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

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  • November 28, 2010
  • 03:08 AM
  • 667 views

Seizures Triggered by Strawberry Syrup

by The Neurocritic in The Neurocritic

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  

  • November 23, 2010
  • 05:13 AM
  • 751 views

Mirror Neuron Dance Party for Autism Spectrum Disorders

by The Neurocritic in The Neurocritic

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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  • November 12, 2010
  • 06:23 PM
  • 903 views

Tetris Helps Prevent Unpleasant Memories of Gory Film in Happy People

by The Neurocritic in The Neurocritic

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 »

  • November 5, 2010
  • 07:05 AM
  • 773 views

Research Domain Criteria for Classifying Mental Disorders

by The Neurocritic in The Neurocritic

"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  

  • October 23, 2010
  • 08:29 PM
  • 2,350 views

Celebrity Neurostigma

by The Neurocritic in The Neurocritic

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 »

  • October 17, 2010
  • 02:51 AM
  • 664 views

Dr. Charles Hamilton Hughes, Alienist and Neurologist

by The Neurocritic in The Neurocritic

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 »

  • October 6, 2010
  • 05:26 AM
  • 838 views

The Tragedy of Othello Syndrome

by The Neurocritic in The Neurocritic

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
... Read more »

Miller, M., Kummerow, A., & Mgutshini, T. (2010) Othello Syndrome. Journal of Psychosocial Nursing and Mental Health Services, 48(8), 20-27. DOI: 10.3928/02793695-20100701-05  

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  

  • September 19, 2010
  • 05:25 PM
  • 752 views

Mania and Artistic 'Surprise' Induced by Deep Brain Stimulation

by The Neurocritic in The Neurocritic

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  

  • September 15, 2010
  • 06:51 AM
  • 739 views

Modern Tract-Tracing for Historical Psychosurgery

by The Neurocritic in The Neurocritic

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

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

  • September 6, 2010
  • 04:23 AM
  • 609 views

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

by The Neurocritic in The Neurocritic

What is palliative care? Until quite recently, it's something I haven't given much thought. Although there was a highly regarded article on hospice and palliative care by Atul Gawande in last month's New Yorker, I didn't read it or think it applied to my life. All that changed less than two weeks ago, when my father was hospitalized in critical condition after collapsing. First he went to the ER, then the transitional ICU, and finally he was placed in the palliative care unit by the time I arrived. You see, my father has metastatic lung cancer, for which he had refused treatment for more than a year. Instead, he decided to stay home with my mother, watch DVDs, go out to eat, and do yard work.1A recent paper in the New England Journal of Medicine demonstrated that the introduction of palliative care shortly after the diagnosis of metastatic lung cancer not only improved the patients' quality of life, but also extended median survival from 8.9 months to 11.6 months (Temel et al., 2010). According to the American Academy of Hospice and Palliative Medicine:The goal of palliative care is to prevent and relieve suffering and to support the best possible quality of life for patients and their families, regardless of the stage of the disease or the need for other therapies. Palliative care is both a philosophy of care and an organized, highly structured system for delivering care. Palliative care expands traditional disease-model medical treatments to include the goals of enhancing quality of life for patient and family, optimizing function, helping with decision-making and providing opportunities for personal growth. As such, it can be delivered concurrently with life-prolonging care or as the main focus of care.This finding is critically important for providers of medical care for terminally ill cancer patients as well as for health policy, because it provides categorical, scientific proof that the notion of "death panels" is false. As stated in the New York Times:“It shows that palliative care is the opposite of all that rhetoric about ‘death panels,’ ” said Dr. Diane E. Meier [@DianeEMeier], director of the Center to Advance Palliative Care at Mount Sinai School of Medicine and co-author of an editorial in the journal accompanying the study. “It’s not about killing Granny; it’s about keeping Granny alive as long as possible — with the best quality of life.”A straw man in the 2009 health care debate, "death panels" invoked the specter of rationing medical procedures provided for the sick and the elderly. In the name of cost cutting, blared the phony rhetoric on talk radio and Sarah Palin's Facebook page, the Obama administration would sanction euthanasia for elders and the terminally ill under provisions of the health care bill. This would save on expensive treatments that prolong patients' lives but increase the deficit, claimed the conservative crew. However, these scare tactics were an outright lie, as we learn from the Wall Street Journal:Palin’s “Death Panels” Charge Named “Lie of the Year”...“Of all the falsehoods and distortions in the political discourse this year, one stood out from the rest,” writes 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

  • August 30, 2010
  • 12:58 PM
  • 986 views

Ketamine for Depression: Yay or Neigh?

by The Neurocritic in The Neurocritic

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

  • August 15, 2010
  • 06:47 PM
  • 1,188 views

Airplane Headache

by The Neurocritic in The Neurocritic

Cartoon Reenactment of JetBlue Flight Attendant’s Dramatic ExitNo, the term "airplane headache" does not refer to disgruntled JetBlue flight attendant Steven Slater (or to being a passenger on that flight). Instead, it refers to a recently characterized type of headache that occurs during take-off and landing (Atkonson & Lee, 2004). The pain appears to be unique to plane travel and not associated with other conditions. Neurological exam and brain imaging results in all published cases (n=14) have been normal.A new case study of a man with airplane headaches has been reported by Domitrz (2010). Clinical details are as follows:A 29-year-old healthy man, who works as a psychologist, reported that during his last airplane journey, he developed a very severe and sudden jabbing headache located in the left frontal region with radiation into the left eye. It started during take-off, diminished during the 2-h flight, a very mild pain was present during the flight and increased during plane’s descent and lasted until a few minutes after landing. Then, the pain completely and spontaneously subsided. The same situation took place 3 days later when the patient was returning. He remembers that he had similar, but milder headaches during previous flights. However, they occurred only during airplane flights and did not develop during jumbo jet flights. Similar headache did not appear in other altitude variation moments, e.g. in mountain trips.The pain was always located in the left frontal region with radiation into the left eye without any autonomic symptoms and neurological focal problems. He could not move until the headache disappeared. The patient has no medical history of sinus problems and using any medications. The family history has shown only tension type headache in patient’s 4 years older sister. General (including blood pressure and heart rate), neurological, otolaryngological and ophthalmological examinations were normal. Brain magnetic resonance imaging also with angiography excluded any structural lesions and arterial malformations. Domitrz (2010) further notes that most reported cases have been in young males, as is her patient. She is also puzzled by why he gets these headaches only on airplanes that are not jumbo jets -- perhaps it is connected with differences in air pressure, she speculates.What causes this specific type of headache? One view is that barotrauma is involved, with pressure changes affecting the trigeminovascular system (Berilgen & Müngen, 2006):We think that barotrauma caused by pressure changes in the cabin during take-off and landing could affect ethmoidal nerves (branching from the ophthalmic branch of the trigeminal nerve) that carry the senses of the mucosa on the inner surface of the paranasal sinuses, and/or nociceptors in ethmoidal arteries, thereby activating the trigeminovascular system and leading to headache.It's enough to make someone attempt an emergency exit!ReferencesAtkonson V, Lee L. (2004). An unusual case of an airplane headache. Headache 44:438–439Berilgen MS, Müngen B. (2006). Headache associated with airplane travel: report of six cases. Cephalalgia 26:707-11.Domitrz, I. (2010). Airplane headache: a further case report of a young man. The Journal of Headache and Pain DOI: 10.1007/s10194-010-0245-9

... Read more »

  • August 7, 2010
  • 11:14 PM
  • 2,910 views

Bad News for the Genetics of Personality

by The Neurocritic in The Neurocritic

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

  • July 25, 2010
  • 07:25 PM
  • 672 views

What Color Is Your Cuneus?

by The Neurocritic in The Neurocritic

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

  • July 19, 2010
  • 07:57 AM
  • 2,865 views

Tales of Passion and Disgust

by The Neurocritic in The Neurocritic

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

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

  • July 17, 2010
  • 04:46 AM
  • 693 views

Pleasure or Pain?

by The Neurocritic in The Neurocritic

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

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

  • July 8, 2010
  • 07:11 AM
  • 723 views

Erotic or Disgusting?

by The Neurocritic in The Neurocritic

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

  • July 2, 2010
  • 08:43 PM
  • 2,873 views

Living and Forgetting

by The Neurocritic in The Neurocritic

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

  • June 24, 2010
  • 05:03 AM
  • 3,112 views

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

by The Neurocritic in The Neurocritic

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

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

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

  • June 13, 2010
  • 11:21 PM
  • 1,325 views

The Unique Case of “50 First Dates” Amnesia

by The Neurocritic in The Neurocritic

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

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

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