The Neurocritic

The Journal of Chatroulette Studies

2012-05-26T21:16:00.005-07:00

"Men do not share women’s desire to be desired. Instead, they emulate their bonobo brethren: The internet is saturated with penis self-portraits from every nation on Earth. At any given moment, one in four cameras on the webcam network ChatRoulette are aimed at a penis."
-Ogi Ogas

A new scholarly journal has published its inaugural issue,¹ with a ground-breaking cover article by Dr. Ogi Ogas and Dr. Sai Gaddam on the evolutionary underpinnings of exhibitionism, from primates to humans. A précis of this trenchant paper (by Dr. Ogas) recently appeared in Wired:

The Urge to Sext Naked Self-Portraits Is Primal
Over the past two years, more photographs of bare-naked celebrity anatomy have been leaked to the public eye than over the previous two centuries: Scarlett Johansson snapping a blurry self-portrait while sprawled on her bed, Vanessa Hudgens posing for a cellphone in a bracelet and a smile, Congressman Wiener touting a Blackberry and a mirror in the House Members Gym, Jessica Alba, Christina Aguilera, Miley Cyrus, Ron Artest, Charlize Theron, Chris Brown, Bret Favre, Rihanna, Pete Wentz, Ke$ha, and dozens more.
This flood of celebrity skin has prompted folks to wonder, ‘Why are so many famous people exhibitionists?’ The source of all this au naturel flaunting lies not in the culture of fame, but in the design of our sexual brains. In fact, research has unveiled two distinct explanations: Female exhibitionism appears to be primarily cortical, while male exhibitionism is mainly subcortical.

You mean there have been neuroimaging studies of sexting and other forms of exhibitionism?

No, not really. The other definitive sources for this piece are Girls Gone Wild, MySpace, Facebook, an adult networking site, primatologist Frans de Waal's Peacemaking Among Primates (1990), and Reddit’s heterosexual Gone Wild forum (2010).

The précis also coincides with the release of the paperback version of A Billion Wicked Thoughts, their authoritative treatise on internet sex. Some of you might remember Ogas and Gaddam from the Neurofanfic queries of 2009, when the proto-title of their book was Rule 34: What Netporn Tells Us About The Brain. Some of their innovative research involved polling the writers and consumers of online fanfic:

Hi,

I'm a cognitive neuroscientist at Boston University writing a book for Dutton (an imprint of Penguin) about how the Internet reveals new insights into some of the oldest circuits in our brain which control romantic attraction and sexual behavior. I was very much hoping you might be willing to chat about Crack Van on LJ.
. . .
For our research, we're quite interested in learning about how people creatively use text and fiction to express and explore sexuality. If you're willing, we'd like to ask questions about Crack Van and about adult fanfic in general. If you'd like, we'd be happy to include a positive mention of you and/or Crack Van in the book (or respect your privacy, if you'd prefer).
If you have any questions about our research or book, please don't hesitate to ask! I look forward to hearing from you! :)
Dr. Ogi Ogas
Department of Cognitive and Neural Systems
Boston University

However, some were not prepared for such forward-looking methods, so the poll generated an enormous amount of controversy in the fanfic community. [They're a very prolific bunch.] For a summary of this fantastic dialogue, I recommend Sex, Lies and IRB Tape: Netporn to SurveyFail at Neuroanthropology.

And I urge you to check out the other titles in this prestigious academic series, the Journal of Speed Dating Studies and the Journal of Facebook Studies.

For more on the gendered evolutionary roots of sexting, see Jezebel and the Columbia Journalism Review.

Footnote

¹ Disclaimer: this post is a spoof, and these are not real APS journals.

Blast Wave Injury and Chronic Traumatic Encephalopathy: What's the Connection?

2012-05-17T19:23:00.002-07:00

Fig. 3 (Goldstein et al., 2012). Single-blast exposure induces CTE-like neuropathology in wild-type C57BL/6 mice.

In a tour de force, a group of 35 Boston-area scientists¹ (Goldstein et al., 2012) developed a mouse model of blast-related neurotrauma that resulted in pathological changes similar to chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease seen most often in athletes with repeated concussions. They also reported post-mortem neuropathological findings from the brains of war veterans and amateur football players who had sustained concussions and traumatic brain injuries (TBIs).

Diagnosis of CTE occurs after autopsy, because the brain tissue has to be stained for characteristic protein abnormalities which cannot be visualized in a living human. A defining pathological feature is tauopathy - abnormal accumulations of the tau protein seen in other dementias (e.g., Alzheimer's disease). Aggregations of hyperphosphorylated tau into neurofibrillary tangles (NFTs) are a defining feature, as in frontotemporal lobar degeneration and amyotrophic lateral sclerosis - yet CTE is distinct from both of these (McKee et al., 2009). CTE results in cognitive and behavioral changes including memory impairments, poor impulse control, alterations in mood, suicidal behavior, disorientation, and ultimately dementia.

Can Blast Waves Cause Chronic Traumatic Encephalopathy?

The major conclusion drawn from the human data in this study is that exposure to blasts from IEDs causes CTE (Goldstein et al., 2012). However, my contention is that the cause of tauopathies in these military veterans is unclear. Three of the four had histories of concussion from other events.

Much of what you've read about this paper in the media is wrong.

The worst offender by far was Business Insider:

Scientists Looked Inside The Brains Of Troops Killed By Bombs And Made This Shocking Discovery

Trauma from exposure to a single improvised explosive device (IED) blast can result in long-term brain impairment, according to new research.
The study, published today in the journal Science Translational Medicine, is the first to examine postmortem brains of U.S. military personnel who were exposed to a blast and/or a concussive injury.
It found evidence that a single blast from a typical IED can cause traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE).

Really?

1) None of the troops were killed by bombs -- they all died from other causes.

2) None of the troops had a single isolated blast exposure.

3) It is not the first study to examine postmortem brains of U.S. military personnel who were exposed to a blast and/or a concussive injury. That would be the paper by Omalu, Hammers, et al. (2011). I wrote about it here.²

4) The evidence that a single IED blast can cause TBI and CTE did not come from looking inside the brains of troops, it was obtained from a mouse model of neurotrauma.

Next, let's take a look at what the paper actually did.

Part 1 - Human CTE

The brain banks at the Center for the Study of Traumatic Encephalopathy and the Alzheimer's Disease Center at Boston University provided the brains of 12 human subjects:

4 male military veterans (ages 22-45 yrs) with histories of explosive blast and/or concussive injury 1 to 6 years before death
4 male athletes (ages 17-27 yrs) with histories of repetitive concussive injury, including 3 football players and a professional wrestler
4 male controls (ages 18-24 yrs) with no known blast exposure, trauma history, or neurological disease

Case histories of the military veterans are presented below, to show that 3 of the 4 had concussions that were not due to explosive blast.

Case 1, a 45-year-old male U.S. military veteran with a single close-range IED blast exposure, experienced a state of disorientation without loss of consciousness that persisted for ~30 min after blast exposure. He subsequently developed headaches, irritability, difficulty sleeping and concentrating, and depression that continued until his death 2 years later from a ruptured basilar aneurysm. His medical history is notable for a remote history of concussion associated with a motor vehicle accident at age 8 years.

Case 2, a 34-year-old male U.S. military veteran without a history of previous concussive injury, sustained two separate IED blast exposures 1 and 6 years before death. Both episodes resulted in loss of consciousness of indeterminate duration. He subsequently developed depression, short-term memory loss, word-finding difficulties, decreased concentration and attention, sleep disturbances, and executive function impairments. His neuropsychiatric symptoms persisted until death from aspiration pneumonia after ingestion of prescription analgesics.

Case 3, a 22-year-old male U.S. military veteran with a single close-range IED blast exposure 2 years before death. He did not lose consciousness, but reported headache, dizziness, and fatigue that persisted for 24 hours after the blast. He subsequently developed daily headaches, memory loss, depression, and decreased attention and concentration. ... He was diagnosed with PTSD 3 months before death from an intracerebral hemorrhage. His past history included 2 years of high school football and multiple concussions from fist fights.

Case 4, a 28-year-old male U.S. military veteran with two combat deployments, was diagnosed with PTSD after his first deployment 3 years before death. His history was notable for multiple concussions as a civilian and in combat, but he was never exposed to blast. ... He died from a self-inflicted gunshot wound 2 years after his last concussion.

In brief, Case 1 had a concussion in a car accident as a child, Case 3 had multiple concussions from football and fist fights, and Case 4 had major concussions at 12 yrs (bicycle accident with loss of consciousness and amnesia), 17 yrs (football injury with no loss of consciousness), 25 yrs (altered mental status during military deployment), and 26 yrs (accident with loss of consciousness and amnesia).

Case 4 had no history of blast exposure at all, so his results are not even related to the title of the paper. Only Case 2 had blast exposures with no other cause of concussion. And here we don't know the duration of unconsciousness, so it's difficult to know the severity of the TBIs.

Part 2 - Mouse CTE

In addition to reporting the post-mortem pathology, the authors developed an animal model of blast injury. The paper was truly a collaborative effort, as it involved physics, engineering, immunology, neuropathology, immunohistochemistry, neuroanatomy, electron microscopy, behavioral neurobiology, electrophysiology, and biochemistry. I'm surprised there weren't more than 35 authors. You'd certainly need a small army of bloggers to adequately describe all the experiments, so I'll merely outline some of the methods and results in the Appendix at the end of this post.

The take home message is that CTE-like pathology, cellular dysfunction, and impairments in learning and memory were observed within 2 weeks of a single blast exposure. Two weeks.

What does it all mean for veterans and athletes with brain injury?

We don't know the full implications yet. Many questions remain.

1) Do such dramatic changes really occur within 2 weeks of a single blast wave or concussive injury in humans? Most individuals (up to 90%) with a single concussion recover fully within 3 months (Bigler, 2008).

2) Would the mice continue to get worse if followed over a longer time interval? CTE is a degenerative disease, yet most individuals with concussions improve over time.

3) Is the damage dose-dependent? How many hits do you need for cognitive and behavioral changes to occur? Two of the athletes had such severe injuries that they died shortly after the last concussion.

4) Are some people more susceptible to developing CTE? One might guess that's the case, or else there would be hundreds of thousands of former athletes with very severe cognitive and psychiatric issues.

5) Studies have shown there are risk genes, such as polymorphisms of apolipoprotein E (APOE), that influence outcomes after head injury (Teasdale et al., 1997; Omalu, Bailes et al., 2011). It would be nice to have a more complete picture of the cases reported here.

6) I believe none of the CTE pathology is evident from in vivo MRI scans of various sorts. That's why diagnosis is done at autopsy. However, it might be time to explore the use of 18F-FDDNP (Shin et al., 2011; Small et al., 2012), a molecular imaging probe that labels tau and NFTs, in PET studies of living persons considered at risk for CTE.

Footnotes

¹ ...with 26 separate sources of funding.

² This case also involved multiple concussions from football and auto accidents in addition to blasts. Omalu et al. linked the pathology to PTSD rather than concussion. I argued there was Little Evidence for a Direct Link between PTSD and Chronic Traumatic Encephalopathy.

References

Bigler ED. (2008). Neuropsychology and clinical neuroscience of persistent post-concussive syndrome. J Int Neuropsychol Soc. 14:1-22.

Goldstein, L., Fisher, A., Tagge, C., Zhang, X., Velisek, L., Sullivan, J., Upreti, C., Kracht, J., Ericsson, M., Wojnarowicz, M., Goletiani, C., Maglakelidze, G., Casey, N., Moncaster, J., Minaeva, O., Moir, R., Nowinski, C., Stern, R., Cantu, R., Geiling, J., Blusztajn, J., Wolozin, B., Ikezu, T., Stein, T., Budson, A., Kowall, N., Chargin, D., Sharon, A., Saman, S., Hall, G., Moss, W., Cleveland, R., Tanzi, R., Stanton, P., & McKee, A. (2012). Chronic Traumatic Encephalopathy in Blast-Exposed Military Veterans and a Blast Neurotrauma Mouse Model. Science Translational Medicine, 4 (134), 134-134 DOI: 10.1126/scitranslmed.3003716

McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA. (2009). Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol. 68:709-35.

Omalu B, Bailes J, Hamilton RL, Kamboh MI, Hammers J, Case M, Fitzsimmons R. (2011). Emerging histomorphologic phenotypes of chronic traumatic encephalopathy in American athletes. Neurosurgery 69:173-83; discussion 183.

Omalu B, Hammers JL, Bailes J, Hamilton RL, Kamboh MI, Webster G, & Fitzsimmons RP (2011). Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide. Neurosurgical focus 31 (5): E3.

Shin J, Kepe V, Barrio JR, Small GW. (2011). The merits of FDDNP-PET imaging in Alzheimer's disease. J Alzheimers Dis. 26 Suppl 3:135-45.

Small GW, Siddarth P, Kepe V, Ercoli LM, Burggren AC, Bookheimer SY, Miller KJ, Kim J, Lavretsky H, Huang SC, Barrio JR. ( 2012). Prediction of cognitive decline by positron emission tomography of brain amyloid and tau. Arch Neurol. 69:215-22.

Teasdale GM, Nicoll JA, Murray G, Fiddes M. (1997). Association of apolipoprotein E polymorphism with outcome after head injury. Lancet 350:1069-71.

Appendix

Part 1 - Human CTE

Athletes

Case 5, a 17-year-old male high school football player who died from second impact syndrome 2 weeks after concussion
Case 6, an 18-year-old high school football and rugby player with a history of 3-4 previous concussions, one requiring hospitalization, who died 10 days after last concussion
Case 7, a 21-year-old male college football player, who played as a lineman and linebacker but had never been diagnosed with a concussion during 13 seasons of play beginning at age 9, and who died from suicide
Case 8, a 27-year-old male professional wrestler who experienced more than 9 concussions during his 10-year professional wrestling career who died from an overdose of OxyContin

Controls

Case 9, an 18-year-old male who died suddenly from a ruptured basilar aneurysm
Case 10, a 19-year-old male who died from a cardiac arrhythmia
Case 11, a 21-year-old male who died from suicide
Case 12, a 24-year-old male who died from suicide

Fig. 1 (modified from Goldstein et al., 2012). CTE neuropathology in postmortem brains from military veterans with blast exposure and/or concussive injury and young athletes with repetitive concussive injury.

Part 2 - Mouse CTE

Developed a blast neurotrauma model (using a compressed gas blast tube) to investigate the mechanistic linkage between blast exposure, CTE neuropathology, and neurobehavioral sequelae

Measured intracranial pressure dynamics and head kinematics during real or sham blasts

Assessed subsequent CTE-linked neuropathology, ultrastructural pathology, and phosphorylated tau proteinopathy

Examined brains 2 weeks after single blast or sham
Gross examination was unremarkable, but immunohistochemical analysis revealed marked neuropathology in the blasted brains, which included:

reactive astrocytosis throughout the cortex, hippocampus, brainstem, etc.
enhanced phosphorylated tau CP-13 immunoreactivity in superficial cortical layers
hippocampal CA1 neurons intensely Tau-46–immunoreactive with evidence of frank neurodegeneration in hippocampal CA1 and CA3 subfields and dentate gyrus
activated perivascular microglia throughout the brain, especially in the cerebellum

Examined ultrastructural pathology using electron microscopy

Confirmed the presence of phosphorylated tau proteinopathy using immunoblot analysis of tissue homogenates prepared from mouse brains 2 weeks after single-blast or sham-blast

Immunoblot analysis revealed a significant blast-related elevation of various phosphorylated tau protein epitopes

Found persistent functional impairments in hippocampal neurophysiology

Slowed axonal conduction
Deficient long-term potentiation (LTP) of activity-dependent synaptic transmission (a candidate mechanism of memory storage)

Single-blast exposure induced long-term behavioral deficits

Acquisition and long-term retention of hippocampal-dependent spatial learning and memory was impaired
These deficits were prevented by head immobilization during blast exposure

Fatal Hypernatraemia from Excessive Salt Ingestion During Exorcism

2012-05-15T02:06:00.002-07:00

Scene from The Exorcist (1973)

Now here's something you don't see every day (fortunately!):

Fatal voluntary salt intake resulting in the highest ever documented sodium plasma level in adults (255 mmol L−1): a disorder linked to female gender and psychiatric disorders (Ofran et al., 2004).

Excessive ingestion of salt is a well-recognized cause of hypernatraemia in children, is uncommonly recognized in debilitated elderly persons, but is rarely diagnosed in healthy, independent adults. We report a case of fatal salt poisoning in a 20-year-old lady who suffered of post-natal depression and ingested large quantities of salt as part of exorcism ritual. She presented with the highest ever documented serum sodium level of 255 mmol L⁻¹, associated with severe neurological impairment that was unresponsive to aggressive hypotonic fluid replacement. Post-mortem examination ruled out any other possible probable cause of death. The medical literature was reviewed, and 16 previous cases of severe hypernatraemia in adults secondary to excessive salt ingestion were retrieved. Common features of all reported cases included female gender (95% of cases) and evidence of underlying cognitive or psychiatric disorders (all reported cases). We conclude that women with documented cognitive or psychiatric disorders, in particular depression, are susceptible for psychogenic salt poisoning. Awareness should be raised to the potentially life-risking use of salty beverages as emetics or as part of ‘exorcism’ rituals.

Although the patient received a prescription for Prozac to treat her postpartum depression, her family also advised her to undergo an exorcism. She reportedly drank six glasses of a mixture of 1 kg table salt in a liter of water! That's more than what's in your average container of Morton salt.

In another fatal case (Hédouin et al., 1999), a 19 year old woman with post-surgical epilepsy was severely flogged and forced to drink 5 liters of salt water as part of an exorcism. The imam involved in this case was arrested and charged with torture.

A summary of the literature on salt poisoning is presented below (from Ofran et al., 2004).

-- click on image to enlarge --

The third horrific report involved the exorcism of a 36 year old woman forcibly administered 1 kg of salt (Raya et al., 1992):

Five hours after admission, the patient showed clinical criteria of brain death, confirmed by electroencephalogram. Postmortem examination showed evidence of dehydration with a great decrease in the volume of the whole brain, several foci of parenchymal hemorrhage, and subarachnoid hemorrhage. ...
...we cannot rule out the possibility of rectal or vaginal administration of salt in our patient in the context of fanatic superstitious rituals and activities of an exceptional nature as those referred to in the case presented herein.

Pass the unsalted popcorn??

References

Hédouin V, Révuelta E, Bécart A, Tournel G, Deveaux M, Gosset D. A case of fatal salt water intoxication following an exorcism session. Forensic Sci Int. 1999 Jan 4;99(1):1-4.

Ofran Y, Lavi D, Opher D, Weiss TA, Elinav E. Fatal voluntary salt intake resulting in the highest ever documented sodium plasma level in adults (255 mmol L-1): a disorder linked to female gender and psychiatric disorders. J Intern Med. 2004 Dec;256(6):525-8.

Raya A, Giner P, Aranegui P, Guerrero F, Vazquez G. Fatal acute hypernatremia caused by massive intake of salt. Arch Intern Med. 1992 Mar;152(3):640, 646.

An Orgy of Self-Referential Blogging...

2012-05-12T14:24:00.003-07:00

...may follow from a new PLoS ONE paper on bloggers whose posts are aggregated at ResearchBlogging.org (Shema et al., 2012):

The average RB blogger in our sample is male, either a graduate student or has been awarded a PhD and blogs under his own name.

The Neurocritic has never been one for meta-blogging.¹ I don't like to draw attention to my existence as an actual person, and I don't have time to discuss things like the pros/cons of blogging, scientific outreach, gender imbalances, scientist bloggers vs. science writer bloggers, commenting policies, and blogging networks. It's not that these aren't worthwhile topics, it's just that it's not my thing.

For those issues, I recommend reading Scicurious, who has blogged thoughtfully (and extensively) about them. As you can see in the figure below, she's a major player in the RB science blogging tweeting universe.

Figure 3 (modified from Shema et al., 2012). Twitter interconnections – followers.

In a way, I feel like this article is the peer-reviewed equivalent of a link bait site that names you as a Top Fifty Psychology Blog, just asking for egotistical bloggers to post about it.

Well I'm not falling for it...

Footnote

¹ That said, The Neurocritic's last post jokingly mentioned self-referential processing in the context of linking to oneself, but that was only because I actually have written extensively on spindle neurons, aka von Economo neurons.

Reference

Shema, H., Bar-Ilan, J., & Thelwall, M. (2012). Research Blogs and the Discussion of Scholarly Information. PLoS ONE, 7 (5) DOI: 10.1371/journal.pone.0035869

Spindle Neurons in Macaques?

2012-05-10T04:49:00.001-07:00

Spindle neurons, or Von Economo neurons (VENs), are a unique type of large, bipolar neuron found primarily in layer Vb in the anterior cingulate cortex and the frontoinsular cortex of humans.¹ In 1999, Nimchinsky and colleagues discovered that among the 28 nonhuman primate species they examined, only great apes had VENs [see Spindle Neurons: The Next New Thing?].

Spindle neurons are also seen in humpback, fin, sperm, and killer whales (Hof & Van der Gucht, 2007), elephants (Hakeem et al., 2009), and cetaceans such as the bottlenose dolphin, Risso’s dolphin, and the beluga whale (Butti et al., 2009).

Because VENs are only found in large-brained, highly evolved social species, and are potentially implicated in certain neurological and psychiatric disorders, their hypothesized functions include empathy, conscious awareness, and self-referential processing. A 2011 review by Allman and colleagues reiterated that only great apes (bonobos, chimpanzees, gorillas, orangutans) have VENs and suggested they...

...may be a specialization related to very large brain size. The large size and simple dendritic structure of these projection neurons suggest that they rapidly send basic information from FI [frontoinsular cortex] and LA [limbic anterior area] to other parts of the brain, while slower neighboring pyramids send more detailed information. Selective destruction of VENs in early stages of frontotemporal dementia (FTD) implies that they are involved in empathy, social awareness, and self-control, consistent with evidence from functional imaging.

VENs: Not Only for Great Apes Any More!

But now, a new study has identified these special neurons in the insular cortex of macaque monkeys (Evrard et al., 2012).

Figure 1 (Evrard et al., 2012). The Von Economo Neuron Is Present in Layer 5b in a Restricted Portion of the Agranular Anterior Insula in the Macaque Monkey (A) High-magnification photomicrographs demonstrating the identical morphology of the macaque and human VENs. Scale bar represents 25 μm.

Why weren't they found in the earlier studies that looked for them?

Three reasons: (1) they're a lot smaller in monkeys; (2) they're more fragile in monkeys; and (3) they're confined to a more limited anatomical region.

First, the large human VENs unambiguously stand out at low microscope magnifications. Searching for relatively smaller VENs among the densely packed cell population in layer 5 in the monkey required the highest microscope magnification, which would be unusual for anyone accustomed to examining the more obvious VENs in hominids. Second, the cytoskeletal matrix of the small monkey VENs might be more fragile during histological processing than that of the larger human VENs. ... Third, in the major prior study, the number of VENs in humans and great apes was counted in consecutive sections that were apparently spaced at 1 mm intervals ... such a sampling paradigm would likely have been inadequate for the identification of VENs within the small VEN-containing region of the ventral AAI that measures ∼2 × 2 × 1 mm³ in macaques.

The authors pointed out a major advantage of their new discovery, namely that more invasive studies are now possible (i.e., you can't do single cell neurophysiology in dolphins or bonobos).

But wait... are they really VENs?

The morphology, size, laminar distribution, and proportional distribution of the monkey VEN suggest that it is at least a primal anatomical homolog of the human VEN.

Allman, Hof, and colleagues might have something more to say on the matter, based on their earlier findings (e.g., Allman et al., 2011):

The VENs are illustrated at higher magnification in Figure 3, which shows that they have very similar morphology in the great apes and humans. In primates, the VENs are present in FI only in great apes and humans. This is the same taxonomic distribution as was found for the VENs in LA, which suggests that the VENs emerged as a specialized neuron type in the common ancestor of great apes and humans.

Figure 3 (Allman et al., 2011). VENs in area FI of humans and great apes.

The new paper concedes that:

The presence of VENs in the macaque does not discredit prior evidence for a crucial role of the VENs and AIC in the emergence of self-awareness and social cognition in humans (Craig, 2009; Allman et al., 2011). VENs in humans appear to be disproportionally slightly larger than in macaques (see above); they may also have an enhanced immunopositivity (and perhaps gene expression) for proteins that are typically involved in homeostasis, which perhaps favors higher interoceptive sensitivity.

Are they confined to the anterior insula in macaques? No, VENs were also found in the ACC, but that will be reported separately (a lesson for all you junior scientists).

Now that they've been found in monkeys [and can be studied physiologically], will spindle neurons finally catch up with their more glamorous elder cousins, the mirror neurons? Are they really the next new thing? Six years ago, I pondered these points:

Somehow, the "spindle neuron" meme hasn't caught on like the "mirror neuron" meme. Is it because spindle neurons have been only been described anatomically (not physiologically), while the reverse is true for mirror neurons? Anatomically speaking, do we know much about mirror neurons?

Evrard, Forro, and Logothetis are all over it:

...invasive studies of their organization, hodology, and physiology could provide significant insights into the evolutionary basis for self-awareness and empathy in humans. Regarding the latter, it would be particularly interesting to examine whether the VENs share functional similarities with the “mirror” neurons of the ventral premotor cortex (Gallese et al., 2004).

Finally, a commentary in Neuron by Critchley and Seth (2012) wonders if studies of the macaque insula will reveal the neural mechanisms of self-referential processes underlying conscious awareness. If VENs indeed mediate self-referential processing, then they were largely involved in writing this post.

More Reading

Spindle Neurons: The Next New Thing?

Spindle Neurons in Humpback Whales

Spindle Neurons and Frontotemporal Dementia

Spindle Neurons and Science Writing

Spindle Neurons in Elephants and Dolphins: Convergent Evolution in Large-Brained Mammals?

Footnotes

¹ The VENs and other large pyramidal cells in cortical layer V are projection neurons that provide output to more distant regions.

References

Allman JM, Tetreault NA, Hakeem AY, Manaye KF, Semendeferi K, Erwin JM, Park S, Goubert V, Hof PR. (2011). The von Economo neurons in the frontoinsular and anterior cingulate cortex. Ann NY Acad Sci. 1225:59-71.

Butti, C., Sherwood, C., Hakeem, A., Allman, J., & Hof, P. (2009). Total number and volume of Von Economo neurons in the cerebral cortex of cetaceans. Journal of Comparative Neurology 515:243-259.

Evrard, H., Forro, T., & Logothetis, N. (2012). Von Economo Neurons in the Anterior Insula of the Macaque Monkey. Neuron, 74 (3), 482-489 DOI: 10.1016/j.neuron.2012.03.003

Hakeem, A., Sherwood, C., Bonar, C., Butti, C., Hof, P., & Allman, J. (2009). Von Economo Neurons in the Elephant Brain. The Anatomical Record: Advances in Integrative Anatomy and Evolutionary Biology 292:242-248.

Hof PR, Van Der Gucht E. (2007). Structure of the cerebral cortex of the humpback whale, Megaptera novaeangliae (Cetacea, Mysticeti, Balaenopteridae). Anatom Rec Part A, 290:1-31.

Nimchinsky EA, Gilissen E, Allman JM, Perl DP, Erwin JM, Hof PR. (1999). A neuronal morphologic type unique to humans and great apes. Proc Natl Acad Sci 96:5268-73.

Neurophysiological Explanation for the Perception of Poltergeists

2012-05-05T15:10:00.001-07:00

Poltergeist (1982) - IMDb ¹

Poltergeists are defined as paranormal, mischievous ghostly presences that appear to a select group of people. As paranormal entities, they are beyond investigation by rational scientific means. Or are they? Odd sensations, visions, felt presences, out-of-body experiences, etc. have all been explained by unusual brain activity. Hence, neuroscientists should consider that poltergeists exist in the mind of the perceiver, not as a physical reality in the external world.

A new paper by parapsychologist William G. Roll and colleagues reported on the case of a woman who experienced paranormal phenomenon after suffering a head injury (Roll et al., 2012):

People who report objects moving in their presence, unusual sounds, glows around other people, and multiple sensed presences but do not meet the criteria for psychiatric disorders have been shown to exhibit electrical anomalies over the right temporal lobes. This article reports the striking quantitative electroencephalography, sLORETA results, and experimental elicitation of similar subjective experiences in a middle-aged woman who has been distressed by these classic phenomena that began after a head injury. She exhibited a chronic electrical anomaly over the right temporoinsular region. The rotation of a small pinwheel near her while she 'concentrated' upon it was associated with increased coherence between the left and right temporal lobes and concurrent activation of the left prefrontal region. The occurrence of the unusual phenomena and marked 'sadness' was associated with increased geomagnetic activity; she reported a similar mood when these variations were simulated experimentally. Our quantitative measurements suggest people displaying these experiences and possible anomalous energies can be viewed clinically and potentially treated.

Previous work by Roll and Michael ["god helmet"] Persinger (2001) suggested that individuals who experience "anomalous energies" around them might have complex partial epilepsy with a temporal lobe focus, usually on the right side.

The current patient, Ms. S, was in a motor vehicle accident which resulted in two days of coma and a severe brain injury. After the head injury,

...the relationship with her first husband deteriorated because he insisted she was not the same person. This ‘change in personality’ is a frequent report by spouses of individuals who have sustained TBIs. According to her reports one night he tried to kill her. The anomalous phenomena began that night and have been intermittent since that time. Their intensity and frequency have increased during the last 2–3 years. The anomalous phenomena include mechanical, electronic, and visual effects. She reports experiences of sounds, perceived as ‘taps’ that she estimates to be between 3 and 4 Hz with sound pressure equivalents between 40 and 60 db. Occasionally there may be a single louder sound. The durations of clusters are often between 3 and 10 seconds with intervening periods of 4–8 or 16–24 seconds. The clusters are usually localized along her left side.
. . .
Ms. S. reported she feels overwhelmed by a deep sadness after the occurrence of the phenomena and cries, even if nothing ‘bad happens’. Since the beginning of these phenomena she hears voices of multiple ‘imaginary’ friends who she has named; the two major ones are identified as male. They presumably help her minimize the distress of the experiences...

EEG recordings revealed chronically abnormal activity at a right temporal lobe electrode (T4), which showed persistently elevated amplitude. Strangely, this enhanced activity declined when the doors to the recording chamber were closed, as in Fig 1C below.

Figure 1. Sample EEG activity over 19 channels displayed by Ms. S. Note the persistent high amplitude (100 μV) over the right temporal lobe compared to all other lobes (about 20 μV). (A and B) are separated by one day. (C) Shows the attenuation of the T4 anomaly after the doors of an acoustic chamber were closed.

The authors attributed this to a reduction of geomagnetic fields, to which the TBI patient is exquisitely sensitive [supposedly]:

The right temporal lobe anomaly attenuated within about 20 seconds to 1 minute after the doors to the acoustic chamber were closed. In addition to providing above average silence, this procedure reduces the static background geomagnetic field from 50,000 nT to about half that value. When the T4 anomaly was not distinguishable and she was sitting within the closed-door chamber she reported experiences as if she was ‘missing’ something that was similar to a ‘craving’.

But maybe she was just more relaxed in the dim lighting and quiet environment of the chamber...

From here on in, the authors resort to bizarre atmospheric explanations: instabilities in global geomagnetic activity and a K-6 level geomagnetic storm accounted for perceptions of tapping sounds in her hotel bedroom window, the presence of ‘entities’, and unusual lights around objects.

Here's my suggestion: Why don't you take a closer look at her EEG activity in relation to these anomalous perceptions, independent of the spooky magnetic fields?? Is it because your research in parapsychology and neurotheology might float away into the ether?

Footnote

¹ The young actress here, Heather O'Rourke, died at the age of 12 due to "medical error."

References

Roll, W. G. and Persinger, M. A. 2001. “Poltergeists and haunts”. In Hauntings and poltergeists: Multidisciplinary perspectives, Edited by: Houran, J. and Lange, R. 123–163. Jefferson, NC: McFarland & Company.

Roll, W., Saroka, K., Mulligan, B., Hunter, M., Dotta, B., Gang, N., Scott, M., St-Pierre, L., & Persinger, M. (2012). Case report: A prototypical experience of ‘poltergeist’ activity, conspicuous quantitative electroencephalographic patterns, and sLORETA profiles – suggestions for intervention. Neurocase, 1-10 DOI: 10.1080/13554794.2011.633532

WHY A POLTERGEIST WON’T HURT YOU

Little Evidence for a Direct Link between PTSD and Chronic Traumatic Encephalopathy

2012-04-29T17:43:00.006-07:00

Fig. 2 (Omalu et al., 2011). Photomicrographs of tau-immunostained section of the frontal cortex.

Nicholas Kristof wrote an op-ed piece in the New York Times the other day about an Iraq War veteran with post-traumatic stress disorder (PTSD) and alcohol use problems who ultimately took his own life.

Veterans and Brain Disease
By NICHOLAS D. KRISTOF
Published: April 25, 2012
He was a 27-year-old former Marine, struggling to adjust to civilian life after two tours in Iraq. Once an A student, he now found himself unable to remember conversations, dates and routine bits of daily life. He became irritable, snapped at his children and withdrew from his family. He and his wife began divorce proceedings.
This young man took to alcohol, and a drunken car crash cost him his driver’s license. The Department of Veterans Affairs diagnosed him with post-traumatic stress disorder, or P.T.S.D. When his parents hadn’t heard from him in two days, they asked the police to check on him. The officers found his body; he had hanged himself with a belt.

This tragic but all-too-common story had an unusual ending. An autopsy of the veteran's brain revealed signs of chronic traumatic encephalopathy (CTE), a progressive neurodegenerative disease seen most often in athletes with repeated concussions from contact sports such as professional football and boxing. CTE results in cognitive and behavioral changes including memory impairments, poor impulse control, alterations in mood, suicidal behavior, disorientation, and ultimately dementia (Lakhan & Kirchgessner, 2012).

Diagnosis of CTE is usually post-mortem, because the brain tissue has to be stained for characteristic protein abnormalities which cannot be visualized in a living human. A defining pathological feature is tauopathy - abnormal accumulations of the tau protein seen in other dementias (e.g., Alzheimer's disease). In particular, aggregations of hyperphosphorylated tau into neurofibrillary tangles and accumulations of neuronal TAR DNA-binding protein-43 (TDP-43) are seen, as in frontotemporal lobar degeneration and amyotrophic lateral sclerosis (Lakhan & Kirchgessner, 2012).

There have been a string of high profile media reports about CTE pathology found at the autopsy of several American football players: Mike Webster, Terry Long, Chris Henry, Tom McHale, Owen Thomas, and others. Dr. Bennett Omalu and his colleagues at the Brain Injury Research Institute have conducted some of these autopsies (e.g., Omalu, Bailes et al., 2011).¹

Now, Omalu and colleagues have put forth the speculative idea that PTSD is on a continuum with CTE (Omalu, Hammers et al., 2011). Why? PTSD needn't be associated with concussions or traumatic brain injury (TBI) at all. The traumatic event exposure for PTSD (from DSM-IV-TR) "...must have involved both (a) loss of 'physical integrity', or risk of serious injury or death, to self or others, and (b) a response to the event that involved intense fear, horror, or helplessness (or in children, the response must involve disorganized or agitated behavior)." Head injury isn't part of the definition.

Omalu's target population is soldiers and veterans with TBI from the war (not, for instance, survivors of the 2011 earthquake and tsunami in Japan):

Following our elucidation of CTE in athletes, we hypothesized that PTSD in war veterans may belong to the CTE spectrum given that active military personnel are high-risk cohorts for repeated subconcussive and concussive traumatic brain injuries; for example, bomb blasts can cause traumatic brain injuries from primary pressure wave and acceleration-deceleration injury mechanisms. We expanded our CTE surveillance and brain tissue analyses to include deceased military veterans who were diagnosed with PTSD.

OK, that sounds reasonable -- if there's well-documented evidence of subconcussive and concussive brain injuries. Which brings us back to Kristof's article:

That Marine was the first Iraq veteran found to have C.T.E., but experts have since autopsied a dozen or more other veterans’ brains and have repeatedly found C.T.E. [NOTE: none of these cases has been published.] The findings raise a critical question: Could blasts from bombs or grenades have a catastrophic impact similar to those of repeated concussions in sports, and could the rash of suicides among young veterans be a result?
“P.T.S.D. in a high-risk cohort like war veterans could actually be a physical disease from permanent brain damage, not a psychological disease,” said Bennet Omalu, the neuropathologist who examined the veteran.

Oh no! Here we have an unfortunate example of mind-body dualism. PTSD is a physical brain disease, and this is independent of exposure to bomb blasts. There is ample evidence that exposure to traumatic events can physically change the brain (Sapolsky, 1996, 2001). Stress increases the levels of glucocorticoids, which in turn damage the hippocampus. This is visible on MRI scans (Bremner, 2006). The amygdala, a subcortical area involved in processing fear and other emotions, is overactive in those with PTSD while frontal lobe regions controlling the amygdala are underactive (Koenigs & Grafman, 2009).

However, it needn't result in permanent brain damage! In his 2006 review, Bremner notes that effective PTSD treatments can improve memory and restore hippocampal volume.

With this background in mind, let's return to the case report of the 27 yr old Marine. I believe there could be causes of CTE pathology that are unrelated to his military service in Iraq. I'll introduce these items as bullet points and then go into detail about each.

Committed suicide by hanging.
After deployment, played football in a league on base.
One hit from the side caused him to fall to the ground; after this, he was confused and showed signs of a concussion [in my view].
He continued to play football and hockey but was not diagnosed with a concussion (although he suffered his “bell rung”).
Motor vehicle accident under the influence of alcohol, flipped his car, woke up later hanging upside down in the car.

Any or all of these incidents might have injured his brain in a way that could result in (or at least exacerbate) CTE, yet the authors either dismissed them as insignificant or minimized their impact. I am not a neuropathologist so I won't address the actual autopsy findings at this point. However, I do believe there are legitimate questions about the cause(s) of CTE in this Marine, as outlined below.

Suicide by hanging - this causes anoxia, or a lack of oxygen to the brain. Anoxia causes permanent damage and shrinkage of certain brain regions. It also produces astrogliosis, which was reported in the present case study. But can it cause any of the other microscopic neuropathological findings? Perhaps not, but a few relevant papers are listed in the Appendix.

Football - this is a classic cause of CTE. The Marine suffered at least one concussion after his service in Iraq (described below) and had his "bell rung" a number of times (possible subconcussive events):

After his deployments he was stationed at a base and played football in a base league. During a football game in 2009, approximately 9 months after his second deployment, he reported being hit from the side causing him to fall to the ground. He stood up, stumbled, fell again, and then continued the game. Other players noticed that he was confused and kept asking the count and details of the next play and he had to be removed from the game. The events of the following week were unclear and he reported residual headaches and memory problems.

There were no significant findings on a conventional CT scan, but this is standard (as the authors themselves have noted).

The Marine also had a remote injury that resulted in a nasal bone fracture and other possible blows to the head before and after deployment. Yet the authors speculate:

It is our belief that his eventual CTE risk outcome occurred as a result of his lifetime and cumulative exposure to repeated subconcussive and concussive traumatic brain injuries, with his military exposures being the primary injuries that precipitated CTE.

Very little information is provided about his history of blast exposures in Iraq so it seems highly speculative to attribute CTE to those events primarily.

Motor vehicle accident

He woke up later hanging upside down in the car. It was not clear whether he lost consciousness from a head injury or from stuporous alcohol intoxication. He noted the following morning that he suffered from headaches and vomited; however, it was not also clear whether these symptoms were alcohol-related or head injury–related. He lost his driver's license after this crash for driving under the influence and refusing a blood-alcohol test.

But the loss of consciousness, headaches, and vomiting could very well be due to a TBI or concussion he suffered in the car accident!

Military Service:

Reported exposures to mortar blasts and IED blasts less than 50 m away (but was never diagnosed with TBI)
During the second deployment he was court marshaled twice for acting out, insubordination, fighting, hazing, and assault, and was dropped 1 rank.

"Described only a few incidents during his deployment that he found bothersome":

There was an incident during the 3rd week of his first deployment when he witnessed a vehicle in his patrol blown up, and marines killed and wounded. In another incident, approximately 2 weeks later, while hooking up their disabled vehicle to tow, 2 marines in his section were shot and he helped to patch them up. In yet another incident, he witnessed a school bus full of Iraqi citizens, many of whom were children, blown up by an IED.

Diagnoses: PTSD with hyperarousal (irritability and insomnia) and numbing. Also alcohol abuse... In a clinic visit 2 months prior to his suicide, he reported persistent PTSD symptoms.

He visited a Veteran Affairs Medical Center the day before he committed suicide and reported having a new job as a football coach with his old high school, and was currently attending a community college. His driving under the influence charges had been dismissed.

This is certainly a very tragic case study, and I'm in favor of autopsies to consider possible causes of suicides in military veterans. But to speculate that PTSD is a permanent degenerative brain disease on the basis of one published case,² without adequate explanation and appropriate caveats, is irresponsible and damaging.

Let's return to Kristof's opinion piece:

The discovery of C.T.E. in veterans could be stunningly important. Sadly, it could also suggest that the worst is yet to come, for C.T.E. typically develops in midlife, decades after exposure. If we are seeing C.T.E. now in war veterans, we may see much more in the coming years.
So far, just this one case of a veteran with C.T.E. has been published in a peer-reviewed medical journal. But at least three groups of scientists are now conducting brain autopsies on veterans, and they have found C.T.E. again and again, experts tell me. Publication of this research is in the works.
The finding of C.T.E. may help answer a puzzle. Returning Vietnam veterans did not have sharply elevated suicide rates as Iraq and Afghan veterans do today. One obvious difference is that Afghan and Iraq veterans are much more likely to have been exposed to blasts, whose shock waves send the brain crashing into the skull.

Kristof must not have read Omalu et al. very closely, because in that paper they described an earlier autopsy conducted on a Vietnam veteran who died of natural causes.

In 2010 we encountered CTE changes in the brain of a 61-year-old deceased Vietnam war veteran, who died suddenly as a result of coronary atherosclerotic disease. This case was reported in the Stars and Stripes news magazine of the Department of Defense. The case was not published because we did not have comprehensive access to the medical records and family and social histories.

Yes, that study was presented in Stars and Stripes, a military newspaper:

“This is a sentinel case,” Omalu said. “The brain findings in this deceased Army veteran are similar to the brain findings in the retired contact-sport athletes. Now, we need to look at more brains.”
The case suggests that some veterans diagnosed with post-traumatic stress disorder, a psychological disorder, may actually have brain disease caused by concussions, he said.

...and why don't we go ahead and speculate about TBI even though there are no records of such:

Though he cannot prove the veteran suffered head trauma from blasts in combat, Omalu said it’s possible, because the former soldier had never shown any signs of psychotic behavior or drug use prior to going to Vietnam, according to family members and medical records.

It's also possible that the veteran was traumatized by events in Vietnam and started using stimulant drugs, which can cause psychotic behavior. Returning to case published in Neurosurgical Focus:

The authors report this case as a sentinel case of CTE in an Iraqi war veteran diagnosed with PTSD to possibly stimulate new lines of thought and research in the possible pathoetiology and pathogenesis of PTSD in military veterans as part of the CTE spectrum of diseases, and as chronic sequelae and outcomes of repetitive traumatic brain injuries.

Now that's a study for Medical Hypotheses, isn't it?

But seriously, I'm not denying CTE "as chronic sequelae and outcomes of repetitive traumatic brain injuries." And I mean absolutely no disrespect to the veterans and families who are affected by PTSD, concussions, and perhaps CTE in some cases.

Kristof again:

Frankly, I was hesitant to write this column. Some veterans and their families are at wit’s end. If the problem in some cases is a degenerative physical ailment, currently incurable and fated to get worse, do they want to know?
I called Cheryl DeBow, a mother I wrote about recently. She sent two strong, healthy sons to Iraq. One committed suicide, and the other is struggling. DeBow said that it would actually be comforting to know that there might be an underlying physical ailment, even if it is progressive.
“You’re dealing with a ghost when it’s P.T.S.D.,” she told me a couple of days ago. “Everything changes when it’s something physical. People are more understanding. It’s a relief to the veterans and to the family. And, anyway, we want to know.”

What would I tell Ms. DeBow? That PTSD is indeed a physical brain disease. It's not a ghost. And it isn't necessarily permanent.

Yes, it's easier to understand a brain injury that is caused by a physical force outside the head, instead of by a state of turmoil, sadness, and grief inside the head. But PTSD is a physically real injury nonetheless.

Footnotes

¹ The other major CTE research group is the Center for the Study of Traumatic Encephalopathy at Boston University (e.g., McKee et al., 2009).

² Yes, Kristof keeps mentioning other unpublished cases. Perhaps I'll amend this post or do a follow-up once they're published. Or even if I find them online in abstract form.

UPDATE (May 17, 2012): A new paper by Goldstein et al., 2012 reports on 4 new cases of CTE in military veterans, linking the pathology to blast exposure. However, 3 of the 4 also had concussions from other events. See Blast Wave Injury and Chronic Traumatic Encephalopathy: What's the Connection?

References

Bremner JD. (2006). Traumatic stress: effects on the brain. Dialogues Clin Neurosci. 8:445-61.

Koenigs M, Grafman J. (2009). Posttraumatic stress disorder: the role of medial prefrontal cortex and amygdala. Neuroscientist 15:540-8.

Lakhan SE, Kirchgessner A (2012). Chronic traumatic encephalopathy: the dangers of getting "dinged". SpringerPlus 1:2 doi:10.1186/2193-1801-1-2.

McKee AC, Cantu RC, Nowinski CJ, Hedley-Whyte ET, Gavett BE, Budson AE, Santini VE, Lee HS, Kubilus CA, Stern RA. (2009). Chronic traumatic encephalopathy in athletes: progressive tauopathy after repetitive head injury. J Neuropathol Exp Neurol. 68:709-35.

Omalu B, Bailes J, Hamilton RL, Kamboh MI, Hammers J, Case M, Fitzsimmons R. (2011). Emerging histomorphologic phenotypes of chronic traumatic encephalopathy in American athletes. Neurosurgery 69:173-83; discussion 183.

Omalu B, Hammers JL, Bailes J, Hamilton RL, Kamboh MI, Webster G, & Fitzsimmons RP (2011). Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide. Neurosurgical focus, 31 (5) PMID: 22044102

Sapolsky RM. (1996). Why stress is bad for your brain. Science 273:749-50.

Sapolsky RM. (2001). Atrophy of the hippocampus in posttraumatic stress disorder: how and when? Hippocampus 11:90-1.

Appendix

Anoxia/hypoxia:

Acute hypoxia promote[s] the phosphorylation of tau via ERK pathway - hyperphosphorylated tau is a hallmark of CTE, but it did not appear to result in neurofibrillary tangles in this case.

Morphological analysis of astrocytes in the hippocampus in mechanical asphyxiation

Pathological role of hypoxia in Alzheimer's disease - mostly about amyloid beta, not tau.

TDP-43 immunoreactivity in anoxic, ischemic and neoplastic lesions of the central nervous system - did not exhibit TDP-43 inclusions, however.

[NOTE: It could have been that the cause of death was entirely irrelevant, but a statement to that effect would be reassuring.]

New York Times Opinion Page or Medical Hypotheses?

2012-04-28T15:05:00.001-07:00

Medical Hypotheses is an Elsevier journal that publishes highly speculative oddball ideas. The previous editor, Bruce G. Charlton, published pretty much anything he wanted without sending it out for peer review. This got him into a great deal of trouble with legitimate scientists (and ultimately, the publisher) when the dangerous HIV denialism of Peter Duesberg was accepted for publication (only to be later WITHDRAWN). Although savvy researchers know Medical Hypotheses is an outlet for cranks, its articles do appear in PubMed, lending it an air of legitimacy in the eyes of the unsuspecting public.

The journal is now edited by Mehar Manku and its mandate is:

...to give novel, radical new ideas and speculations in medicine open-minded consideration, opening the field to radical hypotheses which would be rejected by most conventional journals. Papers in Medical Hypotheses take a standard scientific form in terms of style, structure and referencing. The journal therefore constitutes a bridge between cutting-edge theory and the mainstream of medical and scientific communication, which ideas must eventually enter if they are to be critiqued and tested against observations.

Submitted manuscripts are now reviewed by both the Editor and external reviewers. But why publish your highly speculative scientific [or pseudoscientific] ideas in a relatively esoteric forum, when you can reach millions and millions of readers with NO PEER REVIEW whatsoever? What sort of journal is this, you ask?

It's not a scientific journal at all, it's..... the Opinion Pages of the venerable New York Times!!

NYT Opinion Page or Medical Hypotheses? The Game!

The rules of NYTOPORMHTG are simple: guess which of the two outlets published the propositions and recommendations listed below.

(1) Meat is brain food

(2) Take magnesium if you're depressed

(3) Masturbate if you're congested

(4) Masturbate if you have restless legs syndrome

(5) Micron strokes cause Alzheimer's disease

(6) Joblessness causes suicide in U.S. military veterans

(7) Chronic traumatic encephalopathy causes suicide in veterans

(8) A noxious factor released into the third ventricle causes depression

(9) Enhanced activity in the anterior insula proves we love our iPhones

(10) Enhanced activity in the anterior insula proves disgust with John Edwards

(11) If you're about to have a panic attack, watch a scary movie

(12) Yoga is good for everything

(13) Stimulants cause PTSD

(14) PTSD causes chronic traumatic encephalopathy

(15) High heels cause schizophrenia

ANSWERS BELOW

NYT - 1, 6, 7, 9, 10, 12, 13, 14

MH - 2, 3, 5, 8, 11, 12, 15

Sleep Medicine (trick question!) - 4

Of the recent opinion pieces in the NYT, I found item #14 by Nicholas Kristof to be particularly egregious, inaccurate, and irresponsible. He cites one terrible (albeit published) case study claiming that chronic traumatic encephalopathy can be caused by post-traumatic stress disorder and considers no alternate explanations. I will address the issues he raised in a future post.

Item #13 by Dr. Richard A. Friedman was speculative and bothersome but ultimately less objectionable. He suggested there's a causal relationship between higher rates of stimulant prescriptions in the US military and rising rates of PTSD. I was very skeptical (because there's no evidence for that) and critical because the article leads the lay reader to believe that Ritalin and other stimulants cause PTSD. Ultimately, he put a "correlation does not equal causation" caveat at the very end, but by then the rhetorical damage was already done.

References

(1) Meat Is Brain Food - NYT

(2) Magnesium for treatment-resistant depression: A review and hypothesis - MH

(3) Ejaculation as a potential treatment of nasal congestion in mature males - MH

(4) Sexual intercourse and masturbation: Potential relief factors for restless legs syndrome? - SM

[also see Orgasm for Relief of Restless Legs Syndrome: A Case Study]

(5) The Micron Stroke Hypothesis of Alzheimer’s Disease and Dementia - MH

(6) The Best Medicine Just Might Be a Job - NYT

(7) Veterans and Brain Disease - NYT

(8) Depression as an evolutionary adaptation: Anatomical organisation around the third ventricle - MH

(9) You Love Your iPhone. Literally. - NYT

[also see This Is Your Brain on Bad fMRI Studies and This Is Your Brain on Additional Critiques]

(11) Aborting panic attacks using false misattribution: a new treatment option - MH

(12) Effects of yoga on the autonomic nervous system, gamma-aminobutyric-acid, and allostasis in epilepsy, depression, and post-traumatic stress disorder - MH and Why Are We Discussing This? - NYT

(13) Why Are We Drugging Our Soldiers? - NYT

(14) Veterans and Brain Disease - NYT

(15) Is there an association between the use of heeled footwear and schizophrenia? - MH

Appendix: The Neurocritic on Medical Hypotheses

The pseudonymous ‘quant bloggers’- Figureheads, ghost-writers and pseudonymous quant bloggers: The recent evolution of authorship in science publishing.

Noxious mystery substance released into the third ventricle is the cause of depression! - Depression as an evolutionary adaptation: Anatomical organisation around the third ventricle.

JFK Neurotoxin Conspiracy Theory Published in Medical Hypotheses - President Kennedy's death: a poison arrow-assisted homicide.

Mirror Neuron Dance Party for Autism Spectrum Disorders - Synchronized dance therapy to stimulate mirror neurons in autism.

The Journal of Truly, Truly Outrageous Medical Hypotheses - Two for one! The classic, Is there an association between the use of heeled footwear and schizophrenia? and Two manic-depressives, two tyrants, two world wars.

More Truly, Truly Outrageous Medical Hypotheses - Ejaculation as a potential treatment of nasal congestion in mature males.

Magic Buttons, Silver Linings, and Two-Edged Swords

2012-04-23T01:26:00.001-07:00

The Subjective Ups and Downs of Mood Disorders

The last post, Suffering for art is still suffering, took a critical look at studies claiming that individuals with bipolar disorder are more creative.¹ And instead of romanticizing the tortured bipolar artist, it considered the toll the disorder can take on those who live with it (and the people around them).

Some readers might have objected to the overly pessimistic tone of that post, prompting them to say things like, "It was a very negative post and clearly you are down on bipolar disorder, if not people who have it." That was not my intent.

So why don't we take a look at the sunnier side of serious mental illness!

The 'Magic Button Question'

“If you could live your life again, would you press the ‘magic button’ to experience life without a mood disorder?”

That's the question Parker et al. (2012) asked 885 patients attending an affective disorders clinic.² Of that number, 335 patients (38%) returned the questionnaires: 111 with bipolar disorder and 224 with unipolar depression. The authors wanted to assess whether the respondents perceived any advantages to their disorders.

Such positives are rarely volunteered, more commonly emerging only when the individual contemplates whether, if they were to live their life again, they would choose to have their mood disorder. A variant of this question was evident in Stephen Fry's BBC documentary (Wilson, 2006) where he explored his and others' experiences of a bipolar disorder. He asked several people to imagine there was “a button” that, if pressed, “…would take away every aspect of your bipolarity and cyclothymia”, and questioned whether they would press that button.

The results of Parker et al.'s study are based on a biased sample of patients who returned the survey: 83% of the bipolar population was diagnosed with Bipolar II (n=92), compared to only 17% with Bipolar I (n=19). In New Zealand,³ the lifetime prevalence of Bipolar I is 1.0%, compared to 0.7% for Bipolar II (Merikangas et al., 2011; see their Table 2). In the US, the figures are 1.0% and 1.1%, respectively. So we know right away the sample is highly self-selected.

Individuals with Bipolar II were three times more likely to endorse advantages to their disorder than those with Bipolar I.⁴ Because of the small number of individuals with Bipolar I, the authors collapsed across subtypes [which doesn't make sense] and found that 62% of bipolar people claimed some positive elements to their illness, compared to only 22% of the unipolar depressed group. "Thematic analyses" suggested that the four most common benefits named by bipolar individuals were:

increased empathy (18%) ⁵
increased creativity (14%)
increased self-awareness (12%)
increased productivity (8%)

Not to belabor the obvious, but this means that 86% did not identify creativity as a benefit, and 92% did not see productivity as an advantage of being bipolar. Hmm. Hardly a ringing endorsement for the bipolar advantage.

In the unipolar depressed group, 14% listed increased empathy as a positive aspect of depression; 9% mentioned self-awareness, 1% creativity and 0% productivity.

Wait, what about the 'magic button' question? The questionnaires didn't ask directly. Despite the title of the paper and four other references to buttons, Parker et al. never did get their answer.

Clouds and Silver Linings

An older paper by Dr. Kay Redfield Jamison and colleagues didn't ask the 'magic button' question either, but it left a sunnier impression of bipolar's positive side. In 1980, Jamison et al. wrote:

Although the psychiatric literature is replete with case reports, symptom checklists, and rating forms designed to assess changes during different mood states, to our knowledge there has been no systematic study of short-term, or state-dependent, positive experiences of affective, behavioral, and perceptual changes perceived by the patients themselves. Nor have patients been asked what long-term benefits they feel they derive from their mood disorders. For these reasons we did a preliminary, admittedly subjective investigation of such experiences in patients with primary affective disorders. We were interested in which changes during hypomania were evaluated as the most important and enjoyable. ... Although the usual caveats about retrospective and self-report data apply, the purpose of our study necessarily makes them less applicable than for other types of research.

Their sample consisted of 61 patients attending an outpatient clinic: 35 were diagnosed as bipolar and 26 as unipolar. The format of the questionnaire was more constrained than that of Parker et al. (2012). While euthymic (asymptomatic) or only mildly depressed, the patients were asked:

“Do you feel that your mood swings have resulted in overall personality characteristics that make you different from most people in the following ways?” for each of the several attributes: overall psychological sensitivity, sexual enjoyment, productivity, creativity, and social outgoingness and ease. Response choices were 1) yes, definitely, 2) probably, 3) probably not, and 4) definitely not.

The bipolar individuals were queried further about specific changes they perceived during episodes of mania or hypomania. Of particular interest was whether the phenomenology of hypomania differed between men and women. The authors readily admit that the phrasing of their questions might have elicited a positive response bias, and that the participants' answers were based on perceptions (and not necessarily reality). Perhaps this can account for the much higher percentage of very positive or somewhat positive ratings for productivity and creativity (relative to the study of Parker et al., 2012), as shown below.

Women in general endorsed "very much increased" positive attributes more often than men, but when collapsed across "very much" and "somewhat" increased, only productivity reached statistical significance. The authors noted that...

...it is interesting that manic-depressive illness -- which ostensibly carries with it more negative social, financial, and interpersonal sequelae and results in more frequent episodes of dysfunction and mood swings (which might also account for its perceived greater influence) than unipolar illness -- is assessed by most patients as making positive contributions to their lives in one or more important ways.

One issue of note for clinicians is the possibility of medication non-compliance. If manic or hypomanic episodes are very enjoyable, a bipolar individual may be inclined to go off medication so as not to blunt or eliminate such experiences.

Two-Edged Swords

Finally, a recent paper in the Journal of Affective Disorders (Lobban et al., 2012) appeared to be the most positive of all, but also the most biased [at least to me] and therefore limited in its generalizability. It presented the opinions of 10 bipolar people in the UK using qualitative methodology:

Interpretative Phenomenological Analysis (IPA) was used to understand the data. This approach is grounded in interpretive epistemology and emphasises the perceptions and experiences of individual participants from their point of view. It attempts to understand how participants make sense of their world and, in this instance, the positive aspects of their bipolar experiences. IPA recognises the active role of the interviewer and analysts and, therefore, prior to the interviews the authors documented their expectations about what the study would find and made explicit
their underlying assumptions where possible. The interviewer also informed all participants of her own diagnosis of BD at the outset of the interview.

While the experiences of these 10 people are certainly valid, it was odd for me to see them represented in a peer-reviewed medical journal. In brief:

Positive aspects were numerous, highly valued and participants welcomed the opportunity to discuss them. Three important themes emerged: 1) Direct positive impact of bipolar experiences on everyday life including amplification of internal states, enhanced abilities and more intense human connectedness; 2) Lucky to be bipolar – the sense of having been given a special gift; 3) Relationship between the self and bipolar experiences.

The participants were all recruited from outside a formal mental health setting and were (perhaps) more likely to see the bright side of their diagnoses. In the words of one participant:

Alan: “It's almost as if it opens up something in the brain that isn't otherwise there, and er I see colour much more vividly than I used to. .....So I think that my access to music and art are something for which I'm grateful to bipolar for enhancing. It's almost as it's a magnifying glass that sits between that and myself.”

Footnotes

¹ Based on Rothenberg's 2001 critique of the work of Andreasen and Jamison.

² The Black Dog Institute Depression Clinic, based in Sydney, Australia.

Patients are requested to complete a detailed series of questionnaires prior to attending the clinic, with salient questions asking them to describe the “best” and “worst” aspects of having a mood disorder, to agree or disagree with the statement that “having a mood disorder can have advantages” and, if the latter is affirmed, to describe any such advantages they had experienced. Questionnaire data were collected from patients referred to the clinic over the 2008–2011 period.

³ Sorry, Australia, you weren't included in that study.

⁴ The numbers given in the paper to support this statement make absolutely no sense, so I won't reproduce them here.

⁵ However, some studies have reported a decrease in cognitive empathy.

References

Jamison KR, Gerner RH, Hammen C, & Padesky C (1980). Clouds and silver linings: positive experiences associated with primary affective disorders. The American journal of psychiatry, 137 (2), 198-202 PMID: 7352574

Lobban, F., Taylor, K., Murray, C., & Jones, S. (2012). Bipolar Disorder is a two-edged sword: a qualitative study to understand the positive edge. Journal of Affective Disorders DOI: 10.1016/j.jad.2012.03.001

Merikangas KR, Jin R, He JP, Kessler RC, Lee S, Sampson NA, Viana MC, Andrade LH, Hu C, Karam EG, Ladea M, Medina-Mora ME, Ono Y, Posada-Villa J, Sagar R, Wells JE, Zarkov Z. (2011). Prevalence and correlates of bipolar spectrum disorder in the world mental health survey initiative. Arch Gen Psychiatry 68:241-51.

Parker, G., Paterson, A., Fletcher, K., Blanch, B., & Graham, R. (2012). The ‘magic button question’ for those with a mood disorder — Would they wish to re-live their condition? Journal of Affective Disorders, 136 (3), 419-424 DOI: 10.1016/j.jad.2011.11.008

Wilson, R., (Director). 2006. Stephen Fry: The secret life of a manic depressive [Motion Picture - YouTube]. BBC: Scotland.

Suffering for art is still suffering

2012-04-13T01:30:00.002-07:00

Edvard Munch, Self-Portrait in Hell (1903)

"I inherited two of mankind's most frightful enemies — the inheritance of consumption and insanity — disease and madness and death were the black angels that stood at my cradle."¹
-Edvard Munch

Many contemporary observers believe that Edvard Munch, the brilliant Norwegian artist best known for The Scream, had bipolar disorder. According to Rothenberg (2001):

A diagnosis of bipolar disorder with psychosis is based on his own diary descriptions of visual and auditory hallucinations, a multiply documented instance of his travelling throughout Europe manifesting manic disrupted behavior that culminated in his shooting two joints off the ring finger of his left hand, and his psychiatric hospitalization in 1908 for an intensification of auditory hallucinations, depression, and suicidal urges. He also suffered from bouts of alcoholism.

In the same article, the abstract expressionist painter Jackson Pollock was raised as another example of the innovative, tortured, bipolar artist. This might be taken as support for the view that creative individuals are more likely be bipolar than those in the general population. Clinical psychologist Kay Redfield Jamison, herself a prolific and talented person with bipolar disorder, has written extensively on this topic (Jamison, 1989, 1993). However, Rothenberg is actually critical of this general notion:

...it has been alleged that the illness makes creative persons more sensitive because of depressive diatheses and more productive while undergoing manic episodes. These allegations represent a romantic notion about creativity—the saga of the suffering artist—with little evidence to support them. Only comedians such as Jackie Gleason and Dick Van Dyke have seemed to derive direct benefit in their work from manic and hypomanic tendencies. Artistic products containing depressive or manic flight of ideas content have, only at particular times in history, been of social and aesthetic interest.

He continues with specific critiques of the methods used by Andreasen (1987) and Jamison (1989). In her sample, Andreasen found that 43% of writers attending the prestigious University of Iowa Creative Writing Program were bipolar, but only 10% of the controls (who included “hospital administrators, businessmen, social workers, lawyers, medical and computer science students”). The groups were not matched for socioeconomic status, peer recognition, intelligence, or success. Finally, Rothenberg notes that "the Iowa Program has long served as a retreat for writers at times of career shifts or setbacks" -- when they might be more likely to be depressed or otherwise affected by a mental illness.

He's even more scathing about Jamison's study of 47 prizewinning British artists and writers:

Stating that the design of the study could not allow for systematic diagnostic inquiry regarding mania and hypomania, Jamison reported that 38% of the sample had been treated for an “affective” illness. No controls, however, were used in the study. Investigator interviews here also were not “blind” and no attempt at differential diagnosis was made. Subjects were asked only “whether or not they had received treatment, and the nature of that treatment, for a mood disorder” (p. 126), and no further diagnostic assessment was reported. This problem was compounded by the fact that subjects were self-selected which, in the absence of controls, introduces the possibility of an overrepresentation of psychiatric illness in the group.

In the last few days, author and blogger David Dobbs (whom I respect and admire) has written about mental illness and creativity. In Jonah Lehrer Meets Stephen Fry – The Paradoxes of Bipolar and Creativity, he discussed Andreasen's work and the third chapter of Lehrer’s new book Imagine:

...[Andreasen] adds that the ideas one comes up with during such phases tend to be quite original, as the manic person, in a set of long-distance synaptic leaps that Lehrer explains earlier, draws associations that lie beyond the reach of more ordinary modes of thought. (NB: Not everyone with bipolar gets these manic “highs.”)* ² The ideas they come up with, in short, can be a bit crazy. If they spit them out then and published them, they’d likely be of little worth. But, as Lehrer explains,

then the mania ebbs. The extravagant high descends into a profound low. While this volatility is horribly painful, it can also enable creativity, since the exuberant ideas of the manic period are refined during the depression.

In other words, the emotional extremes of the illness reflect the extremes of the creative process: there is the ecstatic generation phase, full of divergent thoughts, and the attentive editing phase, in which all those ideas are made to converge. This doesn’t take away, of course, from the agony of the mental illness, and it doesn’t mean that people can create only when they’re horribly sad or manic. But it does begin to explain the significant correlations that have been repeatedly observed between depressive syndromes and artistic achievement.

A new idea is borne during mania, refined when it subsides. If you read only that, you can mistakenly think bipolar disorder is a good thing to have, to let run amok. Lehrer is quick to note that but fairly quickly to move on — he’s writing a book about creativity, not depression.

These ideas sparked a discussion and a follow-up post at Neuron Culture, Madness Ain’t All It’s Cracked Up to Be: A Corrective.³ David graciously included an update, saying that "These links between madness and creativity don’t make the more severe manifestations of depression or bipolar disorder any less destructive or painful." Then he quoted me:

Sometimes I think those who talk about bipolar and creativity haven’t been around many severely manic individuals. There’s overspending, lying, cheating, alienating friends, paranoia, psychosis, taking off and abandoning family, etc. I don’t think there’s anything especially creative about that.

Here’s another idea about bipolar and creativity: the percentage of manic people who engage in creative pursuits exceeds that in the general population. However, much of the output is incoherent. Some small percentage might be brilliant (either during or in between episodes), but then how many people are Kay Redfield Jamison or Stephen Fry (collapsing across bipolar subtypes)?

At any rate, bipolar can be a very destructive illness, and I hope those that romanticize it (or are viewed as romanticizing it) truly understand that. End of rant.

Kay Redfield Jamison is an extremely impressive woman, and a wonderful writer and speaker. I don't mean to detract from all she's done in her professional and personal lives to advance understanding of manic-depressive illness. But how many others (with or without bipolar) are as accomplished? You might as well ask, how many of us will win an Oscar or a Nobel Prize? Not many. Expecting that severe mental illness should confer special creativity is a mistake.

In An Unquiet Mind, Jamison said: “I have often asked myself whether given the choice, I would choose to have manic depressive illness…..strangely enough I think I would” (pp 217–218).

Not everyone feels this way, and the title of this post is taken from the quote below (from an anonymous person with Bipolar I disorder):

"...I've read a fair bit about bipolar disorders and creativity, some interesting theories, and have analyzed my own cycles.
But, this disorder destroyed my life and whatever moments of brilliance I may have had during episodes were not at all worth it. Suffering for art is still suffering.
A few people have found good outlets and moods enhance their work. Good for them. Kay Redfield Jamison is an example. Various famous people. Hemingway. Kurt Cobain. Wonder what they'd say about the mad pride movement?"

Footnotes

¹ Translations are by Bente Torjusen, Words and Images of Edvard Munch.

² David kindly added some of my cranky suggestions:

*Added 4/10/12, 6:13 a.m. EDT. Thanks to a friend for a prod on this. Fry addresses it in the film, but I forgot to include that definitional wrinkle in my post the first time through.

³ NOTE: I found the Rothenberg critique after our exchange, while writing the present post. One thing we did discuss was the difference between Stephen Fry's cyclothymia (Fry has called it "bipolar lite") and the full-blown mania of Bipolar I reflected in my quote.

References

Andreasen NC. (1987). Creativity and mental illness: Prevalence rates in writers and their first degree relatives. American Journal of Psychiatry 144:1288–1292.

Jamison KR. (1989). Mood disorders and patterns of creativity in British writers and artists. Psychiatry 52:125-34.

Jamison KR (1993). Touched With Fire: Manic-Depressive Illness and the Artistic Temperament. New York: Free Press (Macmillan).

Jamison KR (1996). An Unquiet Mind. Crown Publishing Group/Random House, New York, NY.

Rothenberg, A. (2001). Bipolar Illness, Creativity, and Treatment. Psychiatric Quarterly, 72 (2), 131-147 DOI: 10.1023/A:1010367525951

Edvard Munch, Self-Portrait with Skeleton Arm (1895)

What is art -
Art grows from joy and
sorrow - but mostly
from sorrow -
It grows from man's life -
Is art a description of
this life this movement -
Shall one depict the different
pleasures - the different
misfortunes - or shall one
only see the flower - whose
nature substance and vibration
are determined by
the joy and the pain -

I do not believe in an art which
has not forced its way out through
man's need to open his heart -
All art literature as well as
music must be brought out
with one's heart blood -

-E.M., Words and Images of Edvard Munch

Morbidly Curious Blog

2012-04-11T03:29:00.004-07:00

Chicago Cultural Center
78 E. Washington Street
Chicago, IL 60602

Skull Table

While I was in Chicago for the CNS Meeting, I saw the Morbid Curiosity exhibit:

The exhibition explores the ways in which artists and cultures use skulls, bones and skeletons to explore human experiences and perceptions of mortality. Our awareness of death while we are still alive gives shape and meaning to our existence. Mortality is a universal theme in all arts, found repeatedly throughout time and across many cultures. The human body in skeleton form is a rich source of inspiration for contemporary artists as it was for our ancestors, from ancient civilization to the present.

As it is experienced here, the human skeleton represent more than the death. It reveals our shared identity as a species, our most profound common denominator. Signs of race, gender, status and identity melt away. Comntemporary artists use this aspect of the skeleton as an image to represent the ways in which human beings physically interact with the worlds..

Ancient trephined Skull
Pre-Columbian / 16th century human skull with brown patina

The exhibition also includes an extensive Dia de los Muertos (Day of the Dead) section, a small Rembrandt, Albrech Durer's Four Horsemen of the Apocalypse (1518 woodcut), the humorous My Portrait in 1960 (James Ensor, 1888), Death and the Woman by Käthe Kollwitz [who may have had Alice in Wonderland syndrome], and a very memorable mixed media piece by Steve Dilworth:

Hanging Figure [close-up]
1979 / Human skeleton, heart, liver, meat, horsehair, seagrass

Even more gruesome, however, was this sculpture made entirely of wax (and other artificial materials):

Are You Still Mad at Me? By John Isaacs
2001 / steel, wax, artificial blood, mixed media

John Isaacs is interested in the physical functioning of the human body, and this figure is shocking in its realism. Isaacs studied biology and once created a replica of his own body in the style of a wax anatomical model. This modern reinterpretation of the vanitas theme emphasizes the fragility of the human body.

Check out the great blog for Morbid Curiosity: The Richard Harris Collection to see more morbid images!

tDCS Symposium Stimulates Giant Brain in Chicago

2012-04-08T06:07:00.001-07:00

The 2012 Cognitive Neuroscience Society Meeting was held in Chicago from March 31 to April 3. The schedule was packed with three and a half days of symposia, slide sessions, and posters. One well-attended event was Symposium Session 2, on non-invasive brain stimulation.

Using Non-Invasive Brain Stimulation to Enhance Cognitive and Motor Abilities in the Typical, Atypical, and Aging Brain

Chair: Roi Cohen Kadosh, University of Oxford
Speakers: Roi Cohen Kadosh, Jenny Crinion, Paulo S. Boggio, Leonardo G. Cohen

The talk by Dr Jenny Crinion, a speech and language therapist who has gone over to the "dark side" of research (as she put it), drew a lot of attention and media coverage. It's no wonder, given her clinically relevant results.

Jolt to brain aids language recovery
Stroke patients improve on picture-naming task after stimulation treatment
By Laura Sanders
Web edition : Monday, April 2nd, 2012
CHICAGO — A brain zapping technique helps people recover language after a stroke, new research shows. The results may point to a better way for people to relearn how to talk after a brain injury.

The "brain zapping" technique is transcranial direct current stimulation. According to a 2010 review by George and Aston-Jones, it is a very old method undergoing a recent revival:

Transcranial direct current stimulation (tDCS) is perhaps one of the simplest ways of focally stimulating the brain. Similar techniques were practiced almost immediately after electricity was 'discovered' in the late 1880s. Passing a direct current through muscle, or the brain, was in vogue in Europe. For example, one of Charcot's residents, Georges Duchenne de Boulogne, traveled around Paris with a small battery and passed electricity through patients' muscles, examining the effects on numerous disorders and using it to better understand muscle–nerve innervations, particularly in the muscular dystrophies (George, 1994).

How does it work?

Quite simply, tDCS involves passing a weak (usually ≤ 1 mA) direct current through the brain between two electrodes. The current enters the brain from the anode, travels through the tissue, and exits out the cathode. Some researchers refer to this as either cathodal tDCS or anodal tDCS depending on which electrode is placed over the region that is being modified (Figure 5).

Figure 5 (George & Aston-Jones, 2010). A tDCS device uses an anode and cathode connected to a direct current source much like a 9 V battery (a). The direct current passes through the intervening tissue, with some shunting through the skull but much of it passes through the brain and changes resting electrical charge, particularly under the cathode (b).

Crinion started her talk by saying she originally wanted to use transcranial magnetic stimulation (TMS) -- another non-invasive brain stimulation technique -- but this would be too painful if applied over the left inferior frontal cortex (Broca's area). She lamented the NHS limit of 12 hours of speech therapy for stroke patients with aphasia. These individuals would benefit from more intensive therapy (e.g., phonemic cueing) for a longer period of time. From a practical standpoint, then, would tDCS maximize the results obtained during a truncated retraining period?¹ What sort of behavioral and neural effects might be expected with such a regimen?

She continued by describing a study in control participants that combined behavioral priming for overt picture naming, true and sham tDCS, and fMRI (Holland et al., 2011). Anodal tDCS² was applied over the left IFC.³

What are the effects of tDCS on echo planar imaging (EPI)? Any potential for artifacts, you ask? No problem! Supposedly there's signal dropout at the scalp/skull but not the brain. See?

This is what I first saw on the slide. "EPI is not affected," apparently, but the images looked mighty odd to me. What the &^$% kind of brain is that??

It's not a brain, it's a watermelon! Oh...

Figure S1. Effects of A-tDCS on Echo-Planar Images (EPI). Field distortions from control (watermelon) and one participant.
(A) Multi-slice coronal view of watermelon field distortion with indices for each slice. Blue bar indicates the location of anodal electrode... Perturbations were localized to the surface layer only of the watermelon.

Here's more, from Holland et al. (2011).

Figure S1. (D) Consistent with the control data, perturbations in the participants’ data were also localized to the scalp surface only. Here we illustrate in one participant’s coronal sections the effect of the anode electrode on B0 field map data.

All right, so what were the effects of tDCS on picture naming times?

My god, what a giant effect! Oh wait... It's more like a 25 msec improvement (see below), which is still statistically significant.⁴

Figure 1 (modified from Holland et al., 2011). Behavioral Effects of Anodal Transcranial Direct Current Stimulation. Main effects of order, i.e., position of run during scanning session (P1 versus P2; A) ... and stimulation (sham vs. A-tDCS; C), on naming reaction times (n = 10). ... Error bars indicate standard error of the mean (SEM). ^∗∗∗p < 0.001, ^∗∗p < 0.05.

How about the effects of tDCS on the BOLD response? Briefly, stimulation decreased naming-related activity in two localized regions: left inferior frontal sulcus and left ventral premotor cortex (suggestive of neural facilitation):

A-tDCS—by depolarizing neurons nearer to threshold—can reduce the amount of excitatory input required to produce a naming response. Thus, we can have a situation in which there is increased excitability (manifest as a faster response time to a given input) accompanied by reduced BOLD (less synaptic input for a given output, in this case naming).

Finally, the preliminary results of a clinical study were presented. Thirteen participants with aphasia received 60 hours of behavioral training with specific pictures. Patients receiving tDCS over intact left IFC (n=6) or sham stimulation (n=7) were compared. Picture naming accuracy for the trained items improved by 56% in the sham group and by 92% in those getting real stimulation. There was no improvement on the untrained items in either group.

These results are very impressive. However, a quick PubMed search of tDCS, aphasia revealed 20 published articles already⁵ [which was surprising to me, as it wasn't mentioned in the talk. Or else I forgot about it. Or didn't hear it]. Turns out some of these were reviewed in Holland and Crinion (2011). Nevertheless, none of this detracts from the current findings:

This gap persisted after the initial testing, though it diminished in size. Three months out, volunteers who received the stimulation performed 82 percent better than they had performed before treatment, while those receiving sham treatment held steady with a 55 percent improvement. “These are huge effects,” Crinion said. “It’s really encouraging.”

The 3 month followup is longer than previous studies (e.g., Baker et al., 2010; Fridriksson et al, 2011; Marangolo et al., 2011). Crinion and colleagues also plan on publishing the brain imaging results from their ongoing trial.

Where do things go from here? DIY treatment kits? Perhaps (Holland & Crinion, 2011)...

Due to its appeal as a potential treatment tool, some manufacturers (NeuroConn, Germany, personal communication) are exploring mini-tDCS kits for patient's self-administration at home with stimulation dosages pre-programmed by their clinician. Some additional precautions should be considered for safe use of tDCS: (i) patients should have no metallic implants near the electrodes, and (ii) personnel conducting tDCS should be appropriately trained before applying the technique, as experience with the method is still limited and the risk profile of stimulation is not yet completely known.

Further Reading:

Give your brain an electric shock, learn stuff faster

How To Electrify Your Brain To Be Smarter With a 9-Volt Battery -- Kids! Don't try this at home!

DARPA Study Uses Video Game to Research tDCS, Finds More Amps Mean More Frags

Australian Researchers Create “Thinking Cap”, Scheme to Breed Army of Nobel Laureates and Mad Scientists

Neurostimulation - The Genius Machine? -- covers the latest from Richard Chi and Allan "thinking cap" Snyder.

Footnotes

¹ Surprisingly, the NHS website mentions both tDCS and TMS as treatment modalities for aphasia, although no coverage is provided.

It has been suggested that both tDCS and TMS may help to stimulate parts of the language centre that have been damaged and encourage a certain degree of recovery and repair. For example, initial research has found that these types of treatment may help people to improve their ability to remember the names of certain objects, people and places.
As transcranial stimulation is a new method of treatment, access is currently limited to people who are willing to take part in a clinical trial.

² Anodal tDCS (A-tDCS) is thought to increase cortical excitability.

³ MNI coordinates were -48 20 19. More about location and parameters:

A-tDCS stimulation was generated by a specially designed MRI-compatible neuroConn stimulator system and delivered at 2 mA continuously for 20 min via a pair of identical MRI-compatible leads and rectangular rubber MRI-compatible electrodes (5 × 7 cm), allowing for a current density of 0.057 mA/cm². For all participants, the anode was placed over the left IFC (equivalent to electrode position FC5 in a 10-10 EEG nomenclature), with the cathode placed over the contralateral frontopolar cortex.

⁴ More fine print...

Participants were selected based on previous behavioral performance during a speech-priming fMRI task. The main criterion for selection was a word versus control cue priming effect of greater than 85 ms.

...and:

Participants reported no adverse sensations during A-tDCS and sham. They could detect a difference between the two conditions (p = 0.07), but they were unable to reliably distinguish which was A-tDCS.

⁵ Not all of these were double-blind treatment studies, though.

References

Baker JM, Rorden C, Fridriksson J. (2010). Using transcranial direct-current stimulation to treat stroke patients with aphasia. Stroke 41:1229-36.

Fridriksson J, Richardson JD, Baker JM, Rorden C. (2011). Transcranial direct current stimulation improves naming reaction time in fluent aphasia: a double-blind, sham-controlled study. Stroke 42:819-21.

George, M., & Aston-Jones, G. (2009). Noninvasive techniques for probing neurocircuitry and treating illness: vagus nerve stimulation (VNS), transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS). Neuropsychopharmacology, 35 (1), 301-316. DOI: 10.1038/npp.2009.87

Holland, R., & Crinion, J. (2011). Can tDCS enhance treatment of aphasia after stroke? Aphasiology, 1-23. DOI: 10.1080/02687038.2011.616925

Holland, R., Leff, A., Josephs, O., Galea, J., Desikan, M., Price, C., Rothwell, J., & Crinion, J. (2011). Speech Facilitation by Left Inferior Frontal Cortex Stimulation. Current Biology, 21 (16), 1403-1407. DOI: 10.1016/j.cub.2011.07.021

Marangolo P, Marinelli CV, Bonifazi S, Fiori V, Ceravolo MG, Provinciali L, Tomaiuolo F. (2011). Electrical stimulation over the left inferior frontal gyrus (IFG) determines long-term effects in the recovery of speech apraxia in three chronic aphasics. Behav Brain Res. 225:498-504.

Morbid Curiosity in Chicago

2012-04-03T00:01:00.000-07:00

Chicago Cultural Center
78 E. Washington Street
Chicago, IL 60602

If you're still in Chicago for the last day of the 2012 CNS Meeting (and can spare the time), I highly recommend this exhibit.

"I have accumulated over 1500 objects exploring the related themes of death and mortality."
-Richard Harris

More about the skulls (and the conference) will be forthcoming...

Critical Theory in Neurocinematics: Gaspar Noe's 'Irreversible' as Neural Network Reconfiguration

2012-03-31T22:24:00.003-07:00

Cinematic enfant terrible Gaspar Noé has been shocking audiences with his artistic films of graphic violence for over 20 years. In IMDb he is quoted as saying:

"There is no line between art and pornography. You can make art of anything. You can make an experimental movie with that candle or with this tape recorder. You can make a piece of art with a cat drinking milk. You can make a piece of art with people having sex. There is no line. Anything that is shot or reproduced in an unusual way is considered artistic or experimental."

I haven't seen a Noé film myself, so I can't offer any personal opinions. The descriptions themselves are so graphic and repellent that I've avoided them.

What can Noé and neuroscience possibly have in common? Neurologist/cognitive neuroscientist Dr. Guillén Fernández and colleagues have been showing clips from Irréversible to participants in fMRI studies.

The film employs a non-linear narrative and follows two men as they try to avenge a brutally raped girlfriend. ... Several reviewers declared it one of the most disturbing and controversial films of 2002.¹

Why would researchers show this film to [perhaps unsuspecting]² college students? To quickly induce a state of extreme psychological stress. In brief, Fernandez et al. are interested in studying the brain under acute stress. A PubMed search suggests there are at least 16 articles using this methodology.

One such study examined rapid changes in neural network connectivity induced by the Irréversible stress-induction procedure³ (Hermans et al., 2011):

During exposure to a fear-related acute stressor, responsiveness and interconnectivity within a network including cortical (frontoinsular, dorsal anterior cingulate, inferotemporal, and temporoparietal) and subcortical (amygdala, thalamus, hypothalamus, and midbrain) regions increased as a function of stress response magnitudes.

The data analysis strategy employed the methods of "neurocinematics" (Hasson et al., 2008) to find inter-subject correlations (ISCs) in the BOLD response during free viewing of the film clips. Then the regions that responded to the aversive film to a greater extent were identified. These included areas associated with interoception and autonomic-neuroendocrine control, peripheral stress effector systems and catecholaminergic signaling, and sensory and attentional (re)orienting.

Fig. 1 (Hermans et al., 2011). ISCs. Maps are thresholded at P < 0.05, whole-brain FWEcorrected, and overlaid onto cortical surface renderings (A and B) and a canonical structural MRI (C). FI, frontoinsular cortex; SMA; supplementary motor area; PCC, posterior cingulate cortex; (v)mPFC, (ventro)mPFC; IFG, inferior frontal gyrus; Th, thalamus; Mb, midbrain; Hy, hypothalamus.

Then "multisession tensorial probabilistic independent component analysis" was used to test for functional connectivity between these regions, which overlapped with the "salience network" observed in resting state studies (Seely et al., 2007). Finally, pharmacological manipulations suggested that the stress-induced connectivity within this network was decreased by blocking β-adrenergic receptors [via propranolol], but not cortisol synthesis [via metyrapone].

If you happen to be in Chicago for the 2012 CNS Meeting, you can learn more from Dr. Fernandez himself, who will be speaking in Symposium Session 1:

Talk 4: Equipped to Survive: Large-Scale Functional Reorganization in Response to Threat Enables Optimal Behavior

Unfortunately, this presentation conflicts with Joshua Carp's talk, mentioned in the previous post -- How vulnerable is the field of cognitive neuroscience to bias?

Footnotes

¹ Watch the trailer for Irreversible [NOTE: This video has been age-restricted].

² Participants with "regular exposure to extremely violent movies or computer games" are excluded from the studies.

³ The presented film clips were described as follows:

Fragments (both 140 s) from two different movies entitled "Irréversible" (2002), by Gaspar Noé, and "Comment j’ai tué mon père" (2001), by Anne Fontaine, were selected to serve as aversive and neutral control movie clips, respectively. ... Matching for audiovisual characteristics (see table S1) was performed by the authors by selecting aversive and neutral clips out of a set of candidate clips which best matched on the following measures: presence of faces in the foreground, presence of background actors, amount of distinct camera movements, and percentage of time the camera was moving. Selected aversive scenes contained extreme male-to-male aggressive behavior and violence in front of a crowd. Neutral control scenes also contained people interacting in the foreground in the presence of a background crowd. Fragments were equalized in luminance. Both movies are French spoken, but selected movie clips contained minimal speech.

References

Hasson U, Landesman O, Knappmeyer B, Vallines I, Rubin N, Heeger DJ. (2008). Neurocinematics: The Neuroscience of Film. Projections 2:1-26. [PDF]

Hermans, E., van Marle, H., Ossewaarde, L., Henckens, M., Qin, S., van Kesteren, M., Schoots, V., Cousijn, H., Rijpkema, M., Oostenveld, R., & Fernandez, G. (2011). Stress-Related Noradrenergic Activity Prompts Large-Scale Neural Network Reconfiguration. Science, 334 (6059), 1151-1153 DOI: 10.1126/science.1209603

Seeley WW, Menon V, Schatzberg AF, Keller J, Glover GH, Kenna H, Reiss AL, Greicius MD. (2007). Dissociable intrinsic connectivity networks for salience processing and executive control. J Neurosci. 27:2349-56.

Further Reading:

Neurocinema, Neurocinematics

The Hyperscanning of 'Paranormal Activity': A Neurocinematic Study of Collective Fear

How vulnerable is the field of cognitive neuroscience to bias?

2012-03-31T09:22:00.001-07:00

That's the opening sentence in an abstract by Joshua Carp, who will be presenting tomorrow in Slide Session 3 at the 2012 CNS Meeting in Chicago. The question caught my eye in light of the Psych Science paper on False-Positive Psychology ["undisclosed flexibility in data collection and analysis allows presenting anything as significant"] and the recent blog post by Dr Daniel Bor on The dilemma of weak neuroimaging papers.

Slide Session 3

Sunday, April 1, 10:00 am - 12:00 pm, Red Lacquer Room

Estimating the analytic flexibility of functional neuroimaging: Implications for uncertainty and bias in cognitive neuroscience

Joshua Carp; University of Michigan

How vulnerable is the field of cognitive neuroscience to bias? According to a recent mathematical model, the potential for scientific bias increases with the flexibility of analytic modes. In other words, the greater the range of acceptable analysis strategies, the greater the likelihood that published research findings are false. Thus, the present study sought to empirically estimate the analytic flexibility of fMRI research. We identified five pre-processing decisions and five modeling decisions for which two or more analysis strategies are commonly used in the research literature. By crossing each of these strategies and decisions, we identified 4,608 unique analysis pipelines. Next, we applied each of these pipelines to a previously published fMRI study of novelty detection in an auditory oddball task. We found that activation estimates were highly dependent on methodological decisions: contrasts that yielded significant positive activation under one pipeline were associated with non-significant positive activation or even with negative activation under other pipelines. Some analysis decisions contributed more to this variability more than others, and each decision exerted a unique pattern of variability across the brain. The effects of a given decision also varied across contrasts, subjects, and other analysis parameters. In sum, we found considerable quantitative and qualitative variability across analysis pipelines, suggesting that the results of cognitive neuroimaging experiments may be more uncertain than they seem. Indeed, given a supercomputer, a sufficiently motivated analyst might observe almost any imaginable pattern of results.

Reference

Simmons JP, Nelson LD, Simonsohn U. (2011). False-positive psychology: undisclosed flexibility in data collection and analysis allows presenting anything as significant. Psychol Sci. 22:1359-66.

Nineteenth Annual Cognitive Neuroscience Society Meeting

2012-03-29T13:27:00.000-07:00

The 2012 CNS Meeting will be held in Chicago from March 31 to April 3. The schedule is packed with three and a half days of symposia, slide sessions, posters, and distinguished lectures.

It will be quite an Event, with sessions on Music and the Brain, Your Brain on Food, and more!

See you in Chicago!

Symposium Session 4

Tuesday, April 3, 10:00 am - 12:00 pm, Grand Ballroom

The Brain on Food: Investigations of motivation, dopamine and eating behaviors

Chair: Laura Martin, University of Kansas Medical Center
Speakers: W. Kyle Simmons, Susan Carnell, Dana M Small, Laura M Holsen

Food is a highly motivating stimulus in our environment. We eat for many non-homeostatic reasons, such as celebration, comfort, and hedonic pleasure. Novel investigations of the neural basis of healthy and disordered eating reveal that throughout the multisensory process of food consumption, sensory, reward processing and cognitive control brain regions work together to keep track of how rewarding the experience is and help us decide whether or not to continue eating. A complete cognitive neuroscience model of food motivation requires understanding the sensory, reward, and cognitive mechanisms associated with healthy eating, and how those mechanisms can run amok. The first talk will review recent fMRI studies in lean individuals which identify how neural systems involved in retrieving food taste and reward information contribute to food motivation and food-related decision making. The second talk describes a study that uses multi-modal (visual and auditory) food cues to examine a dynamic, distributed reward-related network specifically associated with subjective ratings of cue-induced desire to eat in lean and obese women. The third talk provides evidence suggesting that overweight individuals show deficits in dopamine-dependent learning, as indicated by reduced error signal generation in the OFC and ventral striatum, and impaired insula-mediated flavor-nutrient conditioning. The final talk will bring together evidence across the spectrum from healthy to disordered eating behaviors by examining the neural circuitry underlying differences in food motivation between anorexia, healthy weight, obese, and Prader-Willi syndrome populations. Together, the talks will provide a stimulating introduction to the networks involved in food motivation.

I Feel Your Pain... and I Enjoy It

2012-03-23T04:10:00.003-07:00

Dennis Rader - the BTK Killer

Court Transcript of BTK's Confession
. . .
The Court: -- you were engaged in some kind of fantasy during this period of time?
The Defendant: Yes, sir.
The Court: All right. Now, where you use the term “fantasy,” is this something you were doing for your personal pleasure?
The Defendant: Sexual fantasy, sir.

The Archives of General Psychiatry has published a neuroimaging study of nonconsensual sexual sadism in a forensic setting (Harenski et al., 2012), sure to be controversial among BDSM practitioners, DSM-5 critics, and Christian fundamentalists alike.

Here's a brief background and rationale for the study:

Context Sexual sadism is a psychiatric disorder in which sexual pleasure is derived from inflicting pain, suffering, or humiliation on others. While the psychological and forensic aspects of sexual sadism have been well characterized, little is known about the neurocognitive circuitry associated with the disorder. Sexual sadists show increased peripheral sexual arousal when observing other individuals in pain. The neural mechanisms underlying this unusual response are not well understood. We predicted that sadists relative to nonsadists would show increased responses in brain regions associated with sexual arousal (amygdala, hypothalamus, and ventral striatum) and affective pain processing (anterior cingulate and anterior insula) during pain observation.

The participants were 15 violent sexual offenders housed at Sand Ridge Secure Treatment Center: 8 sadists and 7 nonsadists, as rated on the Severe Sexual Sadism Scale.¹ One additional participant with an ambiguous score was excluded. The groups were fairly well-matched for age (about 50 yrs), education (12 yrs), IQ (92-97), substance use, and level of psychopathy.

The subtitle of the paper is Preliminary Findings and one must keep this in mind, given the small n in the groups.

The experimental design involved presenting a set of three images depicting (a) one person inflicting pain upon another ("Pain"), and (b) control images with two people but no pain inflicted ("No Pain"). The participants rated the severity of pain inflicted for each stimulus set on a 0-4 scale. A third condition depicted one person causing damage to an object, but those results were not presented in the paper.

Figure 1 (Harenski et al., 2012). Example of pain and no-pain picture sets, along with the pain severity rating scale.

By definition, sexual sadists obtain pleasure and gratification via the suffering of others. Here are the DSM-IV-TR diagnostic criteria (APA, 2000) for Sexual Sadism (see Krueger, 2010; PDF):

A. Over a period of at least 6 months, recurrent, intense sexually arousing fantasies, sexual urges, or behaviors involving acts (real, not simulated) in which the psychological or physical suffering (including humiliation) of the victim is sexually exciting to the person.
B. The person has acted on these sexual urges with a nonconsenting person, or the sexual urges or fantasies cause marked distress or interpersonal difficulty.²

So it comes as no surprise that brain regions associated with sexual arousal were predicted to show greater activity to Pain in the sadists. What are the "sexual arousal areas"? According to the authors, these include the amygdala, hypothalamus, and ventral striatum. The problem is that none of these areas is selectively involved in sexual arousal [with the possible exception of specific hypothalamic nuclei]. In fact, the amygdala is more often related to fear, so greater activity might also be expected in those who take the perspective of the victim.

The other major prediction was that activity in the "affective pain areas" (anterior cingulate cortex and anterior insula)³ would be greater to Pain images in the sadists, because they are actually more sensitive to the suffering of others. This might seem counterintuitive in such callous individuals, but...

In any scenario where pain is imminent, sadists may pay closer attention than nonsadists to the thoughts and feelings of the victim because this enhances their sexual arousal when pain is inflicted. In other words, whereas sadists lack sympathy for their victims, they may exhibit empathy (simulating their victims' feelings) when consistent with their goals.

In support of this view, the sadists rated Pain pictures as higher in severity than the nonsadists did. The two groups did not differ in their ratings of No-Pain pictures. In the future, comparison to a control population of nonviolent offenders would be helpful.

Since Sand Ridge does not have its own scanning facility [gasp!], running the fMRI experiment involved use of a mobile unit.

Kent Kiehl outside the mobile scanner he has used to look at the brains of inmates at a New Mexico prison. Credit: Nature News.

What were the results of the imaging study? The sadists showed greater activity to Pain (vs. No-Pain) in the left amygdala, but the nonsadists did not. The right ventral striatum showed a main effect of group (greater activation in the sadists) which did not differentiate between Pain and No-Pain pictures. No significant effects were observed in the hypothalamus.

Figure 3 (Harenski et al., 2012). A, Interaction in the left amygdala, representing increased response during pain vs no-pain picture viewing in sadists but not in nonsadists. B, The mean parameter estimates are for the cluster at Montreal Neurological Institute coordinates x = –21, y = –6, z = –21. Bars indicate standard errors.

Overall, it's not clear whether the amygdala result is related to sexual arousal at all. The participants were not asked if they found the pictures arousing (nor were any peripheral signs of this measured).

Finally, activity in a region of the left anterior insula showed a positive correlation with pain severity ratings in the sadists but not in the nonsadists. This could mean they were more attuned to the suffering of others, but it could also mean they experienced a higher level of disgust (unlikely, but see Jabbi et al., 2008).

The authors end on a speculative (and controversial) note, wondering whether the "neural abnormalities" of incarcerated sadistic sexual predators would generalize to those who engage in consensual sadism:

It is interesting to consider whether the neural abnormalities that characterize incarcerated sexual sadists generalize to individuals in the community with sadistic sexual preferences. Sadists who offend may differ from those who do not in early environment (eg, abuse or inadequate social and family environment). Individuals involved in consenting sadomasochistic relationships are also different from criminal sadists because criminal sadists do not generally engage in sadomasochism, nor do those in sadomasochistic relationships generally victimize others. Nonetheless, all experience sexual arousal to pain infliction. Therefore, whether the present results generalize to all sadists is a question for future research.

Footnotes

¹ This scale is:

an 11-item scale rated according to history of sexual behavior. Items are rated yes (1 point) or no (0 points) and include the following: (1) engages in gratuitous violence toward or wounding of victim; (2) exercises power, control, or domination over victim; (3) humiliates or degrades victim; (4) is sexually aroused by the act; (5) tortures victim or engages in acts of cruelty to victim; (6) shows evidence of ritualism in offense; (7) abducts or confines victim; (8) inserts object or objects into victim's bodily orifice or orifices; (9) mutilates sexual parts of victim's body; (10) mutilates nonsexual parts of victim's body; and (11) keeps trophies (eg, underwear or identification) of victim or keeps records of the offense. To meet sexual sadist criteria, an offender's behavior must include at least 4 items (3 of which must be items 2-5 or item 9).

It is considered more reliable than DSM-IV and PPG-based (penile plethysmography) diagnoses.

² Krueger noted [PDF]:

The change in the B. criterion from DSM-IV to DSM-IV-TR represents one of the few changes in criteria from DSM-IV to DSM-IV-TR. This change was made to all of the paraphilias which involved a victim, to remove any ambiguity about whether acting out sexual urges with others was sufficient for a diagnosis; some had argued that an individual with a paraphilia who was not distressed about his or her behavior could not be diagnosed with a paraphilia, and this new wording allowed for a diagnosis to be made in such a circumstance.

The addition of "nonconsensual" was also instituted in 2000, thereby depathologizing those who engage in consensual BDSM activities.

³ To avoid becoming too pedantic, I won't expound on how anterior cingulate and insular cortices are not specific to affective pain processing. These two regions are activated by most everything:

...(the insular cortex) is a brain region that is active in as many as one third of all brain imaging studies.

References

Harenski, C., Thornton, D., Harenski, K., Decety, J., & Kiehl, K. (2012). Increased Frontotemporal Activation During Pain Observation in Sexual Sadism: Preliminary Findings. Archives of General Psychiatry, 69 (3), 283-292. DOI: 10.1001/archgenpsychiatry.2011.1566

Jabbi M, Bastiaansen J, Keysers C. (2008). A common anterior insula representation of disgust observation, experience and imagination shows divergent functional connectivity pathways. PLoS One 3(8):e2939.

Krueger RB (2010). The DSM diagnostic criteria for Sexual Sadism. Arch Sex Behav. 39:325-45 [PDF].

Further Reading

"None of us are saints"
-serial child killer and cannibal, Albert Fish

Humor, Hot Flashes, and Empathy for Pain

Hah-Ha!

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

Pleasure or Pain?

Tales of Passion and Disgust

The Disconnection of Psychopaths

- click for a larger view -

More info on BTK

Does the Human Dorsal Stream Really Process Elongated Vegetables?

2012-03-19T03:44:00.007-07:00

What do zucchini and hammers have in common? Both might be processed by the dorsal stream.

The primate visual system is divided into ventral ("what") and dorsal ("where") visual streams that are specialized for object recognition and spatial localization, respectively (Mishkin et al., 1983; Haxby et al., 1991).

Goodale and Milner (1992) conceptualized the two pathways as "vision for perception" and "vision for action":

We propose that the ventral stream of projections from the striate cortex to the inferotemporal cortex plays the major role in the perceptual identification of objects, while the dorsal stream projecting from the striate cortex to the posterior parietal region mediates the required sensorimotor transformations for visually guided actions directed at such objects.

Other researchers have extended the degree of specialization shown by the visual and semantic systems. Some studies have suggested there might be category-specific processing of living and non-living things (e.g., animals and tools), although the reasons for this specialization are a matter of debate (Caramazza & Shelton, 1998; Thompson-Schill et al., 1999). Chao and Martin (2000) found that pictures of tools activated the left posterior parietal cortex in the dorsal stream to a greater extent than pictures of animals, houses, and faces. The idea is that objects with salient motor-based properties (hammers) should recruit "vision for action" cortical regions to a greater extent than objects without such affordances (zucchini).

More recently, Almeida and colleagues (2008) used two different visual masking techniques in a priming study designed to isolate the influence of the dorsal stream:

We used two techniques to render prime pictures invisible: continuous flash suppression (CFS), which obliterates input into ventral temporal regions, but leaves dorsal stream processes largely unaffected, and backward masking (BM), which allows suppressed information to reach both ventral and dorsal stream structures.

Their results suggested that categorically related primes suppressed under CFS still facilitated reaction times to tool targets, but not to animal targets. In other words, participants were faster to classify tools when preceded by a picture of a tool than when preceded by a picture of an animal, and this priming effect held up when the ventral stream was unavailable.

A new study by Sakuraba et al. (2012) wanted to clarify which specific attributes of tools are processed by the dorsal stream, so they used a greater variety of categorically related and unrelated prime stimuli suppressed under CFS, as shown below.

Fig. 1 (Sakuraba et al., 2012). Procedure using CFS. Different images were presented into the subject's left and right eyes by using anaglyphs. Dynamic high-contrast random-noise patterns (10 Hz) were presented to the dominant eye, while low-luminance, low-contrast prime stimuli were presented to the nondominant eye. Subjects could report the dynamic noise but not the static image. Each trial started with a fixation cross for 500 ms, followed for 200 ms by a prime stimulus suppressed by CFS. Finally, a target stimulus masked by 70% additive noise was presented until the subject responded (maximum duration: 3 s) by pressing a key to indicate the category of the target stimulus.

One of the manipulated attributes was shape. Non-elongated ("stubby") tools, elongated vegetables, and stubby vegetables¹ were used as primes for elongated tools (e.g., hammer, ax, fork, etc.). Other conditions used geometric shapes as primes.

In Experiment 2, we used tool pictures without elongated shape components, namely stubby tools (e.g., a punch, a squeezer, a mouse, and so on). ... In Experiment 3, elongated stick figures were used as prime stimuli. In Experiment 4, elongated and stubby vegetable pictures were presented as prime stimuli. Because the elongated shapes involve an orientation component, we could not exclude the possibility that orientation, rather than shape attribute, explained the results. Therefore, we conducted Experiment 5 to clarify this. We used elongated stick figures, diamond shapes, and cut circles that were rotated in 45° increments as prime stimuli.

Interestingly, membership in the category of tools per se was irrelevant; it was the shape of the prime that mattered.

Fig. 4 (Sakuraba et al., 2012). Priming effect in Experiment 4 and 5.² Light and dark gray bars represent mean priming effects to tool targets and animal targets, respectively. Error bars indicate SEM. The pictures represent examples of the prime stimuli we used.

This throws a wrench (so to speak) into the dorsal stream as the vision for action pathway, unless you normally use a zucchini to pound your nails into the wall. The less dramatic interpretation is that the categorical information obtained by viewing pictures of tools isn't neatly respected by the dorsal stream, but visually-guided reaching and grasping remain unscathed.

Footnote

¹ The "stubby vegetables" were my favorite part of the paper.

² You might want to quibble with the size and functional significance of the priming effect. Although statistically significant, it was rather small.

References

Almeida J, Mahon BZ, Nakayama K, Caramazza A. (2008). Unconscious processing dissociates along categorical lines. Proc Natl Acad Sci. 105:15214-18.

Caramazza A, Shelton JR. (1998). Domain-specific knowledge systems in the brain: the animate-inanimate distinction. J Cogn Neurosci. 10:1-34.

Chao LL, Martin A. (2000). Representation of manipulable man-made objects in the dorsal stream. Neuroimage 12:478-84.

Goodale MA, Milner AD. (1992). Separate visual pathways for perception and action. Trends Neurosci. 15:20-5.

Haxby JV, Grady CL, Horwitz B, Ungerleider LG, Mishkin M, Carson RE, Herscovitch P, Schapiro MB, Rapoport SI. (1991). Dissociation of object and spatial visual processing pathways in human extrastriate cortex. Proc Natl Acad Sci 88:1621-5.

Mishkin M, Ungerleider LG, Macko KA (1983). Object vision and spatial vision: two cortical pathways. Trends Neurosci. 6:414-7.

Sakuraba S, Sakai S, Yamanaka M, Yokosawa K, & Hirayama K (2012). Does the human dorsal stream really process a category for tools? The Journal of Neuroscience, 32 (11), 3949-53. PMID: 22423115

Thompson-Schill SL, Aguirre GK, D'Esposito M, Farah MJ. (1999). A neural basis for category and modality specificity of semantic knowledge. Neuropsychologia 37:671-6.

The Art of Manliness on How to Handle a Hammer.

Scrumptious Skulls

2012-03-17T16:59:00.002-07:00

Image from Cakehead Loves Evil.

Marina Malvada is a painter, musician and chocolatier who makes anatomically correct skulls out of the finest imported chocolate. How does she get them to look so realistic? The confections are cast from an actual human skull:

I once had the unique opourtunity to borrow an authentic human skull and make a mold of it to cast in plaster. When I purchased my supplies, I discovered the availability of food grade materials, and instantly, the notion of chocolate skulls came to mind!

These chocolate skulls are available in three flavors: bone chocolate (a "signature blend of Belgian white and creamy milk chocolate"), dark chocolate, and semi-sweet chocolate.

Custom made to order online. Allow 3 weeks for hand casting, plus time for delivery.

SEAL OF DISAPPROVAL

2012-03-09T06:05:00.002-08:00

How Much of the Neuroimaging Literature Should We Discard?

Since sub-optimally designed and analyzed fMRI studies continue to influence the field, there should be some mechanism for identifying discredited publications. This discussion was initiated by Professor Dorothy Bishop's critical analysis of a flawed paper. In response, Dr Daniel Bor wrote a thoughtful post on The dilemma of weak neuroimaging papers. He covered corrected and uncorrected statistics, a culture of sloppy neuroimaging publications, and whether a bad paper can be harmful or should be retracted.

Does Discarding Mean Retraction?

By "discarding" I meant disregarding the results from flawed articles, not retracting them from the literature entirely. This point was misunderstood by some. It seems that all commenters on Bor's post agreed that retraction is problematic.

Bor: "...it’s almost certainly impractical to retract these papers, en masse."

Neuroskeptic: "Retracting them all… never going to happen, but even it did, I don’t think it would help at all. Much better would be for readers to educate themselves or be educated to the point where they know how to spot sloppy stats."

Bishop: "I don’t think it’s realistic to expect a retraction, and certainly not just on the basis of reporting of uncorrected statistics. I think we should disregard the results of this study because of the constellation of methodological problems..."

Poldrack: "I think retraction of papers that report uncorrected statistics is a bit much to ask for; after all, most of the results that were published in the days before rigid statistical corrections were common have turned out to replicate, and indeed large-scale meta-analyses have shown a good degree of consistency..."

This is not a new debate. In cellular and molecular biology, there have been cases of technical artifacts which resulted in failures to replicate. Retraction Watch, your authoritative source for all retraction news in the scientific literature, discussed this issue at length last year (e.g., So when is a retraction warranted? The long and winding road to publishing a failure to replicate). In a subsequent post, Ivan Oransky concluded:

So to get back to those Retraction Watch threads to which we referred: Yes, failure to replicate seems a good reason to retract. And notices should explain what went wrong. Allowing authors to get away with failing to do so, in some well-intentioned but misguided attempt to lower the barrier to retractions — as the Journal of Neuroscience does, for example — is part of why some people seem to think that retractions mean fraud.

This prompted a response from Isis the Scientist, who asked What Warrants a Retraction?

This story and controversy is still evolving. To retract the paper now, without evidence of overt fraud or negligence, will mark it with the scarlet watermark of fraud. Because a retraction is the foremost boner-killer of science, the retraction is a weapon to be wielded carefully. It should be used in cases of fraud and negligence, but not in cases where there remains active debate or inconclusive evidence.
Even then, there is value to leaving errors and conflict in the literature and there must be a better tool than the retraction watermark...

...but no one seems to know what that better tool is. Until now.

Introducing STAMPS OF DISAPPROVAL, by Heather K. Phillips

Gone are the days of tearing work from the wall. These days, disapproval often takes the form of ambiguous encouragements. Put the language of critique in your hands with this series of 12 rubber stamps. Each stamp bears of fragment of abridged feedback associated with critique.
Now available for purchase at Schooled

But seriously, improvements in how the field corrects itself will require "a structured information overlay for all academic papers," according to Ben Goldacre. Databases of failures to replicate and post-publication assessment are needed. Some scientists would like to overturn the current system of peer review entirely.

Or maybe we can incorporate a creative system that uses the STAMPS OF DISAPPROVAL...

Last Chance to Vote in the Neuro Film Festival

2012-03-08T01:10:00.001-08:00

Public voting in the 2012 Neuro Film Festival closes today, March 8, 2012. The contest includes 105 entries, available for viewing on a YouTube channel. Some videos cover well-known neurological disorders such as Parkinson's disease, epilepsy, and dementia.

Other entries feature lesser-known disorders such as Central Pain Syndrome (CPS), the worst possible pain with no relief in sight. A Message from Hell educates the public about the immense suffering experienced by patients with CPS and encourages researchers to study this neurological condition. "Doesn't every pharmaceutical company want to find a disease that isn't fatal and requires constant medication to control?"

Thus far, The Neurocritic has featured Aphasia Speaks and Sister Rose - My Brain Story. Channel N has covered Everything Moves and Could You Pick Me Out of a Crowd. Here are two more entries for your consideration.

The Experimental Man

While brushing his teeth, a 47 year old man suffered a carotid artery dissection that caused a major stroke in his right hemisphere, leaving his left side mostly paralyzed. He describes some bizarre theories and hallucinations he experienced while hospitalized. Foremost among these was a nurse with a hemicraniectomy who was thought to be the granddaughter of Eva Braun. The images accompanying this story are definitely worth the 3:39 total viewing time. He also describes the (real) procedures involved in supercooling his blood. He is currently participating in a study with an electrical stimulation device to improve his ability to walk.

Sometimes There Can Be More Than 1 (No Walk In The Park)

Dia DiCristino was well on her way to becoming a successful opera singer when she was struck by bad health. In fact the same week she was due to sing for a very prestigious opera company's mangers, she suddenly was scheduled to have life saving brain surgery. One brain surgery turned into over 25 neurological procedures and an endless stream of medical problems that forced her to retire at only 26 years of age from her opera career.

DiCristino had an arachnoid cyst that caused hydrocephalus, or an accumulation of cerebrospinal fluid (CSF) that compressed her brain. The "More Than 1" neurological problem included palinopsia, dysphasia, aphasia, spasticity, chronic headaches, startle myoclonus, seizures, sleep apnea and more. Despite all this, the very talented DiCristino wrote and performed the music featured in this video.

How Much of the Neuroimaging Literature Should We Discard?

2012-03-06T23:18:00.002-08:00

Guilty article in PNAS (2003).

Just a quick pointer to a pair of posts on how sub-optimally designed and analyzed fMRI studies can continue to influence the field. Professor Dorothy Bishop of Oxford University posted a scathing analysis of one such paper, in Time for neuroimaging (and PNAS) to clean up its act:

Temple et al (2003) published an fMRI study of 20 children with dyslexia who were scanned both before and after a computerised intervention (FastForword) designed to improve their language. The article in question was published in the Proceedings of the National Academy of Sciences, and at the time of writing has had 270 citations. I did a spot check of fifty of those citing articles to see if any had noted problems with the paper: only one of them did so.

Bishop noted at least four major problems in the paper that invalidated the conclusions, including:

The authors presented uncorrected whole brain activation data. This is not explicitly stated but can be deduced from the z-scores and p-values. Russell Poldrack, who happens to be one of the authors of this paper, has written eloquently on this subject: “…it is critical to employ accurate corrections for multiple tests, since a large number of voxels will generally be significant by chance if uncorrected statistics are used. .. The problem of multiple comparisons is well known but unfortunately many journals still allow publication of results based on uncorrected whole-brain statistics.” Conclusion 2 is based on uncorrected p-values and is not valid.

Indeed, Dr. Russ Poldrack of the University of Texas at Austin is a leader in neuroimaging methodology and a vocal critic of shoddy design and overblown interpretations. And yes, he was an author on the 2003 paper in question. Poldrack replied to Bishop in his own blog:

Skeletons in the closet
As someone who has thrown lots of stones in recent years, it's easy to forget that anyone who publishes enough will end up with some skeletons in their closet. I was reminded of that fact today, when Dorothy Bishop posted a detailed analysis of a paper that was published in 2003 on which I am a coauthor.

I'm not convinced that every prolific scientist has skeletons in his/her closet, but it was nice to see that Poldrack acknowledged this particular bag of bones:

Dorothy notes four major problems with the study:
There was no dyslexic control group; thus, we don't know whether any improvements over time were specific to the treatment, or would have occurred with a control treatment or even without any treatment.
The brain imaging data were thresholded using an uncorrected threshold.
One of the main conclusions (the "normalization" of activation following training") is not supported by the necessary interaction statistic, but rather by a visual comparison of maps.
The correlation between changes in language scores and activation was reported for only one of the many measures, and it appeared to have been driven by outliers.
Looking back at the paper, I see that Dorothy is absolutely right on each of these points. In defense of my coauthors, I would note that points 2-4 were basically standard practice in fMRI analysis 10 years ago (and still crop up fairly often today). Ironically, I raised two of of these issues in my recent paper for the special issue of Neuroimage celebrating the 20th anniversary of fMRI, in talking about the need for increased methodological rigor...

But are old school methods entirely to blame? I don't think so. It seems that some of these errors are errors in basic statistics. At any rate, I highly recommend that you read these two posts.

Many questions remain. How self-correcting is the field? What should we do with old (and not-so-old) articles that are fatally flawed? How many of these results have replicated, or failed to replicate? Should we put warning labels on the failures?

Professor Bishop also noted specific problems at PNAS, like the "contributed by" track allowing academy members to publish with little or no peer review. The "pre-arranged editor" track is another potential issue. I suggest a series of warning labels for such articles, such as the one shown below.

Sister Rose Pacatte Explains It All For You

2012-03-05T01:15:00.001-08:00

Sister Rose - My Brain Story

This is my story of living with MS, living with the mystery in hope. As you can tell, I made it myself!

Another entry in the 2012 Neuro Film Festival, starring an engaging and media savvy nun who is living with multiple sclerosis. Sister Rose Pacatte is an author, blogger, and director of the Pauline Center for Media Studies in Culver City, CA. Here she notes that her first symptom of MS was an impairment in eye tracking - internuclear ophthalmoplegia - and interviews her neurologist, Dr. Barbara Giesser.

@SrRoseMovies - "Movie critic, cinema and spirituality lover, media literacy ed specialist, nun!"

Public voting will close on March 8, 2012.

Speaking of Aphasia...

2012-02-29T23:41:00.001-08:00

Aphasia Speaks

A 34-year-old physical therapist, Kristen, who suffered a stroke in 2008 relates her journey and rebuilds her life with Aphasia. Aphasia is a language disorder that affects the language center of the brain and is caused by stroke, brain surgery or other traumatic brain injuries. Kristen's positive attitude has taken her down a new path for helping others. With the help of further intense speech therapy Kristen hopes to inspire other with Aphasia.

Kristen's stroke has likely affected her left frontal lobe. She has speech output problems but speaks fluently enough to not be characterized with a classic Broca's aphasia. She has some motor weakness on the right (contralateral) side of her body, but with adaptive technology is able to drive. She continues to go to physical therapy and has a positive outlook and an active life.

The American Academy of Neurology (AAN), a professional organization for neurologists, is hosting the 2012 Neuro Film Festival at their Annual Meeting in New Orleans. The contest YouTube channel features 105 entries. Videos cover well-known neurological disorders such as Parkinson's disease, epilepsy, and dementia. Other entries feature lesser-known disorders including multiple system atrophy, Batten disease, and arachnoid cysts. Public voting will close on March 8, 2012.

2012 Neuro Film Festival

2012-02-28T13:55:00.001-08:00

The American Academy of Neurology (AAN), a professional organization for neurologists, is hosting the 2012 Neuro Film Festival at their Annual Meeting in New Orleans:

Now in its third year, the Neuro Film Festival is a contest by the American Academy of Neurology Foundation to help raise awareness about why more research is needed to cure brain diseases, such as Alzheimer's disease, stroke, autism, Parkinson's disease and multiple sclerosis.
Public voting will close on March 8, 2012, with the winner of the "Fan Favorite" award receiving a certificate and recognition at the 2012 Neuro Film Festival on April 22, 2012, in conjunction with the American Academy of Neurology's 64th Annual Meeting, the world's largest meeting of neurologists with 10,000 attendees.

Entries closed on January 31, but the introductory video below explains the purpose of the contest: "to raise awareness through film and video about brain disorders and the need to support research into preventions, treatments and cures."

The contest YouTube channel features 105 entries. Videos cover well-known neurological disorders such as Parkinson's disease, epilepsy, and dementia. Other entries feature lesser-known disorders including multiple system atrophy, Batten disease, and arachnoid cysts.

AAN has a Twitter feed, which you can follow for updates on the film fest in April.

Watch The Neurocritic and Channel N Video for the next week to see some of our favorites!