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

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  • January 22, 2009
  • 08:49 PM

When I Get That Feeling, I Need Sexual Sweating

by The Neurocritic in The Neurocritic

Did you know that male "sexual sweat" differs from ordinary sweat? Apparently so, according to a new paper in the Journal of Neuroscience (Zhou & Chen, 2008). Curiously, the article did not cite any references for this, nor did it specify the chemical composition of sexual sweat. Nonetheless, the results of an fMRI experiment suggested that the orbitofrontal cortex and the fusiform region in 20 female participants responded differently when smelling the two substances. How was such a study conducted, you might ask?And here the fun begins...Sweat collection. From 2 d before the experiment until the end of the experiment, 20 heterosexual male donors in a larger study refrained from using deodorant/antiperspirant/scented products, and used scent-free shampoo/conditioner, soap, and lotion provided by the experimenter. They reported to have experience with watching sexually explicit videos, and signed informed consent before participation. Subjects kept a 4" x 4" pad (rayon/polyester for maximum absorbance) in each armpit while they watched 20-min-long video segments intended to produce the emotions of sexual arousal (sexual intercourse between heterosexual couples) and neutrality (educational documentaries), respectively. ... Over the course of the 20 min video segments, donors experienced greater arousal (measured by skin conductance) while watching erotic videos than while watching neutral videos... Three healthy, male nonsmokers (aged 26, 29, and 29 years) were subsequently selected for the current study mainly because of their higher level of the self-reported sexual arousal.How were the female participants selected?We recruited only women for their superior sense of smell and sensitivity to emotional signals. Twenty right-handed females (mean age = 23.4 years) were selected from a group of 42 women on the basis that they reported to have no rhinal disorders or neurological diseases, and that they showed superior olfactory sensitivity to PSP [the putative sex pheromone androstadienone] and PEA [phenyl ethyl alcohol]. They either were in a heterosexual relationship or had been in one within the previous year. They were not on hormone contraceptives, and were tested during the periovulatory phase of their menstrual cycles. ... Subjects were informed that the study was on brain activations to natural compounds. They were blind to the nature of the smells used in the experiment.The scanning was performed while the women were inhaling......the sweat of sexual arousal in comparison with two other social chemosensory compounds (PSP and the sweat of neutrality) and a nonsocial smell [phenyl ethyl alcohol (PEA)].The sweat of neutrality. The sweat of sexual arousal! [plus the two others.] The subjects rated the four inhalants (presented 10 times each) on intensity and pleasantness, as shown below. And the smell of sexual sweat was not particularly pleasant...Figure 1. Mean intensity and pleasantness ratings. There are four types of olfactory stimuli, and SE bars are shown. For intensity, 1 refers to no smell, 2 little smell, 3 moderate smell, 4 quite a bit smell, and 5 strong smell. For pleasantness, 1 refers to very unpleasant, 2 unpleasant, 3 neutral, 4 pleasant, and 5 very pleasant. Sex, Sexual sweat; Neutral, neutral sweat. Sexual sweat and PSP were perceived to be more intense than neutral sweat; PEA was perceived to be more pleasant than sexual sweat and neutral sweat.At the end of the experiment, the participants gave verbal descriptions of the smells. Only one characterized sexual sweat as "sweaty/human." So the women were not [consciously] aware that the odor was obtained from sexually aroused men.The right hypothalamus showed increased activity to sexual sweat relative to alcohol, but so did androstadienone and neutral sweat. The two brain regions that responded more to sexual sweat than to the other odors are illustrated below. The right orbitofrontal cortex is an olfactory region, but the right fusiform gyrus is a high-level visual region. The authors say their fusiform region1 falls in the vicinity of the fusiform face area (FFA) and fusiform body area (FBA). Hmm.Figure 3. a. Coronal view showing an area in the right orbitofrontal cortex (33, 40, –1) activated in the omnibus ANCOVA F test (svc, p less than 0.005). d. Sagittal view showing a region in the right fusiform gyrus (35, –51, –7) activated in the omnibus ANCOVA F test (uncorrected p less than 0.0005, cluster size = 49 mm3).The authors took a giant leap when speculating about visual imagery of faces and bodies:The Talairach coordinates of the fusiform region identified in our experiment fall in the range of the coordinates for FFA and FBA. Such anatomical location likely reflects a recognition of the human quality in the sexual sweat, whose emotional nature may have also contributed to the activation. Considering its functional connectivity to the right hippocampus/ parahippocampal gyrus, the recognition may arise from implicitly associating the sexual sweat with humans based on past experience. The fact that most subjects did not perceive the sexual sweat as human related suggests that the effects we observed occurred at a subconscious level. Implicit face/body visual processing in response to a sexual chemosensory cue? But nothing specific in the hypothalamus or amygdala? That's a hard one to swallow.Footnote1 The FFA and FBA have been dissociated with scanning at high resolution.ReferenceW. Zhou, D. Chen (2008). Encoding Human Sexual Chemosensory Cues in the Orbitofrontal and Fusiform Cortices Journal of Neuroscience, 28 (53), 14416-14421 DOI: 10.1523/JNEUROSCI.3148-08.2008Chemosensory communication of affect and motivation is ubiquitous among animals. In humans, emotional expressions are naturally associated with faces and voices. Whether chemical signals play a role as well has hardly been addressed. Here, we use functional magnetic resonance imaging to show that the right orbitofrontal cortex, right fusiform cortex, and right hypothalamus respond to airborne natural human sexual sweat, indicating that this particular chemosensory compound is encoded holistically in the brain. Our findings provide neural evidence that socioemotional meanings, including the sexual ones, are conveyed in the human sweat.... Read more »

  • December 17, 2008
  • 10:46 PM

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, 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  

  • February 20, 2011
  • 10:30 PM

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 »

  • May 14, 2009
  • 08:40 PM

Suicide Rates in Greenland Are Highest During the Summer

by The Neurocritic in The Neurocritic

by: crdagainSeasonal affective disorder (SAD) is a cyclical depressive disorder that typically recurs every year during the shorter days and longer nights of late fall-early winter. Much of the research on SAD has focused on changes in the photoperiod and the accompanying effects on circadian rhythms during winter. So it might come as a surprise that in Greenland, the suicide rate peaks during the summer months of continuous sun (especially at the highest latitudes). However, the rate of homicides and the sales of beer do not show the same seasonal variation (Björkstén et al., 2009). Why might this be? Most suicides in Greenland are of the impulsive variety and are committed using violent methods. The authors' previous work observed the summer suicide spike (Björkstén et al., 2005), and now they wanted to determine whether homicides show the same seasonal pattern. They reviewed the evidence on serotonin, impulsivity, and violence, and hypothesized that altered serotonin turnover might be a common factor in both violent suicides and violent homicides (reasoning that increased serotonin turnover in spring and summer might enhance impulsiveness and aggression).How was this assessed? Northern Greenland (obviously) shows the greatest seasonal extremes in the amount of light and darkness. The country maintains good statistics, and the Inuit population is considered to be relatively homogeneous. Thus, Björkstén, Kripke, and Bjerregaard (2009) examined computerized records listing the causes of all deaths in Greenland during the time period of 1968-2002. To determine whether alcohol consumption played a role in the rates of suicides and murders, the pattern of beer purchases at a major chain store from July 2005 to June 2006 were used as a proxy ("Detailed sales data are secret for business reasons").The authors note some extremely tragic statistics:The suicide rate in Greenland increased during the 1970’s from a historically very low level to one of the highest levels in the world, 107 per 100,000 person-years in 1990-1994. The increase has been most pronounced among teenagers and young adults. A rapidly increasing suicide rate has been reported from other areas going through radical changes like in Eastern Europe after the fall of communism and among aboriginal people confronted with modern lifestyle.We have previously demonstrated that the vast majority of suicides in West Greenland are violent and peak in the summer when the Northern half of Greenland has constant day-light and the Southern half has extremely long days. Depression has, however, been reported uncommon and the majority of suicides seem impulsive rather than depressive.The overall homicide rate in Greenland has been reported much higher than that of the other Nordic countries. Homicides are almost exclusively impulsive and committed under the influence of alcohol...Continuing in a depressing vein, there were 1351 suicides (80.5 % were men) and 308 homicides during the 35 year period under study.Persons in upper teens and young adults were heavily over-represented among the suicide cases. Median age was 25 years...In 391 out of the 1351 cases (29%), the death certificate included a psychiatric diagnosis. In 214 cases (15.8%), there was a diagnosis of alcoholism or alcohol intoxication; two cases also had a diagnosis of psychosis. In only 52 cases (3.8%), there was a diagnosis of affective disorder, either unspecified or in the depressive state. In 104 cases, there was a diagnosis of psychosis. In addition to the 104 cases (7.7%), there were two with alcoholism and psychosis.However, affective disorders could have been underdiagnosed in the population... we don't really know for sure. What we do know is that violent methods of suicide were used in 95% of all cases (n=1286), with men using violent methods 97% of the time and women 86% of the time (the latter percentage in stark contrast to the general population outside of Greenland). Figure 3a below shows the seasonal variation in all suicide cases. The annual peak occurred on June 11th and the trough in November-January, and the effect of seasonality was significant (p... Read more »

  • March 15, 2009
  • 12:52 AM

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 »

  • March 20, 2011
  • 06:30 PM

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

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 »

  • May 26, 2008
  • 05:01 PM

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 »

  • March 26, 2011
  • 07:04 PM

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

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 10, 2012
  • 08:22 AM

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 »

  • December 21, 2010
  • 02:07 PM

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  

  • May 12, 2010
  • 08:10 AM


by The Neurocritic in The Neurocritic

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

  • June 19, 2008
  • 05:01 AM

Mirror Neurons Control Hard-ons?

by The Neurocritic in The Neurocritic

from MR BEAN IN TOILETEveryone knows that mirror neurons control the universe. Now, a study by Mourus and colleagues supposedly tells us that mirror neurons control the most important thing in the universe!Mirror neurons control erection response to porn14:15 16 June news serviceAlison Motluk. . .Harold Mouras, at University of Picardie Jules Verne in Amiens, France, and his colleagues wanted to understand the cerebral underpinnings of visually-induced erections.They suspected there might be a role for mi... Read more »

  • February 14, 2011
  • 07:09 PM

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 ( 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 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  

  • October 26, 2009
  • 06:37 AM

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 »

  • August 11, 2009
  • 12:06 AM

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 »

  • April 25, 2008
  • 06:02 AM

I have to praise you like I should

by The Neurocritic in The Neurocritic

OR, why most people (in Japan, at least) do give a damn about their bad reputation.MTV's Artist of the Week 04.21.08: GossipIn the burgeoning field of neurorewardspotting, the equation is pretty simple:Money = Chocolate = Sex = Fairness = Beauty = Punishing Bad Players = Alcohol = Cocaine = Nicotine = Methamphetamine = etc. AND NOW... acquiring a good reputation in the eyes of others.So add the new paper by Izuma et al. (2008) to the growing list of studies claiming that all rewards are alike (at least, as far as the striatum i... Read more »

  • April 2, 2009
  • 09:24 PM

Heterotopagnosia: When I point at parts of your body

by The Neurocritic in The Neurocritic

Heterotopagnosia is an unusual neurological syndrome, as described below by Laurent Cleret de Langavant and colleagues:Heterotopagnosia is the acquired inability of brain-lesioned patients to point at someone else's body parts when prompted. The cognitive basis of this disorder is unclear. It might result from a biological function deficit critical for communication in human beings; alternatively, it could result from the disruption of a body representation. Here, we report three patients with heterotopagnosia following a recent left parieto-occipital stroke and a previous insular lesion. The patients were tested on their ability to name, point out and grasp several targets including body parts (own, real others’ and figurative others’). Language, visuo-spatial deficits or any confounding neuropsychological disorders were controlled for. We found that the patients erroneously pointed to their own body parts when asked to point at someone else's. Strikingly, their ability to grasp someone else's body parts was largely unimpaired. The dissociation between their grasping and communicative pointing abilities supports the hypothesis that heterotopagnosia is a disorder of communicative function conveyed by pointing but not by grasping. In addition, pointing performance in our patients varied according to the target: the more similar the target was to a real person, the worse the patients’ pointing performance. We suggest that communicative pointing might require a specific representation of the addressee's body and point of view, a heterocentric representation. In the patients described here this phenomenon resulted from a combined insulo-parietal lesion, which may explain why, in contrast to other patients described previously, the heterotopagnosia was long-lasting.The area of maximum lesion overlap was a region in the left parieto-occipital cortex, as shown in this drawing depicting the area of damage shared by all three patients.Fig. 3. (Cleret de Langavant et al., 2009). The overlap of the left parieto-occipital junction lesion (Brodmann area 19), common to all three patients. Note that there is no overlap within the insular region for the three patients since COG has a left insular lesion and ROM and BEG a right one.What can explain this unusual disorder? First, the authors ruled out several possibilities:The features of heterotopagnosia set this pointing disorder apart from any other known neurological disorder. The patients’ preserved performance in grasping and touching body parts rules out any causal visual or spatial impairment based on the size, type, complexity or componential analysis of the target. Likewise, a language deficit cannot account for the patients’ performance in pointing. The spared ability of patients in naming body parts they cannot point to, their use of possessive and demonstrative grammatical indices and their perfect understanding of pointing exclude a category-specific lexical impairment.Instead, they suggested the patients exhibited a deficit selective for another person's body, problems with self-referencing behavior, and a dissociation between impaired pointing versus intact grasping/touching. The authors concluded by asking......why is pointing interesting if its impairment has no consequences in daily life? We suggest that pointing is a residual function that is fundamental in infant development. It marks the construction of the three-way relationship of communication (self-addressee-object or I-you-he/she/it), as a keystone for the development of language and theory of mind. In adults, its impairment is compensated by abilities that have integrated and supplanted it, leaving intact relationships with others (e.g. verbal communication and knowledge concerning others).ReferenceCleret de Langavant, L., Trinkler, I., Cesaro, P., & Bachoud-Lévi, A. (2009). Heterotopagnosia: When I point at parts of your body. Neuropsychologia DOI: 10.1016/j.neuropsychologia.2009.02.016... Read more »

Cleret de Langavant, L., Trinkler, I., Cesaro, P., & Bachoud-Lévi, A. (2009) Heterotopagnosia: When I point at parts of your body. Neuropsychologia. DOI: 10.1016/j.neuropsychologia.2009.02.016  

  • September 7, 2011
  • 07:07 AM

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:/

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