romantic love (1-17 months in duration).I could go on about the analysis methods, and whether reporting the single voxel with highest activity is appropriate [see Voodoo Correlations]. Or I could go on about the subject selection criteria: the 17 heterosexual participants (10 women, 7 men, ages 39-67 yrs, married 10-29 yrs) had an annual household income ranging from $100,000-$200,000 (perhaps not representative of the general population).But what about the main findings? Am I just being a cynic when it comes to love? It's true, some of the expected dopamine/reward areas [ventral tegmental area (VTA) and substantia nigra (SN)] showed greater activation when looking at the long-term Partner, which was very much like what was seen in the young lovers.Fig. 2A (Acevedo et al., 2011). Individuals self-reporting intense love for a long-term spouse show significant neural activation in dopamine-rich, reward regions of the VTA/SN in response to images of their partner vs a highly familiar acquaintance.Ultimately, the paper sends a positive message that in certain relationships, the exciting, obsessive, and rewarding period of intense romantic love can last for over 20 yrs, well beyond the typical and oft-cited (oprah.com)3 18 month to 3 year duration: IMPLICATIONSIndividuals in long-term romantic love showed patterns of neural activity similar to those in early-stage romantic love. These results support theories proposing that there might be mechanisms by which romantic love is sustained in some long-term relationships. For example, the self-expansion model suggests that continued expansion and novel, rewarding events with the beloved may promote increases in romantic love. Novel, rewarding experiences may use dopamine-rich systems (Schultz, 2001; Guitart-Masip et al., 2010) similar to those activated in this study.Beyond reporting relationship length (and sexual frequency), the participants filled out questionnaires including the Passionate Love Scale, the Love Attitudes Scale, the inclusion of other in the self (IOS) Scale, and the friendship-based love scale. All indicators suggested that the subjects were still "madly in love" with their partners. Did we really need neuroimaging to tell us that? Maybe...Footnotes1 The mean sexual frequency was 2.2 times a week.2 The HFN has been known about as long as the Partner, but is substantially less close than both the Partner and the Close Friend.3 If anyone can find a better reference for this than oprah.com or Tennov, D., 1979. Love and limerence. The Experience of Being in Love. Stein and Day, New York -- let me know.ReferencesAcevedo BP, Aron A, Fisher HE, & Brown LL (2011). Neural correlates of long-term intense romantic love. Social cognitive and affective neuroscience PMID: 21208991Aron A, Fisher H, Mashek DJ, St... Read more »

Acevedo BP, Aron A, Fisher HE, & Brown LL. (2011) Neural correlates of long-term intense romantic love. Social cognitive and affective neuroscience. PMID: 21208991  

  • November 15, 2009
  • 12:19 AM
  • 1,093 views

I Feel Your Pain, I REALLY Do: Synaesthesia for Another's Pain

by The Neurocritic in The Neurocritic

"I feel your pain"Empathy for another person's pain is a hot topic of study in the glamorous field of social cognitive neuroscience. The capacity for empathy supposedly involves mirror neurons, those media darlings of The Young, [The Not-So-Young], and The Neuro:A mirror neuron is a neuron that fires both when an animal acts and when the animal observes the same action performed by another. Thus, the neuron "mirrors" the behavior of the other, as though the observer were itself acting.These magical cells have even inspired famous neuroscientists to utter ridiculous hyperbole:The mirror neurons, it would seem, dissolve the barrier between self and others. I call them "empathy neurons" or "Dalai Llama neurons".-- MIRROR EURONS AND THE BRAIN IN THE VAT by V.S. Ramachandran Synesthesia for pain, a newly described syndrome, goes one step further (Fitzgibbon et al., 2009):In synaesthesia for pain a person not only empathises with another's pain but experiences the observed or imagined pain as if it was their own. Neural mechanisms potentially involved in synaesthesia for pain include “mirror systems”: neural systems active both when observing an action, or experiencing an emotion or sensation and when executing the same action, or personally experiencing the same emotion or sensation. For example, we may know that someone is in pain in part because observation activates similar neural networks as if we were experiencing that pain ourselves. We propose that synaesthesia for pain may be the result of painful and/or traumatic experiences causing disinhibition in the mirror system underlying empathy for pain.And what is synesthesia, exactly? According to Edward M. Hubbard's website, SYNESTHESIA can be defined as...an unusual conscious experience, in which stimulation of one sensory modality leads to a sensory experience in a second, unstimulated sensory modality. For example, seeing letters might lead some people to see colors. Others report that the days of the week or months of the year are arranged like a map in space. Still others report that hearing voices or music cause them to see colors, or that hearing words makes them taste foods...in fact, almost any sensory modality can be involved in synesthesia.One of the more common forms of synesthesia (illustrated above) is grapheme-color synesthesia, where numbers and letters are consistently associated with specific colors (Ward et al., 2005). A more unusual form is lexical-gustatory synesthesia, in which spoken and written words elicit specific taste sensations that remain constant (Ward & Simner, 2003). For instance, Tony Blair tastes like desiccated coconut.According to the recent review of the literature by Fitzgibbon et al. (2009), amputees with phantom limb pain comprise the vast majority of those with synaesthesia for pain:Known Characteristics of Synaesthesia for Pain in a Sample of Amputees with Phantom PainBrought on by viewing others in pain and/or observing pain on the television and in movies.Brought on both when observed pain matches that of the amputated site and/or any general painBrought on regardless of the identity of the observed person in pain, i.e. can be a loved one or a stranger.The experience is similar to the experiences of phantom pain, for example, described as a short sudden ‘electric shock’.Experienced in the phantom limb and/or stump.The researchers propose that:pain experiences may cause disinhibition of mechanisms underlying empathy for pain, resulting in synaesthesia for pain. This proposal is supported by studies that have found mirror activity to be involved in the pain matrix (e.g. Ochsner et al., 2008 and Singer et al., 2004); however, the specific processes that weaken these inhibitory mechanisms are unclear...Ultimately, in synaesthesia for pain, "there is no self–other distinction in the observation of pain in another person."ReferencesFitzgibbon, B., Giummarra, M., Georgiou-Karistianis, N., Enticott, P., & Bradshaw, J. (2009). Shared pain: From empathy to synaesthesia. Neuroscience & Biobehavioral Reviews DOI: 10.1016/j.neubiorev.2009.10.007Ward J, Simner J. (2003). Lexical-gustatory synaesthesia: linguistic and conceptual factors. Cognition 89:237-61.Ward J, Simner J, Auyeung V. (2005). A comparison of lexical-gustatory and grapheme-colour synaesthesia. Cognitive Neuropsychology 22:28-41.
... Read more »

Fitzgibbon, B., Giummarra, M., Georgiou-Karistianis, N., Enticott, P., & Bradshaw, J. (2009) Shared pain: From empathy to synaesthesia. Neuroscience . DOI: 10.1016/j.neubiorev.2009.10.007  

  • September 14, 2009
  • 08:05 AM
  • 1,089 views

Great and Desperate Cures for Addiction

by The Neurocritic in The Neurocritic

《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 »

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