Monday, December 08, 2014

Hipster Neuroscience

According to Urban Dictionary,
Hipsters are a subculture of men and women typically in their 20's and 30's that value independent thinking, counter-culture, progressive politics, an appreciation of art and indie-rock, creativity, intelligence, and witty banter.  ...  Hipsters reject the culturally-ignorant attitudes of mainstream consumers, and are often be seen wearing vintage and thrift store inspired fashions, tight-fitting jeans, old-school sneakers, and sometimes thick rimmed glasses.

by Trey Parasuco November 22, 2007 

Makes them sound so cool. But we all know that everyone loves to complain about hipsters and the endless lifestyle/culture/fashion pieces written about them.

And they're so conformist in their nonconformity.

Recently, Jonathan Touboul posted a paper at arXiv to model The hipster effect: When anticonformists all look the same:
The hipster effect is this non-concerted emergent collective phenomenon of looking alike trying to look different. Uncovering the structures behind this apparent paradox ... can have implications in deciphering collective phenomena in economics and finance, where individuals may find an interest in taking positions in opposition to the majority (for instance, selling stocks when others want to buy). Applications also extend to the case of neuronal networks with inhibition, where neurons tend to fire when others and silent, and reciprocally.

You can find great write ups of the paper at Neuroecology and the Washington Post:
There are two kinds of people in this world: those who like to go with the flow, and those who do the opposite — hipsters, in other words. Over time, people perceive what the mainstream trend is, and either align themselves with it or oppose it.

What if this world contained equal numbers of conformists and hipsters? No matter how the population starts out, it will end up in some kind of cycle, as the conformists try to catch up to the hipsters, and the hipsters try to differentiate themselves from the conformists.

But there aren't equal numbers of conformists and hipsters. And this type of cycle doesn't apply to neuroscience research, which is always moving forward in terms of trends and technical advances (right)?

It may be the Dream of the 1890s in Portland, but it's BRAIN 2015 all the way (RFA-MH-15-225):

BRAIN Initiative: Development and Validation of Novel Tools to Analyze Cell-Specific and Circuit-Specific Processes in the Brain (U01)

Although hipsters are in their 20s and 30s, the august NIH crowd (and its advisors) has set the BRAIN agenda that everyone else has to follow. When the cutting-edge tools (e.g., optogenetics) become commonplace, you have to do amazing things with them like create false memories in mice, or else develop methods like Dreadd2.0: An Enhanced Chemogenetic Toolkit or Ultra-Multiplexed Nanoscale In Situ Proteomics for Understanding Synapse Types.

The BRAIN Initiative wants to train the hipsters and other "graduate students, medical students, postdoctoral scholars, medical residents, and/or early-career faculty" in Research Tools and Methods and Computational Neuroscience. This will "complement and/or enhance the training of a workforce to meet the nation’s biomedical, behavioral and clinical research needs."

But this is an era when the average age of first-time R01 Principal Investigators is 42 1 and post-docs face harsh realities:
Research in 2014 is a brutal business, at least for those who want to pursue academic science as a career. Perhaps the most telling line comes from the UK report: of 100 science PhD graduates, about 30 will go on to postdoc research, but just four will secure permanent academic posts with a significant research component. There are too many scientists chasing too few academic careers.

How do you respond to these brutal challenges? I don't have an answer.2  But many young neuroscientists may have to start pickling their own vegetables, raising their own chickens, and curing their own meats.


1  The average age of first-time Principal Investigators on NIH R01 grants has risen from 36 in 1980 to 42 in 2001, where it remains today (see this PPT). So this has been going on for a while.

2  Or at least, not an answer that will fit within the scope of this post. Some obvious places to start are to train fewer scientists, enforce a reasonable retirement age, and increase funding somehow. And decide whether all research should be done by 20 megalabs, or else reduce the $$ amount and number of grants awarded to any one investigator.

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Monday, November 24, 2014

The Humanities Are Ruining Neuroscience

Photo illustration by Andrea Levy for The Chronicle Review

Inflammatory title, isn't it. Puzzled by how it could possibly happen? Then read on!

A few days ago, The Chronicle of Higher Education published a piece called Neuroscience Is Ruining the Humanities. You can find it in a Google search and at reddit, among other places. The url is {notice the “Neuroscience-Is-Ruining” part.}

Oh wait. Here's a tweet.

At some point along the way, without explanation, the title of the article was changed to the more mundane The Shrinking World of Ideas. The current take-home bullet points are:
  • We have shifted our focus from the meaning of ideas to the means by which they’re produced.
  • When professors began using critical theory to teach literature they were, in effect, committing suicide by theory.

The author is essayist Arthur Krystal, whose 4,000+ word piece can be summarized as “postmodernism ruined everything.” In the olden days of the 19th century, ideas mattered. Then along came the language philosophers and some French historians in the 1920s/30s, who opened the door for Andy Warhol and Jacques Derrida and what do you know, ideas didn't matter any more. That's fine, he can express that opinion, and normally I wouldn't care. I'm not going to debate the cultural harms or merits of postmodernism today.

What did catch my eye was this: “...what the postmodernists indirectly accomplished was to open the humanities to the sciences, particularly neuroscience.”

My immediate response: “that is the most ironic thing I've ever heard!! there is no truth [scientific or otherwise] in postmodernism!” Meaning: scientific inquiry was either irrelevant to these theorists, or something to be distrusted, if not disdained. So how could they possibly invite Neuroscience into the Humanities Building?

Let's look at Krystal's extended quote (emphasis mine):
“...By exposing the ideological codes in language, by revealing the secret grammar of architectural narrative and poetic symmetries, and by identifying the biases that frame "disinterested" judgment, postmodern theorists provided a blueprint of how we necessarily think and express ourselves. In their own way, they mirrored the latest developments in neurology, psychology, and evolutionary biology. [Ed. warning: non sequitur ahead.] To put it in the most basic terms: Our preferences, behaviors, tropes, and thoughts—the very stuff of consciousness—are byproducts of the brain’s activity. And once we map the electrochemical impulses that shoot between our neurons, we should be able to understand—well, everything. So every discipline becomes implicitly a neurodiscipline, including ethics, aesthetics, musicology, theology, literature, whatever.”

I'm as reductionist as the next neuroscientist, sure, but Krystal's depiction of the field is either quite the caricature, or incredibly naïve. Ultimately, I can't tell if he's actually in favor of "neurohumanities"...
In other words, there’s a good reason that "neurohumanities" are making headway in the academy. Now that psychoanalytic, Marxist, and literary theory have fallen from grace, neuroscience and evolutionary biology can step up. And what better way for the liberal arts to save themselves than to borrow liberally from science?

...or opposed:
Even more damning are the accusations in Sally Satel and Scott O. Lilienfeld’s Brainwashed: The Seductive Appeal of Mindless Neuroscience , which argues that the insights gathered from neurotechnologies have less to them than meets the eye. The authors seem particularly put out by the real-world applications of neuroscience as doctors, psychologists, and lawyers increasingly rely on its tenuous and unprovable conclusions. Brain scans evidently are "often ambiguous representations of a highly complex system … so seeing one area light up on an MRI in response to a stimulus doesn’t automatically indicate a particular sensation or capture the higher cognitive functions that come from those interactions." 1

Then he links to articles like Adventures in Neurohumanities and Can ‘Neuro Lit Crit’ Save the Humanities? (in a non-critical way) 2  before meandering back down memory lane. They sure don't make novelists like they used to!

So you see, neuroscience hasn't really ruined the humanities.3 Have the humanities ruined neuroscience? Although there has been a disturbing proliferation of neuro- fields, I think we can weather the storm of Jane Austen neuroimaging studies.


1 Although I haven't always seen eye to eye with Satel and Lilienfeld, here Krystal clearly overstates the extent of their dismissal of the entire field (which has happened before).

2 Read Professor of Literary Neuroimaging instead.

3 The author of the Neurocultures Manifesto may disagree, however.

link via @vaughanbell

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Wednesday, November 12, 2014

Public Health Relevance Statements vs. Actual Translational Potential

“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

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Saturday, November 01, 2014

Fright Week: Fear of Mirrors

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


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

2 The 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.

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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’.


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


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.


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.


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.


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.


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.”


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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