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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Sunday, September 07, 2014

A Dangerous New Dish


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)


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





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.






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.

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Sunday, August 31, 2014

Whitman Was Not a Neuroscientist


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.




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

1 Do 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

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