The Neurocritic

Neural prosthetics, brain-computer interfaces (BCI), “closed-loop” deep brain stimulation (DBS) devices, and a world without human brain disorders. The first three of these are already here... is the last one possible?

In the utopian world of The Hedonistic Imperative, an ambitious, admirable (and unlikely) 1995 manifesto by philosopher David Pearce, the goal is to “eradicate suffering in all sentient life” through paradise engineering— which involves sophisticated applications of nanotechnology, genetic engineering, and psychopharmacology. And going beyond the eradication of suffering, “Life-long happiness of an intensity now physiologically unimaginable can become the heritable norm of mental health.” ¹

Lest you think such speculation is limited to those wacky transhumanists, respected neuroscientists Kent Berridge and Morten Kringelbach have written seven reviews on the neuroscience of happiness and pleasure and well-being. In contrast to the vegan and animal rights supporter Pearce, however, Berridge & Kringelbach (e.g., 2012) see animal research as the key to unlocking the brain mechanisms of human pleasures.

Sure, we have BRAIN 2025 and the DARPA deep brain stimulation awards. But we're getting ahead ourselves here, aren't we? Using neuroscience to alleviate human suffering takes precedence over the attainment of “a sublime and all-pervasive happiness” in wealthy Western post-industrial societies (doesn't it)? Doesn't it??

“Neurofutures that aren't mine”

There used to be a blog called Neurofuture (“Brain Science and Neofuturism”), written by Sandra K. It covered topics like HedWeb and neuroscience nanotechnology and NeuroArm and the Blue Brain Project back in 2006-2007.

Since February 2012, there's been an unrelated NeuroFuture twitter feed @NeuroFutureNews (“Mind-blowing tweets! Follow me if you are interested in brain, bionics, BCI, robotics and mind-controlled news”). A guy named wolfgang berke has had the @neurofuture account since March 2010, but he hasn't tweeted once.

And now, there's NeuroFutures 2014, a conference in Seattle starting tomorrow:

NeuroFutures Conference: June 17 - 18, 2014
Thought leaders in research, engineering, industry, and clinical domains will explore how the intersection of neurotechnology innovations in neuromodulation, brain mapping, neuroimaging, big data analytics, and brain computer interfaces will transform our understanding of neural systems and enable life-changing medical treatments.

If you're already in Seattle, you can attend a public lecture by a prominent DBS neurosurgeon today at 7 PM:

NeuroFutures Public Lecture: 7:00 PM, June 16
Dr. Andres Lozano from the University of Toronto will kick off the NeuroFutures summit with a talk on “The Future of Brain Stimulation: Parkinson’s, Depression, Alzheimer’s and beyond" (see his related TED Talk here). Afterwards, he will discuss his work with science educator and author David Heil, and field questions from the audience.

Organizational and industry sponsors include Center for Sensorimotor Neural Engineering, Allen Institute for Brain Science, Cyberonics, and Neurotech Business Report,³among others.

Why NeuroFutures?
Problem: One in four U.S. adults suffer from a diagnosable neurological disorder and a quarter of these are seriously disabled as a result. These patients endure immense physical and emotional suffering, and their family members and caregivers bear a heavy emotional and financial burden. From a scientific standpoint, the human brain is the most sophisticated computing system in the known universe, and we are only starting to understand how it works.
. . .

Plan: To accelerate the pace and impact of innovation we will bring together neurotechnology thought leaders from different disciplines to exchange ideas and forge collaborations at the two-day NeuroFutures Conference on June 17 and 18, 2014 in Seattle, Washington. We will highlight people and resources in the Northwest that position the region to play a leading role in our NeuroFuture...

So what will it be... better living through chemistry (pharmaceuticals), biotechnology, or engineering? With conference sessions on BCI and Neuromodulation Innovations, Learning, Plasticity, and Adaptation in Neural Interfaces, and The Past, Present, and Future of Closed-loop Neuromodulation, one might think it's a great time to be a Neuroengineer at places like the Center for Sensorimotor Neural Engineering, the Brain-Machine Interface Systems Laboratory, and the Neural Prosthetic Systems Laboratory.

Footnotes

¹The HedWeb manifesto has been online in its entirety since 1995, I believe. For many years, the labyrinth of links and early-acquisition domain names such as biopsychiatry.com, huxley.net, mdma.net, opioids.com, cannabis.net, and general-anaesthesia.com were entirely unattributed, except for affiliation with an organization known as BLTC RESEARCH. But be careful, or you could fall down the rabbit hole of supercentenarian.com or reproductive-revolution.com or oxytocin.org or sensualism.com or nootropics.com or.....²

² OMFG! There are 2,244 PARADISE-ENGINEERING BLTC WEBSITES as of JUNE 2014:

Paradise-engineering websites (2014)
Good domains for a better world?

³Neurotech Business Report was the first to break the news about the failed BROADEN clinical trial for treatment-resistant depression, and they've continued their close coverage of the neuromodulation market.

top image via Alternative Media News

Figure 1. Pleasure Cycles (Berridge & Kringelbach, 2012), from Building a neuroscience of pleasure and well-being.

A retrospective of an artist's work gives the viewer insight into their creative process over an extended period of time. In some cases, a retrospective seems to allow access into the artist's mind.

Canadian artist and writer Douglas Coupland adopted this stance more literally by creating a room filled with 5,000 objects he collected over 20 years and carefully arranged in a masterwork called The Brain. Coupland is best known (to Americans at least) as the author of Generation X: Tales for an Accelerated Culture, but his prolific artistic output“over the past 12 years addresses the singularity of Canadian culture, the power of language, as well as the ever-pervasive presence of technology in everyday life.”

Douglas Coupland
everywhere is anywhere is anything is everything
May 31 — Sept 1, 2014

: #CouplandVan

NOTE: the artist encouraged photography and tagging of his work.

This exhibition brings together works made since the early 2000s as well as major new installations created specifically for this presentation. It sheds light on subjects as varied as the distinct nature of Canadian identity, the rise of utopian ideas, the power of words, the ubiquitous presence of digital technologies, the emerging culture of fear and the unshakeable nature of one’s own constitution—ideas that Coupland examines with both optimism and some trepidation.

The retrospective at the Vancouver Art Gallery is divided into six parts, culminating in The Brain. Its impact as a work of art is more effective in the context of what came before it, including a meditation on the distinctiveness of Canadian Identity. Another section examined youth and the optimism of an earlier era: Growing Up Utopian as depicted in Lego blocks.

100 identical Lego houses

The highlight of Words Into Objects is a room of slogans and aphorisms on colorful posters, reminiscent of Jenny Holzer or Barbara Kruger but with a distinctive focus on the internet and technology.

Douglas Coupland, Slogans for the 21st Century (2011-2014).

Returning to The Brain, the massive collection of objects from thrift stores, garage sales, and eBay appeared mighty close to hoarding, in my view. But where is the border between collecting and hoarding objects (e.g., televisions)? Is there a difference if you're hoarding for artistic purposes?

Materials used in the The Brain, 2000–2014, mixed-media installation with readymade objects [NOTE: prior to arrangement]. Courtesy of the Artist and Daniel Faria Gallery. Photo: Trevor Mills, Vancouver Art Gallery.

These questions were quite salient for me because I attended another exhibition at the same gallery in 2010, called Waste Not (by artist Song Dong). This one examined hoarding overtly in the context of culture, scarcity, and loss:

Waste Not—or wu jin qi gong in Chinese—describes the philosophy of life for a generation of people in China, of which Song Dong’s mother was a part, who grew up during the Cultural Revolution with the experience of displacement, poverty and the constant shortage of goods. The installation stands as a record of his mother’s life, as well as a tribute to his father’s death.

After the artist's father died, his mother's compulsive hoarding intensified, which is not uncommon. Over 10,000 objects were on display. The exhibit was quite moving and sad:

...Carefully sorted, arranged, and displayed in the gallery, along with the wooden frame of one of the rooms of her house, these objects include everything from cracked wash basins, chipped tea cups, old radiators, and burnt-out light bulbs to flattened toothpaste tubes, yellowing newspapers, ripped nylon stockings, and empty containers of every description. And all in startling multiples.

The purpose and impact of The Brain was quite different, however. Much of the collection was whimsical and idiosyncratic, with the metaphorical layout designed to represent the contents and organization of Coupland's physical brain, incomprehensible to all but the artist. Without reading the gallery notes, the viewer struggles to find meaning in the chaos, and would miss out on pieces like the amusing Seat of Consciousness (“the elusive site of self-reflexive awareness that scientists have yet to pinpoint”).

The Seat of Consciousness, part of The Brain (by Douglas Coupland)

Highways and byways of The Brain.

The “corpus callosum” divides the installation into left and right hemispheres, which is clearly an overarching metaphor not intended to be accurate [presumably].¹ So we can excuse the artist for placing Language in the Right Brain, because his purpose here isn't a veridical (or even stylized) rendition of the brain destined to win the Brain Art Competition 2014. It's more like the struggle for an external representation of memories, an exploration of why he is who he is. And for this reason it's deeply personal, and at the same time a reflection of a specific culture and era.

COLOUR MEMORY BANK: “a visual representation of the artist's recollections, attractions, and repulsions.”

This is not a pipe or a road sign in Chinese or a bunch of old cans...

Note the aqua-colored Stroop banana.

WHITE MEMORY BANK: “This white structure, built in a Brutalist style, is an archival collection of white objects, including scale models of seminal 20th and 21st century buildings, as well as numerous corporate mascots painted white. ... The fact that the objects are white also tinkers with the brain's need to classify and make sense of structure, the need to interpolate a narrative, not unlike looking for shapes in clouds.”

In total, the effect on the viewer is overwhelming and disorienting, and yet exhilarating (particularly in hindsight).

Objects from Coupland's memory bank here bleed into the signage structures, awaiting information as to where they will be routed. The overall effect is surrealistic and can be interpreted as a snapshot of Coupland's thinking.

Coupland asks, “What is consciousness? Is it a park [sic] that dances through the brain at any given time? A spark that, while it exists, can never be visualized on its own?”

And here he captures the challenge of the “hard problem” of consciousness that has confounded scientists and philosophers alike.

Footnote

¹ It's possible that Coupland is left handed and had a Wada test to demonstrate right hemisphere dominance for language, but this is highly unlikely.

Douglas Coupland, Slogans for the 21st Century (2011-2014) at the Vancouver Art Gallery. #couplandvan

In the 2000s, enthusiasm was high that a novel class of drugs would reach the market as blockbuster treatments for psychiatric disorders. These drugs act on receptors for a group of neuropeptides known as tachykinins (or neurokinins). These peptides — substance P (SP), neurokinin A (NkA), and neurokinin B (NkB) — function as neurotransmitters or neuromodulators in the central nervous system, but are quite different from the usual monoamines targeted by current psychotropic medications prescribed for schizophrenia, depression, and other mental illnesses.

The tachykinin receptors (NK₁, NK₂, NK₃) have varying affinities for the different peptides, being greatest for SP, NkA, and NkB respectively. A series of clinical trials with NK₁ antagonist compounds (i.e., SP blockers) was conducted as potential treatments for major depression, generalized anxiety disorder, alcohol craving, and post-traumatic stress disorder (PTSD). Substance P is released during times of increased stress and localized in brain regions implicated in the stress response (Ebner et al., 2009), so the idea was that dampening the effects of SP would lead to symptom amelioration in these disorders. However, except for some mildly promising results in stressed alcoholics, the trials were disappointing in patients with generalized anxiety and PTSD. Results were mixed in major depression. But those trials, with a GSK compound called orvepitant, were terminated to due serious adverse events (seizures) in several patients.

In contrast, the most promising target for schizophrenia seemed to be the neurokinin 3 (NK₃) receptor. This was because of prominent expression on the midbrain dopamine (DA) cells implicated in the pathophysiology of schizophrenia, and because selective NK₃ antagonists can block NkB-induced excitation of dopamine neurons (Spooren et al., 2005). The original “typical” antipsychotic medications are DA antagonists, which can have untoward side effects with chronic use. Because NK₃ antagonists lack the major extrapyramidal and metabolic side effects of typical and atypical antipsychotics, they were heralded as “the next generation of antipsychotics” in 2005.

How well have they fared since then?

(1) The NK₃ antagonist osanetant was under development by Sanofi-Synthélabo as a potential treatment for schizophrenia:

In October 1999, Lehman Brothers predicted that the probability of the product reaching the market was 10%, with a possible launch in 2003 and potential peak sales of US $200 million in 2011.

However, Sanofi-Aventis stopped any further development of osanetant in 2005.

(2) The NK₃ antagonist talnetant was under development by GlaxoSmithKline, with several clinical trials conducted between 2002 and 2005. But it too was discontinued (in 2007).

In other words, these drugs have not lived up to their original promise as novel treatments for schizophrenia.

“Repurposing” of Drugs

“We should continue to repurpose treatments and to recognise the role of serendipity,” said Geddes and Miklowitz (2013) in a recent review on new treatments for bipolar disorder. Although the article did not hint at any impending pharmacological breakthroughs, the idea that existing drugs can find new indications is especially pertinent in this era of shrinking investment in neuro/psych drug development.

Sometimes the serendipity and repurposing comes from mechanistic preclinical studies that can then be retranslated back to the clinic. Jumping ahead to that possibility, a press release from Emory declares:

Potential drug target for PTSD prevention

Scientists at Yerkes National Primate Research Center, Emory University have identified a drug that appears to make memories of fearsome events less durable in mice.

The finding may accelerate the development of treatments for preventing PTSD. The drug, called osanetant, targets a distinct group of brain cells in a region of the brain that controls the formation and consolidation of fear memories.
. . .

“Potentially, drugs that act on this group of cells could be used to block fear memory consolidation shortly after exposure to a trauma, which would aid in preventing PTSD,” says Kerry Ressler, MD, PhD, professor of psychiatry and behavioral sciences... “PTSD is unique among psychiatric disorders in that we know when it starts – at the time of the trauma. Finding ways to prevent its development in the first place – in the emergency department or the battlefield - is an important and exciting avenue of research in this area.”

NkB and the Consolidation of Fear Memories

A new study in mice found that osanetant could block the consolidation of fear memories when administered within a narrow time window (Andero et al., 2014):

Notably, when osanetant is dosed from 30 min before auditory FC [fear conditioning] up to 1 hr after training, it does not affect fear acquisition but impairs fear memory consolidation as shown by decreased freezing in the fear expression test.

Furthermore, mice previously traumatized by 2 hours of immobilization (a rodent model of PTSD-like behaviors that include impaired fear extinction) also showed reductions in fear memory consolidation when given osanetant (IMO-Osa), compared to placebo (IMO-Veh).

Modified from Fig. 4 (Andero et al., 2014). G:Osanetant given immediately after FC impaired fear memory consolidation in mice that had been previously exposed to a traumatic stress as shown by reduced freezing in the fear expression test, ∗p ≤ 0.05. n = 8 per group.

The starting point of this study, however, was not to test the effects of osanetant on the formation of fear memories. Rather, Andero et al. (2014) began by casting a wide net in search of genes that are regulated during fear conditioning. They found that the Tac2 gene (TACR3 gene in humans) is regulated during fear memory consolidation, specifically in the central nucleus of the amygdala (a “fear learning central” of sorts).

Furthermore, increased expression of the Tac2 gene, NkB peptide, and activation of Nk3R may be involved in stress sensitization and overconsolidation of fear. In contrast, genetic silencing of Tac2-expressing neurons impairs fear consolidation. Blockade of this pathway may provide for a novel therapeutic approach for disorders with altered fear learning such as PTSD.

The clinical potential of this finding is not lost on the authors. If given shortly after a traumatic event (e.g., in an emergency room or combat situation), it's possible that osanetant could reduce the emotional potency of trauma memories:

Finally, one of the most interesting aspects of our data is the potential use of the Nk3R antagonist osanetant as a pharmacological agent to block fear memory consolidation shortly after exposure to a trauma. Additionally, we found that osanetant prevented the upregulation of the Adcyap1r1 gene, which encodes the PAC1 receptor. The PACAP-PAC1R pathway is involved in PTSD, fear conditioning, amygdala excitatory neurotransmission, and stress. All this could be relevant in PTSD prevention since it has previously been found that osanetant is safe in humans, although additional preclinical studies, such as those described herein, are needed first to establish the mechanisms involved. This gives our findings an exciting potential approach to translation to human patients.

This study also provides a perfect example of NIMH's new mandate for specifying a hypothesized mechanism of action for interventions that will be tested in funded clinical trials. Does peri-trauma osanetant (vs. placebo) reduce later development of PTSD symptoms and attenuate amygdala activation to trauma script-driven imagery in fMRI? Is TAC3 gene expression altered in primate models? [The distribution of Nk3R likely differs between mice and primates.] Are there declines in PACAP blood levels in traumatized individuals given osanetant (vs. placebo)? Are there longer-term effects on methylation of ADCYAP1R1 in peripheral blood? These latter measures are biomarkers of an abnormal stress response in PTSD that are currently studied by the Ressler Lab.

At any rate, NIMH Director Insel might as well hand over the money right now...

References

Andero, R., Dias, B., & Ressler, K. (2014). A Role for Tac2, NkB, and Nk3 Receptor in Normal and Dysregulated Fear Memory Consolidation Neuron DOI: 10.1016/j.neuron.2014.05.028

Ebner K, Sartori SB, Singewald N. (2009). Tachykinin receptors as therapeutic targets in stress-related disorders. Curr Pharm Des. 15:1647-74.

Maggi CA. (2000). The troubled story of tachykinins and neurokinins. Trends Pharmacol Sci. 21(5):173-5.

Spooren, W., Riemer, C., & Meltzer, H. (2005). NK3 receptor antagonists: the next generation of antipsychotics? Nature Reviews Drug Discovery, 4 (12), 967-975 DOI: 10.1038/nrd1905

Spooren et al. (2005)

via @mallelis

At the literary/pop culture/feminist/humor blog known as The Toast, the hilarious Mallory Ortberg has skewered those ubiquitous ads from brain training behemoth Lumosity.

The Five Stages Of Lumosity

Stage I – Initiation

. . .
Friend, are you troubled by persistent waking blackouts? Do you tremble and shudder and flicker out of consciousness when asked to recall basic facts about your acquaintances? Does your right eye fill with blood whenever you have to try to remember your PIN? Let Lumosity patch over those mysterious missing blank spots in your sick and addled mind.

“Lumosity: Improving your brain through the science of neuroplasticity, but in a way that just feels like games.”

Lumosity: you can trust us. It doesn’t hurt. It’s normal. It feels normal. Good and normal. Just like a game. Won’t feel a thing. It’s normal, and you’re normal, and your brain is working better now than it was before. Before was bad. Now is good.

Then the user progresses to Stage II – The Audit, Stage III - Saturation, Stage IV – Synergy/Assimilation, and finally to...

Stage V – Full Compliance

The Golden Age of Tech II

Stage V features a series of screenshots taken from a flabbergasting Scientology promotional video (discussed on Reddit).

Ortberg's post is really quite brilliant — the cult-like following, the testimonials from humans ascended to a higher plane, the suspiciously vague ad campaigns that use suspiciously vague terms like "neuroplasticity".

In reality, though, it's hard to imagine two world views more completely out of step than Neuroscience and the bizarre set of beliefs known as Scientology. {floating tone arms, anyone??}

In fact, Scientology is quite vehemently anti-psychiatry and anti-neuroscience. Many of you might remember Tom Cruise's condemnation of Brooke Shields for taking antidepressants to treat her postpartum depression, to which Shields replied: “Tom should stick to saving the world from aliens and let women who are experiencing postpartum depression decide what treatment options are best for them.”

The stance against psychiatric medication goes much further than that: they would like to eliminate NIMH, the major U.S. funding body for biological psychiatry and mental health research. The Secrets of Scientology site maintained by Carnegie Mellon Computer Science Professor David S. Touretzky has covered the sect's excesses for many years, including in a poster presented at the 1998 Society for Neuroscience meeting:

Opposition to Mental Health Research

Scientology demonizes the mental health professions in part because psychology and psychiatry are Scientology's main competitors. But another reason is that all cult groups need an external enemy to rally against. Scientologists are taught that modern psychiatrists still use lobotomy and electroshock treatments to dominate and control their patients.

Despite this, Scientology started out with a materialist model of the mind before it was derailed (perhaps by founder L. Ron Hubbard's alcohol and drug addiction). As Prof. Touretzky explains:

In 1950 Dianetics presented a purely materialistic view of the mind as a simple computer, with frequent references to "memory banks", "circuits", and data recording. The mind was implemented by the brain, and memory was a product of a cellular recording mechanism. Hubbard did not rule out the possibility that psychic phenomena such as ESP or telepathy might some day be demonstrated, but they played no role in Dianetics.

With the introduction of past lives, Hubbard switched from a materialist to a dualist conception of mind. In Dianetics, the "I" that looked at mental image pictures was the analyzer. In Scientology the "I" is the thetan, a spirit, that moves from one body to the next, carrying its reactive mind along with it. And in advanced Scientology auditing, subjects are instructed to communicate with their body thetans "telepathically", not verbally.

The E-Meter

Touretzky's SFN poster again:

The scientific trappings of Scientology extend even to instrumentation: a skin galvanometer called an E-meter (electropsychometer) is said to allow an auditor (therapist) to observe the creation or destruction of "mental mass'' by reading the needle movement.

Mark Super VII Quantum E-meter (Wikimedia Commons)

The E-meter (known variously as the Electropsychometer or the Electroencephaloneuromentimograph)¹ provides a crude measure of skin conductance. How crude? The original model used a pair of tin cans as electrodes. To learn more, you can surf the Internet's most extensive E-Meter site hosted by (you guessed it!) Prof. Touretzky.

According the Church of Scientology's own materials, however, the E-meter is used by auditors to locate areas of spiritual distress or travail:

The E-Meter measures the mental state or change of state of a person and thus is of enormous benefit to the auditor in helping the preclear locate areas to be handled. The reactive mind’s hidden nature requires utilization of a device capable of registering its effects – a function the E-Meter does accurately.
. . .

When the person holding the E-Meter electrodes thinks a thought, looks at a picture, reexperiences an incident or shifts some part of the reactive mind, he is moving and changing actual mental mass and energy. These changes in the mind influence the tiny flow of electrical energy generated by the E-Meter, causing the needle on its dial to move. The needle reactions on the E-Meter tell the auditor where the charge lies, and that it should be addressed by a process.

Different needle movements have exact meanings and the skill of an auditor includes a complete understanding of all meter reactions.

Wow, that is true scientific precision. Impressive, now isn't it? Even the most computationally sophisticated cognitive neuroscientists don't claim to read the hidden mind's reactive nature using multivoxel pattern analysis (MVPA) of fMRI data. Or do they?

‘Neural Valence Meter’

I know the authors of a recent Nature Neuroscience paper that used MVPA to classify subjective affective states² (Chikazoe, Lee, Kriegeskorte, & Anderson, 2014) would be utterly horrified with the analogy, but I thought of the e-meter when I read this quote in a press release:

“It appears that the human brain generates a special code for the entire valence spectrum of pleasant-to-unpleasant, good-to-bad feelings, which can be read like a ‘neural valence meter’ in which the leaning of a population of neurons in one direction equals positive feeling and the leaning in the other direction equals negative feeling,” Anderson explains.

Call it priming by Ortberg if you will, but terminology like 'special code', 'entire valence spectrum', 'leaning in one direction/the other direction', and 'neural valence meter' sounded a little cult-like to me...

E-Meter Controls and Indicators

{imagine that the needle leaning in one direction = 'good' (clear), and in the other direction = 'bad'}

Footnotes

¹ A Gizmodo article that called the device an electroencephaloneuromentimograph is most notable for posting the lengthy complaining e-mail sent by the Church of Scientology.

² Let's call them 'neuroqualia' perhaps - “The entire valence spectrum was represented as a collective pattern in regional neural activity as sensory-specific and abstract codes, whereby the subjective quality of affect can be objectively quantified across stimuli, modalities and people.” (Chikazoe et al., 2014).

Reference

Chikazoe J, Lee DH, Kriegeskorte N, Anderson AK. (2014). Population coding of affect across stimuli, modalities and individuals. Nat Neurosci. Jun 22. doi: 10.1038/nn.3749. [Epub ahead of print]

I wanted to submit a paper for the Frontiers in Human Neuroscience Research Topic on Critical Neuroscience: The context and implications of human brain research, but I couldn't decide what I should write about.

Could I just submit a blog post like Professor of Literary Neuroimaging that critiqued the entrée of fMRI into Literature Departments?

“So literature is abandoning Marxism and psychoanalysis in favor of neuroimaging!! Meanwhile, key neuroimagers have taken up psychoanalysis (Carhart-Harris & Friston, 2010) and socialism (Tricomi et al., 2010).”

Would they accept short humorous pieces like this...

Tenure-Track Position in Neuroetiquette and Gender Theory
Department of Critical Socioneurobiology.

Pending approval of departmental funds, the North Dakota School for Social Research is seeking outstanding candidates for its newly developed Interdisciplinary Program in Architecture, Kitchen Design, Sociology of Gender Roles, and Neuroimaging. State-of-the-art Siemens MAGNETOM 7T MRI and 306-channel planar dc-SQUID Neuromag Vectorview MEG facilities available. Start-up funds of $50K provided. Requirement to teach 3 classes per semester, including Statistics, Introduction to Celebrity Chefs, and Advanced Techniques in Optogenetics. The successful Assistant Professor candidate will be expected to obtain NEA funding, publish in high-impact science journals, give a Top 10 TED talk, and negotiate a major book deal before receiving tenure. Experience as a nationally syndicated advice columnist preferred.

Send CV, design portfolio, writing samples, research manifesto, and 10 letters of recommendation to: Chair of Search Committee, Department of Critical Socioneurobiology, North Dakota School for Social Research. Address inquiries to: neuroetiquette_and_gender_theory@ndsfsr.edu.

NDSFSR is an Equal Opportunity Employer.

...accompanied by a [somewhat] more serious meditation on Neuroetiquette and Neuroculture, which explained that neuroscientists are not taking jobs away from philosophers, sociologists and gender theorists:

I think the neuro-panic among social scientists is overblown. How many philosophers, sociologists, and gender theorists are unemployed because their respective departments have decided to hire neuroscientists instead? How many developmental neurobiologists have applied for this Instructor of Philosophy position at Rochester Community and Technical College? Will a cognitive neuroscientst be able to teach transnational feminism or postcolonial feminism, queer theory, and critical race theory in the Women's and Gender Studies Program at Illinois State University?

Could I have converted all of the above content into a coherent scholarly manuscript that addressed firstly, the pestilent neuro-ization of the academy (and the kitchen),¹ and secondly, the reactionary anti-neuro manifesto pushback? Did I even want to? There was certainly no time (or money) for such a project...

Or how about something on The Mainstreaming of Neurocriticism (followed by its inevitable decline)? That would have been a lot easier for me.

But Is Neurocriticism the same as Critical Neuroscience?

The call for papers said:

Critical neuroscience is an approach that addresses these contested issues surrounding the field of cognitive neuroscience from multiple viewpoints. The aim is to engage neuroscientists with researchers in the humanities and social sciences who deal with the implications of brain-based approaches to fields such as education, law, medicine, social policy, business and with the expansion of neuroscience in the University more broadly. Critical neuroscience encourages collaborative approaches to careful assessments of the status quo, longer-term impacts, potentials and problems of cognitive neuroscience within the laboratory and in the various areas of application. The project has been analyzing methods, technologies and theoretical paradigms, while also drawing on history and philosophy of science, anthropology, sociology and cultural studies, and reaching out to include practitioners from medicine, social policy, counseling and science journalism in order to better understand whether and how neuroscience could have value for these other domains.

Presciently,² the Editors wanted to “address the visions and challenges surrounding new grand-scale initiatives in neuroscience — including the EU-funded Human Brain Project and a comparable initiative planned in the U.S.”

As it so happens, a mere two weeks ago, the €1-billion HBP was roundly criticized in an open letter signed by 156 neuroscientists (the list of signatories and supporters is now over 700):

...the HBP has been controversial and divisive within the European neuroscience community from the beginning. Many laboratories refused to join the project when it was first submitted because of its focus on an overly narrow approach, leading to a significant risk that it would fail to meet its goals. Further attrition of members during the ramp-up phase added to this narrowing .... including the removal of an entire neuroscience subproject and the consequent deletion of 18 additional laboratories...
. . .

In this context, we wish to express the view that the HBP is not on course and that the European Commission must take a very careful look at both the science and the management of the HBP before it is renewed. We strongly question whether the goals and implementation of the HBP are adequate to form the nucleus of the collaborative effort in Europe that will further our understanding of the brain.

A flurry of press and blog coverage ensued, followed by a bigwig defense in New Scientist and an official statement [PDF] from the HBP. Although it's clear there are fundamental differences of opinion about a massively optimistic and expensive attempt to model the human brain, organizational issues of power and control are key as well:

The nixed subproject, called Cognitive Architectures and headed by French neuroscientist Stanislas Dehaene, represented all the neuroscience in Europe that isn't working on a molecular or synaptic level, says Zachary Mainen of the Champalimaud Centre for the Unknown in Lisbon, one of the authors of the letter. HBP “is not a democracy, it’s Henry’s game, and you can either be convinced by his arguments or else you can leave,” Mainen says.

link via Neuroecology

You might think that the current HBP dispute has drifted outside the realm of the “Critical Neuroscience” Research Topic.³ But you'd be wrong, because Extending the mind: a review of ethnographies of neuroscience practice (Mahfoud, 2014) appeared online only one month before the brouhaha:

Ethnographic studies of neuroscience knowledge can potentially offer insight into the relationship between the everyday of scientific practice and reasoning on the one hand and the political and moral economy of science on the other, as well as encouraging conversation between the social and biological sciences, as this special issue aims to do.

So what do I think about the Critical Neuroscience enterprise? The 18 articles are pretty diverse and include fMRI methods papers on Machine Learning Classifiers and deficient approaches to neuroimaging.

I already blogged about one paper in the special issue, on the fun topic of Empirical Neuroenchantment: From Reading Minds to Thinking Critically (Ali et al., 2014). So see The Seductive Allure of Spintronics™ Neuroimaging mock mind reading scanner for that.

Another article is basically a sociocultural mega-thrashing of the NIMH RDoC framework for mental health research. Worth quoting:

In this article we consider the rationale of the RDoC and what it reveals about implicit models of mental disorders. As an overall framework for understanding mental disorders, RDoC is impoverished and conceptually flawed. These limitations are not accidental but stem from disciplinary commitments and interests that are at odds with the larger concerns of psychiatry.

There are also contributions from “historians of science, STS scholars and philosophers.” The acronym highlights a language gap between disciplines, because I had to look up STS scholars — they're not experts in the superior temporal sulcus, they study science, technology and society.⁴ On that note, I'm not sure how many readers will devour a support vector machine classifier using a linear kerneland a critical philosophical investigation of the brain qua image.

But that's the problem with a multiplicity of specialized viewpoints in academic publishing. Maybe someone (the Editors?) can host a series of interdisciplinary blog posts that are comprehensible to a broader audience?

Footnotes

¹ Who can forget Neurokitchen Design? Or The Neuroscience of Kitchen Cabinetry?

² The call for papers went out over a year ago.

³ Unless, perhaps, you want to critique the growing literature on whether Neurocoaching could improve the Neuroleadership skills of HBP oligarch Henry Markram....

⁴ADDENDUM (July 21 2014) - Neuroskeptic has informed me that STS also stands for Science and Technologies Studies. Cornell, Berkeley, Wisconsin, RPI, and UC Davis, for instance, call their programs Science and Technology Studies. Harvard, Stanford and NC State call it Science, Technology, and Society (but Harvard hedges their bets and uses both terms).

The creation of the category “Twitter Psychosis" tells us more about the culture of contemporary psychiatry than it does about the purported dangers of social media overuse. Can Twitter really “cause” psychotic symptoms in predisposed individuals? Or is Twitter merely the latest technical innovation that influences “the form, origin and content of delusional beliefs” (Bell et al., 2005)? Twitter as the new telephone tower, radio waves, microchip implant or personal TV show, if you will.

Via Twitter (@DrShock, @vaughanbell), of course, comes news of a one page paper entitled, Twitter Psychosis: A Rare Variation or a Distinct Syndrome? (Kalbitzer et al., 2014):

The authors report the development of psychosis in a young woman coinciding with excessive use of the online communication system Twitter and the results of an experimental account to argue that Twitter may have a high potential to induce psychosis in predisposed users.

The authors presented the case of a 31 year old woman who was hospitalized for intensive suicidal thoughts and compulsions. She had no previous history of psychiatric illness and denied current hallucinations.¹ Her friends and family said the symptoms began about 8 months earlier. Approximately 4 months prior to that she started using Twitter “excessively” (defined as “several hours a day reading and writing messages, neglecting her social relationships and, sometimes, even meals and regular sleeping hours”).² At some point she came to believe that a famous actor was communicating to her personally (a common delusion), and to see hidden symbolic messages in Tweets:

During the next couple of weeks, Mrs. C increasingly felt that the messages of other users were “meant in a symbolic way” and that she had to react to these “tasks” in a certain manner. After approximately 2 months, she started to discover the same symbols in her real-world environment. She then started to feel that there “must be some organization behind these tasks” and started to suspect a sect, pointing to the development of systematized paranoid delusion.

None of this really seems like a Distinct Syndrome, and I doubt it's even a Rare Variation any more. The authors wanted to discuss (with the larger medical community) “whether they already have to speak of a distinct syndrome of social media-induced psychosis.”

And in fact, Dr. Vaughan Bell is one of the top experts to discuss this issue, and I imagine he will address the authors over at Mind Hacks.

But then the Brief Report completely derails with an “experiment” reported in the remaining paragraphs...

The Ben Goldacre Experiment

"This is a path of brotherhood and love" says the new pope, immediately excluding a cool 4 billion people.
— ben goldacre (@bengoldacre) March 13, 2013

Someone (it's not clear who) created a fake account to address whether “Twitter communication responds to changes in communication style.” [NOTE: I'm not sure what this means.]

To test this, a test person created an account and responded to the messages of Ben Goldacre, the maker of the blog http://badscience.net. Our test person responded to a message of Mr. Goldacre about the pope, but Mr. Goldacre did not reply. However, the authors received an answer from an unknown participant, writing "<our username> Cold blooded RT. XXX: I am in the church: <link>." The link led to different Web pages with commercials.

...when the authors followed the link, they were confused about a flood of useless information (commercials). The authors understood that this was a spam message, but this might not be the case for a person who is predisposed to psychosis and, in addition, in a stressful psychosocial situation.

So from this ill-defined, bizarre and staged interaction with a test person, the authors concluded that “Twitter might combine several aspects that could induce or further aggravate psychosis.” In a presumably peer-reviewed publication.³

This is preposterous. Hopefully we will not see “Twitter causes psychosis” headlines any time soon.

Vaughan should have the last Tweet here:

How did this get published? "Twitter may have a high potential to induce psychosis in predisposed users"http://t.co/uHCcuxFB6S via @DrShock
— Vaughan Bell (@vaughanbell) July 31, 2014

Further Reading

Returning to the title of the post, here's more on Twitter and cultural artifacts:

Twitter as a Cultural Artifact

Tools for Tech Thinking: McLuhan on Twitter

Footnotes

¹ However, Bell et al. (2008) showed that individuals with delusions do not always have anomalous perceptual experiences.

² I imagine “several hours a day” could apply to many individuals without a formal diagnosis of mental illness. I will not deny that Twitter and other forms of social media can have an addictive quality for some people, but the “Twitter addiction” construct is not very useful.

³ Can I put this blog post on my CV?? Here we learn about academic publishing in psychiatry and the propensity to categorize.

Reference

Kalbitzer J, Mell T, Bermpohl F, Rapp MA, & Heinz A (2014). Twitter Psychosis: A Rare Variation or a Distinct Syndrome? The Journal of nervous and mental disease, 202 (8) PMID: 25075647

Today I'm chatting with Dr. Jan Kabitzer, a Physician and Leader of the Neurochemistry Research Group at Charité - Universitätsmedizin Berlin.

Dr. Kabitzer is first author of the “Twitter Psychosis” article that made international news and took social media by storm on August 6, 2014. His provocatively titled paper, “Twitter Psychosis: A Rare Variation or a Distinct Syndrome?”(Kalbitzer et al., 2014), appeared online a week earlier in The Journal of Nervous and Mental Disease. I was struck by the title, of course, and an abstract claiming that “Twitter may have a high potential to induce psychosis in predisposed users.”

I wrote a critical blog post on July 31, 2014 (Twitter Psychosis as a Cultural Artifact) arguing that Twitter resembles other technologies and cultural artifacts that can potentially influence the phenomenology of delusions, citing the work of Vaughan Bell and colleagues (Bell et al., 2005).

It is now August 10, and the media huff has died down a bit. The overarching narrative of this story is very meta — social media about social media. It is in this spirit that I present the interview. ¹

Q: Could you tell me a little about your clinical work and your research?

Since my Ph.D. in Copenhagen at the Neurobiology Research Unit from 2007 to 2009 I have been working clinically at the psychiatric department of the Charité Berlin to specialize in psychiatry. Most of the time I worked on an acute psychiatric ward. We do have some time for research but I did mainly see patients. We are responsible for larger Berlin-Mitte which includes Berlin-Tiergarten and Berlin-Wedding so we see a lot of patients with severe mental disorders who are often in a precarious social situation. My research was initially with PET (positron emission tomography) but over the last year I have changed direction because I became very interested in recovery concepts and right now we are planning a project where we want to study which effect it has to abstain from using diagnostic classifications systems on different measures of mental health and well being. But since February my time as a resident is over and I am actually on paternity leave since then. The reviewing process of this case just took some time.

Q: The first question on everyone's mind is, why did you choose to include the term “Twitter Psychosis” in the title?

We observed the symptoms that we describe only in a few cases but it really disturbed us how these spam bots [Twitter bots] messed with our patients’ perception. We had the impression that abbreviations were intentionally used to create confusion and curiosity to follow the link in the tweet. We saw that this method that was used for commercial purposes can have a destructive effect. So we wanted to spark a discussion about what Twitter does to our minds and chose a provocative title to bring this subject up. But I see now that the main effect was that some news sites, like the Daily Dot, profited insanely from repetitively tweeting their exaggerated headlines. So I would not choose to be that provocative again outside of a closed scientific context. That is sad because I hate ivory towers - but being provocative as a researcher just doesn’t work well with the mass media.

Q: How do you compare the coverage you've seen on blogs vs. mass media?

I have seen both horrible blogs and great blogs. My impression is that in the case of blogs there is more often someone who feels responsible for it which is not always the case with the media (even though there are of course also great journalists).

You would have thought that I was a coveted interviewee during the last week. But I was only contacted by three journalists from NBCNews, betanews and Wired (UK). The NBC guy was great, I told him that I want the article to put things into perspective and he was fine with that. He quoted me exactly how I wrote it and I particularly insisted that he put in the sentence that this is not “real”, what he did. Just the headline wasn't that great. betanews I had never heard of, I just saw all these ads on their page, but I thought I’d rather reply to influence what they write and I think they covered it ok. And I asked them to take down the unbearable picture of a “crazy man” which they used first and they did. And, finally, Wired UK where Liat Clark offered to write against the panic. She interviewed me, but the article isn’t out yet and I am wondering if they will still cover it because the main wave on Twitter and in the news seems to have passed and the interview was Friday evening.

But I did contact some of the newspapers/magazines with the worst headlines myself. The funny thing is that none of them were really interested in an interview with the first author of the study they were writing about. After a while I realized that this is not about me and our article.

Bloggers like you and “Dr. Shock” warned early on and in this case we contacted you and you felt responsible for following up on the story.

Q: The tone of the article was confusing to many people. It wasn't clear if you were being completely serious, somewhat sensationalistic, partially joking, or if it was a joke paper. Your comment gave a brief answer, but could you elaborate here?

The case study had a small political flavor by citing Ben Goldacre (as a homage because I like his critical work about the pharmaceutical industry) but besides that it was completely serious. It would be preposterous to say the we aren’t sensationalistic. Every researcher who likes to publish also likes to be read and to be mentioned. But the fact is that our department is strongly influenced by the ideas of the recovery movement. So we focus on treating our patients according to their individual needs and not according to their diagnoses. So, yes, a ‘Morbus Kalbitzer’ [Kalbitzer's Syndrome] and being famous would be great. But would I get to use it? No. And even if ‘Twitter Psychosis’ entered Wikipedia with us describing it first, it would not have been worth it that all these people all over the world became even more insecure about how they should feel about modern media.

Besides that I think there are two things that contributed to the fact that the paper had such a provocative tone:

1. I love Paul Feyerabend² [a philosopher of science] and I believe that you should always challenge existing research theories with new, provocative hypotheses. I learned during the last week that this holds true if you are among reasonable people but in the context of globalized digital mass media you probably can’t do that with scientific publications.

2. Although we do often complain about the quality of our media in Germany, we are actually quite spoiled, so I was naive. News channels went mad in the US and the UK but it didn’t cross over to Germany. Even though I am sure that German journalists do follow these news channels, nothing went viral here. People in Germany are always a bit intimidated by the intensity of North American News.

But at the core of our paper is clearly a scientific question: is that what we observe on Twitter a new, unique feature that has a distinct effect on the development and course of delusions? While you and Vaughan seem to disagree with this, I believe that it makes a difference whether you are watching TV and believe the talk show host is talking to you or watching something that actually does react to what you do like the stream on Twitter. For example, you watch a morning show and still run around naked and suddenly the guy on TV says that running around naked in the morning can cause athlete's foot. That is what spam bots do on Twitter. This is what we meant by “Twitter communication responds to changes in communication style.” When you don’t use Twitter for a while you get emails that you are missed. And then you log in again and might see a spam tweet that links to a book about loneliness by some social guru. Isn’t that different to seeing a telephone post?

Q: One of the most puzzling things to me was the Twitter “experiment”. The purpose was unclear, the details were sparse, and it was difficult to follow what happened. Can you explain?

This partially got messed up by being reviewed for more than one journal. This one-page case study had probably more reviewers contributing to it than authors. We created several experimental accounts which are all deleted now and wrote tweets to more or less famous people on Twitter to see what kind of spam tweets we get in response to our tweets. We tried out different concepts but it was quite difficult for us to simulate what our patients described. So in the end we just used an example for the features of Twitter we described.

But it doesn’t say anywhere that we did a ‘Twitter experiment’ or a ‘Ben Goldacre experiment’, we just say that we used an experimental account. Instead of writing that we ‘test’ something we could have written something like: here is an example of such a tweet to illustrate the features we are talking about. It was more like psychiatrists who treat a patient who took a new designer drug and then, for the case study, the authors take the drug themselves and describe what they’ve experienced. The funny thing is, though, that we had a hard time simulating what most patients described as losing control, in this case that “it would not stop”. Today I know exactly what they are talking about. I surely had a Twitter overdose. Sometimes I used the live search function and watched the stream of tweets on ‘twitter’ and ‘psychosis’. It was a bit like the 'Listening Post' in the Science Museum in London, just much more disturbing. And after this experience, when thousands of people on Twitter just oafishly retweeted the “news” without looking up the source, and some of these people were psychologists and doctors, I can say that “to twitter” is the right term for what they do. It’s not my cup of tea.

Q: Usually journal articles have a formal Methods section where the authors describe the procedures (hopefully in enough detail so others can try to replicate). In retrospect, would you change the word “Experiment” to something else, like “Demonstration”?

As I said, we presented an example of a tweet that we received when we used an experimental Twitter account. I think what added to the confusion is that this was published as a 'Brief Report'. The Journal of Mental and Nervous Disease doesn’t have a section for case studies so we first submitted the case study as a letter to the editor but were asked to re-submit it as a 'Brief report'. But it is still a regular case report with no experiment, just an experimental Twitter account that we created in order to receive spam messages to, well, yes: demonstrate the features we are talking about.

Q: How do you think scientific articles should be communicated to the public?

I believe that most researchers in social neuroscience are to some degree lay people. Both the PET people who talk about ’the mind’ and the philosophers who want to find the voxel of morality. So I think experiments should be as simple as possible and then be published with absolute transparency and open access (even though I am a bit disturbed by the commercial approach of some open access journals). Then many other 'lay' people will understand what is going on.

I do also believe that you should use scientific data to provoke. In my Ph.D. I wrote in a small paragraph that the whole serotonin - depression story may just be based on mis-interpreting changes in motor activity and vigilance. George Ashcroft already questioned the serotonin story in a similar way. But I guess nobody except my opponents ever read my Ph.D. and they didn’t seem so provoked. It is difficult to find the golden mean.

Now I would like to ask you something! Q: Neurocritic, in your posts you can be fun and ironic but being in contact with you over the last week I realized that you are very serious about your work on this blog. You have been writing extensive and well researched posts for eight years. What is your motivation to do this? Is fighting sensationalistic research your 'Raison d’être‘? And why?

Although it may not be obvious, I am a serious person in real life. I started this blog out of sheer frustration with peer review, during a time when I was facing many rejections. When deeply flawed papers were routinely appearing in top journals, I wondered why all my hard work did not pay off. ³ Since I wanted to critique outrageous claims published in high-profile journals and discussed in the popular press, fighting sensationalistic research is largely my 'Raison d’être.

I saw this as cathartic at the time (since I never expected many readers), but my reasons over the years have evolved to include educating the public and providing a service to the field. I've remained anonymous because the vast majority of peer review is anonymous, which allows reviewers to be rude and insulting. I never want to do that.

However, the humorous and sometimes snarky nature of the blog may have unintended consequences on occasion, and I think that was true in the case of your paper. I try to think about the potential impact of my posts on the authors involved, and in this case I did not anticipate such a media circus. In fact, one of my parting thoughts was, "Hopefully we will not see “Twitter causes psychosis” headlines any time soon."

So overall I'm sorry about this whole ordeal.

And thank you, Jan, for taking the time to answer these questions.

Footnotes

¹ Jan's answers were very lightly edited by me for English language smoothness and formatting.

²Paul Feyerabend was an Austrian philosopher of science who...

...became famous for his purportedly anarchistic view of science and his rejection of the existence of universal methodological rules. He is an influential figure in the philosophy of science, and also in the sociology of scientific knowledge.... His major works include Against Method (published in 1975).

According to the Stanford Encyclopedia of Philosophy, Feyerabend:

made a name for himself both as an expositor and (later) as a critic of Karl Popper's “critical rationalism”, and went on to become one of the twentieth century's most famous philosophers of science. An imaginative maverick, he became a critic of philosophy of science itself, particularly of “rationalist” attempts to lay down or discover rules of scientific method.

³ This was in stark opposition to the "All your hard work will soon pay off" fortune taped to my monitor.

NEUROTECH LIGHT AND DARK »

Tweet length visions of our DARPA-funded future

The Neurocritic has recently blogged about The Neuroscience of the Future:

Neural prosthetics, brain-computer interfaces (BCI), “closed-loop” deep brain stimulation (DBS) devices, and a world without human brain disorders. The first three of these are already here... is the last one possible?

Here’s a sample of Neurotech Light and Dark, a sci fi collection of 16 very short stories about neuroscience and technology, by S. Kay.

A brain-computer interface controls her robotic arm. As easily as not thinking, she uses it to drink another shot of tequila.

Analyzing data from an EEG experiment on reaction times and impulse control disorders, the neuroscientist finds a link to Twitter usage.

Read the rest at Science Creative Quarterly.

And read more about the neurotech of the present, including DARPA's SUBNETS program, the Brain Radio, and other new DBS devices.

“My attention shifts to the fact that the comforting engine hum is eerily gone. Where has the comforting hum of the engines gone. Something has gone very, very wrong, the plane continued to shake.”

-Daniel Goncalves, recalling the terror of Air Transat Flight 236

I'm sitting here in an airport, reading a harrowing first person account of Air Transat Flight 236, which fell out of the sky when it lost all power on Aug. 24, 2001.

The plane was bound from Toronto, Ontario to Lisbon, Portugal when a fuel leak in the right engine began 3 hrs and 46 min after takeoff (at 04:38 UTC). The leak went undetected by the flight crew for over an hour, when it finally became apparent that the remaining fuel was insufficient to reach their destination in Lisbon. At 05:45 UTC, the pilot diverted the flight to Lajes Field on Terceira Island in the Azores, a cluster of islands about 850 miles west of Portugal.

Image: Humberta Augusto/AP – via The Globe and Mail

Air Transat Flight 236 with its emergency slides deployed, sitting on the tarmac of Lajes Field in the Azores island of Terceira, after an emergency landing on Friday, Aug, 24, 2001.

Here, Mr. Goncalves'gripping narrative should speak for itself.

“All lights turn off, TV's off, P.A. system off, emergency lights light up the floors marking the emergency exit door. What the hell is going on? Is this a joke? Another clearly tense voice takes over and tried to address the 300+ passengers without the aid of a P.A. system. "Everyone put on their life vest and prepare for emergency ditching at sea." Huh? What the hell does that mean? Are you kidding me? Disbelief. "The captain has informed us that we are two hours away from Lisbon and we will not make it. We are preparing for an emergency ditch at sea. When you hear BRACE, BRACE, BRACE, lean against the seat in front of you, fold your arms and brace yourself."

WHAT WHAT WHAT WHAT????? Oh my God, what is happening. We're going into the cold and black Atlantic? Now? Why? Is this a Joke? Are we part of that Just for Laughs show? Stop playing, come on. No joke. I was in denial. This fully loaded Airbus A330 was going into the ocean and all I knew was that my poor family were there with me. It hit me. This wasn't going to go away. This was it. This really was it. The end. Unimaginable death by catastrophe.”

-Daniel Goncalves, My Air Transat flight 236 story

I'm reading this story because of a very unique paper published recently in Clinical Psychological Science (McKinnon et al. 2014), a study of post-traumatic stress disorder (PTSD) and memory in survivors of the near-fatal Air Transat flight. Fifteen of the individuals WHO WERE ACTUALLY ON THAT FLIGHT participated in an experiment of autobiographical memory for the event, a shared horror of impending death. The comparison events were the terrorist attacks of September 11, 2001 (9/11) and a neutral event from around the same time.¹

Seven of the survivors had been diagnosed with PTSD, six did not have PTSD, and the status of the remaining two was unknown. This immediately raises the caveat of very small comparison groups, further complicated by the fact that some of the assessment instruments were missing from various participants (e.g., the NEO-Five Factor Inventory of personality was missing from four).

The study was conducted in the lab of Dr. Brian Levine, a well-known memory researcher at the Rotman Research Institute in Toronto. Adding another unexpected twist, the first author of the paper, Dr. Margaret C. McKinnon, was a passenger on Flight AT236!

Now I'm flying in an Airbus 319, returning home. The setting sun to my right is blinding across the aisle.

Here is the series of events on AT236 as recounted by Goncalves:

Timeline:

4:38am-fuel started leaking
5:45am- diverted to Lages Air Base in Azores
5:48am- emergency declared
6:13am- engine no 2 flamed out 217 km from Lages Air Base, full thrust to engine #1 on left wing and plane descended 6,000 feet (this was scary and when when the passengers first found out something was very wrong).
6:23am- Mayday declared
6:26am- engine no 1 flamed out 120 km from Lages Air Base
6:45am- plane touched down hard on runway 33

Then a flight attendant came over the PA system on my flight:

“Ladies and gentlemen, we are experiencing a little turbulence, please return to your seats and fasten your seat belts.”

OK, there's the turbulence, good thing I took an anti-emetic...

But the bumpiness was quite short-lived, so back to our main story.

Image via International Aviation Safety Association

McKinnon et al. (2014) administered the Autobiographical Interview (AI) and a number of other questionnaires to the AT236 survivors. A group of control participants (n=15) were queried about 9/11, a neutral event, and a personally negative event. The AI distinguishes between episodic and non-episodic details (e.g., facts you might hear on the news), and has been used to probe autobiographical memory in number of different patient populations, including those with dementia, mild cognitive impairment, medial temporal lobe amnesia, and epilepsy (Levine et al., 2002).

The results of the study indicated that the passengers recalled vivid details of the flight, which was not surprising. Neither the number of details recalled, nor the accuracy of memories (their veridicality in relation to actual events) was associated with PTSD. Instead, it was recall of extraneous details, repetition of events in the retelling of their stories, and additional commentary or editorializing about the events that was associated with PTSD. This pattern held for all three of the autobiographical events, although some of the statistical results were rather weak.

Fig. 1 (adapted from McKinnon et al., 2014). Mean number of details recalled across all events for passengers (with and without PTSD) and healthy controls (HCs) for the Autobiographical Interview.
[NOTE: Internal = episodic and External = non-episodic (semantic, repetitions, metacognitive statements, external events).]

Cognitive Control Deficits Were Associated With PTSD

The authors suggested that greater difficulty in constraining and editing the content of one's autobiographical narratives, whether recalling the Air Transat flight or a neutral event, was associated with a PTSD diagnosis in this small sample of trauma survivors. This could reflect a more general deficit in cognitive control, i.e. the ability to regulate complex cognitive processes to achieve goal-directed behavior (Lenartowicz et al., 2010).

While a unique and important study, we must keep in mind the limited and perhaps self-selected nature of the population (7 with PTSD, 6 without PTSD). The experiment required recalling the most frightening and horrific 30 min imaginable, and many survivors may have declined to sign up for that.

The authors acknowledged these and other weaknesses:

The participants in this study reflect only a small percentage of the 306 passengers aboard AT Flight 236; we did not have access to the passenger manifest, and individuals with more significant psychopathology may have avoided participation for fear of retraumatization. Thus, the current study was limited to a small number of participants. Moreover, as passengers’ memory was assessed several years after the traumatic incident (approximately 3.5 years later), it remains unknown how trauma might have impacted memory in the more acute stages of trauma exposure among this sample.

NBC News also addressed these issues in a quote from Mr. Goncalves, who wrote about his ordeal in a blog post to avoid having to retell it over and over:

“Just reading something about it, I’ll lose myself in thought, catch myself visualizing it and get sweaty fingers,” said study subject Daniel Goncalves, who was 24 while traveling with his family on Flight 236 to see a dying uncle in Portugal. He was never formally diagnosed with PTSD. “I’m getting goose bumps now, talking about it.” ²

Today, working as a photographer in Dallas, Goncalves, has sometimes shied away from discussing the event. To help friends understand, he wrote a blog post about those the 32 minutes so “I can send them over there instead of going through the whole ordeal and avoid getting emotional.”

Daniel Goncalves, My Air Transat flight 236 story:

“Later on we found out that those white knuckle, torturous last few seconds which were filled with terrible thoughts waiting for impact stretched to fill an unbearable 32 minutes of misery. I still can't explain how terrible it was waiting, expecting it to be any second now and that going on for 32 mins. It felt like an eternity of waiting for a very bad thing to happen. During these 32 minutes the plane never stopped shaking. You could hear the plane cut through the air, no engine noise, muttering of prayers, crys, pleads. The whole time.”

In the end, Captain Robert Piché, the heroic pilot, was able to glide the powerless plane to a safe landing at Lajes Field. None of the 306 passengers died, and there were only 18 minor injuries. Many thought of this feat as a miracle, or at least “a moment of miraculous relief.” Daniel Goncalves considered this the day he was reborn.

Footnotes

¹ The neutral event was uniquely generated by each participant prior to the start of the autobiographical memory interviews, I believe.

² These symptoms are all highly consistent with a PTSD diagnosis.

Reference

McKinnon, M., Palombo, D., Nazarov, A., Kumar, N., Khuu, W., & Levine, B. (2014). Threat of Death and Autobiographical Memory: A Study of Passengers From Flight AT236. Clinical Psychological Science DOI: 10.1177/2167702614542280

Link to Daniel Goncalves' blog via NBC News.

Do I contradict myself?

Very well then I contradict myself,

(I am large, I contain multitudes.)

-Walt Whitman, "Song of Myself" (from Leaves of Grass)

Science is the search for objective truth based on physical laws of the universe. Scientific theories try to explain the consistent and predictable behavior of natural systems. They are generally reductionist, meaning that complex systems are reduced to simpler and more fundamental elements. The principles of physics, for instance, are expressed in the form of beautiful equations that are the envy of the softer sciences.

xkcd: Purity

The enterprise of explaining how human brains produce complex thought (or how any nervous system produces observable behavior, for that matter) is notably lacking in the realm of grand unifying theories, a topic of discussion recently in the New York Times:“What would a good theory of the brain actually look like?”

But the “search for a general ‘bridging theory’ may be a fruitless one” – like Awaiting a theory of neural weather. The “bridge, some way of connecting two separate scientific languages — those of neuroscience and psychology” may not exist.

I'm not sure why the question, “What would a good theory of the brain actually look like?” was even posed in the first place (or posed in that fashion, like a single theory should be expected to explain “the brain”). Adam Calhoun asked what I think is a more productive question: Are these the equations of the brain?

English theoretical physicist Paul Dirac said, “A physical law must possess mathematical beauty.” Are these equations beautiful? ¹

I cannot say. I am neither physicist nor mathematician. I traffic in matters less sublime. All I can do here is to include this citation from neuroaesthetician Semir Zeki and colleagues (2014), who reported that the neural correlates of perceiving mathematical beauty are the same as those that appreciate fine visual art. To be more precise, ratings of mathematical beauty were parametrically related to BOLD signal in field A1 of the medial orbitofrontal cortex, a part of the brain involved in emotion, reward, and decision making.

At the phenomenological level of subjective experience, this knowledge of brain activity does no more to explain what it's like to behold Dirac’s wave equation than the Temporal Difference Learning equation describes what it's like to feel this emotionally rewarding experience — the Nagelian conundrum of qualia.

We sail the arctic sea, it is plenty light enough,

Through the clear atmosphere I stretch around on the wonderful beauty,

The enormous masses of ice pass me and I pass them, the scenery is plain in all directions,

-Whitman, ibid

What does any of this have to do with Walt Whitman? Yesterday I saw a pair of articles that encapsulate Whitman's principle of “I am large, I contain multitudes” when applied to neuroimaging studies of unclear psychological phenomena.

“The results obtained suggest that dysfunctional [lower] activation of the SMA [supplementary motor area] for response inhibition is one of the candidate mechanisms of IGD [internet gaming disorder].”

“...adults with IGD have ... greater activation of the fronto-striatal network in order to maintain their response inhibition performance.”

The first study claimed that reduced recruitment of the SMA (a motor control area) could be responsible for the impulsivity seen in individuals with internet gaming disorder (an actual “Condition for Further Study” in the DSM-5). The second study suggested that enhanced activity in the fronto-striatal network (implicated in motor control as well, but also in reward) was necessary for IGD participants to maintain the same restrained behavior as control participants.

So which is it?

These results are not consistent. They contradict themselves. This is not unusual. The greater problem is that the discrepant results were reported by the same lab, each without any reference to the other study.

Do I contradict myself?

Very well then I contradict myself

This world view makes for profound and transcendent poetry, but unacknowledged internal contradiction should not be adopted as the optimum path to scientific enlightenment.

Empirical falsification, on the other hand, is a staple of the scientific method.

I don't mean to single out this particular lab (which is why I did not include in-line citations), but this is a pet peeve of mine, along with a refusal to acknowledge any and all evidence that refutes one's signature theory. There's no shame in obtaining inconsistent results (or at least, there shouldn't be). But at least say so, try to come up with a plausible explanation, and do more experiments.

Clear and sweet is my soul, and clear and sweet is all that is not my soul.

Lack one lacks both, and the unseen is proved by the seen,

Till that becomes unseen and receives proof in its turn.

-Whitman, ibid

Additional Reading

Awaiting a theory of neural weather

Song of Myself

The Beauty of Brain Science

The Trouble With Brain Science

Footnote

¹Do the equations of the brain give insights into its fundamental structure and function? Do they have the power to describe the brain? In the 1993 Dirac Lecture (Freeman, 1994), physicist Daniel Z. Freeman said:

Many quotations remind us of Dirac’s ideas about the beauty of fundamental physical laws. For example, on a blackboard at the University of Moscow where visitors are asked to write a short statement for posterity, Dirac wrote: “A physical law must possess mathematical beauty.” Elsewhere he wrote: “A great deal of my work is just playing with equations and seeing what they give.”. And finally there is the famous statement: “It is more important for our equations to be beautiful than to have them fit experiment.” This last statement is more extreme than I can accept. Nevertheless, as theoretical physicists we have been privileged to encounter in our education and in our research equations which have simplicity and beauty and also the power to describe the real world. It is this privilege that makes scientific life worth living, and it is this and its close association with Dirac that suggested the title for this talk [SOME BEAUTIFUL EQUATIONS OF MATHEMATICAL PHYSICS].

References

Chen, C., Huang, M., Yen, J., Chen, C., Liu, G., Yen, C., & Ko, C. (2014). Brain correlates of response inhibition in Internet gaming disorder. Psychiatry and Clinical Neurosciences DOI: 10.1111/pcn.12224

Daniel Z. Freedman (1994). Some beautiful equations of mathematical physics. CERN-TH.7367/94 arXiv: hep-th/9408175v1

Ko, C., Hsieh, T., Chen, C., Yen, C., Chen, C., Yen, J., Wang, P., & Liu, G. (2014). Altered brain activation during response inhibition and error processing in subjects with Internet gaming disorder: a functional magnetic imaging study. European Archives of Psychiatry and Clinical Neuroscience DOI: 10.1007/s00406-013-0483-3

Zeki, S., Romaya, J., Benincasa, D., & Atiyah, M. (2014). The experience of mathematical beauty and its neural correlates. Frontiers in Human Neuroscience, 8 DOI: 10.3389/fnhum.2014.00068

I bequeath myself to the dirt to grow from the grass I love,

If you want me again look for me under your boot-soles.

You will hardly know who I am or what I mean,

But I shall be good health to you nevertheless,

And filter and fibre your blood.

Failing to fetch me at first keep encouraged,

Missing me one place search another,

I stop somewhere waiting for you

-Whitman, ibid

Bibimbop Brugmansia *

* Do NOT try this at home.

Edible flowers can make for a beautiful garnish on salads and trendy Brooklyn cocktails, but these decorative flourishes can be a disaster for the oblivious amateur. An unusual case report in BMC Research Notes summarizes what happens when you sprinkle toxic flower petals on your bibimbop (Kim et al., 2014).

A 64 year old Korean woman came to the emergency room with incoherent speech and fluctuations in attention, orientation and comprehension. She had called her daughter for help but couldn't remember why. (Hint: that's because she ingested flowers containing scopolamine and atropine, two potent anticholinergic compounds that can cause amnesia).

In contrast to these alterations in her mental state, she did not show dilated pupils, dry mouth, increased heart rate, or other changes to the autonomic nervous system typically observed with anticholinergics [which seems odd to me]. After 10 hours had elapsed, she became fully conscious and remembered that she had added a few flowers to her bowl of bibimbop, a traditional Korean dish. Twenty-four hours later, her memory for the entire episode was hazy.

Angel's Trumpet (Brugmansia), a popular ornamental shrub, has a long history in ethnobotany and toxicology as a deliriant, differentiated from the psychedelic and dissociative hallucinogens. There are numerous case reports of presumed Angel's Trumpet poisoning in the literature. A 2003 review reported on 33 patients, 31 of whom deliberately consumed a brewed tea (Isbister et al., 2003). Dilation of the pupils (mydriasis) was seen in 100% of the patients, which is why it's odd that Kim et al. did not observe this.

In fact, one paper reported on accidental unilateral mydriasis in a 11 year old girl who touched “a nice pink flower, similar to a trumpet” and then rubbed her eye (Andreola et al., 2008).

But the most infamous case of deliberate Angel's Trumpet abuse is the young man who severed his own penis and tongue after drinking a tea, “illustrating that consuming this beautiful flower with the name of an angel and the poison of the devil can be very dangerous” (Marneros et al., 2006).

Scopolamine blocks M1 muscarinic acetylcholine receptors that are prominently distributed in the cerebral cortex, amygdala, and hippocampus. The septo-hippocampal cholinergic system plays an important role in learning and memory, accounting for the oft-observed amnesia.

Brugmansia was (and is) used by Native groups in South America for religious ceremonies. According to Lockwood (1979), the Jivaro in eastern Ecuador used Brugmansia in a boyhood rite of passage. The adults understood the potential danger of the delirious and hallucinatory state and closely supervised the child:

When a Jivaro reaches the age of six he seeks an arutam wakani, an acquired soul. ... To acquire an arutam soul, the boy, usually accompanied by his father, makes a pilgrimage to a sacred waterfall where he bathes, fasts, and drinks infusions of fresh tobacco water. If no vision or apparition appears, recourse may be to drink maikua, the juice of Brugmansia...
. . .

The arutam seeker is watched over by men not taking the maikua, in order to protect him from accidents or self-inflicted harm that might occur during the initial violent stages when the drug is taking effect. If the boy is fortunate, the arutam will appear to him, usually in the form of a pair of large creatures, often animals such as jaguars or anacondas.

In more recent times, the street drug 'burundanga' has been used by criminals to incapacitate potential victims, as Vaughan Bell has explained.

So the question arises, with such a long and distinguished literature, why was a new case study of Brugmansia poisoning published? Obviously, there are vast cultural differences between indigenous South American peoples, curious German and Australian youth, and elderly Korean women.

Heungmi kkotjeon (Pan-fried Sweet Black Rice Cake with Flower Petals)

CC BY-SA 2.0

The beautiful Korean dish above is made with non-toxic edible flowers. Another (similar?) dish is hwajeon, or "flower cake". Might this lead to a greater danger in accidentally eating toxic flowers? Kim et al. conclude:

This case is unique in that AT was ingested as an ingredient of a traditional Korean dish. ... Considering the fact that one can purchase it from virtually any florist without much difficulty, and that the number of adolescent recreational drug users is increasing, AT could be misused in the near future. The flowers of AT are occasionally used to garnish foods, so raising the awareness of the toxicities of this plant to the general public is important.

Further Reading

The tree of drunkeness

Hallucinations and hospitalizations: Angel’s Trumpet

The plant of human puppets

Cultural Chemistry - the plant that robs you of your free will?

Is free will spent by a knock-out drug?

Mind controller: What is the 'burundanga' drug?

If you must, 23 Recipes That Will Feed Your Inner Flower Child at Buzzfeed

Microleave & Edible Flower Salad - mycookinghut

References

Andreola B, Piovan A, Da Dalt L, Filippini R, Cappelletti E. (2008). Unilateral mydriasis due to Angel's trumpet. Clin Toxicol (Phila). 46(4):329-31.

Isbister, G., Oakley, P., Dawson, A., & Whyte, I. (2003). Presumed Angel's trumpet (Brugmansia) poisoning: Clinical effects and epidemiology. Emergency Medicine Australasia, 15 (4), 376-382 DOI: 10.1046/j.1442-2026.2003.00477.x

Kim, Y., Kim, J., Kim, O., & Kim, W. (2014). Intoxication by angel’s trumpet: case report and literature review. BMC Research Notes, 7 (1) DOI: 10.1186/1756-0500-7-553

Tommie Lee Lockwood, summarized by Evans Schultes, R., & Plowman, T. (1979). The ethnobotany of Brugmansia. Journal of Ethnopharmacology, 1 (2), 147-164 DOI: 10.1016/0378-8741(79)90004-7

Marneros A, Gutmann P, Uhlmann F. (2006). Self-amputation of penis and tongue after use of Angel's Trumpet. Eur Arch Psychiatry Clin Neurosci. 256(7):458-9.

Cocktail Garnishes [Photo: Michael Dietsch]

More Photo credits: Bibimbop by Agnes Ly, via Wikimedia Commons and Brugmansia (angel’s trumpet) by Asit K. Ghosh Thaumaturgist, via Wikimedia Commons. Neurocritic Remix CC BY-SA 3.0.

"Individual risk attitudes are correlated with the grey matter volume in the posterior parietal cortex suggesting existence of an anatomical biomarker for financial risk-attitude," said Dr Tymula.

This means tolerance of risk "could potentially be measured in billions of existing medical brain scans."¹

-Gray matter matters when measuring risk tolerance

Let's pretend that scientists have discovered a neural biomarker that could accurately predict a person's propensity to take financial risks in a lottery. Would it be ethical to release this information to policy makers? That seems to be the conclusion of a new paper published in the Journal of Neuroscience (Gilaie-Dotan et al., 2014):

The results will also provide a simple measurement of risk attitudes that could be easily extracted from abundance of existing medical brain scans, and could potentially provide a characteristic distribution of these attitudes for policy makers.

If we accept this line of thinking, it's not much of a stretch to imagine that financial institutions, employers, consumer reporting agencies, and dating services could use this information in a discriminatory, preemptive fashion to screen out potentially risky applicants. Or perhaps casinos, lotteries, and predatory lending companies could target these individuals with personalized ads.

Conversely, investment firms could vie for traders with the largest right posterior parietal cortices, since they would have the highest tolerance for risk.

Or am I being alarmist about the breach of ethics involved in releasing protected medical information to outside entities? Although the authors subtly deter extrapolation to this invasive scenario by using phrases like "characteristic distribution" and "risk attitudes of populations" (as opposed to risk attitudes of individuals), they're pretty clear about the promise of their gray matter measure to inform policy (Gilaie-Dotan et al., 2014):

Our finding suggests the existence of a simple biomarker for risk attitude, at least in the midlife [sic] population we examined in the northeastern United States. ... If generalized to other groups, this finding will also imply that individual risk attitudes could, at least to some extent, be measured in many existing medical brain scans, potentially offering a tool for policy makers seeking to characterize the risk attitudes of populations.

Now let's all take a step back and evaluate whether this is currently feasible. The short answer is no (in my view, at least).^1A

First, we have to be somewhat skeptical of the study's major conclusion. Voxel-based morphometry (VBM) was to quantify cortical volume from structural MRIs.² Gray matter volume in a small chunk of the right posterior parietal cortex (PPC) was the only place in the entire cerebral cortex that correlated with individual attitudes toward financial risk. In humans, right lateralized PPC has been strongly implicated in visuospatial attention.

Doesn't it seem more plausible that a region like the orbitofrontal cortex (OFC), which has been activated in numerous functional neuroimaging studies of decision making and risk, would show such an association? Studies in primates have demonstrated that economic risk is coded by single neurons in the OFC (O'Neill & Schultz, 2014), and in rats risk preference can be differentiated by OFC neuronal responses (Roitman & Roitman, 2010).

The authors do cite an extensive literature on the role of parietal neurons in decision making, but fMRI studies have observed effects of risk preference in left PPC, and uncertainty in bilateral PPC (Huettel et al., 2005, 2006).

But what is the purpose of having a larger gray matter volume in PPC in relation to financial risk attitude? Does it allow for a higher "computational capacity" that can accommodate greater risk tolerance? We don't actually know, as Gilaie-Dotan et al. (2014) explain:

We do not know precisely how GM volume translates to the neural level. It is possible that volume differences reflect synaptogenesis and dendritic arborization (Kanai and Rees, 2011), but to-date there is no clear evidence of correlation between GM volume measured by VBM and any histological measure, including neuronal density (Eriksson et al., 2009).

In contrast to the neural correlate of risk attitude, a participant's attitude toward ambiguity was not associated with structural differences anywhere in the cortex (Gilaie-Dotan et al., 2014). How were these attitudes (or preferences) measured? Experimental economics methods were used to estimate individual preferences for risk (uncertainty with known probabilities) and ambiguity (uncertainty with unknown probabilities).

Participants played a game where they could choose between lotteries that varied in monetary value and in the degree of either risk or ambiguity. In the example trial below, the participant chooses either this option, where they stand a 38% chance of winning $18, or the reference option that offers a 50% chance of winning $5.

Modified from Fig. 1A (Gilaie-Dotan et al., 2014).

There were five reward levels ($5, $9.50, $18, $34, and $65), each fully crossed with three probabilities of winning and three levels of ambiguity around the winning probability, as shown below.

Figure 1 (Levy et al., 2012). Risky and ambiguous stimuli.A) In risky stimuli the red and blue areas of each image are proportional to the number of red and blue chips. Three outcome probabilities were used: 13, 25 and 38%. B) In ambiguous stimuli the central part of the image is obscured with a gray occluder. In the gray area the number of chips of each color is unknown, and thus the probability of drawing a chip of a certain color is not precisely known. Three levels of ambiguity were used, where 25, 50 or 75% of the image is occluded.

Using a maximum likelihood procedure, the choice data of each participant was fit to a logistic function. Fitting the choice data with a choice function provided estimates for the risk attitude (α) and ambiguity attitude (β) for each person. These were included in multiple regression analyses to determine the neuroanatomical correlates of risk and ambiguity based on the model estimates.³

Two populations of subjects were tested. The first was a group of 21 individuals who participated in the fMRI study of Levy et al. (2010) at NYU; thus the first analysis was entirely post hoc, and 7 more people were added later to make the total n=28 (mean age = 25).⁴

The second group, which served as a validation sample, consisted of 33 healthy subjects from the University of Pennsylvania (mean age = 21.34).⁵ A region of interest (ROI) analysis created spheres of six different sizes around the right PPC peak that were compared to control ROI spheres in primary motor/primary somatosensory areas. The right PPC finding replicated at p<.05 or p<.01, whereas there was no correlation between risk attitudes and gray matter volume in the M1/S1 control area.

If you're wondering, like me, whether any other part of the cortex showed a relationship to either risk or ambiguity in Group #2, one sentence in the Results assures us that no other regions were implicated in risk with a standard VBM whole-brain analysis.

Unlike the sweeping conclusions about the policy implications of their results (which were mentioned three times), the authors were appropriately cautious about causality, saying it's not possible to determine whether a big PPC causes higher risk tolerance, or having a higher risk tolerance leads to an increase in PPC gray matter volume. They also warn against assuming any relationship between genetics and risk attitudes. Finally, they acknowledge that the results may not generalize beyond their populations of students at Northeastern universities who are in their early to mid 20s, a time when the prefrontal cortex isn't fully developed.

I suspect we'll soon see studies that examine risk attitude and gray matter volume across the life span, given the interest of these researchers in Separating Risk and Ambiguity Preferences
Across the Life Span: Novel Findings and Implications for Policy (PDF).

Footnotes

¹ It's impossible that there are "billions of existing medical brain scans" because the entire world population is currently 7.19 billion. Dr. Tymula could have been quoted in error, but this exact phrase appeared in both ScienceDaily and the original University of Sydney press release. In the Yale press release on the study, the number was downgraded to millions:

"Based on our findings, we could, in principle, use millions of existing medical brains scans to assess risk attitudes in populations," said Levy. "It could also help us explain differences in risk attitudes based in part on structural brain differences."

It's commendable that the title of the Yale press release (Brain structure could predict risky behavior) was more circumspect than the one given to the J Neurosci article itself.

^1AADDENDUM (Sept 16 2014): The billions [i.e. millions] of existing medical brain scans are not all high-resolution T1-weighted anatomical images (1 × 1 × 1 mm³) acquired using a 3T Siemens Allegra scanner equipped with a custom RF coil. In other words, most may not have the anatomical resolution to measure such a small brain area.

² Gray matter volume in the whole cerebral cortex was quantified, but you'll notice that no subcortical structures (e.g., striatum, nucleus accumbens, cerebellum) were measured.

³ More methodological details:

The age and gender of the participants and global GM volume (following ANCOVA normalization) were included in the design matrix as covariates of no interest, and were thus regressed out. F contrasts were applied first with p < 0.001 uncorrected as the criterion to detect voxels with significant correlation to individual’s risk attitudes. Whole-brain correction procedures were then applied...

⁴ The authors stated that this did not affect the outcome.

⁵ Oddly, these two groups of young people (mean ages of 25 and 21 yrs) were called "midlife" adults three times in the paper.

References

Gilaie-Dotan, S., Tymula, A., Cooper, N., Kable, J., Glimcher, P., & Levy, I. (2014). Neuroanatomy Predicts Individual Risk Attitudes. Journal of Neuroscience, 34 (37), 12394-12401 DOI: 10.1523/JNEUROSCI.1600-14.2014

Huettel SA, Song AW, McCarthy G. (2005). Decisions under uncertainty: probabilistic context influences activation of prefrontal and parietal cortices. J Neurosci. 25(13):3304-11.

Huettel SA, Stowe CJ, Gordon EM, Warner BT, Platt ML. (2006). Neural signatures of economic preferences for risk and ambiguity. Neuron 49(5):765-75.

Levy, I., Rosenberg Belmaker, L., Manson, K., Tymula, A., & Glimcher, P. (2012). Measuring the Subjective Value of Risky and Ambiguous Options using Experimental Economics and Functional MRI Methods. Journal of Visualized Experiments (67) DOI: 10.3791/3724

Levy I, Snell J, Nelson AJ, Rustichini A, Glimcher PW. (2010). Neural representation of subjective value under risk and ambiguity. J Neurophysiol. 103(2):1036-47.

O'Neill M, Schultz W. (2014). Economic risk coding by single neurons in the orbitofrontal cortex. J Physiol Paris. Jun 19. pii: S0928-4257(14)00025-4.

Roitman JD, Roitman MF. (2010). Risk-preference differentiates orbitofrontal cortex responses to freely chosen reward outcomes. Eur J Neurosci. 31(8):1492-500.

Fig. 2 (Gilaie-Dotan et al., 2014)

For immediate release — SEPTEMBER 26, 2014

Research from the UCL lab of Professor Geraint Rees has proven that the recent craze for suggesting that rats have “regrets” or show “disappointment” is solely due to the size of the left temporal-parietal junction (TPJ) in the human authors of those papers (Cullen et al., 2014). This startling breakthrough was part of a larger effort to associate every known personality trait, political attitude, and individual difference with the size of a unique brain structure.

Cullen and colleagues recruited 83 healthy behavioral neuroscientists and acquired structural brain images using a 1.5-T Siemens Sonata MRI scanner. The participants completed the Individual Differences in Anthropomorphism Questionnaire (IDAQ), along with 698 other self-report measures. Factor analysis of the IDAQ yielded a two factor solution: anthropomorphism of 1) non-human animals, and 2) non-animals (technology and nature).

Voxel-based morphometry (VBM) was used to quantify gray matter volume from the structural MRIs. To do this, the authors constructed a “mentalizing mask” to divine which regions of interest (ROIs) would yield the best results.

Based on the intuitions of Psychic Love Doctor Anabella (and results from previous studies on theory of mind and social cognition), six 12 mm spheres were drawn in the left and right medial prefrontal cortices (x y z MNI coordinates = ±10, 51, 34), the temporal poles (±43, 8, −34), and the posterior superior temporal sulcus/TPJ (±52, −56, 23).

Separate analyses were done using another “mentalizing mask” with different coordinates as well as an anatomically-based mask. But the authors went with the Psychic Love Doctor mask after all. They also did a whole brain analysis, by the way.

“You’ll Never Believe What Happened Next.”

A tiny little cluster of 24 voxels in the left TPJ correlated with scores on the animal IDAQ scale. This means that the neuroscientists responsible for studies on regret (Steiner & Redish, 2014) and disappointment (Shabel et al., 2014) in rats had the largest L TPJs, by far. Besides publishing in Nature Neuroscience and Science, respectively, these participants were most inclined to attribute human mental states to non-human animals.

Fig. 1 (Cullen et al., 2014). The region where grey matter volume showed a correlation with anthropomorphism of non-human animals is shown overlaid on a T1-weighted MRI anatomical image. The cross hair identifies the cluster at the left temporoparietal junction (−45,−54, 27) showing a statistically significant (P < 0.05 FWE-corrected for volume examined) positive correlation with anthropomorphism of non-human animals as measured by the animal IDAQ.

However, readers of io9 and theNewerYork will be sorely disappointed that no areas of the brain were correlated with anthropomorphization of robots.

What does this mean for the future of neuroscience research? Given the prestigious outlets that publish papers in the hot new field of Anthropomorphic Neuroscience, here's what I envision: transcranial direct current stimulation (tDCS) labs will be overrun with modest scientists who study spatial memory, hoping a stimulating, L TPJ-induced portrayal of rats as taxi drivers will land them in the pages of Nature.

-----

Disclaimer: Although this post is based on a real study, some of the details are fictionalized. I leave it to the discerning reader to separate fact from fiction. My sincerest apologies to all the authors.

Further Reading

Of Mice and Women: Animal Models of Desire, Dread, and Despair– are they really adequate stand-ins for the human condition?

Post-modern Anthropomorphism– rat “regret” author A. David Redish, Ph.D. on the use of human cognitive terms for non-human animal behavior.

Rats Regret Making the Wrong Decision– accessible summary.

Scientists Discover “Dimmer Switch” For Mood Disorders– strains credulity to go from rat “disappointment” to a depression dimmer switch in humans.

Not tonight dear, I had zymosan A injected into my hind paw– Hypoactive Sexual Desire Disorder, in rats. You decide.

Liberals Are Conflicted and Conservatives Are Afraid– discusses the Colin Firth study on political orientation and brain structure (Kanai, Feilden, Firth & Rees, 2011).

References

Cullen, H., Kanai, R., Bahrami, B., & Rees, G. (2014). Individual differences in anthropomorphic attributions and human brain structure Social Cognitive and Affective Neuroscience, 9 (9), 1276-1280 DOI: 10.1093/scan/nst109

Shabel, S., Proulx, C., Piriz, J., & Malinow, R. (2014). GABA/glutamate co-release controls habenula output and is modified by antidepressant treatment Science, 345 (6203), 1494-1498 DOI: 10.1126/science.1250469

Steiner, A., & Redish, A. (2014). Behavioral and neurophysiological correlates of regret in rat decision-making on a neuroeconomic task Nature Neuroscience, 17 (7), 995-1002 DOI: 10.1038/nn.3740

Contact UCL Media Relations for a high resolution photo of Prof Rees

September 30 is the last day of the fiscal year for the US government. So it's no coincidence that President Obama's BRAIN Initiative¹ ended the year with a bang. The NIH BRAIN Awards were announced on the last possible day of FY2014, coinciding with the White House BRAIN Conference. A total of $46 million was dispersed among 58 awards involving over 100 scientists.

I watched most of the conference live stream. The entire video is now available for viewing on YouTube (and conveniently embedded at the bottom of this post). Below are a few idiosyncratic highlights.

I missed the early announcements (e.g., that the correct hashtag was #WHBRAIN) and introduction of the first speaker, a female graduate student. Next was John Holdren, senior advisor to the President on science and technology issues. My notes from his talk consisted of a series of buzz words and phrases, befitting a politician:

“grand challenge”
“moon shots”
“game-changing innovations”
“dynamic understanding of how the brain works”
“at the speed of thought”
“new generation tools and technology”
quoting Obama: “Americans can accomplish anything we set our minds to.”

The first year budget is $100 million, with another $300 million allocated so far. A recurrent theme was the need for a sustained commitment to funding. Holdren (and others) mentioned the 12 year strategy for NIH, BRAIN 2025, which focuses on technologies, cells, and circuits.

The disconnect with reality came when he mentioned the burden of brain disorders and the prospect of curing them:

“Imagine if no family had to grapple with the helplessness and heartache of watching of a loved with Parkinson's or traumatic brain injury. Imagine if Alzheimer's or ALS or chronic depression were eradicated in our lifetimes.” [NOTE: Holdren is 70]

Ultimately we'd all like to eradicate these diseases, but that's not going to happen by 2025. Is it a good idea to mislead the public about the immediate clinical treatments arising from the NIH BRAIN Awards? How do we educate the public about the importance of basic science and technology development? DARPA is taking a different approach with their fast-tracking of deep brain stimulation treatments in humans. Their goals are even more ambitious: over a 5 year period, conduct clinical trials in human patients with 7 specified psychiatric and neurological disorders, some of which have never been treated with DBS.

Moving right along to the first panel, Cori Bargmann and Mark Schnitzer both did a fine job of discussing advances in circuits/networks and engineering/technology (see Storify below). The next panelists were clinician/researchers Geoffrey Manley on traumatic brain injury and Kerry Ressler on post-traumatic stress disorder. Ressler was bullish on new PTSD therapies, suggesting that it might be the most tractable psychiatric disorder. Manley, on the other hand, had a sobering assessment of TBI treatments derived from cellular neurobiology, noting that the field is on its 32nd or 33rd failed clinical trial.²

This is probably not what the White House wanted to hear, particularly since this panel was brought on to slyly connect the NIH BRAIN Awards to clinical disorders. But this is exactly what people need to hear to understand the utter complexity of trying to cure brain disorders, or at least treat them more effectively.

Further Reading

NEW! Indispensable coverage of Next Generation Human Imaging
(by @practiCal fMRI):
i-fMRI: My initial thoughts on the BRAIN Initiative proposals

A Tale of Two BRAINS: #BRAINI and DARPA's SUBNETS

BRAIN Initiative Funding Opportunites at NIH

Humble BRAIN 2025

And the DARPA deep brain stimulation awards go to...

Footnotes

¹The BRAIN Initiative badge should be awarded by President Obama to research supported by his $100+ million Brain Research through Advancing Innovative Neurotechnologies Initiative. This bold research effort will include advances in nanotechnology and purely exploratory efforts to record from thousands of neurons simultaneously. Recipients of BRAIN Awards from NIH, DARPA, and NSF are free to use this fictitious badge made by me.

²The failure of a very promising clinical trial of progesterone for TBI was very recently announced ("based on 17 years of work with 200 positive papers in pre-clinical models"), although I couldn't find it. Here's the listing in ClinicalTrials.gov.

View the story "White House BRAIN Conference" on Storify

Two Croatian academics with an anti-neuro ax to grind have written a cynical history of neuroword usage through the ages (Mazur & Rinčić, 2013). Actually, I believe the authors were being deliberately sarcastic (at times), since the article is rather amusing.¹

Placing that phenomenon of "neuroization" of all fields of human thought and practice into a context of mostly unjustified and certainly too high – almost millenarianistic – expectations of the science of the brain and mind at the end of the 20th century, the present paper tries to analyze when the use of the prefix neuro- is adequate and when it is dubious.

Ključne riječi [keywords]:
brain; neuroscience; word coinage

Amir Muzur and Iva Rinčić are both on the Faculty of Medicine at the University of Rijeka, in the Department of Humanities and Social Sciences in Medicine. Their interests include the history of bioethics, bioethics and sociology, the history of medicine, and neuroscience.

The pre-BRAIN Initiative paper² begins with a reminder of President George Bush Senior's proclamation of the Decade of the Brain:

Let aside the fact that a new decade did not begin in 1990 but a year later, with such pathos, George Bush Senior started an unprecedented avalanche of expectations, pompousness, and grants which will be lasting up today. The motives of launching the "Decade of the brain" were inspired by increasing awareness and fear of the treath [sic] of Alzheimer’s disease and neural sequels of drugs and AIDs, more than by the declared fascination by brain function.

Neurocriticism

The authors did intend to seriously critique the excesses of “neuroization” (since the title of the paper includes the word “Neurocriticism” after all), although it can be tricky to determine exactly when they're going over the top:

Scientists researching the brain cherish the idea that their work is extremely important, unique, and indispensable. They often venture into other fields and sciences without feeling any inferiority complex, convinced that their knowledge on human brain be sufficient to understand and interprete [sic] everything. ... Modern neuroscientists are like ancient alchemists, believing they are up to discover the most important secrets of the life elixir and the philosophers’ stone. Is not the hyperproduction of new names for (psudo)disciplines [sic] also a result of that arrogance?

A short primer of neuro-disciplines

Mazur and Rinčić (2013) then present their history of neurowords from 1681 to 2006, focusing on those that have become legitimate (or pseudo-legitimate) fields of study, some of which they characterize as “awkward caricatures” (e.g., neuroeconomics and neuromarketing).³

Neuromarketing– the application of neuroimaging methods to product marketing (studying consumers’ sensorimotor, cognitive, and affective response to marketing stimuli) – was coined by Ale Smidts in 2002.

In the same year, it seems that two more new neuro-terms were coined: neuroethics, meaned [sic] for the neuroscience of ethics and the ethics of neuroscience (four years later, in May 2006, a Neuroethics society came to be at a conference in Asilomar in California), and neuroesthetics, as the study of the neural bases for the contemplation and creation of a work of art.

Neuroeconomics studies the neural underpinnings of making decisions, taking risks, and evaluating rewards. Probably the first to formulate the name was Paul Glimcher in 2003.⁴

The article confirms that the recent fad for “neuroization” is not justified. And not surprisingly, it ends on a pessimistically snarky (and utterly hyperbolic) note, putting all neuroscientists in their place:

In fact, nothing crucial has been discovered in neuroscience for quite a while, and the premordial entrapment in the mind-body problem still lasts: why, then, that explosion of "interest" in the brain at the end of the 20th and at the beginning of the 21st centuries? Is not it a contemporary variation of a historical periodical millenaristic movement, invoking a panacea for a society in general crisis? Neuro- seems to provide not only a desperate ultimate attempt at being original in science where everything has been said and done, but, morover [sic], a guaranty of attracting attention and simulating importance.

Further Reading

I've written my own idiosyncratic history of neurowords in Journomarketing of Neurobollocks, which told Steven Poole he didn't invent neurobabble, neurobollocks, or neurotrash (and reminisced about the 2006 neuroword contest hosted by Neurofuture).

Befitting a blog that started as its own made-up neuroword, here are some selections from the archives:

Neuroetiquette and Neuroculture

Neurokitchen Design?

Neurocoaching?

Neuroleadership?

Neuro-Gov

NeuroPsychoEconomics!

The Luxury Of Neurobranding

Footnotes

¹though an expert in Croatian humor I am not.

²A significantly shorter version of this paper was presented at 9th Lošinj Days of Bioethics, Mali Lošinj, Croatia, May 16-19, 2010.

³ Interestingly, they note that neuropolitics was probably coined by Timothy Leary in 1977 and neurotheology even earlier, by Aldous Huxley in his 1962 utopian novel Island.

⁴The sources for these neuroword origins are included in the footnotes of the paper:

50 http://en.wikipedia.org/wiki/Neuromarketing

51 A. Roskies, "Neuroethics for the new millennium," Neuron 35 (2002): 21-23.

52 http://en.wikipedia.org/wiki/Neuroesthetics#cite_note-0; cf. also "The statement on neuroesthetics" by Semir Zeki ( http://www.neuroesthetics.org/statement-on-neuroesthetics.php)

53 Paul W. Glimcher, Decisions, Uncertainty, and the Brain: The Science of Neuroeconomics (Cambridge, MA: The MIT Press, 2003).

However, in my own coverage of neurowords, I found that neuroeconomics has been around since the late 1990s.

Reference

Amir Muzur, Iva Rinčić. Neurocriticism: a contribution to the study of the etiology, phenomenology, and ethics of the use and abuse of the prefix neuro-. JAHR – European Journal of Bioethics, Vol.4 No.7 Svibanj 2013. pp. 545-555.

What happens in the brain during a highly immersive reading experience? According to the fiction feeling hypothesis (Jacobs, 2014), narratives with highly emotional content cause a deeper sense of immersion by engaging the affective empathy network to a greater extent than neutral narratives. Emotional empathy — in this case, the ability to identify with a fictional character via grounded metarepresentations of ‘global emotional moments’ (Hsu et al., 2014) — relies on a number of brain regions, including ventromedial prefrontal cortex (PFC), dorsomedial PFC, anterior insula (especially in the right hemisphere), right temporal pole, left and right posterior temporal lobes, inferior frontal gyrus, and midcingulate cortex.

A group of researchers in Germany used text passages from the Harry Potter series to test the fiction feeling hypothesis, specifically that readers will experience a greater sense of empathy for and identification with the protagonists when the content is suspenseful and scary (Hsu et al., 2014). This would be accompanied by greater activations in specific brain regions during an fMRI scan.

The experimental stimuli were 80 passages from the Harry Potter novels. The authors selected 40 ‘fear-inducing’ and 40 ‘neutral’ passages, each about 4 lines long.¹ These were screened and rated by a set of independent participants. Unfortunately, the authors did not provide any examples, so I'm going to have to improvise here.

Given that I've not read any of the Harry Potter books (or seen the movies), I'm not the best person to run a popular blog serial on NeuroReport's Harry Potter and the _______ books. Or to to launch an academic publishing franchise on fMRI studies of epic fantasy novels.²

But here's a sampler anyway, based on Ayn Rand’s Harry Potter and the Prisoners of Collectivism: ³

He felt the unnatural cold begin to steal over the street. Light was sucked from the environment right up to the stars, which vanished. The cold was biting deeper and deeper into Harry’s flesh [and lighting up his pain matrix in an eerie glow against the dark and lonely night].

Then, around the corner, gliding noiselessly, came Dementors, ten or more of them, visible because they were of a denser darkness than their surroundings, with their black cloaks and their scabbed and rotting hands. Could they sense fear [and an overactive amygdala] in the vicinity? ...

Suddenly he heard them: Marxists.
. . .

“Only together, collectively, can we achieve anything of lasting significance,” he heard one of them say. Harry moaned in pain[his anterior cingulate and insular cortices writhing from such cognitive dissonance and social exclusion].

“The fortunate owe it to society to contribute to those who cannot work,” another chanted. Harry closed his eyes and collapsed [his ventral posteriorlateral thalamic nuclei and somatosensory cortex no longer able to endure the intolerable battering].

My poorly written additions in maroon prefigure the focus of the study — empathy for pain. I'm not exactly sure why this was so (for either literary or scientific reasons). At any rate, Hsu et al. (2014) made the following predictions:

we expected (i) higher immersion ratings for fear-inducing passages, which often describe pain or personal distress, as compared with neutral passages, and (ii) significant correlations of immersion ratings with activity in the affective empathy network, particularly AI [anterior insula] and mCC [mid-cingulate cortex], associated with pain empathy for fear-inducing, but not for neutral, passages.

AI and mCC have been implicated in the affective component of personally felt pain, as well as in empathy for another person's pain (Jackson et al., 2006). So the expected result would be greater activations in AI and mCC for the Fearful vs. Neutral comparison. They didn't do this exact contrast, but they did look for differential correlations between “immersion ratings” and BOLD responses for Fear > fixation (a low-level control condition) and Neutral > fixation.

A separate group of individuals (not the ones who were scanned) rated the Fearful and Neutral passages for immersion by rating their subjective experience, ‘I forgot the world around me while reading’ on a scale from 1 (totally untrue) to 7 (totally true). Although the difference between Fear (mean = 3.75) and Neutral (mean = 3.18) was statistically significant, the level of immersion wasn't all that impressive, being below the midpoint even for the scary texts.

The major fMRI result was a cluster in the mid-cingulate cortex (corrected cluster-level P = 0.037) that showed a higher correlation between immersion ratings and BOLD for Fear than for Neutral.

Fig. 1B (modified from Hsu et al., (2014). The mid-cingulate gyrus showing a significant correlation difference between passage immersion ratings and BOLD response in the Fear versus Neutral conditions, cross-hair highlighting the peak voxel [8 14 39].

No such relation was observed in the anterior insula, which was explained by postulating that “motor affective empathy” was more prominent than “sensory affective empathy”:

Craig [12] considered mCC to be the limbic motor cortex and the site of emotional behavioural initiation, whereas AI is the sensory counterpart. With respect to our stimuli from Harry Potter series, in which behavioural aspects of emotion are particularly vividly described, the motor component of affective empathy (i.e. mCC) might predominate during emotional involvement, and facilitate immersive experience.

This is obviously a post-hoc explanation, one that's hard to judge in the absence of actual exemplars of the experimental stimuli. Although the results were a bit underwhelming, I was happy the authors did not venture out on a rickety and hyperbolic limb, as the NYT did (gasp!) in Can ‘Neuro Lit Crit’ Save the Humanities? and Next Big Thing in English.

Footnotes

¹ The Fearful and Neutral passages were matched for many factors that can affect reading:

...numbers of letters, words, sentences and subordinate sentence per passage, the number of persons or characters (as the narrative element), the type of intercharacter interaction and the incidence of supranatural events (i.e. magic) involved in text passages across the emotional categories.

² Perhaps Neuroskeptic is more qualified for that...

³ Also from Mallory Ortberg at The Toast, we have Ayn Rand’s Harry Potter and The Order of Psycho-epistemology :

“You’re a prefect? Oh Ronnie! That’s everyone in the family!”

Ron looked nervously at Harry. Harry betrayed nothing. You can be a wizard, Ron remembered, and you can be a man; it is good to be both, if you can, but if you must choose, it is better to be a man and not a wizard than a wizard and not a man.

Further Reading

Professor of Literary Neuroimaging: “An unfocused and rambling article in the New York Times the other day was excited about the potential use of neuroimaging to revive the gloomy state of university literature departments. It also tried to convey the importance of evolutionary psychology in explaining fiction.”

References

Hsu CT, Conrad M, & Jacobs AM (2014). Fiction feelings in Harry Potter: haemodynamic response in the mid-cingulate cortex correlates with immersive reading experience. Neuroreport PMID: 25304498

Jackson PL, Rainville P, Decety J. (2006). To what extent do we share the pain of others? Insight from the neural bases of pain empathy. Pain 125:5-9.

Jacobs AM. (2014). Neurocognitive Model of Literary Reading.

Nightmares can seem very real at times, but then we wake up and realize it was all a bad dream. Now imagine having a vivid nightmare with all the reality of waking life and then... it turns out you're actually awake through it all!

This happened to an 11 year old Italian boy who reported frightening auditory and visual hallucinations of Voldemort, the archenemy of Harry Potter, for three straight days. These hallucinations began after a bout of sore throat and fever (38°C). As Vita et al. (2008) report:

The day after the resolution of fever, he began to present hallucinations. Hallucinations occurred in the afternoon, after watching TV. They were polymodal: he saw and heard Voldemort (an evil character of the Harry Potter saga). He did not realize his hallucinations were not real; he was extremely frightened, and he cried and searched his parents for protection. The episode lasted several hours, and was not associated with modification of vigilance or consciousness. ... Two days later, a new hallucinatory episode occurred: again, he saw Voldemort, who appeared threatening, and he fought against him. A further episode, with the same features, occurred the following day. He interacted with the characters of the hallucination, and on one occasion, he wore a sword and helmet to fight against Voldemort. When asked to recall the hallucinations, the boy said that they appeared real to him.

Neurological exam, EEG, and CSF cultures for bacteria, viruses, and fungi were all negative. CSF titers of antibodies were normal, and there was no evidence of autoantibodies. However, an MRI scan showed abnormal signs in the boy's brainstem. Several small lesions were observed in the pons, in the vicinity of a region implicated in REM sleep.

Fig. 1 (modified from Vita et al., 2008). MRI after the onset of hallucinations. Small areas of signal hyperintensity (lesions) are indicated by the arrows.

The etiology and phenomenology of the boy's condition seem consistent with peduncular hallucinosis, “a rare form of visual hallucination often described as vivid, colorful visions of people and animals.” The exact cause is unknown, but most cases have been related to lesions in the midbrain, thalamus, or brainstem (Dogan et al. 2013; Penney & Galarneau, 2014; Talih, 2013). In some instances the patients are aware that the hallucinations are not real, but other cases present as a psychiatric disorder and can include auditory or tactile hallucinations, in addition to visual.

Here, Vita et al. (2008) speculate that dreaming and REM sleep have become dissociated: the boy was literally dreaming while awake. Fortunately, his nightmarish condition disappeared after treatment with immunoglobulins. The exact diagnosis was unclear, but it might have been a transient demyelinating syndrome, which involves the loss of white matter, or myelin, that surrounds the axon.

The authors cited a model of REM sleep in which GABA-containing “REM-on” neurons inhibit GABAergic “REM-off” neurons located in the ventrolateral periaqueductal gray matter (vlPAG) and lateral pontine tegmentum (LPT), and vice versa.

Fig. 1 (modified from Vita et al., 2008). MRI after the onset of hallucinations. Three small lesions are indicated by the arrows.

Turns out the lesions (shown in gray stippling below) could include some of these neurons, especially those in the REM-off areas (vlPAG and LPT).

Fig. 1 (modified from Vita et al., 2008). Schematic of the REM-on and REM-off areas in the pons. Gray stippling indicates the lesions. REM-on region in black, REM-off regions in white.¹

The authors speculated that transient dysfunction of REM-off cells, caused by the inflammatory demyelinating syndrome, resulted in weaker inhibition of REM-on cells, allowing a dream-like state to ooze into wakefulness.

Luckily the boy won out over Voldemort in the end, assisted by a team of doctors at Catholic University in Rome.

Footnote

¹ Detailed figure legend:

D: scheme of the REM-on and REM-off areas in the pons. In black: the REM-on region (locus subceruleus-α [sLCα]). In white: the REM-off region: ventrolateral periaqueductal gray (vlPAG) and lateral pontine tegmentum (LPT). In gray the REM modulatory regions: in rostrocaudal order, pedunculopontine tegmentum (PPT), laterodorsal tegmentum (LDT), dorsal raphe nucleus (DRN), and locus ceruleus (LC). Gray dotted areas: sites of the inflammatory lesions.

References

Dogan VB, Dirican A, Koksal A, Baybas S. (2913). A case of peduncular hallucinosis presenting as a primary psychiatric disorder. Ann Indian Acad Neurol. 16(4):684-6.

Penney L, Galarneau D. (2014). Peduncular hallucinosis: a case report. Ochsner J. 14(3):450-2.

Talih FR. (2013). A probable case of peduncular hallucinosis secondary to a cerebral peduncular lesion successfully treated with an atypical antipsychotic. Innov Clin Neurosci. 10(5-6):28-31.

Vita MG, Batocchi AP, Dittoni S, Losurdo A, Cianfoni A, Stefanini MC, Vollono C, Della Marca G, & Mariotti P (2008). Visual hallucinations and pontine demyelination in a child: possible REM dissociation? Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 4 (6), 588-90 PMID: 19110890

In the mirror we see our physical selves as we truly are, even though the image might not live up to what we want, or what we once were. But we recognize the image as “self”. In rare instances, however, this reality breaks down.

In Black Swan, Natalie Portman plays Nina Sayers, a ballerina who auditions for the lead in Swan Lake. The role requires her to dance the part of the innocent White Swan (for which she is well-suited), as well as her evil twin the Black Swan — which is initially outside the scope of her personality and technical abilities. Another dancer is favored for the role of the Black Swan. Nina's drive to replace her rival, and her desire for perfection, lead to mental instability (and a breathtaking performance). In her hallucinations she has become the Black Swan.¹

The symbolic use of mirrors to depict doubling and fractured identity was very apparent in the film:

Perhaps Darren Aronofsky [the director's] intentions for the mirror was its power to reveal hidden identities. If you noticed the scenes where Nina saw herself in the mirror, it reflected the illusion of an evil. The mirror presented to her the darkness within herself that metaphorically depicted the evolution into the black swan.

How can the recognition of self in a mirror break down?

Alterations in mirror self-recognition

There are at least seven main routes to dissolution or distortion of self-image:

psychotic disorders
dementia
right parietal-ish or otherwise right posterior cortical strokes and lesions
the ‘strange-face in the mirror' illusion
hypnosis
dissociative disorders (e.g., depersonalization, dissociative identity disorder
body image issues (e.g., anorexia, body dysmorphic disorder)

Professor Max Coltheart and colleagues have published extensively on the phenomenon of mirrored-self misidentification, defined as “the delusional belief that one’s reflection in the mirror is a stranger.” They have induced this delusion experimentally by hypnotizing highly suggestible participants and planting the suggestion that they would see a stranger in the mirror (Barnier et al., 2011):

Following a hypnotic suggestion to see a stranger in the mirror, high hypnotizable subjects described seeing a stranger with physical characteristics different to their own. Whereas subjects' beliefs about seeing a stranger were clearly false, they had no difficulty generating sensible reasons to explain the stranger's presence. The authors tested the resilience of this belief with clinically inspired challenges. Although visual challenges (e.g., the hypnotist appearing in the mirror alongside the subject) were most likely to breach the delusion, some subjects maintained the delusion across all challenges.

Ad campaign for the Exelon Patch (rivastigmine, a cholinesterase inhibitor) used to treat Alzheimer's disease. Photographer Tom Hussey did a series of 10 award-winning portraits depicting Alzheimer's patients looking at their younger selves in a mirror (commissioned by Novartis).

Mendez et al. (1992) published a retrospective study of 217 patients with Alzheimer's disease. They searched the medical records for caregiver reports of disturbances in person identification of any kind. The most common type was transient confusion about family members that resolved when reminded of the person's identity (found in 33 patients). The charts of five patients contained reports of mirror misidentification, which was always associated with paranoia and delusions. Although not exactly systematic, this fits with other studies reporting that 2–10% of Alzheimer's patients have problems recognizing themselves in a mirror.

A thorough investigation of the topic was actually published 50 years ago, but largely neglected because it was in French. Connors and Coltheart (2011) translated the 1963 paper of Ajuriaguerra, Strejilevitch, & Tissot into English. The Introduction is quite eloquent:

The vision of our image in the mirror is a discovery that is perpetually renewed, one in which our being is isolated from the world, from the objects surrounding it, and assumes, despite the fixed quality of reflected images, the significance of multiple personal and potential expressions. The image reflected by the mirror furnishes us not only with that which is, but also how our real image might be changed. It therefore inextricably combines awareness, indulgence and critique.

They examined how 30 hospitalized dementia interacted with mirrors in terms of (1) recognition of their own reflection; (2) use of reflected space; and (3) identifying body parts. The patients sat in front of a mirror and answered the following questions:

What is this?
Who is that?
How old would you say that person is?
How do you think you look?

Then the experimenter stood behind them and asked questions about himself (e.g., “who is that man?”), and showed them objects in the mirror (e.g., an orange or a pipe– very funny).

Eight patients did not recognize themselves in the mirror:

Three didn't understand the concept of a mirror. They didn't pay attention to any reflections until directed to do so, and then they became transfixed. They also failed to recognize photos of themselves or their caretakers.

Another three eventually admitted it might be themselves when prodded several times.

Those six individuals had severe Alzheimer's disease.

The final two recognized themselves the second time, and displayed considerably more anxiety. This sounds terribly frightening:

These patients were attentive to their own reflections and those of the researchers, whom they identified. The first patient seemed a bit anxious; she began by touching herself, then laughed, then proclaimed “that is not quite me, it sort of looks like me, but it's not me.” When she was shown her photo head-on and then from the side, she immediately identified herself when the photo was head-on but from the side said “that's not quite me.”

These two individuals were in an earlier state of dissolution and likely had more awareness of what was happening to them.

Other patients with mirrored-self misidentification show greater sparing of cognitive abilities. Chandra and Issac (2014) presented brief case summaries of five mild to moderate dementia patients with “mirror image agnosia, a new observation involving failure to recognize reflected self-images.” This is obviously not a new observation, but the paper includes two videos, one of which is embedded below.

Sixty-two-year-old female was brought to the hospital with features of forgetfulness and getting lost in less familiar environment. ... She was then shown the mirror 45 cm × 45 cm. She could identify it as a mirror. She showed unusual attraction to the mirror and ignored the physician and people around. She would go to the mirror and converse with her own image as if the image is another person but could correctly identify the reflected face of her daughter in law and the resident but she was asking her own reflection for the name and communicated to others saying that ‘here is a woman who does not know her name’.

from Chandra & Issac (2014)

Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported

LAST BUT NOT LEAST we have the Strange-face-in-the-mirror illusion (Caputo, 2010). When gazing upon one's reflected face in a dimly lit room, after a minute or two...

The participants reported that apparition of new faces in the mirror caused sensations of otherness when the new face appeared to be that of another, unknown person or strange `other' looking at him/her from within or beyond the mirror. All fifty participants experienced some form of this dissociative identity effect, at least for some apparition of strange faces and often reported strong emotional responses in these instances.

try this if you dare,

on halloween night...

Further Reading

The strange-face-in-the-mirror illusion– Mind Hacks, with 271 comments.

Visual perception during mirror gazing at one's own face in schizophrenia– The strange-face-in-the-mirror illusion with schizophrenics (seems a little mean to me)

Mirrors in film– a list

Reflections and Mirrors in film– discussion board

Footnote

¹ As an aside, Natalie Portman (who has published in NeuroImage) won the 2011 Best Actress Academy Award for this performance. Her male counterpart, Colin Firth (who has published in Current Biology) won the Best Actor Award.

References

Ajuriaguerra, J. de, Strejilevitch, M., & Tissot, R. (1963). A propos de quelques conduites devant le miroir de sujets atteints de syndromes démentiels du grand âge [On the behaviour of senile dementia patients vis-à-vis the mirror]. Neuropsychologia, 1, 59–73.

Barnier AJ, Cox RE, Connors M, Langdon R, & Coltheart M (2011). A stranger in the looking glass: developing and challenging a hypnotic mirrored-self misidentification delusion. The International journal of clinical and experimental hypnosis, 59 (1), 1-26 PMID: 21104482

Chandra SR, & Issac TG (2014). Mirror image agnosia. Indian journal of psychological medicine, 36 (4), 400-3 PMID: 25336773

Connors MH, & Coltheart M (2011). On the behaviour of senile dementia patients vis-à-vis the mirror: Ajuriaguerra, Strejilevitch and Tissot (1963). Neuropsychologia, 49 (7), 1679-92 PMID: 21356221

Mendez MF, Martin RJ, Smyth KA, & Whitehouse PJ (1992). Disturbances of person identification in Alzheimer's disease. A retrospective study. The Journal of nervous and mental disease, 180 (2), 94-6 PMID: 1737981

- this looks like a strange one -

When I was a kid, I watched this scary TV show called One Step Beyond. It was kind of like The Twilight Zone, except the stories were more haunting and supernatural.

An especially frightening episode was called The Clown. Everyone loves the circus. Everyone loves a clown.¹

John Newland, the show's narrator: "Laughter is an international language, and the clown, the prince of laughter."

"Look, a clown!"

A jealous husband behaves in a physically and verbally abusive fashion towards his young wife any time she's near another man. Why, he's even jealous of Pippo the Clown, a simple and silent entertainer who brings balloons and joy to the diner patrons.

Mr. Abusive sees the clown touching his wife's blond hair and freaks out. He grabs Pippo's scissors and cuts off a chunk of her hair. The wife screams and runs away into the carnival campgrounds, which is conveniently nearby. Pippo acts in a menacing fashion and scares the husband away.

The wife wanders around the carnival grounds and into the clown's tent, where she cries into a wig. Pippo returns and tries to fix her hair and cheer her up. She eventually starts laughing and hugs the clown.

Then the obnoxious lout hears laughter and enters the trailer, finding his wife with the clown. "You dirty cheap one, I've had it..." He grabs her and slaps her and throws her down to the ground.

Pippo gets defensive and angry and starts choking the husband, who grabs those handy scissors and stabs........ HIS WIFE! Killing her!

Pippo picks her up, husband drops the scissors and slips away, and guess who becomes the leading murder suspect. The simple clown, who keeps trying to revive the dead girl by making her laugh.

The Strong Man: "Help, help, somebody help, the clown's killed a dame!" [it's 1960]

The husband wanders around in a daze, stopping in front of a pawn shop with a mirror in the window.

Mr. Killer glances away from the mirror for a moment and guess who appears, trying to strangle him.

He whips around to see the clown and.... there's no one there!!

This happens a few more times, where the clown appears in the mirror, the guy turns around and there's nobody there...

Now this was very scary and horrifying when I was a small child. I was afraid to look at a mirror for weeks. The thought of seeing Pippo the Clown standing behind me, strangling me, was terrifying. For a brief period I had Spectrophobia (also known as Catoptrophobia), a fear of mirrors:

Generally, an individual that deals with Spectrophobia has been traumatized in an event where they believe they have seen or heard apparitions or ghosts. The individual could also become traumatized by horror films, television shows, or by nightmares. This fear could be the result of a trauma involving mirrors. It could also be the result of the person’s superstitious fear of being watched through the mirror.

"Traumatized" is a bit excessive... I got over it. Watching the episode today, I see how campy and cheesy it is, with its soundtrack of "vampy" music as a stand-in for the wife's sex appeal. Her aura of youthful innocence was over the top, and the husband comes off as a creepy pedophile.²

And fortunately, I never developed a fear of clowns...

But I have to say, I didn't make it through the OCULUS Trailer, not on Halloween night. And I think I'll have to try the ‘strange-face in the mirror' illusion another night.

I hope you enjoyed Fright Week. Check out the other spooky posts:

The Stranger in the Mirror

The Waking Nightmare of Lord Voldemort

Footnotes

¹ Everyone knows about coulrophobia, the very common fear of clowns.

²The Flaming Nose TV Blog informs us that the actors playing the husband and wife were 40 and 18 years old, respectively. No wonder he comes off as an abusive pedophile... The strangling clown gif is also from the Flaming Nose.

“Research on the brain is surging,” declared the New York Times the other day:

Yet the growing body of data — maps, atlases and so-called connectomes that show linkages between cells and regions of the brain — represents a paradox of progress, with the advances also highlighting great gaps in understanding.

So many large and small questions remain unanswered. How is information encoded and transferred from cell to cell or from network to network of cells? Science found a genetic code but there is no brain-wide neural code; no electrical or chemical alphabet exists that can be recombined to say “red” or “fear” or “wink” or “run.” And no one knows whether information is encoded differently in various parts of the brain.

Yet we still understand so little, they say. And most people don't care.

The Public Find Brain Science Irrelevant and Anxiety-provoking, based on the outcome of a small qualitative study of 48 London residents (O'Connor & Joffe, 2014):

The Brain Is Something That Goes Wrong

Though the brain was ordinarily absent from participants’ mental landscapes, there was one route by which this habitual inattention could be ruptured. The second theme articulates the finding that for many, neurological pathology was the only aspect of brain research that held clear personal relevance. This foregrounding of pathology constituted the brain as a vulnerable, anxiety-provoking organ and anchored brain research in the domain of medicine.

So people may not care about the brain, unless something in theirs is broken. When they'll find it's important that doctors know how to fix it. And perhaps realize this knowledge comes from basic research.

This adds new meaning to the Public Health Relevance Statement required for NIH grant applications (see p. I-65 of this PDF):

For NIH and other PHS agencies applications, using no more than two or three sentences, describe the relevance of this research to public health. In this section, be succinct and use plain language that can be understood by a general, lay audience. If the application is funded, this public health relevance statement will be combined with the project summary (above) and will become public information.

Anyone can look up grants at NIH RePORTER and read the Public Health Relevance Statement for each. Not that most people will be doing this. But what might they find for a basic science grant that studies invertebrates? Say the central pattern generating circuits found in the crustacean stomatogastric ganglion, which controls the rhythmic muscle contractions that grind and move food through the gut? Here's one:

Public Health Relevance Statement: Mental illness may result from relatively minor imbalances in circuit parameters that nonetheless result in significantly disordered functions. To understand what kinds of circuit parameters when perturbed lead to mental illness, it is necessary to understand how different neuronal excitability and synaptic strengths are in normal healthy brains, and how individual neuronal processes compensate for each other.

I chose this example because the Principal Investigator, Dr. Eve Marder, has done such groundbreaking work on neuromodulation and circuit dynamics over the duration of her illustrious career. Last year she was awarded the $500,000 Gruber Neuroscience Prize for Pioneering Contributions to the Understanding of Neural Circuitry:

...Early in her career, Marder revealed that the STG was not "hard-wired" to produce a single pattern of output, but that it was a remarkably plastic circuitry that could change both its parameters and function in response to various neuromodulators while still maintaining its morphologic connectivity. This discovery marked a paradigm shift in how scientists viewed the architecture and function of neural circuits, including those in the human brain.
. . .

More recently, Marder's research has focused on how neural circuits maintain stability, or homeostasis, over long periods of time despite constantly reconfiguring themselves. This research has broad implications for the study of many neurological diseases linked to dysfunctional neural circuitry, such as schizophrenia, depression, epilepsy, post-traumatic stress disorder (PTSD), and chronic pain.

What if PIs were required to provide a detailed description of how their findings will actually lead to new treatments? It's one thing to say “our findings will have broad implications for the study of many neurological diseases” but quite another to explain exactly how this this will happen, even if you're studying humans (not to mention if you're studying a system of 30 neurons in the crab gut). The down side here is that the public might expect too much —“Hey, why haven't you cured Alzheimer's yet? Haven't we, the taxpayers, given you billions of dollars?”

On the other hand, politicians are falling all over each other saying, “I'm not a scientist, but...” I'll go ahead and make ignorant policy decisions and second guess independent peer review of grants. So it's critical that neuroscientists can communicate the “broader implications” of their work and yes, how their research may eventually lead to improved treatments for brain diseases.

For that reason, I've been pondering the relative translational potential of neural engineering, pharmacological, and regenerative medicine approaches to neurological and psychiatric disorders... We'll see what (if anything) I can come up with, at least from a comparative perspective.

Cheesy Bench to Bedside Image Credit: UAMS

NeuroFutures Conference: June 17 - 18, 2014

NeuroFutures Public Lecture: 7:00 PM, June 16

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