Sunday, November 29, 2009

Noxious mystery substance released into the third ventricle is the cause of depression!

The Ventricles of the Brain (Ross & Wilson)

You can always count on the journal Medical Hypotheses (published by Elsevier) for a good laugh. The Editor-in-Chief (Bruce G. Charlton) accepts all sorts of completely speculative crackpot articles. Who can forget the classic, Is there an association between the use of heeled footwear and schizophrenia? [see The Journal of Truly, Truly Outrageous Medical Hypotheses.] Or the crowd favorite, Ejaculation as a potential treatment of nasal congestion in mature males? [see More Truly, Truly Outrageous Medical Hypotheses.]

The latest masterwork (Hendrie & Pickles, 2009) contends that major depression is an evolutionary adaptation triggered by damage to one's reproductive potential, which in turn causes the release of a yet-to-be-discovered nasty substance into the third ventricle:
...depression is an evolutionary adaptation that emerged where displaced dominants needed to make a transition to lower social status and that is now triggered, in those individuals that have this adaptation, by damage to reproductive potential from any source. The behavioural cluster associated with depression includes adoption of a hunched posture, avoidance of eye contact, loss of appetite for food and sex and sleep disruption. This behavioural cluster serves to reduce an individuals’ attack provoking stimuli and so facilitates this social change. When viewed in this context, it becomes clear that many of the brain areas that mediate these behaviours (e.g. the pineal, hypothalamus and amygdala, whose main output, the stria terminalis passes through) all lie in close physical proximity to the third ventricle. In consequence, it is proposed that depression has its origins within this ventricle. Disruption of circadian rhythms, appetite for sex and food and fear/defence responses would all ensue if structures that border the third ventricle, or whose main connections pass through it, were damaged. Therefore, it is hypothesised that the behavioural expression of this adaptation is mediated by a single or pulsatile release of a yet to be identified noxious factor into the ventricular space.
Where did these ideas come from?? Like most everyone else, Hendrie and Pickles (2009) are not satisfied with the current crop of antidepressants or with the monoamine hypothesis of depression (Hirschfeld, 2000), which is incomplete at best. Then they take a giant leap and make up one of those evo psych just-so stories:
...damage to reproductive potential is now the key stimulus that triggers depression in those modern humans that have this adaptation, rather than loss of status per se.This analysis accounts for why it is life events such as the death of a spouse or a child that are major causes of depression.
How about the death of a sister or a grandmother or an uncle? Or a beloved pet? Do these tragic events damage the reproductive potential of those who are prone to depression in such circumstances?

And why is the third ventricle so important?
...many of the brain areas mediating the behavioural cluster associated with depression are in close physical proximity to the third ventricle. For example, the pineal is involved with the regulation of sleep/wake cycles, the hypothalamus regulates appetite for food and sex and the amygdala, whose main output, the stria terminalis passes through the third ventricle has an influence on social affiliation as well as fear and defensive behaviours. Hence, it is proposed that this may well be the site where the behavioural expressions of depression are initiated.

Fig. 3 (Hendrie & Pickles, 2009). Functions of structures closely associated with the third ventricle. The table shows those structures that directly border the third ventricle and those that are connected to it via structures that pass through. The function of the behavioural cluster associated with depression is to reduce the emission of attack provoking stimuli. This is achieved through increased defensiveness, decreased motivation to engage in consummatory behaviours and sleep disturbance, so that there are activity peaks at times when other individuals are inactive. The damage produced by the release of a noxious substance into the CSF [cerebrospinal fluid] is not under precise control...

Uh huh. And how are we supposed to identify this unknown toxin released into the CSF in order to develop new treatments? They come up with two ideas:
The first is to try and identify the proposed substance that is causing the damage with a view to blocking its action or preventing its’ release. This would however be technically difficult as it relies on obtaining samples of CSF from the third ventricle at a precise time, to catch the pulse or pulses. As this would probably not be possible in humans, animal models will be of importance...

The second approach is to develop treatments that target the damage and so reverse its effects. Given that for purely statistical reasons, it is mostly glial cells that are affected, as may also be reflected in alterations to peripheral measures, growth factors such as BDNF and GDNF could be of benefit. ... Nonetheless, treatment using this approach will always be vulnerable to a second or subsequent release of the causative agent and hence the identification of that remains the real prize.
Any takers? What a wonderful project for a graduate student!


Hendrie, C., & Pickles, A. (2009). Depression as an evolutionary adaptation: Anatomical organisation around the third ventricle. Medical Hypotheses DOI: 10.1016/j.mehy.2009.10.026

Hirschfeld RM. (2000). History and evolution of the monoamine hypothesis of depression. J Clin Psychiatry 61 Suppl 6:4-6.

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Friday, November 27, 2009

Does "Internet Addiction" Really Shrink Your Brain?

Internet addiction is a murky and controversial disorder that is the subject of intense debate over whether it should be included in the new DSM-V. Here are the proposed diagnostic criteria as developed by Dr. Kimberly Young:
  1. Do you feel preoccupied with the Internet (think about previous online activity or anticipate next online session)?

  2. Do you feel the need to use the Internet with increasing amounts of time in order to achieve satisfaction?

  3. Have you repeatedly made unsuccessful efforts to control, cut back, or stop Internet use?

  4. Do you feel restless, moody, depressed, or irritable when attempting to cut down or stop Internet use?

  5. Do you stay on-line longer than originally intended?

  6. Have you jeopardized or risked the loss of significant relationship, job, educational or career opportunity because of the Internet?

  7. Have you lied to family members, therapist, or others to conceal the extent of involvement with the Internet?

  8. Do you use the Internet as a way of escaping from problems or of relieving a dysphoric mood (e.g., feelings of helplessness, guilt, anxiety, depression)?

Answering "yes" to five or more questions may mean you suffer from Internet addiction over a six month period and when not better accounted for by a manic episode.
You can rate your own level of addiction by taking the Internet Addiction Test (sponsored by The Center for Internet Addiction, of course).

Dr. Young was featured in a recent article, along with Dr. Vaughan Bell (of Mind Hacks fame) taking the contrary position:
Internet addiction: New-age diagnosis or symptom of age-old problem?

. . .

Kimberly Young, director of the online resource The Center for Internet Addiction, says that internet addiction may not yet be clearly defined, but you know it when you see it.

. . .

Young: “The internet has inherent value and utility, and there are many good things about it, but there is this dark side.”

Or is there? Not according to Vaughan Bell, a visiting research fellow with the Department of Clinical Neuroscience, Institute of Psychiatry at King's College London in the United Kingdom. Bell has argued that the internet is not an activity, and therefore internet addiction is a flawed idea (J Ment Health 2007;16[4]:445-57).

“Fundamentally, the internet is a medium of communication,” says Bell, who claims that one can no more be addicted to the internet than to radio waves. “The concept itself doesn’t make sense.”

Bell acknowledges that some people use the internet and other technologies to excess, but believes they do so to avoid dealing with underlying problems, such as depression or social anxiety disorder, which have well-established treatments.
Other prolific bloggers who are noted opponents of the IA diagnosis include Dr. Shock and Dr. John Grohol.1

On the other hand, internet addiction is accepted as a major a problem in several Asian countries, including China and South Korea. Some of you might be familiar with the stories of [alleged] abusive and illegal clinics in China. With this as background, it was inevitable that someone would do a neuroimaging study of individuals with IA, and it was a group in Shanghai that was the first to do so (Zhou et al., 2009).

In their study, 18 teenagers (2 females and 16 males, mean age = 17.23 ± 2.6) with IA were compared to 15 age-matched control participants. Structural MRIs were performed and quantified using voxel-based morphometry (VBM):
VBM is a neuroimaging analysis technique that allows investigation of focal differences in brain anatomy, using the statistical approach of so-called statistical parametric mapping. ... VBM registers every brain to a template, which gets rid of most of the large differences in brain anatomy among people. Then the brain images are smoothed so that each voxel represents the average of itself and its neighbors. Finally, the image volume is compared across brains at every voxel.
The paper was very light on analytic methods and mum on important details about possible co-morbid psychiatric diagnoses in the kids with IA. As noted by Vaughan, depression and social phobia -- along with bipolar disorder, obsessive-compulsive disorder, various addictions, and other impulse control disorders -- could compel one to spend more time on the internet for gambling, gaming, chatting, porn-watching, etc.

With all these caveats in mind, the results are shown below.
...the VBM of the MRI data illustrated that the IA group had lower GMD [gray matter density] in the left anterior cingulate cortex (ACC), left posterior cingulate cortex (PCC), left insula, and left lingulate gyrus. No significant difference was found in the white matter change between the two groups.

Fig. 1 (Zhou et al., 2009). Regions of decreased GM shown on the template in the left anterior cingulate cortex (A), left posterior cingulate cortex (B), left insula (C), and left lingual gyrus (D) in IA subjects compared with the controls.

Most of the changes look pretty small, so it's hard to know what to make of them. On top of that, some of the regions seem mislabeled (the posterior cingulate in particular looks way off). And the findings only demonstrate correlation, not causation.

So in the end we have no idea if "internet addiction" shrinks your brain...


1 Blogging and social media are not addictive at all. Right?


Zhou, Y., Lin, F., Du, Y., Qin, L., Zhao, Z., Xu, J., & Lei, H. (2009). Gray matter abnormalities in Internet addiction: A voxel-based morphometry study. European Journal of Radiology DOI: 10.1016/j.ejrad.2009.10.025

xkcd - Bored With the Internet

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Sunday, November 22, 2009

The Extrastriate Body Area and Visual Distortions in Anorexia

Contour Drawing Rating Scale (Thompson & Gray, 1995) - established as a reliable and valid measure of body size perception.

Anorexia nervosa, an obsessive and unrelenting quest for thinness, is one of the most deadly psychiatric disorders. The documented mortality rate ranges from 3.3% to 18% in different studies (Herzog et al., 2000), and those with the disorder are ten times more likely to die from their illness than a comparable healthy population. A severe distortion of body image is a cardinal feature of anorexia:
Disturbance in the way in which one's body weight or shape is experienced, undue influence of body weight or shape on self-evaluation, or denial of the seriousness of the current low body weight.
An excellent recent review covered the alterations in widespread neural circuits observed in those with anorexia, along with abnormalities in the neurotransmitters serotonin and dopamine (Kaye et al., 2009):
New brain imaging technology provides insights into ventral and dorsal neural circuit dysfunction — perhaps related to altered serotonin and dopamine metabolism — that contributes to the puzzling symptoms found in people with eating disorders. For example, altered insula activity could explain interoceptive dysfunction, and altered striatal activity might shed light on altered reward modulation in people with anorexia nervosa.
Another angle to examine is the reason for such pervasive distortions of self-image. Are there literally changes in visual cortex function that correlate with this symptom?

But first, a few words on some confusing neuroanatomical terminology. The striatum is a subcortical structure that consists of the caudate nucleus and the putamen. As mentioned above, the striatum is involved in reward processing (among other things). On the other hand, the primary visual cortex, or V1 (at the back of the occipital lobe) is sometimes referred to as striate cortex. Higher levels of visual cortex beyond V1 are known as extrastriate cortex. And there is where our story begins.

In 2001, an fMRI study demonstrated that a specific region in extrastriate cortex, in the lateral occipitotemporal cortex, showed selective responses to pictures of bodies and body parts relative to other types of visual stimuli (Downing et al., 2001). The authors dubbed this region the "extrastriate body area" (EBA). An earlier study in epileptic patients (McCarthy et al., 1999) found regions that showed selective responses to hands, relative to faces and objects (they didn't test other body parts). Instead of using fMRI, McCarthy and colleagues recorded from electrode grids placed directly on the cortical surface for the purpose of monitoring for seizures, prior to surgical resection of the epileptogenic tissue. They observed a specific electrophysiological response, which was evoked 230 msec after the subjects viewed pictures of hands.

So the question arises, are there neuroanatomical and functional changes in the extrastriate body area of individuals with anorexia? Suchan et al. (2009) quantified the structural MRIs of 15 women with anorexia and 15 healthy control women. They also localized the EBA using functional MRI -- participants viewed the stimuli used in the study of Downing et al. (freely available for download). The participants also completed the Contour Drawing Rating Scale, and the scores were compared to those given by 10 independent female raters who viewed photos of the subjects.

Not surprisingly, the women with anorexia (BMI=16.0, see images of Christian Bale in Anorexia, Insomnia, and Paranoia for an example) overestimated their body size. Conversely, the healthy women (BM=22.0) underestimated their body size. And using a whole-brain voxel-based morphometric analysis, gray matter density was indeed reduced in the left EBA of the anorexic participants.

Fig. 2 (Suchan et al. (2009). Activation of the extrastriate body area (EBA) localizer scans from healthy age matched controls (blue), women with anorexia nervosa (AN; green) and reduction of gray matter in the EBA of the AN group (white). Overlap between EBA activation of healthy, age matched controls and AN is coloured in light-blue.

Of course, whether the neuroanatomical change is a cause or an effect of the disease is unknown, as acknowledged by the authors:
Although the present study is the first to demonstrate focused gray matter volume reduction in the EBA, several open questions remain. First, the causality is unclear. Future studies using a longitudinal design should focus on the question of whether the EBA volume reductions precede the onset of the AN and therefore might be of etiological relevance or whether they are a result of the disorder.
Nevertheless, preliminary evidence supports a role for visual perceptual deficits contributing to body image distortion in anorexia nervosa.

I'll leave you with the music video for Tunic (Song for Karen) by Sonic Youth. It's a weirdly arty but touching depiction of Karen Carpenter's struggle with anorexia and bulimia, with Kim Gordon as Karen.

dreaming, dreaming of a girl like me
hey what are you waiting for - feeding, feeding me
I feel like I'm disappearing - getting smaller every day
but I look in the mirror - I'm bigger in every way


Downing PE, Jiang Y, Shuman M, Kanwisher N. (2001). A cortical area selective for visual processing of the human body. Science 293:2470-3.

Herzog DB, Greenwood DN, Dorer DJ, Flores AT, Ekeblad ER, Richards A, Blais MA, Keller MB. (2000). Mortality in eating disorders: a descriptive study. Int J Eat Disord. 28:20-6.

Kaye WH, Fudge JL, Paulus M. (2009). New insights into symptoms and neurocircuit function of anorexia nervosa. Nat Rev Neurosci. 10:573-84.

McCarthy G, Puce A, Belger A, Allison T. (1999). Electrophysiological studies of human face perception. II: Response properties of face-specific potentials generated in occipitotemporal cortex. Cereb Cortex 9:431-44.

Suchan, B., Busch, M., Schulte, D., Grönermeyer, D., Herpertz, S., & Vocks, S. (2010). Reduction of gray matter density in the extrastriate body area in women with anorexia nervosa. Behavioural Brain Research, 206 (1), 63-67 DOI: 10.1016/j.bbr.2009.08.035

Thompson MA, Gray JJ. (1995). Development and validation of a new body-image assessment scale. J Pers Assess. 64:258-69.

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Anorexia, Insomnia, and Paranoia

The Machinist, a 2004 film directed by Brad Anderson, features the emaciated skeleton of Christian Bale as a haunted character named Trevor Reznik. He suffers from chronic insomnia ("haven't slept in a year" [which is impossible]), a cleanliness obsession that compels him to scrub his hands and bathroom floor with bleach, and a massively unhealthy case of anorexia complete with regular weigh-ins.

Reznik was involved in a horrible tragedy, is an outcast at work (even before causing an accident that amputates a co-worker's arm), and begins interacting with elusive individuals. You wonder how he has the energy to do anything, let alone work in a machine shop. He can only find solace in the arms of the proverbial hooker with a heart of gold, with Jennifer Jason Leigh in the typecast role. While they're in bed together, it seems the petite Jason Leigh might crush him.

I recently watched the film for the first time, and Bale's anorexic body obviously played the starring role. The 6 foot (1.83 m) tall actor lost 60 pounds (27 kg) for the part, reaching a low weight of 119 (54 kg). This put his body mass index (BMI) at 16.1, clearly in the range that should not have been allowed by the film crew.

He supposedly starved himself for 4 months, consuming only coffee, apples, and tuna. Was that really necessary? No. 140 pounds would have been sufficient. Usually anorexia is viewed as a disorder that only occurs in girls, but it can affect boys (and men) as well (Woodside et al., 2001; Scagliusi et al., 2009).

But Christian Bale is definitely not one who goes in for moderation, either in his personal life or his acting choices. For a nice analysis of Bale's performance and the spectacle (and specter) of his body in The Machinist, see Weight Watching: Method Acting as a Label and Subtext in The Machinist.


Scagliusi FB, Nakagawa KA, Campos RM, Kotait M, Fabbri A, Sato P, Cordás TA. (2009). Nutritional knowledge, eating attitudes and chronic dietary restraint among men with eating disorders. Appetite. Sep 3. [Epub ahead of print]

Woodside DB, Garfinkel PE, Lin E, Goering P, Kaplan AS, Goldbloom DS et al., (2001). Comparisons of men with full or partial eating disorders, men without eating disorders, and women with eating disorders in the community. American Journal of Psychiatry 158:570–574.

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Friday, November 20, 2009

Bleed It Out

I've opened up these scars
I'll make you face this
I pulled myself so far
I'll make you, face, this, now!
---Linkin Park

Deliberate self-harm, or self-injury, is becoming increasingly recognized as a problem affecting adolescents and young adults. Rates are difficult to determine, as the behaviors are often concealed. One recent study tracked a group of 1400 Midwestern US high school students over a 5 year period (Muehlenkamp et al., 2009). Rates of non-suicidal self-injury (NSSI) over 2001-205 were as follows:

Besides being associated with depression and eating disorders (especially among girls), the current psychiatric bible (DSM-IV-TR) includes self-injury as one of nine diagnostic criteria for Borderline Personality Disorder:
Recurrent suicidal behavior, gestures, threats or self-injuring behavior such as cutting, interfering with the healing of scars (excoriation) or picking at oneself.
Other criteria of BPD include:
  • A pattern of unstable and intense interpersonal relationships characterized by alternating between extremes of idealization and devaluation.
  • Identity disturbance: markedly and persistently unstable self-image or sense of self.
  • Impulsivity in at least two areas that are potentially self-damaging (e.g., promiscuous sex, eating disorders, binge eating, substance abuse, reckless driving).
  • Affective instability due to a marked reactivity of mood (e.g., intense episodic dysphoria, irritability or anxiety usually lasting a few hours and only rarely more than a few days).
Although it's considered a very serious personality disorder, the diagnostic label is a controversial one, coming under fire from feminists (Shaw & Proctor, 2005) and from some psychiatrists, like Dinah at Shrink Rap (see Over The Border Line).

Why Do Cutters Have Reduced Pain Perception?

An earlier study by Schmahl et al. (2006) examined the Neural correlates of antinociception in borderline personality disorder during the administration of heat pain. Do borderline patients injure themselves to "feel" (or "feel more normal") OR to down-regulate the emotional components of pain? The results didn't really answer this question, but the authors gave two options:
Limbic deactivation has been found to correlate with the degree of coping in aversive situations in general. . . . Thus, in view of these findings, self-inflicted pain may function to normalize neural activity in specific brain regions involved in emotional and cognitive processing. Alternatively, repeated self-injury could lead to an adaptation of pain thresholds and pain processing reflected in the current findings of elevated pain thresholds and disturbed prefrontal and limbic pain processing.
A new fMRI study by Kraus et al. (2009) took a different approach and compared BPD patients and controls who listened to standardized scripts of self-injurious behavior while in the scanner. The procedure was as follows:

Script-driven imagery was utilized to deliberately evoke emotional distress. The segments were Neutral (a woman on a shopping trip), Trigger (the woman watching a dispute between a mother and her child), Cognitive and Emotional Reactions (think about similar situations with your own mother), Self-Injurious Behavior (a typical act is described, from preparation to cutting itself), and Relaxation (presumably including the SI-induced decrease in aversive inner tension in BPD).

For the between-group comparisons, the imaging data weren't particularly strong at revealing robust differences. The primary finding was reduced activity in left orbitofrontal cortex in the BPD patients during the Cognitive and Emotional Reaction phase, possibly reflecting dysregulation of emotional control. However, the most intriguing finding in my view was deactivation in mid-cingulate cortex during the Self-Injury script. Although the authors didn't plot this result, the coordinates for the deactivation overlap with regions of the anterior cingulate involved in the affective components of pain (Rainville et al., 1997).

What's plotted below is the result of a coordinate-based meta-analysis of the neuroimaging literature on pain perception using the activation likelihood estimation (ALE) method. Articles on physical pain were identified in the BrainMap database (see Hypnosis and Pain Control for details). Of relevance for our current purposes is this midsaggital slice showing strong activation across studies of pain perception in a region of the anterior cingulate cortex that showed deactivation in the BPD patients during the self-injury script (the precise focus is indicated by the blue crosshairs). Although very preliminary, this finding may suggest that imagining an act of self-injury may downregulate the affective component of pain in individuals with borderline personality disorder.

As always, there are limitations with such a pilot study. The authors even list them at the outset:
  • Fixed-effects analyses limit the ability to generalize from the study sample to the larger population of patients with borderline personality disorder (BPD).
  • Due to the study design, a single section of the script could not be repeatedly presented, thus possibly diminishing the effect size of our results.
  • As no control script was used, it cannot be determined whether our findings are related to self-injurious behavior (SIB) per se or to BPD features in general.
Nonetheless, Kraus et al. are continuing to expand on this work with fMRI studies that more closely mimic SIB than the present script design.


Kraus, A., Valerius, G., Seifritz, E., Ruf, M., Bremner, J., Bohus, M., & Schmahl, C. (2009). Script-driven imagery of self-injurious behavior in patients with borderline personality disorder: a pilot FMRI study. Acta Psychiatrica Scandinavica DOI: 10.1111/j.1600-0447.2009.01417.x

Muehlenkamp JJ, Williams KL, Gutierrez PM, Claes L. (2009). Rates of non-suicidal self-injury in high school students across five years. Arch Suicide Res. 13:317-29.

Rainville P, Duncan GH, Price DD, Carrier B, Bushnell MC. (1997). Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science 277:968-71.

Schmahl C, Bohus M, Esposito F, Treede RD, Di Salle F, Greffrath W, Ludaescher P, Jochims A, Lieb K, Scheffler K, Hennig J, Seifritz E. (2006). Neural correlates of antinociception in borderline personality disorder. Arch Gen Psychiatry. 2006 Jun;63(6):659-66.

Shaw C, Proctor G. (2005). Women at the Margins: A Critique of the Diagnosis of Borderline Personality Disorder. Feminism and Psychology 15:483-490.

I bleed it out digging deeper
Just to throw it away
I bleed it out digging deeper
Just to throw it away
I bleed it out digging deeper
Just to throw it away

Just to throw it away
Just to throw it away
I bleed it out

Bleed It Out
---Linkin Park

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Wednesday, November 18, 2009

Good News/Bad News Update on Nucleus Accumbens DBS for Treatment-Resistant Depression

Taken from Fig. 1 (Bewernick et al., 2009). Hamilton Depression Rating Scale (PDF) over time.

Two and a half years ago, The Neurocritic wrote about the very early results of deep brain stimulation (DBS) in the nucleus accumbens for severe, refractory depression. You can read about the details of the procedure and its scientific motivation here:

More About the Nucleus Accumbens

NAcc Localization for DBS

Briefly, the nucleus accumbens (NAcc) is considered one of the brain's PLEASURE CENTRES:
When the cortex has received and processed a sensory stimulus indicating a reward, it sends a signal announcing this reward to a particular part of the midbrain–the ventral tegmental area (VTA)–whose activity then increases. The VTA then releases dopamine not only into the nucleus accumbens, but also into the septum, the amygdala, and the prefrontal cortex.

The nucleus accumbens then activates the individual’s motor functions, while the prefrontal cortex focuses his or her attention.
It makes sense as a DBS target region from the standpoint of anhedonia (inability to experience pleasure from normally pleasurable life events) in major depression. Why not stimulate the "pleasure center" when you're feeling blue? Extensive research in animals and humans has demonstrated "hedonic hot spots" in the NAcc.

The current paper by Bewernick et al., 2009 reports on the results from 10 patients who received NAcc-DBS for at least 12 months. These patients were severely ill and completely non-responsive to any other treatment. On average, they had been continuously depressed for 10 years, were completely unable to work, had been hospitalized numerous times, had failed over 20 medication treatment courses, were currently on 4 different drugs, had received over 20 electroconvulsive therapy (ECT) treatments, and 316 hours of therapy, all to no avail.

The primary results are illustrated in Fig. 1 above. Half the patients (n=5) were considered "treatment responders" who experienced a 50% reduction of depressive symptom severity as assessed by the HDRS, and half did not respond. Anxiety scores also declined in the responders, and engagement in pleasant activities increased.

There were some adverse events related to the surgical procedure (swollen eye in 6 patients, pain and dysphasia in 3), as well as transient adverse events related to stimulation parameter changes e.g., anxiety (n=3), hypomania, paresthesia, and agitation (all n=2). Nonetheless, the authors concluded on a positive note:
DBS to the nucleus accumbens had clinically relevant antidepressant and antianhedonic effects in a patient population that was at least as treatment-resistant as those reported on in other studies of DBS in major depression (Lozano et al., 2008; Malone et al. 2009). The efficacy to adverse event ratio in this small group was favorable. Site-specific antianxiety effects also could be demonstrated.

By targeting one site in a network of brain regions implicated in processing of affective stimuli, it was possible to manipulate anhedonia in particular. Additional studies with larger sample sizes and rigid selection criteria are needed to analyze effects of stimulation to different targets on specific symptoms and clinical phenotypes of depression. In the future, symptom-based DBS therapy, adapted to the individual needs of the patients, could be a plausible treatment option for severe TRD.


Bewernick, B., Hurlemann, R., Matusch, A., Kayser, S., Grubert, C., Hadrysiewicz, B., Axmacher, N., Lemke, M., Cooper-Mahkorn, D., & Cohen, M. (2009). Nucleus Accumbens Deep Brain Stimulation Decreases Ratings of Depression and Anxiety in Treatment-Resistant Depression. Biological Psychiatry DOI: 10.1016/j.biopsych.2009.09.013

Lozano AM, Mayberg HS, Giacobbe P, Hamani C, Craddock RC, Kennedy SH. (2008). Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry 64:461-7.

Malone DA Jr, Dougherty DD, Rezai AR, Carpenter LL, Friehs GM, Eskandar EN, Rauch SL, Rasmussen SA, Machado AG, Kubu CS, Tyrka AR, Price LH, Stypulkowski PH, Giftakis JE, Rise MT, Malloy PF, Salloway SP, Greenberg BD. (2009). Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biol Psychiatry 65:267-75.

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Saturday, November 14, 2009

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

"I feel your pain"

Empathy for another person's pain is a hot topic of study in the glamorous field of social cognitive neuroscience. The capacity for empathy supposedly involves mirror neurons, those media darlings of The Young, [The Not-So-Young], and The Neuro:
A mirror neuron is a neuron that fires both when an animal acts and when the animal observes the same action performed by another. Thus, the neuron "mirrors" the behavior of the other, as though the observer were itself acting.
These magical cells have even inspired famous neuroscientists to utter ridiculous hyperbole:

The mirror neurons, it would seem, dissolve the barrier between self and others. I call them "empathy neurons" or "Dalai Llama neurons".

by V.S. Ramachandran
Synesthesia for pain, a newly described syndrome, goes one step further (Fitzgibbon et al., 2009):
In synaesthesia for pain a person not only empathises with another's pain but experiences the observed or imagined pain as if it was their own. Neural mechanisms potentially involved in synaesthesia for pain include “mirror systems”: neural systems active both when observing an action, or experiencing an emotion or sensation and when executing the same action, or personally experiencing the same emotion or sensation. For example, we may know that someone is in pain in part because observation activates similar neural networks as if we were experiencing that pain ourselves. We propose that synaesthesia for pain may be the result of painful and/or traumatic experiences causing disinhibition in the mirror system underlying empathy for pain.
And what is synesthesia, exactly? According to Edward M. Hubbard's website, SYNESTHESIA can be defined as unusual conscious experience, in which stimulation of one sensory modality leads to a sensory experience in a second, unstimulated sensory modality. For example, seeing letters might lead some people to see colors. Others report that the days of the week or months of the year are arranged like a map in space. Still others report that hearing voices or music cause them to see colors, or that hearing words makes them taste fact, almost any sensory modality can be involved in synesthesia.
One of the more common forms of synesthesia (illustrated above) is grapheme-color synesthesia, where numbers and letters are consistently associated with specific colors (Ward et al., 2005). A more unusual form is lexical-gustatory synesthesia, in which spoken and written words elicit specific taste sensations that remain constant (Ward & Simner, 2003). For instance, Tony Blair tastes like desiccated coconut.

According to the recent review of the literature by Fitzgibbon et al. (2009), amputees with phantom limb pain comprise the vast majority of those with synaesthesia for pain:
Known Characteristics of Synaesthesia for Pain in a Sample of Amputees with Phantom Pain

Brought on by viewing others in pain and/or observing pain on the television and in movies.

Brought on both when observed pain matches that of the amputated site and/or any general pain

Brought on regardless of the identity of the observed person in pain, i.e. can be a loved one or a stranger.

The experience is similar to the experiences of phantom pain, for example, described as a short sudden ‘electric shock’.

Experienced in the phantom limb and/or stump.
The researchers propose that:
pain experiences may cause disinhibition of mechanisms underlying empathy for pain, resulting in synaesthesia for pain. This proposal is supported by studies that have found mirror activity to be involved in the pain matrix (e.g. Ochsner et al., 2008 and Singer et al., 2004); however, the specific processes that weaken these inhibitory mechanisms are unclear...
Ultimately, in synaesthesia for pain, "there is no self–other distinction in the observation of pain in another person."


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

Ward J, Simner J. (2003). Lexical-gustatory synaesthesia: linguistic and conceptual factors. Cognition 89:237-61.

Ward J, Simner J, Auyeung V. (2005). A comparison of lexical-gustatory and grapheme-colour synaesthesia. Cognitive Neuropsychology 22:28-41.

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Sunday, November 08, 2009


You've heard of Neuromarketing, which measures the neural activity of consumers (via fMRI or EEG) in response to various products or advertisements. Now, get ready for Genomarketing! The Neuroethics & Law Blog has alerted us to a recent paper by De Neve and Fowler (2009) reporting that people with a specific low efficiency variant of the gene for monoamine oxidase A are significantly more likely to have credit card debt. Monoamine oxidase A (MAO-A) is an enzyme that breaks down the monoamine neurotransmitters (dopamine, norepinephrine, epinephrine, and serotonin). Using data from the National Longitudinal Study of Adolescent Health, the authors found in that sample of 18-26 year olds,
Having one or both MAOA alleles of the low efficiency type raises the average likelihood of having credit card debt by 7.8% and 15.9% respectively. About half of [the U.S.] population has one or both MAOA alleles of the low type. Prior research has linked this genetic variation to lack of conscientiousness, impulsivity, and addictive behavior.
Is this the foreshadowing of a highly unethical marketing practice? Marketing based on MAO-A genotype, as determined from mailed-in credit card applications and payments? Credit card companies will have in-house labs to extract DNA from stamps and envelope flaps (Sinclair & McKechnie, 2000; Ng et al., 2007).1 Taking it one step further, entire marketing campaigns will be tailored to specific markers in an individual’s genome.2

Is this what it’s coming to? Not so fast. Are there any limitations in the findings of De Neve and Fowler (2009)? There are many!! The paper reported:
Allele frequency for the low grouping is 41% and high grouping is 59% in our sample. In Wave III, subjects were asked “Do you have any credit card debt?" About 41% answered in the affirmative.
However, the ONLY question asked was “Do you have credit card debt?” – not how much debt or anything else. And of course, the interactions between genes and environment are immense, despite what simplistic popular media notions might lead you to believe (see Neuroanthropology for a critique). Without getting into details (which are better left to other blogs), De Neve and Fowler also note that:
Model 2 includes a number of socio-economic factors that influence financial decision-making. Income and education may in fact mediate the relationship between the genes we have identified and credit card usage.
Finally, another recent paper (Beaver & Holtfreter, 2009) found that possessing the high efficiency MAO-A allele (opposite of the one discussed here) predicts involvement in fraudulent behaviors. But only if you hang around with the wrong crowd. Specifically,
Analysis of male participants from the National Longitudinal Study of Adolescent Health (J. R. Udry, 2003) revealed a statistically significant Gene × Environment interaction in which the high-MAOA activity allele increased the odds of fraudulent behaviors, but only among male participants with a high number of delinquent peers.
Fraudulent behavior was determined by two questions. Can you guess them?

(1) How many times during the past 12 months have you used someone else’s credit card or bank card without their permission or knowledge?

(2) How many times during the past 12 months have you deliberately written a bad check?

Ha! Beaver and Holtfreter discuss the contrast of careful and deliberate planning [high-activity alleles] vs. impulsive violence3 [which also has a link to low-activity alleles]:
Genetic imaging research examines whether different alleles of a particular polymorphism are associated with differences in brain structure and functioning. Results have revealed that respondents possessing the low-MAOA activity alleles have limbic volume reductions, decreased cingulate activation, and hyperactivity in the amygdala and hippocampus—differences that may begin to explain the link between MAOA and violence. However, the etiologies of serious violence and fraudulent behaviors may be dissimilar. For example, engaging in fraudulent behaviors may take more time and more planning than is typical of most other antisocial behaviors, which are relatively unplanned and impulsive.
Bernie Madoff vs. Phil Spector? Sort of.


1 This would only work, of course, for those who still conduct such business the old fashioned way. And please note that the cited references use these techniques for legitimate purposes!!

2 See also Please Complete a Genome Scan with Your Mortgage Application. EDIT: and this, too: Overspending: Blame It On Your ‘Debt Gene’?

3 Just stating the obvious here, but having credit card debt in no way, shape, or form implies that one is violent.


Beaver, K., & Holtfreter, K. (2009). Biosocial Influences on Fraudulent Behaviors. The Journal of Genetic Psychology, 170 (2), 101-114. DOI: 10.3200/GNTP.170.2.101-114

De Neve, Jan-Emmanuel and Fowler, James H. The MAOA Gene Predicts Credit Card Debt (August, 18 2009). Available at SSRN:

Ng LK, Ng A, Cholette F, Davis C. (2007). Optimization of recovery of human DNA from envelope flaps using DNA IQ System for STR genotyping. Forensic Sci Int Genet. 1(3-4):283-6.

Sinclair K, McKechnie VM. (2000). DNA extraction from stamps and envelope flaps using QIAamp and QIAshredder. J Forensic Sci. 45(1):229-30.

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Friday, November 06, 2009

A New Outlook

"A New Outlook" is a multimedia installation by Bree Yenalavitch at...
...Project Room G3, an artist run project space found by Sojung Kwon started April 2009, that focuses on work which has a performative, temporal, and non-classical aesthetic. It is located at Angels Gate Cultural Center in San Pedro [in Southern California].

Bree Yenalavitch is a Los Angeles area artist working in multimedia. She received her BA from the University of California Santa Barbara in 2002 and MFA from Otis College of Art and Design in 2006. Her recent online project can be viewed at, where she presents the laboratory of Dr. Specialist - a great woman of science. Bree can also be seen in the Inauguration Show at Project Room G3, where viewers interacting with her participatory project will find their perspective has been rendered askew.

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Everything in its Right Place

Sarah Sze
Things Fall Apart
"010101: Art in Technological Times"

Sarah Sze is a contemporary visual artist (and winner of a MacArthur Fellowship in 2003) who creates unique, site-specific sculptures and installations which make use of ordinary technological and scientific objects.

Even the details in Sarah Sze’s sculptures have details. All her installations are extraordinarily ambitious and are constructed with fastidious precision, consequently, her output is relatively small compared with many other artists. Everything in its Right Place, 2002–03, is one of her most important and most ambitious works.


The multitude of small parts in Sze’s Everything in its Right Place shifts us away from a panoramic spectatorship to inspection mode. The site-specificity of Sarah Sze’s work is best understood through the idea of environments created by overarching structures of collection and models, where narratives and nostalgias intersect as property and space, affecting us through the flickering effect of their soaring elegance and beauty.
And then we have the ever-optimistic Thom York of Radiohead, who has a different idea of the concept...

Everything, everything, everything, everything..
In its right place
In its right place
In its right place
In its right place

What, what is that you try to say?
What, what was that you tried to say?
Tried to say.. tried to say..
Tried to say.. tried to say.. tried to say...

Everything In Its Right Place

Beating Heart - Scott Becker Multimedia

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