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Born in West Virginia in 1980, The Neurocritic embarked upon a roadtrip across America at the age of thirteen with his mother. She abandoned him when they reached San Francisco and The Neurocritic descended into a spiral of drug abuse and prostitution. At fifteen, The Neurocritic's psychiatrist encouraged him to start writing as a form of therapy.
Diagram showing principal systems of association fibers in the human brain. The superior longitudinal fasciculus (SLF) is labeled at the center top (marked by purple arrows).New Scientist covered two journal articles by Rametti and colleagues (2010, 2011), a group of Spanish researchers and clinicians affiliated with Unidad Trastorno Identidad de Género [Gender Identity Disorder Unit]. Using the diffusion tensor imaging (DTI) method, they initially wanted to identify any sex differences in the white mater of the brains of non-transgendered male and female heterosexuals. Then the next step was a prediction that FTM (Female-to-Male) transsexuals would be more like males, while MTF (Male-to-Female) transsexuals would be more like females.Transsexual differences caught on brain scan12:16 26 January 2011 by Jessica HamzelouDifferences in the brain's white matter that clash with a person's genetic sex may hold the key to identifying transsexual people before puberty. Doctors could use this information to make a case for delaying puberty to improve the success of a sex change later.In 5 years of writing this blog, I have come across a multitude of news stories and press releases that make outrageous claims. Here's another one to add to the list. On the basis of two highly variable DTI studies in 36 pre-operative, pre-hormone treatment transgender individuals, now we're supposed to screen children for gender variant behavior and scan them at a young age, so their hormones can be altered before puberty?Returning to the structural imaging experiments, were there any hypotheses at the outset, or were these completely exploratory studies? The authors cite the work of Zhou et al. (1995) on postmortem staining of the bed nucleus of the stria terminalis (BST). This subcortical nucleus connects the amygdala to the septal nuclei, hypothalamus, and thalamus. BST has been shown to play a role in the sexual behavior of male rats. The size of this nucleus in MTF brains was similar to that in female controls, both being smaller than male controls.However, it's not possible to visualize the BST in living humans, so the authors went with DTI to look for cortical white matter changes. The participants in the first study were 18 FTM transgendered persons (before undergoing hormonal treatment), along with 24 male and 19 female heterosexual controls. The major findings in terms of sex differences between groups were located mainly in 3 fiber tracts:anterior and posterior parts of the right superior longitudinal fasciculus - contains connections between the frontal, parietal, occipital, and temporal lobes including language-related areas (Mori et al., 2008).forceps minor (anterior forceps) - fiber bundle connecting the lateral and medial surfaces of the frontal lobes, crossing the midline via the genu of the corpus callosum.corticospinal tract - connects the cerebral cortex and the spinal cord, contains mostly motor axons.In all 3 tracts, males showed higher fractional anisotropy (FA) than females. FA is a measure of local tissue properties including density, coherence, diameter, and myelination.Fig. 1 (Rametti et al., 2010). Sex differences in fractional anisotropy (FA). FA is lower in female than in male controls in the superior longitudinal fasciculus with a posterior (A) and anterior (B) predominance. Control females also show lower than control male FA values in the forceps minor (C) and the corticospinal tract (D). The group skeleton used for the between group contrast study is green. The red color shows the clusters of significantly decreased FA in female compared to male controls. The threshold for significance was set at p < 0.05 corrected for multiple comparisons.FTM individuals showed greater FA values in all 3 tracts than did the control females. They were similar to control males for anterior and posterior SLF and forceps minor, and in between control male and female FA values for the corticospinal tract.What does this mean? Basically, at this point, it's like reading tea leaves. We have no indication of other potential differences between the groups in cognitive, emotional, personality, or motor measures, in alcohol use, or in other psychiatric diagnoses. We do know that testosterone levels of the FTM participants were like those of control females, because they had yet to undergo hormone treatment.Moving right along to the second experiment, which compared MTF individuals to controls (Rametti et al., 2011)... The participants were 18 untreated MTF transsexuals (mean age = 25 yrs), 19 female (mean = 33 yrs) and 19 male controls (mean age = 32 yrs). Yes, the MTF individuals were significantly younger than controls [the human frontal lobe in particular is known to continue maturation processes into the 20's]. Procedures were similar to those used previously. Results in this study showed a greater number of differences in the white matter of male vs. female controls (again, with larger FA values for males): left and the right SLFforceps minorright inferior front-occipital fasciculus (IFOF)corticospinal tract left cingulumSo what's new in this list? Left SLF, Right IFOF, Left cingulum. This finding indicates that individual differences were observed between two groups of male and female control subjects [or else there were unreported methodological differences]. If normal sex differences in DTI studies include IFOF and cingulum here but not there, that presents a problem for comparison to the transgendered populations.Nonetheless, what did that comparison show? The MTF individuals showed FA values between those of male and female controls for all tracts (except for IFOF, where they did not differ from males).Fig. 2 (Rametti et al., 2011). Histograms showing the FA... Read more »
Rametti, G., Carrillo, B., Gómez-Gil, E., Junque, C., Segovia, S., Gomez, �., & Guillamon, A. (2011) White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. Journal of Psychiatric Research, 45(2), 199-204. DOI: 10.1016/j.jpsychires.2010.05.006
Rametti, G., Carrillo, B., Gómez-Gil, E., Junque, C., Zubiarre-Elorza, L., Segovia, S., Gomez, �., & Guillamon, A. (2010) The microstructure of white matter in male to female transsexuals before cross-sex hormonal treatment. A DTI study. Journal of Psychiatric Research. DOI: 10.1016/j.jpsychires.2010.11.007
Bottom image adapted from Fig. 2 of Schumann et al. (2010). Neuroanatomy of the human amygdala postmortem. Nissl-stained section of amygdala nuclei.The amygdala is a subcortical structure located within the medial temporal lobes. It consists of a number of different nuclei, or collections of neurons delineated by commonalities in morphology and connectivity. The amygdala is best known for major roles in fear conditioning (Paré et al., 2004) and responding to emotional stimuli more generally (Phelps & LeDoux, 2005), but its functions extend beyond that.A new study by Bickart and colleagues (2010) examined the relationship between the overall size of the amygdala in a group of 58 volunteers and the number of people in each person's social network. The authors observed a direct correlation between the two: the larger the amygdala, the larger the social network. Why did they expect such a finding? The "social brain hypothesis" (Dunbar, 1998) is cited as providing general evidence in favor of increased brain size in more social animals. However, the major references that motivated the specific hypothesis about the amygdala are book chapters, which seemed rather weak and unscholarly to me.Predictably, a number of silly headlines appeared in the popular press...How to Win Friends: Have a Big Amygdala?Got a big social network? Then you probably have a large amygdala, according to a new study that found a connection between the size of this brain region and the number of social relationships a person has. The complexity of those relationships — as measured by the number of people who occupied multiple roles in a social network such as being simultaneously a friend and a co-worker — was also linked with amygdala size....and in blogs:The Twitter Spot in Your BrainHeavy Facebook users may have weighty amygdalasBut the worst headline of all (because it is patently false) is...Study: More Friends on Facebook Equals A Bigger Amygdala In Your BrainThe number of Facebook friends you have is correlated to the size of your amygdala, the center used to process the memory of your emotional reactions in your brain, according to a new study published in Nature Neuroscience. The volume of your amydala has been connected to the size of the circle of those you come in contact with even with nonhuman primate species before, so Kevin Bickart and his coauthors took the idea and tested it out on people who interact with people on Facebook.Does the Amygdala Have a Social Network?First of all, the size of the amygdala has absolutely nothing to do with Facebook or any other contemporary social networking site. The scale for quantifying social network size and complexity was taken from a 1997 paper on Social Ties and Susceptibility to the Common Cold (Cohen et al., 1997), which in turn cited a book chapter from 1991. There was no such thing as Facebook or Myspace in 1997, only Geocities (1994) and Tripod.com (1995). As for the history of online communities, The WELL was launched in 1985 as a bulletin board system and could be considered as a proto-social networking site.So who was included in Cohen et al.'s (1997) definition of a social network? One requirement was that the participant spoke to the individual in person or on the phone at least once every two weeks:The Social Network Index assesses participation in 12 types of social relationships. These include relationships with a spouse, parents, parents-in-law, children, other close family members, close neighbors, friends, workmates, schoolmates, fellow volunteers (eg, charity or community work), members of groups without religious affiliations (eg, social, recreational, or professional), and members of religious groups. One point is assigned for each type of relationship (possible score of 12)1 for which respondents indicate that they speak (in person or on the phone) to someone in that relationship at least once every 2 weeks. The total number of persons with whom they speak at least once every 2 weeks (number of network members) was also assessed.Results for the amygdalar correlations with social network size and complexity were nearly identical, so the authors focused on the former in the paper. Importantly, amygdala volume did not correlate with life satisfaction or the perceived quality of the relationships. Basically, you could have a large social network that is not of your own choosing. One participant could have a large family, many co-workers, intrusive neighbors, and few real friends, while another is gregarious and parties with different groups of friends every night of the week. This particular study does not distinguish between the two.Were any other parts of the brain correlated with social network size? No! [which I find hard to believe]. For the entire group of 58 participants, no significant results were observed in other subcortical regions (i.e., hippocampus [which served as a control region], brainstem, nucleus accumbens, ventral diencephalon, thalamus, caudate, putamen, and globus pallidus). An exploratory whole-brain analysis of cortical thickness did not reveal any correlations at conventional levels of significance.Are we supposed to believe that only one area of the brain is involved in maintaining social networks? I think not. Even within the article, subgroups of participants (i.e., males, all older subjects)2 showed correlations between hippocampal volume and social network characteristics. This makes intuitive sense, as a better memory might be helpful in keeping track of large numbers of people.What about cortical regions containing spindle neurons (Nimchinsky et al., 1999), a cell type unique to humans, great apes, humpback whales, elephants and dolphins? Spindle neurons (aka von Economo neurons) are found in the anterior cingulate cortex and frontoinsular cortex. Or how about orbitofrontal cortex, with a volume that correlates with social cognitive competence (Powell et al., 2010)? None of these regions were related to network size.What happens to people born without amygdalae due to Urbach-Wiethe disease, a rare genetic disorder? Does "the woman without ... Read more »
Freelance medical and science writer Rob Stepney noticed the rapid growth of "x" and "z"-named products included in the British National Formulary (BNF). So for the Christmas 2010 issue of BMJ (Stepney, 2010), he investigated this phenomenon:Of 1436 products added to the BNF between 1986 and 2005, more than a fifth had names that began with z or x or contained a prominent x or z within them. In 1986, only 19 branded drugs began with one of these letters. Over the next two decades, the number of brands beginning with a z increased by more than 400% (to 63) and those beginning with an x increased by 130% (to 16). In the same period, the overall content of the BNF grew by only 80%. Why did it happen? He first asks whether use of the voiced fricative “zuh” sound might be special in some way, but he quickly dismisses this possibility, along with the popularity of z in the Middle East.Instead, he speculates that x and z might have been perceived as making products stand out in a crowd:Reflecting their infrequent occurrence in English words, x and z count for 8 and 10 points in Scrabble, the highest values (along with j and q) in the game. So names that contain them are likely to seem special and be memorable. “If you meet them in running text, they stand out,” is the way one industry insider explained. Generally, they are also easy to pronounce.In my view, however, the rush to uniqueness resulted in an overcrowded field. The market became saturated with X and Z brand names, which can cause confusion.Fig 1 (Stepney, 2010). Number of drugs with a brand name beginning with z or x listed in March edition of BNF for each year. New formulations of existing brands and zinc related compounds have been excluded.For instance, the August 9, 2007 newsletter from the Institute for Safe Medication Practices discusses Progress with preventing name confusion errors and links to a document on the most problematic look-alike and sound-alike drug names of 2006-2007 (PDF). These include:ZYPREXA (olanzapine) and ZYRTEC (cetirizine)Name similarity has resulted in frequent mixups between Zyrtec, an antihistamine, and Zyprexa, an antipsychotic. Patients who receive Zyprexa in error have reported dizziness, sometimes leading to a related injury from a fall. Patients on Zyprexa for a mental illness have relapsed when given Zyrtec in error.Other frequently confused Z/X pairs:Zantac – XanaxZantac – ZyrtecZestril – ZyprexaZestril – ZetiaZocor – ZyrtecAt any rate, here's Stepney's (2010) conclusion:I suggest that this phenomenon arose because of the fast rate at which new products were being introduced, the fact that the difference between many “me too” drugs was more apparent than real, the immense rewards that were seen to accrue from innovative marketing, and the fact that the ploys available for use in the naming of drugs are so restricted.A full list of the drugs mentioned in the article can be viewed here.ReferenceStepney, R. (2010). A dose by any other name would not sell as sweet. BMJ, 341:c6895 DOI: 10.1136/bmj.c6895
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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
Case Report: novel treatment initiated by the patient to treat her symptoms of ocular neuromyotonia, or spontaneous spasms of the extraocular muscles.
As part of the Christmas 2010 issue of BMJ, Weston et al. (2010) reported the case of a 68 yr old woman with intermittent diplopia, or double vision. A cataract on her left eye was removed, which improved her vision.... Read more »
The Seductive Allure of Neuroscience ExplanationsThe previous post, Voodoo Correlations: Two Years Later, was a retrospective on the neuroimaging methods paper that was widely discussed in the blogosphere before it was considered "officially" published (Vul et al., 2009). The article, a controversial critique of the statistical analyses used by fMRI investigators in social neuroscience, made its initial appearance on Ed Vul's website once it was accepted by Perspectives in Psychological Sciences. This caused considerable consternation among the criticized authors and the journal editor (Ed Diener).Now, as part of the November 2010 issue of the journal (Diener's last as editor), six invited articles on Neuroimaging: Voodoo, New Phrenology, or Scientific Breakthrough? appear in a Special Section on fMRI (Diener, 2010). I was pleased to see that one of the articles addressed The Appeal of the Brain in the Popular Press (Beck, 2010), since this has been a major theme of my blog for almost five years. However, I was disappointed that the word "blog" was not mentioned at all in Beck's article.This should have come as no surprise, given the journal's response to bloggers in May 2009. The Editor's Introduction is worth a mention for the issues it raises about peer review and publication in these modern times.PREPUBLICATION DISSEMINATIONAs soon as I accepted the Vul et al. article, I heard from researchers about it. People around the globe saw the article on the Internet, and replies soon appeared as well. Although my plan was to publish the article with commentary, the appearance of the article on the Internet meant that researchers read the article without the accompanying commentaries and replies that I had planned to publish with it.In some fields such as economics, it is standard practice to widely disseminate articles before they are published, whereas in much of psychology this has been discouraged. An argument in favor of dissemination is that it speeds scientific communication in a fast-paced world where journal publication is often woefully slow. An argument against dissemination of articles before publication is that readers do not have the opportunity to simultaneously see commentary and replies. ... In the Internet age, the issue of prepublication distribution becomes all the more important because an article can reach thousands of readers in a few hours. Given the ability of the Internet to communicate so broadly and quickly, we need greater discussion of this issue.In reply, I wrote:Bloggers have discussed this specific issue months ago. For example, as noted in Mind Hacks,The paper was accepted by a peer-reviewed journal before it was released to the public. The idea that something actually has to appear in print before anyone is allowed to discuss it seems to be a little outdated (in fact, was this ever the case?).And The Neurocritic opined that...[The aggrieved authors] are not keeping up with the way that scientific discourse is evolving. Citing "in press" articles in the normal academic channels is a frequent event; why should bloggers, some of whom are read more widely than the authors' original papers, refrain from such a practice? Is it the "read more widely" part?-from The paper formerly known as "Voodoo Correlations in Social Neuroscience", by The NeurocriticDiener originally solicited six commentaries on the Vul et al. paper for the May 2009 issue of the journal. Ironically, authors on two of the papers have serious blogs:Statistical Modeling, Causal Inference, and Social Science is a blog written by Andrew Gelman, a Professor of Statistics and Political Science at Columbia. He was one of the first to blog about the paper in Suspiciously high correlations in brain imaging studies, with a more detailed post a month later (More on the so-called voodoo correlations in neuroscience). Lindquist and Gelman (2009) applauded the discussion engendered by "pre-publication dissemination":Their article has in a short time given rise to a spirited debate about key statistical issues at the heart of most functional neuroimaging studies. The debate provides a useful opportunity to discuss core statistical issues in neuroimaging and ultimately provides a chance for the field to grow and move forward.  is the blog kept by Tal Yarkoni, a Post-Doc at the University of Colorado Boulder. He happens to be an expert in statistics for fMRI analysis, and another one of the authors invited to submit a paper for the Vul, Harris, Winkielman, and Pashler festschrift/verdammung (Yarkoni, 2009):In this article, I argue that Vul et al.'s primary conclusion is correct, but for different reasons than they suggest. I demonstrate that the primary cause of grossly inflated correlations in whole-brain fMRI analyses is not nonindependence, but the pernicious combination of small sample sizes and stringent alpha-correction levels. Far from defusing Vul et al.'s conclusions, the simulations presented suggest that the level of inflation may be even worse than Vul et al.'s empirical analysis would suggest. His blog started in October 2009, after the commentaries were published.The Appeal of the Brain in the Popular PressThat brings us back to the article by Diane Beck, an Assistant Professor in Psychology and Cognitive Neuroscience at the University of Illinois Urbana-Champaign. She examines the distorted media coverage of neuroimaging studies, and possible reasons for it (Beck, 2010):Since the advent of human neuroimaging, and of ... fMRI in particular, the popular press has shown an increasing interest in brain-related findings. In this article, I explore possible reasons behind this interest, including recent data suggesting that people find brain images and neuroscience language more convincing than results that make no reference to the brain (McCabe & Castel, 2008; Weisberg, Keil, Goodstein, Rawson, & Gray, 2008). I suggest that part of the allure of these data are the deceptively simply messages they afford, as well as general, but sometimes misguided, confidence in biological data. In addition to cataloging some misunderstandings by the press and public, I highlight the responsibilities of the research scientist in carefully conveying their work to the general public. While reading through the examples of poor media coverage, imagine the shock of recognition if you were to realize that you have written several trenchant blog posts criticizing these very articles. Yet all this work (and the writings of many others) is rendered invisible to the mainstream of the Association for Psychological Science.Why is blogging so non-existent in these circles? There's a large thriving community of science blogs. Go to ResearchBlogging.org and look under ... Read more »
Neurokitchen Design is the latest fad among the rich and famous, according to a poorly researched article in the Wall Street Journal:A Kitchen to Comfort Your SoulCombining psychology and neuroscience, Johnny Grey is an interior designer with a special recipeBy TARA LOADER WILKINSON'You can tell a lot about a person from their kitchen," says Johnny Grey, an award-winning interior designer specializing in "happy kitchens," a design philosophy that focuses on bringing emotional, physical and psychological well-being into kitchen planning.. . .Mr. Grey ... takes an unusual approach to interior design. He and his team spend up to 80 hours with clients, understanding what makes them tick, often going round for dinner and even staying over at their home. His aim? To create a domestic utopia tailored to their personality, using the principles of neuroscience, or the scientific study of the nervous system, to answer their emotional needs and subliminal desires, as well as building a seamlessly practical kitchen. It appears to work.However, Mr. Grey does not have an EEG lab to record the brain waves of his clients, as depicted in the image above. Nor does he have access to an MRI scanner, to my knowledge. For Mr. Grey to actually use the principles of neuroscience to design customized kitchens for his clients, he would need a method that records brain activity, whether it's electrical (EEG) or hemodynamic (fMRI).Is Neurokitchen Design the latest manifestation of explanatory neurophilia (Trout, 2008)?Credibility is a cherished currency in science, but its cues can be counterfeit. A novel series of experiments by Weisberg and her colleagues  show that non-expert consumers of behavioral explanations assign greater standing to explanations that contain neuroscientific details, even if these details provide no additional explanatory value. Here, we discuss the part that this ‘placebic’ information might play in producing a potentially misleading sense of intellectual fluency and, consequently, an unreliable sense of understanding.Even though it's likely that Grey's [pseudo]neuroscientific analysis provides no additional explanatory value, clients will pay more for a "scientifically designed" kitchen.A kitchen is a place where you prepare and clean upBut it's so more than that now..."A kitchen is no longer just for cooking. Often, the only time a couple will spend together awake, is in the kitchen," says the British architect [Grey], whose clients include Apple co-founder Steve Jobs, British singer Sting and millionaire publisher Felix Dennis.Isn't that nice! But as far as I can tell, the WSJ gets a number of details wrong in this paragraph, which nonetheless has the best quote of all:John Ziesel [Zeisel], a San Diego-based neuroscientist [sociologist] at the Salk Institute [I could find no listing for him there], meanwhile, is researching what he refers to as measurement-based design, which shows how spaces can shape our behavior. He uses everything from hormone studies, brain scans and targeted psychological experiments to foster his research. "A kitchen is a space loaded with emotional and behavioral cues," he says. "Neuroscience can help us understand what goes on behind the shiny surfaces and layout of kitchen cabinetry."Although they might seem to make strange bedfellows, the idea that neuroscience research can inform building design is not new. The Academy of Neuroscience for Architecture (ANFA) was founded in 2003.The Salk Institute in La Jolla, California, that architectural monument to science overlooking the Pacific Ocean, is indeed a focal point for ANFA. Jonas Salk himself enlisted architect Louis Kahn to design a research campus with lab space that would promote collaboration and creativity. The AFNA Board of Directors includes an impressive list of neuroscientists: Tom Albright, Michael Arbib, and Fred Gage to name but a few. Salk scientists Gage, Albright, and Terrence Sejnowski were on the original Advisory Board in 2003.In April 2004 the Dana Foundation presented a manifesto of sorts from ANFA founding president John P. Eberhard and freelance writer Brenda Patoine:Architecture with the Brain in MindA soaring cathedral, a brightly lit classroom, a dim maze of hospital corridors: Most of us associate certain emotions, energy levels, and even mental states with the various spaces in which we spend our lives. What underlies these responses? How important are they? Architects and neuroscientists now beginning to grapple with those questions are coming up with discoveries that have important implications for how we design spaces as diverse as neonatal care units, schools, and residences for people with Alzheimer’s disease. The beneﬁts of collaboration between brain science and architecture are sure to increase, writes architect John Eberhard, founding president of the new Academy of Neuroscience for Architecture. Some research even suggests that certain designed environments encourage the proliferation of new brain cells.Five years later, the Institution of Engineering and Technology was more circumspect in its analysis of the trend:Architecture and neuroscienceEmpirical evidence demonstrating how buildings affect the function and structure of our brains is still thin on the ground. Fred Gage, a neuroscientist at the Salk Institute in La Jolla, California, says that, while architects have plenty of intuitions, the key will be to construct experiments to test the influence of the spatial environment on the brain. Despite the founding of the Academy of Neuroscience for Architecture (ANFA) in San Diego in 2003 - of which Gage is a director and past-president - “we have not yet accomplished as much as we aspired to,” he says. However, neuroscience has taught us much about how our brains construct our sense of place and how certain environments might stimulate the growth of new neurons.Fortunately, the Architects for Functional Neurogenesis special interest group seems to have escaped unscathed.NEXT UP: How hippocampal place cells have influenced Frank Gehry.Reference... Read more »
Trout, J. (2008) Seduction without cause: uncovering explanatory neurophilia. Trends in Cognitive Sciences, 12(8), 281-282. DOI: 10.1016/j.tics.2008.05.004
Fig 1A (modified from Blauwblomme et al., 2010). Top: coronal and lateral representation of the stereotaxic implantation scheme. Bottom: reflex seizure showing ictal onset in the right insula and secondary spreading in the hippocampus.Reflex epilepsy is a rare neurological condition in which seizures are triggered by a specific type of sensory input (Xue & Ritaccio, 2006). The most common reflex seizures are induced by light, but other reported triggers have included reading, Mah-Jong, music, the voice of a specific television performer,1 bathing, orgasm, and eating.The present case involved a 28 year old woman who had refractory partial seizures triggered by eating, which were preceded by an unpleasant taste in her mouth. Strawberry syrup ingestion was noted to be the easiest way to induce seizures. Nine years earlier, she had surgery to remove a vascular malformation from the right frontal operculum/insular cortex. This region contains gustatory cortex encoding for taste. Because of the uncontrolled nature of her seizures, the surgical team implanted intracranial electrodes to determine the focus of abnormal EEG activity.Two reflex seizures to strawberry syrup intake were recorded, which started with loss of consciousness, followed by facial flushing, oro-alimentary automatisms, repeated swallowing and sialorrhoea [excessive salivation], and ended with postictal confusion and amnesia. From a visual analysis of SEEG (Fig. 1A), seizures began in the anterior inferior portion of the insula with a high-amplitude spike followed by a low-voltage high-frequency discharge with secondary spreading to the hippocampus and then to the temporal neocortex. In the early ictal state, fast gamma band activity (30-120 Hz) showed increased power in the anterior inferior portion of the insula, accompanied by decreased power in the hippocampus.Functional MRI was also performed during strawberry syrup intake to map gustatory cortex, and another session recorded simultaneous resting state fMRI/EEG activity.Fig. 1C (modified from Blauwblomme et al., 2010). Overlay of fMRI and SEEG results. Left: crosshairs on the dorsolateral fronto-parietal region. Right: crosshairs on the anterior insula. The authors reported three major findings from the fMRI/EEG mapping (see Fig 1C): The dorsolateral anterior parietal cortex showed pre-ictal γ [gamma] power decrease (red) and belonged to the fMRI gustatory network (yellow). In the vicinity, the dorsolateral posterior frontal cortex showed preictal γ power increase (magenta) and interictal fMRI/EEG activations (green). Early ictal γ power increase (cyan) showed up in the inferior/middle part of the anterior insula, which also responded to taste fMRI (yellow). A preictal increase in γ power (magenta) was observed in the upper part of the anterior insula. Hippocampus showed early ictal decrease in γ activity (blue).The surgical team identified the specific region of the insula that was the problematic seizure focus (the middle short gyrus), and removed it. Two years later, the patient remains seizure-free, and presumably can enjoy strawberry syrup once again.Footnote1 The identity of said performer was revealed to be Mary Hart, host of Entertainment Tonight. From Science News (Vol. 140, No. 3, p. 45):...the woman had seizures only while watching "Entertainment Tonight."Systematic testing ruled out all but one of the cast members -- cohost Mary Hart, whose voice pattern consistently caused the seizures. [Dr. Venkat] Ramani prescribed anticonvulsant drugs and advised the patient not to watch the program. In the two years since, she has remained "relatively seizure free," he reports.ReferencesBlauwblomme, T., Kahane, P., Minotti, L., Grouiller, F., Krainik, A., Vercueil, L., Chabardes, S., Hoffmann, D., & David, O. (2010). Multimodal imaging reveals the role of γ activity in eating-reflex seizures. Journal of Neurology, Neurosurgery & Psychiatry DOI: 10.1136/jnnp.2010.212696Xue LY, Ritaccio AL. (2006). Reflex seizures and reflex epilepsy. Am J Electroneurodiagnostic Technol. 46:39-48.The Jam Lady
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Blauwblomme, T., Kahane, P., Minotti, L., Grouiller, F., Krainik, A., Vercueil, L., Chabardes, S., Hoffmann, D., & David, O. (2010) Multimodal imaging reveals the role of activity in eating-reflex seizures. Journal of Neurology, Neurosurgery . DOI: 10.1136/jnnp.2010.212696
With your hosts, V.S. Ramachandran and and E.L. Seckel (2010) of VH1's The Surreal Life: Medical Hypotheses....We proposed and provided the first experimental evidence for a dysfunctional MNS [mirror neuron system] in ASD [autism spectrum disorders] (Altschuler et al., 1997). ... Nonetheless evidence at this point is “compelling but not conclusive”.On the assumption that the MNS is not completely missing but “dormant”, could they be revived? We propose having the children look into a room with multiple mirrors at various angles to provide multiple allocentric views of themselves. Three neurotypical volunteers would stand inside the room and dance to a rhythm while the child dances in synchrony with them. This is different from conventional dance therapy in ASD in that our treatment specifically emphasizes synchronous dance movements mimicking others (as well as the simultaneous presence of multiple mirror refections) in order to optimally stimulate any residual MNS. Given the existence of tactile – sensory mirror neurons that fire when you merely watch someone else being touched, one could also deliver varying patterns of touch as the child watches. The use of multiple reflections makes it unavoidable that the child has to see itself [sic] stimulated. One may need to start with simple rhythms and progressively graduate to more complex ones incorporating more elaborate gestures. The subjects could be tested for lasting improvement in behavioral scores which might spill over into more useful domains such as social interactions.MTV is planning to air its own version of this hot new treatment modality, Mirror Neuron Live.ReferencesAltschuler EL, Vankov A, Wang V, Ramachandran VS, Pineda JA. Person See, Person Do: human cortical electrophysiological correlates of monkey see monkey do cells. In: Poster session presented at the 27th annual meeting of the society for neuroscience. LA: New Orleans; 1997.Ramachandran, V., & Seckel, E. (2010). Synchronized dance therapy to stimulate mirror neurons in autism Medical Hypotheses DOI: 10.1016/j.mehy.2010.10.047VS Ramachandran's Modest Proposal: The neurons that shaped civilization.
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Ramachandran, V., & Seckel, E. (2010) Synchronized dance therapy to stimulate mirror neurons in autism. Medical Hypotheses. DOI: 10.1016/j.mehy.2010.10.047
Most everything you've read about the Doctors Prescribing 'Tetris Therapy' study is wrong. That ridiculous headline, courtesy of "fair and balanced" Fox News, is the most egregious lie I could find [if you have other favorites, please leave links in the comments]. Press stories frequently distort research findings, but sometimes the authors themselves shoulder the most blame (Holmes et al., 2010). Misuse of the words "trauma" "flashback" "cognitive vaccine" and "PTSD" are at fault here.The experiment in question is interesting as a memory study. It demonstrated that playing a visuospatial video game (Tetris) 30 min after a disturbing film can lessen intrusive visual memories, but playing a verbal trivia game (Pub Quiz) can have the opposite effect (Holmes et al., 2010). According to Baddeley (1992), this occurs because of two modality-specific working memory systems: the visuospatial sketchpad for visual working memory and the phonological loop for verbal working memory. Tetris interferes with the former, while Pub Quiz interferes with the latter.Sixty participants (18–60 yrs old; mean age=27 yrs; 30 females) took part in Experiment 1. They were carefully screened for trauma history, mood, trait anxiety and depression. Potential subjects were excluded if they had ever been treated for mental illness of any kind. So this is a group of healthy controls -- not depressed, not anxious, minimal exposure to trauma, and no PTSD. They were a happy bunch, with mean scores on the Beck Depression Inventory (BDI) of 5.7-6.2.1The participants were divided into three groups for the different treatment conditions, illustrated below.Figure 1 (from Holmes et al., 2010). Experiment 1 study design overview. Participants completed the trauma film paradigm, a well established experimental analog for PTSD. All participants viewed a traumatic film followed by a 30-min structured break. Participants were then allocated to one of three experimental conditions [Tetris vs. no-task control vs. Pub Quiz] which they completed for 10 min. Afterwards participants in the computer game conditions rated their enjoyment of the game. Flashbacks (involuntary memories) were monitored for 1 week using an intrusion diary. After 1 week, diary compliance was checked and a test of voluntary memory (recognition memory test) for the trauma film was administered.What is the "trauma film paradigm"?The 21-min film [previously used in 22] contained 15 clips of traumatic content including fatal road traffic accidents and graphic scenes of human surgery. Following that link leads you to this description (and a series of other studies):Participants were shown a 13 min film of real-life footage of the aftermath of road traffic accidents (compiled by Steil, 1996). This film has been used extensively in studies using the trauma film paradigm (e.g. Brewin and Saunders, 2001, Hagenaars et al., 2008, Halligan et al., 2002, Holmes et al., 2004, Holmes et al., 2006, Holmes and Steel, 2004 and Stuart et al., 2006). It consists of five separate scenes each introduced by a short commentary providing context for the scene.To begin with, actual trauma isn't forewarned or contextualized in advance. It's surprising and shocking. Granted, ethical considerations require informing the participants at the time of recruitment, but this imposes even more limits as a model of real trauma.Going back to the string of references, the first citation (Steil, 1996) indicates the author studied "Posttraumatic intrusions after road traffic accidents" (not merely watching a road traffic accident film). Nonetheless, let's quickly review some of the other papers, with an eye on the terminology used by the respective authors. Brewin and Saunders (2001) looked at "intrusive memories for a stressful film". Hagenaars et al. (2008) reported on "the development of intrusions after an aversive film". In 2004, Holmes et al. studied "intrusive memory development". Notice that "traumatic" and "flashbacks" aren't yet part of the lexicon. As time went on, Holmes et al., 2006 called it a "traumatic film" but hadn't yet transformed "intrusive memories" into "flashbacks". The language used to describe the experimental phenomena shapes the reader's willingness to view the film paradigm as a proxy for real trauma.What is a true flashback? Here's the relevant section of the DSM-IV Criteria for Posttraumatic Stress Disorder, which describes a flashback episode as a complex, multi-sensory experience and not just a visual memory:(3) acting or feeling as if the traumatic event were recurring (includes a sense of reliving the experience, illusions, hallucinations, and dissociative flashback episodes, including those that occur upon awakening or when intoxicated). Another element of these experimental designs can include ratings of how upset the participants were while viewing the gory film (Holmes et al., 2004):Participants rated their distress associated with viewing the film after it had ended. They also rated their level of depression, anger, happiness, and anxiety both pre- and postfilm. Eleven-point scales were used, with anchors of 0 (not at all) and 10 (extremely).In that study, ratings were 5.1 for a "no task" condition that did not involve a secondary task while watching the video. So these participants were not especially distressed. Furthermore, this unvalidated self-rating scale has no clinical relevance to PTSD. Eleven-point scales were also used to rate [non-clinical] levels of depression, anger, happiness, and anxiety both pre- and postfilm.Finally, to illustrate that the "trauma film paradigm" bears no relation to the lasting effects of real trauma that can cause PTSD is this ethical clarification (Holmes et al., 2004):With respect to the ethical issues of showing a film with traumatic content, ... Read more »
Holmes, E., James, E., Kilford, E., & Deeprose, C. (2010) Key Steps in Developing a Cognitive Vaccine against Traumatic Flashbacks: Visuospatial Tetris versus Verbal Pub Quiz. PLoS ONE, 5(11). DOI: 10.1371/journal.pone.0013706
"The more a delusion is investigated, the more understandable and less bizarre it becomes, often interwoven with the very individual patterns of experiencing relationships, adversities and suffering, and finally, for every delusional content, as bizarre and remote as it may appear, there may be a cultural niche, in which the same content may be considered legitimate and reasonable."-Pfeifer (1999), Demonic Attributions in Nondelusional Disorders.What is psychopathology? According to Wikipedia,Psychopathology is the study of mental illness, mental distress and abnormal, maladaptive behavior. The term is most commonly used within psychiatry where pathology refers to disease processes. Abnormal psychology is a similar term used more frequently in the non-medical field of psychology.But what is "abnormal, maladaptive behavior"? That's such an enormously complicated question that I wouldn't know where to begin. In fact, as a non-clinician I think it would be rather pompous of me to try and define the parameters of what is (and is not) pathological. For that I refer the reader to the ICD-10 or the Diagnostic and Statistical Manual of Mental Disorders (DSM), both voluminous (and imperfect) attempts to diagnose mental illness based on signs and symptoms. As most of you know, the DSM-IV is currently in the process of being revised. The DSM-5 will be the controversial new revision, with a (delayed) publication date of May 2013.The National Institute of Mental Health (NIMH) in the U.S. is starting to take a different approach to the classification of psychiatric disorders, one that incorporates dimensions of observable behavior as well as neurobiological measures. The aim of the Research Domain Criteria (RDoC) project......is to define basic dimensions of functioning (such as fear circuitry or working memory) to be studied across multiple levels of analysis, from genes to neural circuits to behaviors, cutting across disorders as traditionally defined. The RDoC draft outlines some problems with the present DSM approach:However, in antedating contemporary neuroscience research, the current diagnostic system is not informed by recent breakthroughs in genetics and molecular, cellular and systems neuroscience. Indeed, it would have been surprising if the clusters of complex behaviors identified clinically were to map on a one-to-one basis onto specific genes or neurobiological systems. As it turns out, most genetic findings and neural circuit maps appear either to link to many different currently recognized syndromes or to distinct subgroups within syndromes. If we assume that the clinical syndromes based on subjective symptoms are unique and unitary disorders, we undercut the power of biology to identify illnesses linked to pathophysiology and we limit the development of more specific treatments. ... To date, there has been general consensus that the science is not yet well enough developed to permit neuroscience-based classification. However, at some point, it is necessary to instantiate such approaches if the field is ever to reach the point where advances in genomics, pathophysiology, and behavioral science can inform diagnosis in a meaningful way.There is no absolute timeline of when these advances might occur. Instead of providing an immediate replacement for DSM and its clinical diagnoses, RDoC is a long-term project to help the research community by defining more biologically based organizational principles for various psychopathologies:RDoC will follow three guiding principles, all diverging from current diagnostic approaches. First, RDoC is conceived as a dimensional system (reflecting, e.g., circuit-level measurements, behavioral activity, etc.) spanning the range from normal to abnormal. ... Second, RDoC is agnostic about current disorder categories. The intent is to generate classifications stemming from basic behavioral neuroscience. Rather than starting with an illness definition and seeking its neurobiological underpinnings, RDoC begins with current understandings of behavior-brain relationships and links them to clinical phenomena. Third, RDoC will use several different levels of analysis in defining constructs for study (e.g., imaging, physiological activity, behavior, and self-reports of symptoms).What are the biological mechanisms driving abnormalities in the observed behaviors ("constructs") of e.g. fearfulness, reward sensitivity, attention, and self-representation? As shown in the matrix below, five major domains have been proposed to group the behavioral constructs, which can be evaluated at six levels of analysis.The basic idea is that these domains and constructs can go awry in any number of disorders. For instance, if you type "altered reward processing" into PubMed, among the 80 entries are studies in pediatric bipolar disorder, drug addiction, autism, schizophrenia, obesity, pathological gambling, mania, ADHD, and antisocial personality disorder. What are the neural correlates of altered reward processing? Is there a common mechanism across the various diagnostic categories listed above? Are many of the genes that predispose one to altered reward processing shared across disorders?Another problem that RDoC aims to address is extensive co-morbidity in many of the current diagnostic categories. A prime example is the complex construct of borderline personality disorder (BPD), marked by affective instability, unstable interpersonal relationships, and self-destructive behavior. NIMH notes that about 85 percent of people with BPD also meet the diagnostic criteria for another disorder, including:61 percent also have at least one anxiety disorder, most commonly a specific phobia, or social phobia49 percent have an impulse-control disorder, most commonly intermittent explosive disorder38 percent have a substance abuse or dependence disorder, most commonly alcohol abuse or dependence34 percent have a mood disorder, most commonly dysthymia (mild, chronic depression), or major depression.Here, one can view the diagnostic category of BPD as a collection of symptoms (or disorders) that can vary across individuals. The same can be said of schizophrenia. How do alterations in the underlying biological mechanisms drive various manifestations of mental disorders (Sanislow et al., 2010)?...any given disorder can be marked by disruptions among multiple mechanisms, and one particular mechanism may contribute to the psychopathology of a large number of disorders. Thus, the same mechanisms can be implicated in “different” disorders, whereas multiple mechanisms can be implicated in “one” disorder.Is Big Pharma abandoning psychiatry? (see Mind Hacks)The leaders of NIMH have expressed the opinion that the DSM and ICD have hindered the development of new treatments (Insel et al., 2010). Given the limited effectiveness of many pharmaceutical interventions, it is patently obvious that a new approa... Read more »
Sanislow CA, Pine DS, Quinn KJ, Kozak MJ, Garvey MA, Heinssen RK, Wang PS, & Cuthbert BN. (2010) Developing constructs for psychopathology research: Research domain criteria. Journal of abnormal psychology. PMID: 20939653
Celebrity SPECT scan from rehab patientCelebrity Rehab is an American TV reality show on VH1 that exploits the addictions of the rich and C- or D-List famous.“I thought REAL doctors talked to patients in offices behind closed doors.”-Lindsay Lohan [who reportedly turned down six figures to appear 0n the show]Privacy? Confidentiality? Those rights don't apply to the alcoholic and drug-addicted characters who appear on television and other public media outlets as a form of entertainment. How many of you professional psychology and mental health and cog neuro and pharmaceutical types have taken training courses such as the CITI Course in The Protection of Human Research Subjects? All of you?Medical Ethics do not apply to Dr. Drew, the star and chief physician of the Celebrity Addiction franchise:In 2009 [Dr. Drew] Pinsky drew criticism from experts for publicly offering professional opinions of celebrities he has never met or personally examined, based on media accounts, and has also drawn the ire of some of those celebrities.In contradistinction, proper clinicians who make media appearances take great pains to avoid such unethical outbursts. As explained by Dr Petra Boynton:They tried to make me talk about rehab but I said ‘no, no, no’Yesterday I had over 25 emails and phone messages from journalists wanting me to comment on the mental state of several celebrities currently in the press with various drug/relationships problems. And I’ve said no to all of them.At the risk of sounding like a broken record here’s why psychologists (and other experts working with the media) can’t talk about celebrities.If we know the celeb in person (for example as their therapist or healthcare provider) we are breaking their confidence if we speak about them in public. If we do not know them personally we’re simply speculating about them if we were to comment.The same applies to case studies based on people who are not famous.In Season 3 Episode #6, ('Triggers') Dr. Drew takes former NBA star Dennis Rodman to see our favorite neurohuckster, Dr. Daniel G. Amen, for a SPECT scan. Amen claims he can diagnose all sorts of psychiatric and neurological ailments using SPECT (single photon emission computed tomography)1 procedures performed at his clinics.Drew Pinsky exacerbates the unprofessional circus-like atmosphere by making all sorts of unfounded dire predictions about the state of Rodman's brain.Dr. Drew voiceover: It's day 13, and despite nearly 2 weeks of intense treatment, Dennis has rigidly refused to identify as an alcoholic. It's clear to me there's much more going on here. Probably on an organic basis, both in terms of his personality functioning and possibly damage caused by the alcohol itself. I've arranged for Dennis to receive a brain scan to show him objective evidence of what I suspect is going on.Van arrives at the Amen Clinics in Newport Beach, CA and Rodman is placed in the scanner.Cue colorful images of Mr. Rodman's brain appearing on the monitor. All very scientific. Then Dr. Drew introduces him to Dr. Amen.Amen: "So, we did a study called SPECT that looks at how your brain works. And what we see on your scan here, there's some evidence of alcohol damage. When we see this bumpy appearance, I don't like that. I would worry that you could get something like Alzheimer's disease if you don't do a better job of taking care of your brain. Alcoholic dementia is the second most common cause of dementia in the country. The exciting thing is it can be better but without taking good care of it this is going to deteriorate and get worse."Rodman: "Uh... it doesn't matter. All right." (Gets up and leaves).Amen made some rather outrageous statements here. Even though he used the qualifying words something like, there is absolutely no evidence that alcoholism causes the amyloid plaques and neurofibrillary tangles of Alzheimer's disease. In fact, the pathologies are produced by entirely different mechanisms (Aho et al., 2009):In the present study, no statistically significant influence was observed for alcohol consumption on the extent of neuropathological lesions encountered in the three most common degenerative disorders. Our results indicate that alcohol-related dementia differs from VCI [vascular cognitive impairment], AD [Alzheimer's disease], and DLB [dementia with Lewy bodies]; i.e., it has a different etiology and pathogenesis.One meta-analysis even found that heavy drinkers did not have an increased risk of dementia of any kind,2 and regular drinkers had a reduced risk (Anstey et al., 2009).Then brain imaging non-expert Dr. Drew narrates...Dr. Drew voiceover: Dennis's scans were quite dramatic. In addition to there being an unusual pattern of temporal lobe dysfunction, which confirms my feelings about his personality, he also clearly has damage from alcohol.Dr. Drew (to Amen): "It makes me sad thinking about it... if he doesn't change."I see...Where in the temporal lobe did Dr. Drew find the confirmatory evidence of personality disorder? Anterior temporal lobes (semantic memory)? Posterior/inferior temporal regions, such as the fusiform gyrus (high-level vision)? Superior temporal plane (audition)? Region of the left posterior superior temporal gyrus (Wernicke's area for language comprehension)? Area MT/V5 (perception of motion)? The medial temporal lobe memory system? The amygdala and other portions of the limbic system? Yeah, maybe that, but Amen's "bumpy appearance" was located in ventral visual areas.... Read more »
Adinoff, B., & Devous, M. (2010) Scientifically Unfounded Claims in Diagnosing and Treating Patients. American Journal of Psychiatry, 167(5), 598-598. DOI: 10.1176/appi.ajp.2010.10020157
Charles Hamilton Hughes (1839-1916) was the founder and editor of The Alienist and Neurologist. The journal was published from 1880 until his death in 1916, making him the sole editor for all 37 volumes. Remittances for subscriptions ($5 for four issues per year) and "articles or photographs from subscribers or friends and material acceptable for publication" were sent to his address in St. Louis.What is an alienist?An "alienist" is "one who treats mental diseases; a mental pathologist; a 'mad doctor'," according to The Oxford English Dictionary. The OED also defines "alienation" as in this sense as "mental alienation; withdrawal, loss, or derangement of mental faculties; insanity." The insane were thought estranged (alienated) from their normal faculties. The root of "alienist" is the Latin "alienare," to make strange. The word "alienist" came across the Channel to England from France where "aliene" meant insane and an "alieniste" was one who cared for the mentally ill: a psychiatrist.What were Hughes's contributions to neurology and psychiatry? Notable excerpts from his obituary:By the Death of the Founder of the Alienist and Neurologist one of the great pupils of the famed American School of Psychiatry of Rush, Stedman, Brigham, Gait and Ray has passed away. He had imbibed to the full the critical, judicial, radical, yet logically conservative, spirit of this school.. . .In 1880 he founded the Alienist and Neurologist, which soon assumed and kept a prominent position among medical journals. From the beginning it was recognized as of authority by the British Journal of Mental Science, the French Annales Medicopsychologiques, the Berlin Allgemeine Zeitschrift fur Psychiatric, [etc.]. Contributions to the Alienist and Neurologist were therefore widely quoted in Europe, even in circles hostile to America.The personal contributions of Dr. Hughes to psychiatry and neurology were varied, valuable and original. His discovery of the virile reflex1 was widely cited...However, an obituary in the Journal of Nervous and Mental Disease was less flattering:...He early maintained an interest in neurology in what was hardly more than a frontier trading post and where the existence of neurology was hardly dreamed of according of the canons of to-day. It was then a crude product but it was sincere and as he upheld it, it was a light in the wilderness. As St. Louis grew and began to feel itself this early lamp shone less brightly in contrast, but Dr. Hughes, although he may not have kept in touch with the latest advances, still maintained a vital interest and enthusiasm....He became widely known through the Alienist and Neurologist, which he founded in 1880 and which he made the medium for an open discussion of neurological and psychiatrical problems. It was received among European publications, though it never definitely stood for vigorous research and the vigorous pushing forward into, progressive lines which marks the neurology of to-day.Mental AlienationIn The Neurocritic's previous post on Arithmomania, Hughes was credited with an article on "Autopsychorhythmia," or repetition psycho-neurosis (Hughes, 1901). He was clear to distinguish this phenomenon from the related conditions of echolalia (automatic repetition of another's speech) and coprolalia (involuntary uttering of obscenities, which is seen in only 10% of patients with Tourette's syndrome).The constant repetition of a rhythmical movement in the mind, regardless of time or place or circumstance, and which an enfeebled volition cannot regulate to conform to the requirements of environment, characterises this symptom of brain overstrain and psycho-motor automatic impulse. Neuropathic and consequent psycho-motor neurasthenia appear to be at the bottom of this condition...There's an element of "nervous breakdown" and mental exhaustion in some of the case reports, particularly in the patients who made good recoveries. For instance,A gentleman of extensive business affairs who came to me on the verge of financial and business bankruptcy, but who is now after many years of health successful in a new but less harassing line of business, would continuously say to himself : "Too many irons in the fire, too many irons in the fire." His intellect was clear but his brain was jaded and unstable-in that stage of cerebrasthenia that so often precedes the final brain-break of insanity. The closing out and winding up of his business saved him for recuperation and another and less harassing and more successful career. Conversely, other patients remained mired in insanity:I have heard a chronic alcoholic repeat over and over through the day, "Little Bo-Peep, he lost his sheep, and doesn’t know where to find them," etc., and have known chronic lunatics who would repeat some long-ago-learned distich or rhyme or some insanely-constructed jingle of words in maudlin monotone, from the day’s beginning to the ending thereof, in all their waking hours, some of them ringing their peculiar song, like the dying swan, to the end of their unfortunate lives.He considered autopsychorhythmia to be a brain disease, which seems obvious to us today, but he apparently needed to distinguish the centrally located pathology from peripheral motor abnormalies:The pathological lesion of autopsychorhythmia is evidently in the mind area of the brain cortex.2 It is truly transcortical and not localised exclusively in the speech area. It is a psychical and not purely psychomotor involvement-a psychical lesion shown in peculiarity of psychomotor expression.Were there any treatments for such a malady? An 18 year old music student, a handsome and bright young lady, was prescribed a regimen of "rest, change of environment, cessation of study and piano practice, withdrawal from musical companionship, brain-tranquillising galvanisations, ether-menthol evaporating lotions to the head, chemical brain restraint, and pepsines and laxatives." Another charming young lady received "six weeks’ treatment with bromide of potassium, timely hypnotics, tonics, aloetic laxatives and gelsemium."Oh, by the way, The Alienist and Neurologist accepted advertising...Footnotes1 From Hughes (1891):In a previous communication on this subject (vide Alienist and Neurologist for January, 1891), I have called attention to the fact that in a perfectly healthy individual, whose spinal cord is entirely normal, especially in its genitospinal center, placed supine on a couch without headrest, nude about the loins, the sheath of the penis made tense by clasping the foreskin with the left index finger and thumb at about the place ... Read more »
HUGHES, C. (1901) AUTOPSYCHORHYTHMIA OR REPETITION PSYCHO-NEUROSIS. MORBID RHYTHMIC FORMS OF AUTOMATICITY AND RHYTHMIC FORMS OF MENTAL ALIENATION. The Lancet, 157(4051), 1124-1126. DOI: 10.1016/S0140-6736(01)89412-5
Benjamin Evett, John Douglas Thompson, and Mirjana Jokovic in the American Repertory Theatre's production of Othello.O! beware, my lord, of jealousy;It is the green-ey'd monster which doth mockThe meat it feeds on. Iago, Act III scene iii of Shakespeare's OthelloOthello syndrome is a rare psychiatric condition marked by morbid, pathological, or delusional jealousy (Miller et al., 2010). It can occur in the context of schizophrenia, bipolar disorder, alcoholism, or epilepsy, but sometimes it's observed in relative isolation from other delusions (Todd & Dewhurst, 1955). As in the Shakespearean tragedy, the modern day patient with Othello syndrome presents with the potential for violence against his spouse and/or self because of the imagined infidelities.A recent article by Miller and colleagues (2010) provides a helpful overview of this delusional disorder for nurses and other clinicians. They consider treatment options (antipsychotics for those with psychosis, dialectical behavioral therapy for those without), safety issues, nursing care, and best practices. Although cases from the recent literature were reviewed, a classic article from over 50 yrs ago (Todd & Dewhurst, 1955) is a more entertaining treasure trove of paranoid sexual jealousy. Excerpts from several cases are presented below.Case 2: A married man, 43 years old, was first admitted to a mental hospital in June 1951. He complained of feeling "tensed up" as a result of the belief that his wife was unfaithful to him. Careful enquiries showed that there was not a scrap of evidence to support his suspicions, which began when a workmate allegedly asked him whether he had ever suspected his wife of having an affair with another man. His suspicions increased considerably when one day she failed to give what he deemed to be a satisfactory explanation for the origin of a smart pair of bootees in her possession. ... Once, he attempted to strangle his wife but was stopped in the nick of time by the intervention of neighbors. Another time, he rushed scantily clad from the house in a fruitless attempt to catch his wife with a paramour.Although the patient was not deemed to be a chronic alcoholic, his jealousy was closely related to bouts of drinking. His identical twin brother suffered from grand mal epilepsy and committed suicide. The patient's own EEG showed epileptiform discharges, but he never had an overt seizure.Diagnosis: epilepsy with delusions of infidelity.Case 3: A married man, 49 years old, was first admitted to a mental hospital in July 1952. He complained of chronic anxiety arising from a belief that his wife was "carrying on" with a number of men. ... At times, his behavior had been distinctly bizarre. One day, which searching her handbag for "evidence", he had chanced upon a discarded pair of knickers which she had pressed into service as a duster. He insisted that the dilapidated and soiled condition of the garment proved beyond doubt that she had been her employer's mistress. He had, on several occasions, attempted to strangle his wife as a result of his delusions.Diagnosis: paranoid schizophrenia with delusions of infidelity.Case 7: A married man, 39 years old, was admitted to a mental hospital in May 1951, as the direct result of disorderly behavior arising from delusions concerning his wife's fidelity. During the previous year, he had rendered his wife (a virtuous woman) miserable by repeatedly accusing her of infidelity on an enormous scale. He would use field glasses to spy on her from afar, and, after pretending to leave the house, he was wont to re-enter surreptitiously in an attempt to trap her with a lover. ... He threatened several men in the neighborhood with violence because he suspected them of a liaison with his wife, and developed a sinister habit of going abroad with an open razor in his pocket.He also had the charming practice of expressing remorse that he couldn't keep his wife perpetually pregnant, he threatened her with violence, and once even grabbed her by the throat. This bad behavior ran in the family. His brothers were drunk, impotent, jealous, and "unfit to be trusted with a dog, never mind a woman." His father was:a drunkard and libertine, [who] had rendered his wife pregnant on 28 occasions [how can that be possible??]; in addition, he had many extramarital affairs.Diagnosis: epilepsy with delusions of infidelity.Case 7 was given "a course of electro-shock therapy" which isn't such a great idea for someone with epilepsy, and it didn't cure his delusions, either. Chlorpromazine wasn't yet widely available in 1951, but the anticonvulsant Dilantin (phenytoin) was on the market in the 1930s.He was still hospitalized four years later.In their Study in the Psychopathology of Sexual Jealousy, Drs. Todd and Dewhurst (1955) did not seem to prescribe medications of any sort, but they did give a wonderful literary discussion of Boccaccio, Shakespeare, Tolstoy, and Burton's The Anatomy of Melancholy.ReferencesMiller, M., Kummerow, A., & Mgutshini, T. (2010). Othello Syndrome. Journal of Psychosocial Nursing and Mental Health Services, 48 (8), 20-27 DOI: 10.3928/02793695-20100701-05TODD J, & DEWHURST K (1955). The Othello syndrome; a study in the psychopathology of sexual jealousy. The Journal of nervous and mental disease, 122 (4), 367-74 PMID: 13307271What noise is this? Not dead — not yet quite dead?I that am cruel am yet merciful;I would not have the linger in thy painSo, so. Othello, Act V scene ii
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TODD J, & DEWHURST K. (1955) The Othello syndrome; a study in the psychopathology of sexual jealousy. The Journal of nervous and mental disease, 122(4), 367-74. PMID: 13307271
Fig. 2 (Haq et al., 2010). A painting made following initial ALIC-NA [anterior limb of the internal capsule/nucleus accumbens] DBS activation. It was produced after a night-long effort and was described as a ‘surprise’ for the staff. The religious tone is typical of the patient.Deep brain stimulation (DBS) is being tested as an experimental treatment for intractable obsessive-compulsive disorder (OCD), as well as for major depression. A recent review by Mian et al. (2010) discusses the three main brain regions that are targeted by DBS for OCD:Target 1: the anterior limb of the internal capsule (ALIC) and/or the ventral capsule/ventral striatum (VC/VS)1, the most common sitesTarget 2: the subthalamic nucleus (STN) within the basal ganglia, a major DBS target for Parkinson's disease as wellTarget 3: the inferior thalamic peduncle (ITP) linking orbitofrontal cortex and thalamusHaq et al. (2010) reported on the adverse events experienced by a patient receiving DBS in ALIC and the nucleus accumbens (part of the ventral striatum) for severe OCD. A 29 year old woman started experiencing OCD symptoms in early childhood:...obsessions that centered on a need to be clean and a need to please. At the time of enrollment, her compulsions included counting, bra-snapping, pant-pulling and leg scratching. She completed the 12th grade but subsequently had difficulty remaining employed because of her illness. In addition to her history of OCD, she was also diagnosed as having major depressive disorder. Twice, in the remote past, she had attempted suicide via drug overdose. Since she had failed to respond to three different classes of drugs, as well as to cognitive behavioral therapy, she was eligible to enroll in the DBS trial. The implantation surgery was uneventful, and the patient was randomized to have activation of the stimulator begin at 30 days post surgery.In the Introduction, the authors were remarkably honest about how the choice of stimulation parameters can be hit and miss:The published experience with DBS programming for OCD is limited. Parameters (voltage, pulse width and frequency) are commonly adjusted by trial and error with the aim of deriving the greatest possible clinical efficacy while avoiding uncomfortable side effects. As physicians’ experience with DBS programming in OCD has broadened, the potential for stimulation-induced side effects has become increasingly apparent. Novel targets, such as the anterior limb of the internal capsule/nucleus accumbens (ALIC-NA), have introduced novel stimulation-induced effects.And Haq et al. (2010) did see some novel stimulation-induced effects that included mania ("hugging" and pressured speech), insomnia, and worsening of OCD symptoms on the first two days of stimulation (as shown below). Oops. The patient was admitted to inpatient psychiatry the next day.-- click on table for larger image --Table 1 (modified from Haq et al., 2010). Programming settings and patient behavior. PW=pulse width. Contacts were implanted bilaterally, and the parameters were identical for each.The initially stimulated contacts were located in the nucleus accumbens (NAcc), considered to be one of the brain's pleasure centres. Not surprisingly, the NAcc is a rational DBS target for depression too, given the common symptom of anhedonia, i.e. the inability to experience pleasure from normally pleasurable life events (see Good News/Bad News Update on Nucleus Accumbens DBS for Treatment-Resistant Depression).Upon transfer to the psych ward, the patient's medication regimen was extensive: one antidepressant (fluoxetine), three mood stabilizers/anticonvulsants (lamotrigine, pregabalin, topiramate), one benzodiazapine (clonazepam), and one non-benzo sedative/hypnotic (eszopiclone). Nonetheless,Following this initial adjustment [of DBS stimulation parameters], the patient spent most of the night awake, alternating between cleaning the adjoining room and painting (see Fig. 2 above). Her painting and speech were notable for their hyperreligious content. She also reported that her OCD symptoms were more troublesome than in her preoperative state. She developed bruises on her shins and thighs from obsessively rubbing her legs and reported an increase in her counting behaviors. Her fluoxetine dose was decreased to be sure that it was not exacerbating the mania and her topiramate was discontinued.Also, her clonazepam dose was doubled and an atypical antipsychotic (quetiapine) was initiated. Not surprisingly, "The patient showed signs of mild sedation after these changes in medication." Fortunately, her condition stabilized after a week. Her symptoms had improved (from extreme to severe) at the one month follow-up, reaching remission after six months of stimulation at the more conservative intensity.The side effects of mania and hypomania are not uncommon after DBS in NAcc and the ventral capsule (Tsai et al., 2010). As noted by Haq and colleagues (2010):Stimulation-induced mania may result from spread of the stimulation field from the motor regions of gray matter structures into limbic or frontal territories... The ALIC-NA is more richly connected to limbic and frontal regions than the STN or other basal ganglion targets and (based on limited experience) has a correspondingly higher incidence of postoperative psychiatric side effects. The occurrence of transient hypomania with ALIC-NA DBS has been estimated to be as high as 50–67%...The abnormal circuitry implicated in OCD is quite complex, and is thought to include fronto-striatal- thalamic-cortical loops (Maia et al., 2008). A clearer understanding of the connectivity of these regions through the use of tractography may improve the choice of target for DBS in a number of psychiatric disorders.Footnote... Read more »
Haq, I., Foote, K., Goodman, W., Ricciuti, N., Ward, H., Sudhyadhom, A., Jacobson, C., Siddiqui, M., & Okun, M. (2010) A Case of Mania following Deep Brain Stimulation for Obsessive Compulsive Disorder. Stereotactic and Functional Neurosurgery, 88(5), 322-328. DOI: 10.1159/000319960
Figure 3 (Schoene-Bake et al., 2010). Intersection of connectivity maps of Anterior Capsulotomy (red), Anterior Cingulotomy (blue), and Subcaudate Tractotomy (green) tracking results. Overlap of AC and ACT shown with magenta, AC and SCT in yellow, and ACT and SCT in cyan. The white area shows overlapping of AC, ACT, and SCT mean probability-tracking maps in axial (a), coronal (b), and sagittal (c) slices. Acg, anterior cingulate gyrus; ATR, anterior thalamic radiation; CST, corticospinal tract; FM, forceps minor; FP, frontal pole; Nacc, accumbens nucleus; PAG, periaqueductal grey matter; slMFB, superolateral branch of medial forebrain bundle; Thal, thalamus.When I first saw a journal article titled Tractographic Analysis of Historical Lesion Surgery for Depression, I assumed the authors (Schoene-Bake et al., 2010) located some elderly patients who had received psychosurgery in the 1960s, then scanned them using diffusion tensor imaging to trace the white matter tracts affected by the surgeries. This was not the case, however. Instead, the paper is a lesion simulation study that used MRIs from a large sample of control participants.Although this revelation was initially disappointing, the results included the pretty colorized DTI figure shown above.1 And it reviewed the four historical surgical approaches and their anatomical targets, shown in the table below.Jumping ahead to the punchline, what were the conclusions?Shared connectivities between the four surgical approaches mapped onto the most mediobasal aspects of bilateral frontal lobe fibers, including the forceps minor and the anterior thalamic radiations that contacted subgenual cingulate regions [Brodmann area 25]. Anatomically, convergence of these shared connectivities may derive from the superolateral branch of the medial forebrain bundle (MFB), a structure that connects these frontal areas to the origin of the mesolimbic dopaminergic ‘reward’ system in the midbrain ventral tegmental area [VTA]. Thus, all four surgical anti-depressant approaches may be promoting positive affect by converging influences onto the MFB.Putting aside for a moment the actual efficacy of these surgeries, the claim is that disconnection of the "sad cingulate" from the VTA was at least partly responsible for improved mood. In modern times, the subgenual cingulate has been a target for deep brain stimulation (DBS) trials for intractable major depression (Mayberg et al., 2005; Lozano et al., 2008). In contrast to creating a permanent lesion, in DBS a stimulating electrode is stereotaxically implanted in the targeted region. Dr. Helen Mayberg and her colleagues at Emory University are still recruiting patients with treatment resistant depression to participate in a clinical trial using chronic, high frequency stimulation of the subgenual cingulate white matter.To determine the anatomical connectivity of the subgenual cingulate region, these researchers performed tractography (using diffusion-weighted MRI) to trace the pathways mediating treatment response with DBS (Johansen-Berg et al., 2007). The authors compared the connections of the subgenual ACC (sACC, blue/cyan) and the perigenual ACC (pACC, red/yellow).Figure 3 (Johansen-Berg et al., 2007). Connectivity-based parcellation of ACC and location of electrode contacts. (A, B) Population probability maps of connectivity-defined sACC and pACC. Color scales represent the population probability of a voxel belonging to sACC (from 50% [dark blue] to 80% [light blue] probability) or pACC (from 50% [red] to 80% [yellow] probability). Also shown are the locations of effective electrode contacts from 9 patients overlaid in black. Effective electrode locations are mainly localized within the sACC subregion.Resting metabolic activity in subgenual cingulate was shown to be increased in the patients with treatment-resistant depression (Mayberg et al., 2005):The baseline pattern of subgenual cingulate hyperactivity in combination with frontal hypoactivity described here in this TRD patient group is a finding that is in contrast to the hypoactivity reported in a more rostral region of subgenual medial prefrontal cortex in familial bipolar and unipolar depressed patients (Drevets et al., 1997). This distinction suggests important differences across subtypes of depression that are potentially relevant to the pathophysiology of major depressive disorders and perhaps their treatment.Reflecting further on the historical lesion data, one might infer that a hyperactive subgenual cingulate ultimately inhibited activity in the VTA, a dopamine "reward center". The idealized lesions for all four surgical approaches are shown in the simulation below.Figure 1 (Schoene-Bake et al., 2010). Mean probability maps of simulated lesions. (a) Anterior capsulotomy (AC); (b) anterior cingulotomy (ACT), I - sagittal, II - coronal, III - axial; (c) subcaudate tractotomy (SCT); and (d) stereotactic limbic leucotomy (SLL).I would like to see how these simulated lesions compare to the actual surgical lesions from days of yore. Schoene-Bake et al. (2010) hope that a look back at the past will enhance the future of depression treatment:DTI probabilistic connectivity analysis is a useful tool to explore and to simulate the structural and functional impact of past stereotactic lesion surgery app... Read more »
Schoene-Bake, J., Parpaley, Y., Weber, B., Panksepp, J., Hurwitz, T., & Coenen, V. (2010) Tractographic Analysis of Historical Lesion Surgery for Depression. Neuropsychopharmacology. DOI: 10.1038/npp.2010.132
What is palliative care? Until quite recently, it's something I haven't given much thought. Although there was a highly regarded article on hospice and palliative care by Atul Gawande in last month's New Yorker, I didn't read it or think it applied to my life. All that changed less than two weeks ago, when my father was hospitalized in critical condition after collapsing. First he went to the ER, then the transitional ICU, and finally he was placed in the palliative care unit by the time I arrived. You see, my father has metastatic lung cancer, for which he had refused treatment for more than a year. Instead, he decided to stay home with my mother, watch DVDs, go out to eat, and do yard work.1A recent paper in the New England Journal of Medicine demonstrated that the introduction of palliative care shortly after the diagnosis of metastatic lung cancer not only improved the patients' quality of life, but also extended median survival from 8.9 months to 11.6 months (Temel et al., 2010). According to the American Academy of Hospice and Palliative Medicine:The goal of palliative care is to prevent and relieve suffering and to support the best possible quality of life for patients and their families, regardless of the stage of the disease or the need for other therapies. Palliative care is both a philosophy of care and an organized, highly structured system for delivering care. Palliative care expands traditional disease-model medical treatments to include the goals of enhancing quality of life for patient and family, optimizing function, helping with decision-making and providing opportunities for personal growth. As such, it can be delivered concurrently with life-prolonging care or as the main focus of care.This finding is critically important for providers of medical care for terminally ill cancer patients as well as for health policy, because it provides categorical, scientific proof that the notion of "death panels" is false. As stated in the New York Times:“It shows that palliative care is the opposite of all that rhetoric about ‘death panels,’ ” said Dr. Diane E. Meier [@DianeEMeier], director of the Center to Advance Palliative Care at Mount Sinai School of Medicine and co-author of an editorial in the journal accompanying the study. “It’s not about killing Granny; it’s about keeping Granny alive as long as possible — with the best quality of life.”A straw man in the 2009 health care debate, "death panels" invoked the specter of rationing medical procedures provided for the sick and the elderly. In the name of cost cutting, blared the phony rhetoric on talk radio and Sarah Palin's Facebook page, the Obama administration would sanction euthanasia for elders and the terminally ill under provisions of the health care bill. This would save on expensive treatments that prolong patients' lives but increase the deficit, claimed the conservative crew. However, these scare tactics were an outright lie, as we learn from the Wall Street Journal:Palin’s “Death Panels” Charge Named “Lie of the Year”...“Of all the falsehoods and distortions in the political discourse this year, one stood out from the rest,” writes Politifact.com, the non-partisan, Pulitzer Prize-winning site run by the St. Petersburg Times. Palin’s “assertion — that the government would set up boards to determine whether seniors and the disabled were worthy of care — spread through newscasts, talk shows, blogs and town hall meetings.”“Opponents of health-care legislation said it revealed the real goals of the Democratic proposals. Advocates for health reform said it showed the depths to which their opponents would sink,” Polifact.com says.The NEJM study enrolled 151 patients with newly diagnosed metastatic non–small-cell lung cancer. Seventy-four received standard care and 77 patients received palliative care, which included meetings with a member of the palliative care team (board-certified palliative care physicians and advanced-practice nurses). The first meeting was within 3 weeks of enrollment, and subsequent meetings were held on a monthly basis, with additional sessions at the discretion of the patient and the clinical treatment team. Patients assigned to standard care did not meet with the palliative care team (unless requested). All patients continued to receive standard oncology care for the duration of the study.These meetings are the so-called "death panels" that would have been covered by Medicare, as mentioned by the NYT in Palliative Care Extends Life, Study Finds:During the debate over President Obama’s 2009 health care bill, provisions to have Medicare and insurers pay for optional consultations with doctors on palliative and hospice care led to rumors, spread by talk-show hosts like Rush Limbaugh and Glenn Beck and by the former vice-presidential candidate Sarah Palin, that the bill empowered “death panels” that would “euthanize” elderly Americans. [emphasis mine]The primary outcome measure of the study was quality of life at 12 weeks (compared to baseline), as assessed by the Functional Assessment of Cancer Therapy–Lung (FACT-L) scale. Mood was assessed using the Hospital Anxiety and Depression Scale (HADS) and the Patient Health Questionnaire 9 (PHQ-9).Results indicated that patients in the palliative care group had a significantly higher quality of life at 12 weeks (see Table 2) and a lower incidence of depression (but similar levels of anxiety).[click on Table for larger image]Table 2 (Temel et al., 2010). Plus–minus values are means ±SD. Quality of life was assessed with the use of three scales: the FACT-L scale, on which scores range from 0 to 136, with higher scores indicating better quality of life; the lung-cancer subscale (LCS) of the FACT-L scale, on which scores range from 0 to 28, with higher scores indicating fewer symptoms; and the Trial Outcome Index (TOI), which is the sum of the scores on the LCS and the physical well-being and functional well-being subscales of the FACT-L scale (scores range from 0 to 84, with higher scores indicating better quality of life).In addition, patients in the palliative care group lived longer:Despite receiving less aggressive end-of-life care,2 patients in the palliative care group had significantly longer survival than those in the standard care group (median survival, 11.6 vs. 8.9 months; P=0.02).The study has its limitations, however, as noted by Dr. Meier in Palliative Care: We Still Have a Lot to Learn:...The patients (and doctors) were not blinded to their treatment group, that is, they knew which group they were in, which could have affected their outcomes. Also, there was no “attention-control” group—a group that got the same amount of human time and attention that the palliative care group got but without the palliative care skill and expertise.Nonetheless, the purpose and goals of palliative care cannot be understated. As I mentioned in my previous post... Read more »
J.S. Temel et al. (2010) Early Palliative Care for Patients with Metastatic Non–Small-Cell Lung Cancer. N Engl J Med, 733-742. info:/10.1056/NEJMoa1000678
Venn diagram of psychoactive drugs [click for larger image]This post is part of a Nature Blog Focus on hallucinogenic drugs in medicine and mental health, inspired by a recent Nature Reviews Neuroscience paper, The neurobiology of psychedelic drugs: implications for the treatment of mood disorders, by Franz Vollenweider & Michael Kometer. This article will be available, open-access, until September 23. For more information on this Blog Focus, including a Table of Contents, please visit The Great Beyond.The secret history of psychedelic psychiatry is discussed over at Neurophilosophy. Neuroskeptic covers Serotonin, Psychedelics and Depression while Mind Hacks provides a personal look at yagé in Visions of a psychedelic future.Veterinary Anesthetic, Club Drug, or Antidepressant?Club drug "Special K" (aka ketamine) is stepping out of the laser light into the broad daylight of mainstream psychiatry with the publication of a new review article by Vollenweider and Kometer (2010). Long used to anesthetize animals (and children), ketamine was classified as a "dissociative anesthetic" by Domino et al. (1965) for its combined effects of sedation/analgesia and hallucinations. Domino (2010) recently revisited his classic paper, which reported on a study in 20 volunteers incarcerated at the Jackson Prison in Michigan:The first human was given ketamine in an intravenous subanesthetic dose on August 3, 1964. Guenter [Corssen, M.D.] and I gradually increased the dose from no effect, to conscious but “spaced out,” and finally to enough for general anesthesia. Our findings were remarkable! The overall incidence of side effects was about one out of three volunteers. Frank emergence delirium was minimal. Most of our subjects described strange experiences like a feeling of floating in outer space and having no feeling in their arms or legs. The ego death of the "K hole" can be a terrifying experience for some ("I ceased to exist") or transformative for others ("I witnessed myself as a part of the universal collective of strange energy")1. In their Nature Reviews Neuroscience opinion piece, Vollenweider and Kometer considered ketamine a psychedelic, along with the traditional hallucinogens such as LSD, psilocybin, and mescaline. They noted that both classes of drugs may have psychotherapeutic effects through actions on the excitatory glutamate neurotransmitter system.Ketamine is an antagonist of the glutamate NMDA receptor and is thought to work by blocking NMDA receptors on inhibitory GABA-containing interneurons, ultimately promoting glutamate release. In a scientific tour de force, Li and colleagues (2010) demonstrated that the mTOR (mammalian target of rapamycin) protein kinase pathway is rapidly activated by ketamine. This sets off a cascade of events including the formation of new synapses on dendritic spines. Using a combination of cellular, molecular, electrophysiological, behavioral, and phamacological techniques, ketamine was shown to exhibit antidepressant properties in animal models of depression and anxiety, perhaps via rapid induction of synaptic plasticity in the medial prefrontal cortex (PFC). Regions of the medial PFC in humans, particularly the ventral anterior cingulate cortex, have been implicated in the pathophysiology of major depression.Human clinical trials of ketamine as a rapidly acting antidepressant aren't especially new. A randomized, double-blind study in 2000 involved administration of saline or a single subanesthetic dose of ketamine (0.5 mg/kg intraveneously) to nine depressed patients, seven of whom completed the trial (Berman et al., 2000). Within 72 hrs, amelioration of depressive symptoms was observed. Half of the treated patients showed a 50% or greater improvement in depression scores. However, these therapeutic effects weren't very long-lasting, returning to baseline levels in 1-2 weeks. In a larger study, 18 patients with major depression participated in a similar double-blind cross-over design where they received the 0.5 mg/kg dose of ketamine and placebo one week apart (Zarate et al., 2006). The patients were rated at baseline and at 40, 80, 110, and 230 minutes and 1, 2, 3, and 7 days post-infusion on a number of clinical scales, including the Hamilton Depression Rating Scale (HDRS), the Brief Psychiatric Rating Scale (BPRS) positive symptoms subscale, and the Young Mania Rating Scale (YMRS).The primary outcome measure was change in HDRS score, shown in Figure 2 below (top graph). Significant improvements began at the 110 min time point. Scores declined further from 1-3 days and remained below placebo levels for 7 days. However, unusual experiences were noted at 40 min, with substantial increases in scores for psychosis-like and mania-like symptoms. Other adverse events associated with ketamine included......perceptual disturbances, confusion, elevations in blood pressure, euphoria, dizziness, and increased libido. ... The majority of these adverse effects ceased within 80 minutes after the infusion. In no case did euphoria [YMRS] or derealization/depersonalization [BPRS] persist beyond 110 minutes (Figure 2, middle and bottom graphs).Figure 2 (Zarate et al., 2006). Change in the 21-item HDRS, BPRS positive symptoms subscale, and YMRS scores over 1 week (n=18). Values are expressed as generalized least squares means and standard errors for the completer analysis. * indicates PSo here we have several research groups that say yay! to ketamine as an antidepressant. Are there any naysayers?Although the immediate onset of symptom amelioration gives ketamine a substantial advantage over traditional antidepressants (which take 4-6 weeks to work), there are definite limitations (Tsai, 2007). Drawbacks include the possibility of ketamine-induced psychosis (Javitt, 2010), limited duration of effectiveness (aan het Rot et al., 2010), potential long-term deleterious effects such as white matter abnormalities (Liao et al., 2010), and an inab... Read more »
Vollenweider, F., & Kometer, M. (2010) The neurobiology of psychedelic drugs: implications for the treatment of mood disorders. Nature Reviews Neuroscience, 11(9), 642-651. DOI: 10.1038/nrn2884
Cartoon Reenactment of JetBlue Flight Attendant’s Dramatic ExitNo, the term "airplane headache" does not refer to disgruntled JetBlue flight attendant Steven Slater (or to being a passenger on that flight). Instead, it refers to a recently characterized type of headache that occurs during take-off and landing (Atkonson & Lee, 2004). The pain appears to be unique to plane travel and not associated with other conditions. Neurological exam and brain imaging results in all published cases (n=14) have been normal.A new case study of a man with airplane headaches has been reported by Domitrz (2010). Clinical details are as follows:A 29-year-old healthy man, who works as a psychologist, reported that during his last airplane journey, he developed a very severe and sudden jabbing headache located in the left frontal region with radiation into the left eye. It started during take-off, diminished during the 2-h flight, a very mild pain was present during the flight and increased during plane’s descent and lasted until a few minutes after landing. Then, the pain completely and spontaneously subsided. The same situation took place 3 days later when the patient was returning. He remembers that he had similar, but milder headaches during previous flights. However, they occurred only during airplane flights and did not develop during jumbo jet flights. Similar headache did not appear in other altitude variation moments, e.g. in mountain trips.The pain was always located in the left frontal region with radiation into the left eye without any autonomic symptoms and neurological focal problems. He could not move until the headache disappeared. The patient has no medical history of sinus problems and using any medications. The family history has shown only tension type headache in patient’s 4 years older sister. General (including blood pressure and heart rate), neurological, otolaryngological and ophthalmological examinations were normal. Brain magnetic resonance imaging also with angiography excluded any structural lesions and arterial malformations. Domitrz (2010) further notes that most reported cases have been in young males, as is her patient. She is also puzzled by why he gets these headaches only on airplanes that are not jumbo jets -- perhaps it is connected with differences in air pressure, she speculates.What causes this specific type of headache? One view is that barotrauma is involved, with pressure changes affecting the trigeminovascular system (Berilgen & Müngen, 2006):We think that barotrauma caused by pressure changes in the cabin during take-off and landing could affect ethmoidal nerves (branching from the ophthalmic branch of the trigeminal nerve) that carry the senses of the mucosa on the inner surface of the paranasal sinuses, and/or nociceptors in ethmoidal arteries, thereby activating the trigeminovascular system and leading to headache.It's enough to make someone attempt an emergency exit!ReferencesAtkonson V, Lee L. (2004). An unusual case of an airplane headache. Headache 44:438–439Berilgen MS, Müngen B. (2006). Headache associated with airplane travel: report of six cases. Cephalalgia 26:707-11.Domitrz, I. (2010). Airplane headache: a further case report of a young man. The Journal of Headache and Pain DOI: 10.1007/s10194-010-0245-9
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Domitrz, I. (2010) Airplane headache: a further case report of a young man. The Journal of Headache and Pain. DOI: 10.1007/s10194-010-0245-9
CREDIT: RYAN SNOOK (from Holden, 2008).The latest search for genetic variants that underlie differences in personality traits has drawn a blank (Verweij et al., 2010). The researchers conducted a genome-wide association study using personality ratings from Cloninger's temperament scales in a population of 5,117 Australian individuals:Participants' scores on Harm Avoidance, Novelty Seeking, Reward Dependence, and Persistence were tested for association with 1,252,387 genetic markers. We also performed gene-based association tests and biological pathway analyses. No genetic variants that significantly contribute to personality variation were identified, while our sample provides over 90% power to detect variants that explain only 1% of the trait variance. This indicates that individual common genetic variants of this size or greater do not contribute to personality trait variation, which has important implications regarding the genetic architecture of personality and the evolutionary mechanisms by which heritable variation is maintained.But it's still fun and popular for some science writers to assert that personality traits are "hard wired" into our brains, like there's really A Brain Circuit for Bungee Jumping? [thanks for the exciting new info, ScienceNOW.] In reality, some of the major early findings in personality genetics, such as an association between Novelty Seeking and the Dopamine D4 Receptor gene (Benjamin et al., 1996; Ebstein et al., 1996), have failed to replicate (Gelernter et al., 1997; Paterson et al. 1999; Strobel et al., 2002). Fortunately, others writers have pointed out the increasingly obvious difficulties of this endeavor, as did Constance Holden in Parsing the Genetics of Behavior:For some of us, it's satisfying to attribute social awkwardness to anxiety genes or to think that the driver who cuts off other cars as he zips across lanes is pumped up by the "warrior" gene. Was it a bad dopamine receptor gene that made author Ernest Hemingway prone to depression? Can variations in a vasopressin receptor gene--a key to monogamy in voles--help explain adulterous behavior? But as scientists are discovering, nailing down the genes that underlie our unique personalities has proven exceedingly difficult. That genes strongly influence how we act is beyond question. Several decades of twin, family, and adoption studies have demonstrated that roughly half of the variation in most behavioral traits can be chalked up to genetics. But identifying the causal chain in single-gene disorders such as Huntington's disease is child's play compared with the challenges of tracking genes contributing to, say, verbal fluency, outgoingness, or spiritual leanings. In fact, says Wendy Johnson, a psychologist at the University of Edinburgh, U.K., understanding genetic mechanisms for personality traits "is one of the biggest mysteries facing the behavioral sciences."Nonetheless, unscrupulous businesses like My Gene Profile (which offers the "Inborn Talent Genetic Test" for the low low price of $1,397) have capitalized on the public's desire for simple explanations. Now you can find out whether your child has the Split Personality Gene! The Propensity for Teenage Romance Gene! The Self Detoxifying Gene!Returning to the current study, the authors cast a genome-wide net to find genetic variants related to the four dimensions of temperament identified by Cloninger in his Temperament and Character Inventory (TCI), a 240 item self-report questionnaire. As described by Verweij et al., (2010):Novelty Seeking reflects the tendency to respond strongly to novelty and cues for reward as well as relief from punishment, and is thought to play a role in the activation or initiation of behaviours. Harm Avoidance reflects the tendency to respond strongly to aversive stimuli, which leads to learned inhibition of behaviour, and is thought to play a role in the inhibition or ceasing of behaviours. Reward Dependence reflects the tendency to react strongly to rewards and to maintain behaviours previously associated with reward or relief of punishment, and is thought to play a role in the maintenance or continuation of behaviour. Persistence reflects the tendency to persevere despite frustration and fatigue.The participants completed a short form of Cloninger's (1986) original Tridimensional Personality Questionnaire (TPQ).1 The fourth dimension of temperament -- Persistence -- was constructed using a small subset of the Reward Dependence questions. The 1986 version of Cloninger's biosocial theory of personality associated Novelty Seeking with low dopamine activity, Harm Avoidance with high serotonin activity, and Reward Dependence with low noradrenaline activity. These were thought to be independent and heritable aspects of personality that influence responses to reward, punishment, and novelty. The TPQ was later revised to include Persistence and also three character dimensions (Self-Directedness, Cooperativeness, and Self-Transcendence) to form the basis of the TCI (Cloninger et al., 1993).Cloninger's theory of personality is not without its critics. In 2008, Farmer and Goldberg challenged the psychometric validity of the TCI in a target article and in a wonderfully titled reply to Cloninger. A trenchant quote from the latter (Farmer & Goldberg, 2008) is below:Overall, several core theoretical assumptions and predictions associated with the psychobiological model and TCI-R assessment are either non-falsifiable, in conflict with each other, or not supported by empirical evidence. So the question arises, are we dealing with a flawed set of personality constructs to begin with? No matter. The scales are widely used, so we'll go on.For genotyping, single nucleotide polymorphisms (SNPs) across the entire genome were tested for association with each of the four traits. The Illumina and Affymetrix platforms were used. [Those technical and statistical methods are beyond the scope of this blog, so I will leave it to someone else to describe and critique the genotyping aspects of the paper.] Stated succinctly, the results showed that:No SNPs reached genome wide significance (α = 7.2*10-8) and the SNP with the lowest p-value for each personality scale explains less than 0.5% of the total variance.None of the previously identified candidate genes (e.g., serotonin receptor gene, D4 receptor gene) were close to showing a significant relationship with any trait, nor were any of the SNPs with the lowest p val... Read more »
Verweij, K., Zietsch, B., Medland, S., Gordon, S., Benyamin, B., Nyholt, D., McEvoy, B., Sullivan, P., Heath, A., & Madden, P. (2010) A genome-wide association study of Cloninger's Temperament scales: Implications for the evolutionary genetics of personality. Biological Psychology. DOI: 10.1016/j.biopsycho.2010.07.018
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