Thursday, October 30, 2014

Fright Week: The Stranger in the Mirror



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:
  1. psychotic disorders
  2. dementia
  3. right parietal-ish or otherwise right posterior cortical strokes and lesions
  4. the ‘strange-face in the mirror' illusion
  5. hypnosis
  6. dissociative disorders (e.g., depersonalization, dissociative identity disorder
  7. 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 pipevery 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’.


video

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 -


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Saturday, October 25, 2014

Fright Week: The Waking Nightmare of Lord Voldemort



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

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Wednesday, October 15, 2014

Harry Potter and the Prisoner of Mid-Cingulate Cortex


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.


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Monday, October 06, 2014

The use and abuse of the prefix neuro- in the decades of the BRAIN



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

1 though an expert in Croatian humor I am not.

2 A 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.

4 The 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.

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Wednesday, October 01, 2014

White House BRAIN Conference



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

1 The 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.

2 The 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.






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Friday, September 26, 2014

Anthropomorphic Neuroscience Driven by Researchers with Large TPJs



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).




Read more »

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Tuesday, September 16, 2014

Should Policy Makers and Financial Institutions Have Access to Billions of Brain Scans?


"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).


ADDENDUM (Sept 28 2014): The first author, Dr. Gilaie-Dotan, has commented to clarify that voodoo correlations were not used in the paper. I have added the legend for the correlation plot in Fig. 2 at the bottom of the post, which states that it is shown for illustrative purposes only and should not be used for inference. She also explains additional aspects of the data presented in Fig. 4 of the paper (not shown here).


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.

1A ADDENDUM (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.


ADDENDUM (Sept 28 2014): Here is the legend for Fig 2 (Bottom).
To demonstrate that the observed correlations were not driven by outliers, for each individual, GM volume of the PPC cluster (top) is plotted on the x-axis against risk attitude on the y-axis. Note that this should not be used for inference as it is not independent of the whole-brain analysis and is presented for visualization purposes only. No other regions were found to be correlated with risk attitudes.




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