The Neurocritic

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Born in West Virginia in 1980, The Neurocritic embarked upon a roadtrip across America at the age of thirteen with his mother. She abandoned him when they reached San Francisco and The Neurocritic descended into a spiral of drug abuse and prostitution. At fifteen, The Neurocritic's psychiatrist encouraged him to start writing as a form of therapy.

The Neurocritic
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  • June 17, 2012
  • 08:37 PM

Textmania: a Modern Manifestation of Manic Hypergraphia?

by The Neurocritic in The Neurocritic

Continuing with the theme of reading and writing, a new study reports on the case of a 23 yr old woman with bipolar I disorder whose output of text messages was "1333.33% more" during a manic episode (Emeagwali et al., 2012):The patient reported a dramatic increase in the quantity of both texting and sex-texting (or sexting) in addition to a decrease in quality of the message content. In addition, there was a substantial increase in the number of people with whom the patient engaged in simultaneous texting conversations. This case provides evidence for the need to consider non-traditional forms of communication when evaluating a patient’s communication pattern during mania.How many texts per day are we talking about? At least 200, up from her usual 15-20 texts/day.1 In the grand scheme of things, 200 is not all that unusual, because the mean number of text messages sent by young adults in the 18-24 age group is 109.5, according to a Pew Internet Survey.2 The change in the patient's behavior is the critical factor here.Hypergraphia (an overpowering urge to write) is probably seen more frequently in mania than in temporal lobe epilepsy, but the latter gets more attention in the medical literature due to the sometimes spectacular nature of the output (e.g., the novels of Dostoevsky, a 17 million word diary, and a copious collection of rhyming poetry). The neurological case studies are often illustrated with EEG traces showing abnormal spiking activity, along with examples of the person's handwriting (Kalamangalam, 2009):The patient was observed to write for much of her waking hours. The document, a letter to her husband, numbered 29 pages by the time of her discharge from hospital and remained unfinished. The writing was cramped, dense, and used all the available space on both sides of the sheet, including the margins. The contents of the letter were rambling, though with specific details. She wrote about her hospital stay, often mentioning exact times, her intake of medications, and minor details of conversations with staff. -- click on image for a larger view --Fig 1 (left). Sleep EEG, bipolar longitudinal montage: a single spike maximum over the right anterior temporal region (arrow). Fig. 3 (right). Close up of page 16. The patient writes about her medication dosing, including minor details. (modified from Kalamangalam, 2009).You don't see such reports in the psychiatric literature.3 There are no obvious manifestations of a manic episode on EEG or PET scans where you can say, in an individual person, "oh yes, this reduced gamma coherence and inhibition of theta activity in the lateral inferior prefrontal cortex, coupled with increased dopaminergic transmission in the midbrain, are clear indicators of mania." A PubMed search for mania OR manic AND hypergraphia returns one result, while a search for temporal lobe epilepsy and hypergraphia yields 22 hits.There have of course been books on bipolar disorder and creativity, such as Touched With Fire: Manic-Depressive Illness and the Artistic Temperament by Dr. Kay Redfield Jamison. More specifically, Dr. Alice W. Flaherty covered the phenomenology and neurobiology of hypergraphia. In The Midnight Disease: The Drive to Write, Writer's Block, and the Creative Brain:Flaherty writes compellingly of her bout with manic hypergraphia, when "the sight of a computer keyboard or a blank page gave me the same rush that drug addicts get from seeing their freebasing paraphernalia." Dissecting the role of emotion in writing and the ways in which brain-body and mood disorders can lead to prodigious — or meager — creative output, Flaherty uses examples from her own life and the lives of writers from Kafka to Anne Lamott, from Sylvia Plath to Stephen King [and Fyodor Dostoevsky].And certainly the evidence for manic/hypomanic hypergraphia has been plainly obvious for as long as the internet has existed. There are thousands of bipolar bloggers and Tweeters and Facebook users and online journalers before that. Unlike PubMed, Google Blog Search returns 3,670 hits for bipolar hypergraphia and 4,230 hits for manic hypergraphia. And those are just the posts that use the term hypergraphia.4 One could envision a study on quantitative changes5 in written output on Twitter or blogs as a possible sign of bipolar cycling.So it seems that contemporary psychiatrists are not all that interested in publishing case studies about their frantically writing patients, unlike the neurologists. Perhaps it's so commonplace that they just don't see the point?Footnotes1 As you can see, the mathematical calculation quoted in the first sentence is rather imprecise.2 The median, which is less sensitive to the effects of gabby outliers, is 50 texts per day.3 This raises the issue of Neurology vs Psychiatry and the Neurological/Psychiatric Divide.4 For another interesting personal perspective see Bipolar 101 on ... Read more »

Kalamangalam, G. (2009) Hypergraphia in temporal lobe epilepsy. Annals of Indian Academy of Neurology, 12(3), 193. DOI: 10.4103/0972-2327.56323  

Emeagwali, N., Bailey, R., & Azim, F. (2012) Textmania: Text Messaging During the Manic Phase of Bipolar I Disorder. Journal of Health Care for the Poor and Underserved, 23(2), 519-522. DOI: 10.1353/hpu.2012.0062  

  • June 4, 2012
  • 07:27 PM

G r e a t e r / l e t t e r / s p a c i n g / helps reading in dyslexia

by The Neurocritic in The Neurocritic

Simply increasing the spacing between letters improves the reading ability of children with developmental dyslexia, according to a group of Italian and French researchers (Zorzi et al., 2012). Dyslexic children were 20% faster and twice as accurate when reading the altered text. This impressive result was obtained without any prior training whatsoever.The study was based on the phenomenon of crowding, where the recognition of individual letters is impaired by the close proximity of surrounding letters. Children with dyslexia are disproportionately affected by crowding, compared to normally developing children (Martelli et al., 2009). Other aspects of the printed word are known to affect reading ability, but surprisingly little is known about letter spacing. The recommendations of the British Dyslexia Association include optimizing the size and type of font, page layout, headings, type of paper, and line spacing but not letter spacing.1The collaborative effort was a deliberate attempt to compare two languages that have different types of spelling-to-sound translation. Italian has completely regular spelling rules (a transparent orthography), meaning there are no exception words. Each combination of printed letters is always pronounced in a consistent way. By contrast, written French is orthographically opaque, meaning that pesky irregular spellings can trip you up. This is true in English as well: compare the pronunciation of the word "pint" to "hint", "mint", and "lint". The /i/ sound wins out over the /ī/ sound, in terms of regularity.In the study, 34 Italian and 40 French children with dyslexia were tested on two separate occasions at least two weeks apart. They read 24 short sentences, which were written in standard text in one session and highly spaced text in the other. The order of sessions was counterbalanced to control for practice effects, with half assigned to read the spaced text at T1 and the other half at T2. Reading accuracy (number of errors) and reading speed (number of syllables per second) both interacted with test session (p<.0001), indicating a drastic improvement with the highly spaced text. This was true for both the Italian and the French children with dyslexia.Fig. 2 (Zorzi et al., 2012). (C) Reading accuracy (number of errors) in the normal and spaced text conditions for Italian dyslexics, French dyslexics, and a younger group of Italian control children matched for reading level (RL) to the Italian dyslexic sample.It came as quite a surprise to me that no one had demonstrated this letter spacing effect before. But then again, I'm not familiar with the literature on developmental reading disorders, so perhaps Professor Dorothy Bishop or Livia Blackburn can provide a more critical take on an [apparently] amazing finding.Finally, the authors have developed DYS, a free iPhone/iPad application. You can test out the spacing effect for yourself and submit your results anonymously, in the name of science! For more information, see the WSJ Health Blog.Footnote1 Also note that bold is preferable to italic, as the latter induces crowding.ReferencesMartelli M, Di Filippo G, Spinelli D, Zoccolotti P (2009). Crowding, reading, and developmental dyslexia. J Vis 9: 14, 1–18.Marco Zorzi, Chiara Barbiero, Andrea Facoetti, Isabella Lonciari, Marco Carrozzi, Marcella Montico, Laura Bravar, Florence George, Catherine Pech-Georgel, and Johannes C. Ziegler (2012). Extra-large letter spacing improves reading in dyslexia. PNAS. doi:10.1073/pnas.1205566109.

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Marco Zorzi, Chiara Barbiero, Andrea Facoetti, Isabella Lonciari, Marco Carrozzi, Marcella Montico, Laura Bravar, Florence George, Catherine Pech-Georgel, and Johannes C. Ziegler. (2012) Extra-large letter spacing improves reading in dyslexia. PNAS. info:/

  • June 2, 2012
  • 11:05 PM

Compulsion to write caused by seizure, whether at work or at leisure

by The Neurocritic in The Neurocritic

Hypergraphia is a compulsive or overwhelming urge to write, often associated with temporal lobe epilepsy. Influential behavioral neurologist Norman Geschwind included hypergraphia as one of the personality changes that can be observed in persons with temporal lobe epilepsy.An unusual example of hypergraphia was observed by Dr. Mario F. Mendez, who reported the unique case of a 58 year old man who felt utterly compelled to write poetry (Mendez, 2005). The patient reported no previous history of being a poet until the age of 53, when he felt the urge to write in rhyme. He said that words are "continuously rhyming in [my] head" and felt the need to write them down and show them to other people. He didn't speak in verse, nor did he write nonrhyming prose or read others' poetry.Thus, his condition was a very specific hypergraphia for poetry. The rhyming condition coincided with the onset of other behavioral symptoms, namely irritability and anger. Shortly thereafter he began to have partial complex seizures, which typically have foci (or origins) in the medial temporal lobes.His seizures manifested as a sensation "rising" in his stomach followed by a brief alteration of consciousness. Seizure control with phenytoin and gabapentin ameliorated his irritability and anger but did not diminish his constant need to write in rhyme. ... The patient underwent a repeat evaluation. On examination, he was circumstantial and somewhat viscous. He repeatedly emphasized the significance of his symptom of poetry writing, and continually responded in written poetry. Language, mental status, and neurological examinations were otherwise normal except for a slightly broad-based and unsteady gait. He had right temporal spikes on electroencephalograms and small strokes in the right thalamus and the right cerebellum on neuroimaging.However, Mendez (2005) did not think the small right hemisphere strokes caused the patient's hypergraphia. The author was also skeptical that ongoing subthreshold ictal activity was solely responsible, because the seizures were well-controlled yet the poetry continued. Another possible explanation was related to persistent hypofunctioning in the right hemisphere, which could lead to disinhibition or "unmasking" of poetic abilities in the left hemisphere.1 This hypothesis assumes that the right temporal lobe maintains tonic control over neural activity in the left hemisphere, so we don't all turn into Joyce Kilmer.HYPERGRAPHIA, the movieA notoriously hypergraphic writer of poetry and prose was Arthur Crew Inman (1895-1963), who will be the subject of Hypergraphia, a forthcoming film starring John Hurt.Arthur Crew Inman was a reclusive and unsuccessful poet whose 17-million word diary, extending from 1919 to 1963, provides a panoramic record of people, events, and observations from more than four decades of the twentieth century.Footnote1 Most people are left hemisphere dominant for rhyme generation (Krach & Hartje, 2006).ReferenceMendez, M. (2005). Hypergraphia for Poetry in an Epileptic Patient Journal of Neuropsychiatry, 17 (4), 560-561. DOI: 10.1176/appi.neuropsych.17.4.560

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  • May 18, 2012
  • 12:24 AM

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

by The Neurocritic in The Neurocritic

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 DiscoveryTrauma 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 CTEThe 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 death4 male athletes (ages 17-27 yrs) with histories of repetitive concussive injury, including 3 football players and a professional wrestler4 male controls (ages 18-24 yrs) with no known blast exposure, trauma history, or neurological diseaseCase 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 ... Read more »

Goldstein, L., Fisher, A., Tagge, C., Zhang, X., Velisek, L., Sullivan, J., Upreti, C., Kracht, J., Ericsson, M., Wojnarowicz, M.... (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  

  • May 12, 2012
  • 05:32 PM

An Orgy of Self-Referential Blogging...

by The Neurocritic in The Neurocritic

...may follow from a new PLoS ONE paper on bloggers whose posts are aggregated at (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...Footnote1 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.ReferenceShema, 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

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  • May 10, 2012
  • 08:22 AM

Spindle Neurons in Macaques?

by The Neurocritic in The Neurocritic

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-referen... Read more »

  • May 5, 2012
  • 06:30 PM

Neurophysiological Explanation for the Perception of Poltergeists

by The Neurocritic in The Neurocritic

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?Footnote1 The young actress here, Heather O'Rourke, died at the age of 12 due to "medical error."ReferencesRoll, 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.... Read more »

  • April 29, 2012
  • 09:26 PM

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

by The Neurocritic in The Neurocritic

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 DiseaseBy NICHOLAS D. KRISTOFPublished: April 25, 2012He 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 p... Read more »

  • April 23, 2012
  • 12:42 PM

Magic Buttons, Silver Linings, and Two-Edged Swords

by The Neurocritic in The Neurocritic

The Subjective Ups and Downs of Mood DisordersThe 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%) 5increased 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 LiningsAn 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 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 SwordsFinally, a recent paper in the Journal of Affective Disorders (... Read more »

  • April 13, 2012
  • 05:06 AM

Suffering for art is still suffering

by The Neurocritic in The Neurocritic

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 MunchMany 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 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 ... Read more »

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

  • April 8, 2012
  • 09:25 AM

tDCS Symposium Stimulates Giant Brain in Chicago

by The Neurocritic in The Neurocritic

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 OxfordSpeakers: Roi Cohen Kadosh, Jenny Crinion, Paulo S. Boggio, Leonardo G. CohenThe 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 SandersWeb 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.3What 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... Read more »

  • April 1, 2012
  • 09:59 AM

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

by The Neurocritic in The Neurocritic

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 BehaviorUnfortunately, this presentation conflicts with Joshua Carp's talk, mentioned in the previous post -- How vulnerable is the field of cognitive neuroscience to bias?Footnotes1 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.ReferencesHasson U, Landesman O, Knappmeyer B, Vallines I, Rubin N, Heeger DJ. (2008). Neurocinematics: The Neuroscience of Film. Projections 2:1-26. [PDF]... Read more »

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

  • March 23, 2012
  • 11:50 AM

I Feel Your Pain... and I Enjoy It

by The Neurocritic in The Neurocritic

Dennis Rader - the BTK KillerCourt 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.... Read more »

  • March 19, 2012
  • 01:16 PM

Does the Human Dorsal Stream Really Process Elongated Vegetables?

by The Neurocritic in The Neurocritic

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.Footnote1 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.ReferencesAlmeida 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). ... Read more »

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 : the official journal of the Society for Neuroscience, 32(11), 3949-53. PMID: 22423115  

  • February 19, 2012
  • 04:21 AM

That's Impossible! How the Brain Processes Impossible Objects

by The Neurocritic in The Neurocritic

Relativity, by M.C. Escher.The artwork of M.C. Escher is famous for its visual trickery. The human visual system tries to project the two dimensional image onto a three dimensional scene, but the perspective is contradictory: it cannot exist in the real world. These impossible constructions violate the laws of geometry and fascinate consumers of t-shirts, posters, and Apple products.How does the brain represent these illusory staircases and towers? While a fascinating topic of study in the field of object perception (Levy et al., 2004), Escher prints can make for overly complicated stimuli in neuroimaging experiments. Simpler 2D figures, such as the impossible objects drawn by Swedish artist Oscar Reutersvärd, have been used in fMRI experiments (Soldan et al., 2008).An extensive collection of 810 impossible objects is available from Impossible World, which is a fantastic resource1 maintained by Vlad Alexeev.Previous neuroimaging experiments have used the possible/impossible object decision task to study the neural correlates of perceptual priming, an implicit form of memory. Behaviorally, repeated presentation of possible objects results in faster decision times, and this priming effect is smaller (Soldan et al., 2008) or non-existent (Schacter et al., 1995) for impossible objects. Neurally, the phenomenon of repetition suppression, or the reduction in neural activity seen upon repeated stimulus presentation, is thought to reflect facilitated perceptual processing (and perhaps behavioral priming).2 Repetition suppression predicts behavioral priming for possible objects (Habeck et al., 2006):A set of occipital, parietal, and temporal brain regions decreased their activation across presentations, including bilateral middle occipital gyrus, left precuneus, right supramarginal gyrus, as well as some frontal and thalamic areas, such as right inferior frontal gyrus, left cingulate gyrus, and right thalamus. However, no such relationship was observed for impossible objects.The previous studies focused on varieties of repetition priming and whether there is a "structural description system" that facilitates the identification of perceptually coherent objects. A recently published article was specifically interested in the neural basis of impossible figures and how they are represented in the visual cortex (Wu et al., 2012). The stimuli were impossible and possible exemplars of the two-pronged trident (Fig. 1 below), shown at four different angles.Fig. 1 (Wu et al., 2012). Examples of stimulus figures used in impossible condition and possible condition. (a) Is an impossible figure and (b) is a possible figure [that] resembles the former.The paper started by reviewing the basic neuroanatomy of the visual system and its division into dorsal ("where") and ventral ("what") visual streams. Objects are primarily represented in the ventral stream, and the lateral occipital complex (LOC) is one area that seems to be specialized for object recognition. The authors predicted that impossible objects would be difficult for the LOC to process; therefore, additional regions would be recruited:In the present study, we thought that the 3D structures of impossible figures might be difficult to be represented by object-selective regions (such as the LOC), and the impossible perceptions might be derived from detecting the contradiction in interpretation of the 3D structure. Therefore, we postulated that both the brain regions in the dorsal visual pathway, such as the SPC [superior parietal cortex] related to the perceptual ambiguities resolving and perceptual content modifying, and the brain areas related to the object-selective regions in the ventral pathway would be involved in the impossible figures processing.Nineteen participants performed the possible/impossible object decision task (30 trials of each condition) while their brains were scanned. Four participants showed repetition priming in the task (first 15 trials of each condition slower than the last 15) and were excluded. The remaining subjects did not show priming.3 Personally, I would have used 30 unique possible and impossible figures to avoid priming effects entirely.What were the results? As predicted, regions in both dorsal and ventral visual streams showed greater activation for impossible than for possible figures: right superior parietal in the former and right fusiform and inferior temporal gyri in the latter.The right SPG in the dorsal visual pathway might be related to spatial information processing and the right LOC (FG and ITG) in the ventral visual pathway (the object-selective regions) might be related to the representation of the impossible 3D structure. Therefore, our results indicated that the impossible 3D structure might be difficult to be represented by human visual system, and the impossible perception might be derived from the detecting and resolving the contradiction in the subjects’ interpretations according to different perceptions triggered by 3D cues.Fig. 2 (Wu et al., 2012). Brain regions showing significant difference between impossible condition and possible condition [FEW-corrected threshold of P < 0.05 at the cluster level (P < 0.001, 10 contiguous voxels cutoff at the voxel level)].There were no brain regions that showed greater activation for possible objects.... Read more »

  • February 13, 2012
  • 01:35 AM

21st Century Treatments for Insomnia

by The Neurocritic in The Neurocritic

Are you having trouble sleeping? But you're not feeling that 19th century retro hipster insomniac vibe? Try some of these behavioral remedies recommended by the finest scientific and medical journals of today.What a Difference a Day MakesIs Intensive Sleep Retraining (ISR) a new overnight treatment for chronic insomnia (Harris et al., 2012)? ISR is conducted in one 25 hr session at a sleep lab, where the insomniac sleeps a maximum of 3 min every 30 min for a period of 25 hrs. Instant cure! (supposedly). The basic idea is that the person will learn they can fall asleep fairly quickly and easily, and this will translate directly to real life sleeping patterns.In a commentary accompanying the main article in Sleep, Spielman and Glovinsky (2012) describe it as:...a novel insomnia treatment that while radical in procedure is grounded in learning theory, a long-established conceptual framework for understanding insomnia. ISR combines two familiar components of sleep research—sleep deprivation and the polysomnographic recording of sleep onset—to yield an entirely new therapeutic procedure: repeated practice in falling asleep quickly. Massed practice in achieving sleep is here shown to possess a therapeutic value rivaling that of stimulus control therapy (SCT), that mainstay of behavioral sleep medicine, as well as offering a possible additive effect when administered in conjunction with SCT.ISR employs sleep laboratory technology to measure the speed of sleep onset, limit the duration of sleep, and allow immediate feedback to subjects as to whether objectively recorded sleep has occurred. It typically provides dozens of successful entries to sleep over the course of a single night and day. Then it is over, handing off responsibility for good sleep management to sleep hygiene recommendations.In contrast to ISR, there is already strong research support for stimulus control therapy (SCT), which is designed to:...reduce the anxiety or conditioned arousal individuals may feel when attempting to go to bed. Specifically, a set of instructions designed to reassociate the bed/bedroom with sleep and to re-establish a consistent sleep schedule are implimented. These include: 1) Going to bed only when sleepy; 2) Getting out of bed when unable to sleep; 3) Using the bed/bedroom only for sleep and sex (i.e., no reading, watching TV, etc); 4) Arising at the same time every morning; and 5) Avoiding naps.One question, then, is whether ISR is better than SCT, an accepted behavioral therapy for insomnia. Eighty participants in the study of Harris et al. were randomized into one of four groups: (1) ISR + sleep hygeine instruction (SH); (2) SCT + SH; (3) ISR + SCT; (4) SH alone, which served as the control condition. All participants kept a sleep diary, answered questionnaires, and wore an actigraph to measure motor activity. Those in the ISR groups slept no more than 5 hrs the night before they came to the lab.The highly intrusive ISR procedure involved arriving at 21:00.Following an explanation, the signing of an informed consent form, electrode application, and a quiet settling period, treatment began at 22:30. Treatment trials were conducted every half hour, finishing after 23:00 on night 2. Thereby, the ISR treatment routine allowed a series of 50 half-hourly sleep onset opportunities. ... Within each treatment trial, the opportunity for sleep onset was limited to a 20-min period, with the trial stopping if sleep onset had not occurred by this time. For those trials in which sleep was initiated, 3 consecutive minutes of sleep were permitted, prior to being awoken [the method of awakening was not described]. Upon awakening, treatment participants first rated their perception of whether sleep onset had occurred (on a Likert scale of 1 “No, definitely not” to 7 “Yes, definitely”). Following this response, participants were provided with information as to whether sleep onset had or had not occurred.Then they got out of bed to read or watch DVDs. After 10 trials of this nonsense, people were falling asleep in 5 min or less.Ultimately, did this punitive procedure work? Yes. But it wasn't significantly better than SCT for most of the subjective sleep measures used. All three active treatment conditions produced improvements in self-reported duration and efficiency of sleep, relative to the SH control. Of the 16 or so analyses at 2 of 7 selected time points (which did not seem to be corrected for multiple comparisons), there were some instances where ISR or the combined ISR + SCT treatment was better than stimulus control therapy (see below), but nothing earth shattering.In another graph (Fig. 5 - Mean sleep diary wake time after sleep onset), the SCT groups were superior to ISR at Week 1 and Post-Treatment.What about the objective sleep measures obtained by actigraphy?The actigraphy data failed to support significant changes in sleep, despite using an adjusted manual scoring method and a sensitivity setting in the scoring algorithm that calibrated actigraphy TST [total sleep time] to PSG [polysomnography] TST. Actigraphy has similarly failed to mirror subjective sleep changes in other treatment studies in insomnia, and objective measures (i.e., EEG) fail to replicate the extent of subjective sleep changes in clinical insomnia treatment studies.The authors concluded that actigraphy is useless and that subjective sleep report is the only thing that matters (basically).So what's next? Intensive Sleep Retraining is costly and available only from highly specialized centers.1 But the possibility of self-administered ISR is on the horizon, using portable EEG headsets, actigraphs, and vibrating alarms. Is there an app for that?Footnote1 I'm not sure that it's even being offered as a clinical treatment. The RCT was conducted in Australia.References... Read more »

  • January 28, 2012
  • 04:53 AM


by The Neurocritic in The Neurocritic

Today was the sixth anniversary of this blog. I'm not much for meta-blogging or general chattiness, but I thought I would highlight the nine posts (out of 700) with the most comments. Thank you for your support over the years, and keep the comments coming.9. Friston Is Freudian - Friday, March 12, 2010Neuropsychoanalysis is in the news again because of the recent publication of Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. In 2010, first author Carhart-Harris published an expansionist mega-opus (with Karl Friston) on The default-mode, ego-functions and free-energy: a neurobiological account of Freudian ideas, the basis for the present post and its follow-up.8. Is CBT Worthless? - July 03, 2009According to a meta-analysis by Lynch, Laws and McKenna, Cognitive Behavioral Therapy (CBT) is not helpful for those with schizophrenia and bipolar disorder, and any improvements seen in major depression are rather small.7. White Matter Differences in Pre-Op Transsexuals Should NOT be the Basis for Childhood Interventions - January 28, 2011 Contains a number of comments by transgendered individuals who took exception with various aspects of this post.6. The Precuneus and Recovery from a Minimally Conscious State - July 05, 2006 Includes a number of comments, over a two year period, from a father caring for his son.5. Voodoo Correlations in Social Neuroscience - January 05, 2009 On the infamous paper by Edward Vul, Christine Harris, Piotr Winkielman and Harold Pashler, ultimately retitled Puzzlingly High Correlations in fMRI Studies of Emotion, Personality, and Social Cognition.4. Glossolalia - November 04, 2006 Includes personal statements from many individuals who feel they speak in tongues.3. Bad News for the Genetics of Personality - August 07, 2010 A recent search for genetic variants that underlie differences in personality traits came up empty (Verweij et al., 2010).2. The Pseudoscience of Anti-Psychiatry in PLoS Medicine - August 01, 2006 Antipsychiatry is always a hot-button topic, and this early post attracted 44 comments.1. Airplane Headache - August 15, 2010 The winner by a mile, with 72 comments, is on a supposedly rare type of headache that occurs during take-off and landing (Atkonson & Lee, 2004). The pain appears to be unique to plane travel and not associated with other conditions. Neurological exam and brain imaging results in all published cases (n=14) have been normal. Clearly, there are more than 14 people who suffer from these excruciating headaches on airplanes. Triptan drugs (used to treat migraines and cluster headaches) may be effective in preventing airplane headaches (Ipekdal et al., 2011).Thank you for reading!

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

  • January 19, 2012
  • 07:27 PM

Deep Brain Stimulation for Bipolar Depression

by The Neurocritic in The Neurocritic

The Melancholia of Kirsten Dunst and Lars von Trier“Gray wool, clinging to my legs, it's heavy to carry along” The disastrous wedding reception of the severely depressed Justine precedes the end of the world, depicted as a highly stylized and artistic event feared by some but welcomed by others. Kirsten Dunst plays the role of von Trier's own melancholia, which was the inspiration for his film. The image above occurred out of context, at the very beginning, during the bombastic Wagnerian apocalyptic prelude to Part One, "Justine" and Part 2, "Claire." We don't hear Justine say those words until later, when she had lost the ability to care for herself. "She should be hospitalized," I thought at the time, and wondered why no one was getting her psychiatric help. But then we wouldn't have a movie that deals with internal struggle and suffering.Deep Brain Stimulation for Treatment-Resistant DepressionSevere depression that is refractory to treatment, i.e. unresponsive to psychotherapy, multiple trials of antidepressant drugs (often combined with atypical antipsychotics, mood stabilizers, benzodiazepines, etc.) and electroconvulsive therapy (ECT), takes a tremendous toll on the long-suffering patients and their families. An alternative treatment modality, deep brain stimulation (DBS), has been in clinical trials for intractable depression for nearly 10 yrs. It works using the same sort of device used in DBS for Parkinson's disease, which has been remarkably successful in alleviating symptoms. Electrodes are implanted deep in the brain, targeting the ventral portion of the anterior cingulate cortex, in Brodmann's area 25.Other brain regions have been targeted for DBS in major depressive disorder, including the nucleus accumbens, but today we'll focus on the work of Dr. Helen Mayberg and her colleagues at Emory University in Atlanta, Georgia.Figure 1 (Holtzheimer et al., 2012). Surgical targeting. Preoperative MRI shows the sagittal (A) and coronal (B) views of the planned optimal subcallosal cingulate (SCC) white matter target (red circle). The dotted black line indicates the subcallosal plane of interest, parallel to the anterior-posterior commissural line; the dotted white line indicates the rostral limit of the subcallosal plane; and the dotted red line indicates the midsubcallosal plane. The red circle indicates demarcation of the SCC white matter target and surrounding gray matter. C and D, Postoperative computed tomography scan merged with preoperative MRI showing a typical case with the deep brain stimulation electrodes in situ. Note that the contacts span the SCC gray and white matter in the vertical plane proximal to the split of the cingulum bundle and rostral medial frontal white matter tracts (C, red arrows, sagittal view). Contacts are numbered by convention (1-4 on the left, 5-8 on the right), inferior to superior. Contacts 2 and 3 are directly in the SCC white matter, and contacts 1 and 4 are in the inferior and superior gray matter, respectively. Why stimulate subcallosal cingulate/area 25 1 in depression? Previous neuroimaging studies by Mayberg and colleagues (2000) showed that resting glucose metabolism in this region is overly active in depressed people, and a reduction in activity was associated with antidepressant treatment response. Another key observation was made using a mood induction paradigm in healthy volunteers (Mayberg et al., 1999). After the participants remembered a sad autobiographical memory, their SCCs showed greater blood flow relative to a neutral mood state. Thus, the "sad cingulate" was implicated in normal sadness as well as in depression.The most recent DBS report, published in the Archives of General Psychiatry (Holtzheimer et al., 2012), is a follow-up after two years of chronic, high frequency stimulation of the subgenual cingulate white matter. The basic findings have been summarized elsewhere, including Providentia, with a review of possible mechanisms at The Scicurious Brain.The aspect of the study that I'd like to focus on today is the inclusion of patients with Bipolar-Type II (BP-II) for the first time, in addition to those with unipolar depression. Just as with the unipolar patients, those with BP-II had to be in a depressive episode for at least 1 yr.The specific DSM-IV diagnostic criteria for Bipolar II Disorder are:A. Presence (or history) of one or more Major Depressive Episodes. B. Presence (or history) of at least one Hypomanic Episode. C. There has never been a Manic Episode or a Mixed Episode. D. The mood symptoms in Criteria A and B are not better accounted for by Schizoaffective Disorder and are not superimposed on Schizophrenia, Schizophreniform Disorder, Delusional Disorder, or Psychotic Disorder Not Otherwise Specified. E. The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.Are the same neural circuits implicated in treatment-resistant depression also involved in BP-II? Remarkably, there is nothing in the literature that presents a rationale for using DBS for bipolar depression specifically, nor about why the subgenual cingulate white matter should be the target. A 2010 review by Lipsman, Lozano, and others from the Toronto neurosurgical group stated: "There are currently no trials or reports in the literature on the use of DBS for the exclusive treatment of bipolar diseas... 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  • January 14, 2012
  • 04:10 AM

Remembering and Forgetting in Traumatized Ugandan Refugees

by The Neurocritic in The Neurocritic

Gulu, Uganda (vis photography)Most of us have memories from the past that we'd rather forget. When those memories are of a traumatic nature, they can more difficult to expel from our minds. Unwanted memories can be rejected by means of active inhibitory processes (Anderson & Levy, 2009), but these mechanisms are impaired in individuals with post-traumatic stress disorder, or PTSD (Zwissler et al., 2011): Essentially, PTSD patients have trouble remembering what they are supposed to remember and forgetting what they would rather not remember. They appear to have impaired memory control.A group of German investigators conducted a study on memory and forgetting in one of the more unsettling regions of the world: northern Uganda. The Lord's Resistance Army (LRA), a terrorist organization, has waged a long and brutal campaign to overthrow the government of Uganda:Rape, torture, and murder have become the group's hallmarks in the almost fifteen [twenty or twenty-five] years that they have terrorized the citizens of Northern Uganda. The ranks of the LRA are filled in large part (approximately 80%) by children, who are kidnapped and brainwashed into service with the group. Human rights NGOs place the number of children currently fighting with LRA at around 3,000. LRA members also kidnap children, particularly girls, to serve as sex slaves; some have even been given as "gifts" to arms dealers in Sudan.Zwissler and colleagues (2011) recruited severely traumatized participants for a study on directed forgetting, a memory task where instructions are given to remember some items but to forget others during the encoding phase. The participants were 51 young people (mean age=20.8 yrs, range 16–30) living in Internally Displaced Persons (IDP) camps near the city of Gulu in Northern Uganda. All were equally exposed to traumatic events such as abduction, but only 26 were diagnosed with PTSD, an anxiety disorder marked by intrusive memories and flashbacks.The participants had two years of education on average, and many were functionally illiterate. For this reason, pictures were used as the stimuli (instead of words, which are commonly used in this type of study). The pictures were neutral in valence to examine whether memory issues in this population would extend to non-emotional material.In the experiment, 28 pictures (Set A) were presented during an initial encoding phase. Each picture was followed by a symbol that signaled whether the preceding picture should be remembered or forgotten. During the test phase, all 28 pictures were presented, along with new pictures that served as "lures" that were similar to the initial set (Set B; see below).Fig. 1 (Zwissler et al., 2011). Illustration of the picture sets showing three representative target-distractor pairs: (a) set A; (b) Set B. (Original photographs were shown in colour.)For each stimulus, participants were told to indicate whether they had seen it before, regardless of the prior instruction to remember or forget. Overall accuracy in the task is shown in the figure below. The non-PTSD group had better memories for the pictures they were told to remember, compared to those they were told to forget. In contrast, the PTSD group showed no difference in accuracy for the to-be-remembered vs. the to-be-forgotten pictures.Fig 2 (Zwissler et al., 2011). A comparison of the effect of directed forgetting on discrimination accuracy in the two groups. PTSD, post-traumatic stress disorder. *Indicates significant differences.One way to view these results is that the participants with PTSD performed worse than controls for items they were supposed to remember, and were unable to invoke inhibitory processes to suppress memory for the to-be-forgotten items ("trouble remembering what they are supposed to remember and forgetting what they would rather not remember"). Breaking down task performance a little further, the PTSD group was more inclined to make "false alarm" errors to the lures related to pictures they were supposed to remember. This suggests that the details of the to-be-remembered pictures weren't encoded as well, and were more easily confused with related pictures they didn't see.The authors concluded that......traumatized individuals with (but not without) PTSD are impaired in their ability to selectively control episodic memory encoding. This impairment may contribute to clinical features of the disorder such as intrusions and flashbacks.However, "directed forgetting" is usually not a practical strategy when real life events are unfolding. Do these results this imply that the non-PTSD group was better able to dissociate themselves from traumatic events as they were occurring (or shortly thereafter)? Whether such a process can effectively occur at all during horrible tragedies is highly controversial (e.g., Terr vs. Loftus). The phenomenon is more often studied when applied to the retrieval of traumatic or unwanted memories (Anderson & Levy, 2009), not during the encoding phase.Tragically, there appears to be No End to LRA Killings and Abductions in central Africa, according to Human Rights Watch. These ongoing atrocities should not be ignored.So watch the video Dear Obama: A Message from Victims of the LRA.Further Reading on Forgetting:Forgetting is Key to a Healthy MindLetting go of memories supports a sound state of mind, a sharp intellect--and superior recallLiving and ForgettingI Forget...I Forgot......and it's Memory Week at the Guardian.ReferencesAnderson MC, Levy BJ. (2009). Suppressing unwanted memories. Curr Dir Psychol Sci. 18:184-194.... Read more »

  • January 6, 2012
  • 06:34 AM

Subjects Wanted to Drink Bourbon and Watch Erotic Films

by The Neurocritic in The Neurocritic

Our fun New Year's Eve post reviewed the suspected brain mechanisms of an alcohol blackout, or an episode of amnesia after a bout of heavy drinking (Rose & Grant, 2010). Alcohol-induced alterations of hippocampal circuits are thought to disrupt memory encoding, which can lead to two different types of blackout: en bloc, a complete loss of memory for the affected time period; and fragmentary, where bits and pieces of memories remain. The en bloc blackout is more likely to occur when a large quantity of alcohol is ingested in a short period of time.In 1970, less was known about the causes and mechanisms of alcohol blackouts. A study by Goodwin and colleagues set out to learn more:Some psychiatrists believe blackouts to be a functional disturbance, related to guilt or anxiety. Others believe they reflect a toxic effect of alcohol on the brain. There are few data to support either concept. Blackouts usually occur erratically; comparable amounts of alcohol do not always produce memory loss, and it has not been possible to predict when an intoxicated person will suffer amnesia. During the amnesic interval, the person may function reasonably well and perform complicated acts, suggesting that the amnesia is retrograde. To confirm this, however, memory must be observed systematically during drinking periods followed by amnesia, which heretofore has not been done.Human subjects protection programs were less stringent (or non-existent) 40 years ago, so it was no problem to enlist unemployed alcoholic day laborers to drink a pint of bourbon and undergo memory testing of an unusual sort.The subjects were recruited from individuals seeking daily employment at the Casual Labor Division of the Missouri Employment Office in St. Louis. Previous experience with this source had shown that a sizable proportion of the job applicants are alcoholic. Individuals were eligible for the study if they met two criteria; (1) willingness and ability to drink more than a pint of whiskey in a few hours , and (b) good physical health.Ten men (mean age 41 yrs) were recruited as participants. Eight of them were alcoholics, and five experienced frequent blackouts. After fasting for 5 hrs, the experimental procedure was to drink 16-18 ounces of 86 proof bourbon on the rocks in 4 hrs. Cognitive testing began after the first hour of drinking to assess immediate, short-term, and remote memory as well as calculation abilities. In brief, the drunk participants looked at toys and watched porn and were asked to recall these items after a delay (Goodwin et al., 1970):The tests were as follows. (a) Every 30 min the subject was shown a toy for 1 min, after which it was removed from sight. Two minutes later the subject was asked to recall the toy. If recalled correctly immediate memory was considered intact. Thirty minutes later he as asked again to recall the toy to measure short term memory...(b) Every 30 min the subject was shown for 1 min a scene from an erotic movie. He was asked to describe and discuss the scene. If he could recall the scene 2 min later, this was considered a reflexion of intact immediate memory. Thirty minutes later he was again asked to recall the scene to measure short term memory.(c) Remote memory was tested by asking questions about early upbringing (name of schools, teachers, and so on) and events that occurred during the previous 2 days.(d) Ability to perform calculations was tested by asking the subject to do simple multiplication and subtraction tasks.Other than wanting to create a highly desirable means of employment for the target population, why did the authors use erotic movies as stimuli?? (1) So that memory for arousing, emotional material could be compared to memory for the [presumably] more neutral toys; (2) Because very drunk men would be unwilling or unable to cooperate if more boring tests were used; and (3) Toys and porn were highly memorable to sober male subjects 24 hrs later.The results indicated that all 10 subjects performed well when tested at the 2 min retention interval, but half of them showed impaired memory when tested 30 min and 24 hrs later. These same 5 participants were the ones with histories of blackouts. The authors speculated that the faster rise in blood alcohol levels (BAL) in the blackout subjects could be a reason for their amnesia. However, this explanation is implausible because the blackout group had poor memories at the earliest 30 min time point, when there was no difference in BAL between the groups.So what have we learned? Retrieval of remote memories and simple calculation abilities are not impaired by heavy drinking, is possible to predict amnesia during a drinking bout: on formal testing individuals who are later to experience amnesia will have a specific loss of short therm memory correlated in time with the period of amnesia, while other types of memory are intact.A final lesson is that it was much easier to publish in Nature in 1970. Group comparisons with n=5? Fine and dandy. Pesky statistics and error bars on figures? Who needs them? Those were the days my friend...ReferencesGOODWIN, D., OTHMER, E., HALIKAS, J., & FREEMON, F. (1970). Loss of Short Term Memory as a Predictor of the Alcoholic “Blackout” Nature, 227 (5254), 201-202. DOI: 10.1038/227201a0Rose, M. & Grant, J. (2010). Alcohol-Induced Blackout. Journal of Addiction Medicine, 4 (2), 61-73.
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