Saturday, November 27, 2010

Seizures Triggered by Strawberry Syrup

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):
  1. 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).

  2. 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.

  3. 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 in cyan), and removed it. Two years later, the patient remains seizure-free, and presumably can enjoy strawberry syrup once again.


1 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.


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 γ activity in eating-reflex seizures. Journal of Neurology, Neurosurgery & Psychiatry DOI: 10.1136/jnnp.2010.212696

Xue LY, Ritaccio AL. (2006). Reflex seizures and reflex epilepsy. Am J Electroneurodiagnostic Technol. 46:39-48.

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Friday, November 26, 2010

Celebration of Failure

The Failure Of Man
Details the failure of man in every dispensation.

from Dispensational Charts
by Clarence Larkin

In a recent Nature Careers Column, post-doc Melanie Stefan argues that it's helpful to publicize your failures. The idea is that if others know you have failed to obtain funding or publish papers, it makes them feel better. Hopefully not from schadenfreude, but from the common experience of traversing the minefield of attaining (or maintaining) a lasting career in science.

A CV of failures

Keeping a visible record of your rejected applications can help others to deal with setbacks, says Melanie Stefan.

A couple of months ago, I received a letter informing me that my fellowship application had failed....

. . .

As scientists, we construct a narrative of success that renders our setbacks invisible both to ourselves and to others. Often, other scientists' careers seem to be a constant, streamlined series of triumphs. Therefore, whenever we experience an individual failure, we feel alone and dejected.

. . .

So here is my suggestion. Compile an 'alternative' CV of failures. Log every unsuccessful application, refused grant proposal and rejected paper. Don't dwell on it for hours, just keep a running, up-to-date tally. If you dare — and can afford to — make it public. It will be six times as long as your normal CV. It will probably be utterly depressing at first sight. But it will remind you of the missing truths, some of the essential parts of what it means to be a scientist — and it might inspire a colleague to shake off a rejection and start again.

I have periodically engaged in such a masochistic exercise. And no, I have never publicized the List of Failure or the Table of Failure™ (Excel spreadsheet). I'm not that magnanimous...

My setbacks are all too visible to myself. Would it really make you feel better to read about them?


Stefan M (2010). A CV of failures. Nature 468: 467.


Through pain the land of pain,
Through tender exiguity,
Through cruel self-suspicion:
Thus came I to this inch of wholeness.

It was a promise.
After pain, I said,
An inch will be what never a boasted mile.

And haughty judgement,
That frowned upon a faultless plan,
Now smiles upon this crippled execution,
And my dashed beauty praises me.

-Laura Riding

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Tuesday, November 23, 2010

Mirror Neuron Dance Party for Autism Spectrum Disorders

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.


Altschuler 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.2010.10.047

VS Ramachandran's Modest Proposal: The neurons that shaped civilization.

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Friday, November 19, 2010

Random Observations from SfN 2010

SfN Posterface - UCSD graduate student dance party at the San Diego convention center, Hall Gaga.

The 40th annual meeting of the Society for Neuroscience was held Nov. 13-17 in San Diego, CA. Attendance this year was over 31,500. SfN tried to improve the participatory social media coverage of the conference (after last year's #sfn the meh debacle) by highlighting the official Neuroscience 2010 Neurobloggers in a more prominent fashion. I'm still trying to make sense of the 160 posters, talks, and lectures on my itinerary, but in the meantime here are capsule summaries of several posters.

Patients with left temporal lesions [DO NOT] report decreased religious experience. Oops, change of title.

A novel visuospatial test of creativity activated large chunks of both the right AND left cerebral hemispheres in a group of architects. Creativity should no longer be considered the exclusive domain of the right hemisphere, even for a cognitive function that typically shows a right lateralized bias (also see this review by Dietrich and Kanso, 2010).

Remember "Women w/ low libidos have diff brains"? Now the group of women with hypoactive sexual desire disorder no longer show that pesky, problematic activity in the primary motor cortex!

A low dose of red wine impairs planning and problem solving abilities in the Tower of Hanoi task. It also scrambles the normal distribution of EEG frequency bands.

Furthermore, drinking moderate doses of alcohol (BAC=0.055, under the legal limit for driving in the U.S.) will result in the commission of more errors in the Stroop task and a suppression of theta band activity in the medial frontal cortex.

Lady GABA - from the SfN Posterface video.

The SfN Posterface preview.

This crank poster was very crowded: A “Humpty-Dumpty” theory for why we dream. It listed 21 (or so) rebuttals to possible objections. I didn't have the time (or patience) to read them all.

Why do the mere words "Hindu" "Jewish" "Christian" "Muslim" "Atheist" and "Scientologist" constitute exposure to an ingroup or outgroup? Why does n=27 Christians, n=6 Atheists, and n=4 Hindus provide the basis for adequate group comparisons? Because it’s empathic responses for another's pain!

Although drinking red wine was detrimental to cognitive performance, watching erotic videos was not. You'll be glad to hear that complex problem solving abilities in the Tower of Hanoi task were not impaired in moderately sexually aroused males. However, the pattern of cortical EEG correlations was altered.

I'll get him hot, show him what I've got
Oh, oh, oh, oh, ohhhh, oh-oh-e-oh-oh-oh,
I'll get him hot, show him what I've got

------Lady Gaga

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Friday, November 12, 2010

Tetris Helps Prevent Unpleasant Memories of Gory Film in Happy People

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 5.7-6.2.1

The 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, we note that previous studies using the same trauma film (Brewin & Saunders, 2001; Murray, 1997), as well as those using other trauma films (e.g., Davies & Clark, 1998), found that no participants reported ongoing distress subsequent to the end of the experiment. Further, although transiently distressing, the film content is similar to that witnessed by television viewers watching programs such as news coverage of road traffic accidents, or programs about the police or ambulance service work.
I'm not dismissing the possibility that therapies based on these experimental parameters may eventually have clinical usefulness. What I'm suggesting is that the authors show more restaint in their use of terminology (e.g., immediately calling their experimental task a "cognitive vaccine"), and in their extrapolation of experimental findings in healthy subjects to effective treatments for those suffering from PTSD.

Thanks to Sandra of Channel N for helpful discussions.


1 Scoring for the BDI-II is: 0–13: minimal depression; 14–19: mild depression; 20–28: moderate depression; and 29–63: severe depression.


Baddeley A. (1992). Working memory. Science 255:556-9.

Holmes EA, Brewin CR, Hennessy RG. (2004). Trauma films, information processing, and intrusive memory development. J Exp Psychol Gen. 133:3-22.

Holmes, E., James, E., Kilford, E., & Deeprose, C. (2010). Key Steps in Developing a Cognitive Vaccine against Traumatic Flashbacks: Visuospatial Tetris versus Verbal Pub Quiz. PLoS ONE, 5 (11) DOI: 10.1371/journal.pone.0013706

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Friday, November 05, 2010

Research Domain Criteria for Classifying Mental Disorders

"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... 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 phobia
  • 49 percent have an impulse-control disorder, most commonly intermittent explosive disorder
  • 38 percent have a substance abuse or dependence disorder, most commonly alcohol abuse or dependence
  • 34 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 approach is needed. Since the ultimate goal of the RDoC project is to improve treatment outcomes, its authors will have to convince some of the major drug companies to resume their "unprofitable" psychiatry R&D pipelines.

NOTE: This post is part of a blog carnival that addressed the question, "What Is Psychopathology?" {Scicurious isn't very fond of the term; neither am I...} Other contributions are listed at The Thoughtful Animal.


Insel T, Cuthbert B, Garvey M, Heinssen R, Pine DS, Quinn K, Sanislow C, Wang P. (2010). Research domain criteria (RDoC): toward a new classification framework for research on mental disorders. Am J Psychiatry 167:748-51.

Pfeifer S. (1999). Demonic attributions in nondelusional disorders. Psychopathology 32:252-9.

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

NOTE: King Missile III album named after Psychopathology of Everyday Life (1901), by Sigmund Freud.

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