Thursday, August 14, 2014

The Neuro Sci-Fi of the Near Future

NEUROTECH LIGHT AND DARK »

Tweet length visions of our DARPA-funded future


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


Here’s a sample of Neurotech Light and Dark, a sci fi collection of 16 very short stories about neuroscience and technology, by S. Kay.
A brain-computer interface controls her robotic arm. As easily as not thinking, she uses it to drink another shot of tequila.

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

Read the rest at Science Creative Quarterly.


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

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Sunday, August 10, 2014

Interview with Dr. Jan Kalbitzer, author of the "Twitter Psychosis" article



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

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

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

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





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

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


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

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


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

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

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

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

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


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

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

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

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

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

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


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

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

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


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

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


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

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

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


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

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

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

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

So overall I'm sorry about this whole ordeal.



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


ADDENDUM (August 11 2014) - This new article at Wired UK has the clearest coverage: Twitter spam may 'aggravate psychosis' in the vulnerable


Footnotes

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

2 Paul Feyerabend was an Austrian philosopher of science who...
...became famous for his purportedly anarchistic view of science and his rejection of the existence of universal methodological rules. He is an influential figure in the philosophy of science, and also in the sociology of scientific knowledge. ... His major works include Against Method (published in 1975).
According to the Stanford Encyclopedia of Philosophy, Feyerabend:
made a name for himself both as an expositor and (later) as a critic of Karl Popper's “critical rationalism”, and went on to become one of the twentieth century's most famous philosophers of science. An imaginative maverick, he became a critic of philosophy of science itself, particularly of “rationalist” attempts to lay down or discover rules of scientific method.

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

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Thursday, July 31, 2014

Twitter Psychosis as a Cultural Artifact

UPDATE (Aug 6 2014): This story has spun entirely out of control, with breathless coverage at The Daily Dot and Jezebel. Today the hapless first author told NBC News: "No, at this point Twitter psychosis is not 'real.'" 

And no, a woman was not committed to psychiatric hospital with ‛Twitter psychosis’! However, the general confusion created by the ensuing media circus might be what the authors were trying to get at...


The original post resumes below.



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

Via Twitter (@DrShock, @vaughanbell), of course, comes news of a one page paper entitled, Twitter Psychosis: A Rare Variation or a Distinct Syndrome? (Kalbitzer et al., 2014):
The authors report the development of psychosis in a young woman coinciding with excessive use of the online communication system Twitter and the results of an experimental account to argue that Twitter may have a high potential to induce psychosis in predisposed users.

The authors presented the case of a 31 year old woman who was hospitalized for intensive suicidal thoughts and compulsions. She had no previous history of psychiatric illness and denied current hallucinations.1 Her friends and family said the symptoms began about 8 months earlier. Approximately 4 months prior to that she started using Twitter “excessively” (defined as “several hours a day reading and writing messages, neglecting her social relationships and, sometimes, even meals and regular sleeping hours”).2 At some point she came to believe that a famous actor was communicating to her personally (a common delusion), and to see hidden symbolic messages in Tweets:
During the next couple of weeks, Mrs. C increasingly felt that the messages of other users were “meant in a symbolic way” and that she had to react to these “tasks” in a certain manner. After approximately 2 months, she started to discover the same symbols in her real-world environment. She then started to feel that there “must be some organization behind these tasks” and started to suspect a sect, pointing to the development of systematized paranoid delusion.

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

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

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


The Ben Goldacre Experiment


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

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

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

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

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

 Vaughan should have the last Tweet here:



Further Reading

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

Twitter as a Cultural Artifact

Tools for Tech Thinking: McLuhan on Twitter


ADDENDUM Aug 6 2014: The authors have commented on this post to clarify that they were being deliberately provocative with their title and approach to the topic, but serious about the possibility that the interactive social media aspects of Twitter might have unique qualities in how it could affect those with (or predisposed to) psychosis. Furthermore, the authors are not inclined to generate a new host of DSM-5 diagnoses; in fact, Heinz and Friedel (2014) stated: "The inclusion of non-substance, behavioral addictions poses the danger of pathologizing a wide range of human behavior in future revisions of the classification."


Footnotes

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

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

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


Reference

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

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Monday, July 21, 2014

The Neurocritic Critiques Critical Neuroscience

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

Could I just submit a blog post like Professor of Literary Neuroimaging that critiqued the entrée of fMRI into Literature Departments?
“So literature is abandoning Marxism and psychoanalysis in favor of neuroimaging!! Meanwhile, key neuroimagers have taken up psychoanalysis (Carhart-Harris & Friston, 2010) and socialism (Tricomi et al., 2010).

Would they accept short humorous pieces like this...

Tenure-Track Position in Neuroetiquette and Gender Theory

Department of Critical Socioneurobiology.

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

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

NDSFSR is an Equal Opportunity Employer.



...accompanied by a [somewhat] more serious meditation on Neuroetiquette and Neuroculture, which explained that neuroscientists are not taking jobs away from philosophers, sociologists and gender theorists:
I think the neuro-panic among social scientists is overblown. How many philosophers, sociologists, and gender theorists are unemployed because their respective departments have decided to hire neuroscientists instead? How many developmental neurobiologists have applied for this Instructor of Philosophy position at Rochester Community and Technical College? Will a cognitive neuroscientst be able to teach transnational feminism or postcolonial feminism, queer theory, and critical race theory in the Women's and Gender Studies Program at Illinois State University?

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

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


But Is Neurocriticism the same as Critical Neuroscience

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

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

As it so happens, a mere two weeks ago, the €1-billion HBP was roundly criticized in an open letter signed by 156 neuroscientists (the list of signatories and supporters is now over 700):
...the HBP has been controversial and divisive within the European neuroscience community from the beginning. Many laboratories refused to join the project when it was first submitted because of its focus on an overly narrow approach, leading to a significant risk that it would fail to meet its goals. Further attrition of members during the ramp-up phase added to this narrowing ....  including the removal of an entire neuroscience subproject and the consequent deletion of 18 additional laboratories...
. . .

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

A flurry of press and blog coverage ensued, followed by a bigwig defense in New Scientist and an official statement [PDF] from the HBP. Although it's clear there are fundamental differences of opinion about a massively optimistic and expensive attempt to model the human brain, organizational issues of power and control are key as well:
The nixed subproject, called Cognitive Architectures and headed by French neuroscientist Stanislas Dehaene, represented all the neuroscience in Europe that isn't working on a molecular or synaptic level, says Zachary Mainen of the Champalimaud Centre for the Unknown in Lisbon, one of the authors of the letter. HBP “is not a democracy, it’s Henry’s game, and you can either be convinced by his arguments or else you can leave,” Mainen says.
link via Neuroecology


You might think that the current HBP dispute has drifted outside the realm of the “Critical Neuroscience” Research Topic.3 But you'd be wrong, because Extending the mind: a review of ethnographies of neuroscience practice (Mahfoud, 2014) appeared online only one month before the brouhaha:
Ethnographic studies of neuroscience knowledge can potentially offer insight into the relationship between the everyday of scientific practice and reasoning on the one hand and the political and moral economy of science on the other, as well as encouraging conversation between the social and biological sciences, as this special issue aims to do. 

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

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

Another article is basically a sociocultural mega-thrashing of the NIMH RDoC framework for mental health research. Worth quoting:
In this article we consider the rationale of the RDoC and what it reveals about implicit models of mental disorders. As an overall framework for understanding mental disorders, RDoC is impoverished and conceptually flawed. These limitations are not accidental but stem from disciplinary commitments and interests that are at odds with the larger concerns of psychiatry. 

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

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


Footnotes

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

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

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

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

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Sunday, July 13, 2014

Scientology Tropes Enter Mainstream Neuroscience?



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

The Five Stages Of Lumosity

Stage I – Initiation

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


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

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

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

Stage V – Full Compliance

The Golden Age of Tech II


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

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

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




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

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

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

Despite this, Scientology started out with a materialist model of the mind before it was derailed (perhaps by founder L. Ron Hubbard's alcohol and drug addiction). As Prof. Touretzky explains:
In 1950 Dianetics presented a purely materialistic view of the mind as a simple computer, with frequent references to "memory banks", "circuits", and data recording. The mind was implemented by the brain, and memory was a product of a cellular recording mechanism. Hubbard did not rule out the possibility that psychic phenomena such as ESP or telepathy might some day be demonstrated, but they played no role in Dianetics.

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

The E-Meter

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

 
Mark Super VII Quantum E-meter (Wikimedia Commons)


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

According the Church of Scientology's own materials, however, the E-meter is used by auditors to locate areas of spiritual distress or travail:
The E-Meter measures the mental state or change of state of a person and thus is of enormous benefit to the auditor in helping the preclear locate areas to be handled. The reactive mind’s hidden nature requires utilization of a device capable of registering its effects – a function the E-Meter does accurately. 
. . .

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

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

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


‘Neural Valence Meter’

I know the authors of a recent Nature Neuroscience paper that used MVPA to classify subjective affective states2 (Chikazoe, Lee, Kriegeskorte, & Anderson, 2014) would be utterly horrified with the analogy, but I thought of the e-meter when I read this quote in a press release:
“It appears that the human brain generates a special code for the entire valence spectrum of pleasant-to-unpleasant, good-to-bad feelings, which can be read like a ‘neural valence meter’ in which the leaning of a population of neurons in one direction equals positive feeling and the leaning in the other direction equals negative feeling,” Anderson explains.

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



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


Footnotes

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

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


Reference

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

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Thursday, July 10, 2014

Can a Failed Schizophrenia Drug Prevent PTSD?



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

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

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

How well have they fared since then?

(1) The NK3 antagonist osanetant was under development by Sanofi-Synthélabo as a potential treatment for schizophrenia:
In October 1999, Lehman Brothers predicted that the probability of the product reaching the market was 10%, with a possible launch in 2003 and potential peak sales of US $200 million in 2011.
However, Sanofi-Aventis stopped any further development of osanetant in 2005.


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

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


“Repurposing” of Drugs

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

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

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

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

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

NkB and the Consolidation of Fear Memories 

A new study in mice found that osanetant could block the consolidation of fear memories when administered within a narrow time window (Andero et al., 2014):
Notably, when osanetant is dosed from 30 min before auditory FC [fear conditioning] up to 1 hr after training, it does not affect fear acquisition but impairs fear memory consolidation as shown by decreased freezing in the fear expression test. 

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


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


The starting point of this study, however, was not to test the effects of osanetant on the formation of fear memories. Rather, Andero et al. (2014) began by casting a wide net in search of genes that are regulated during fear conditioning. They found that the Tac2 gene (TACR3 gene in humans) is regulated during fear memory consolidation, specifically in the central nucleus of the amygdala (a “fear learning central” of sorts).
Furthermore, increased expression of the Tac2 gene, NkB peptide, and activation of Nk3R may be involved in stress sensitization and overconsolidation of fear. In contrast, genetic silencing of Tac2-expressing neurons impairs fear consolidation. Blockade of this pathway may provide for a novel therapeutic approach for disorders with altered fear learning such as PTSD.

The clinical potential of this finding is not lost on the authors. If given shortly after a traumatic event (e.g., in an emergency room or combat situation), it's possible that osanetant could reduce the emotional potency of trauma memories:
Finally, one of the most interesting aspects of our data is the potential use of the Nk3R antagonist osanetant as a pharmacological agent to block fear memory consolidation shortly after exposure to a trauma. Additionally, we found that osanetant prevented the upregulation of the Adcyap1r1 gene, which encodes the PAC1 receptor. The PACAP-PAC1R pathway is involved in PTSD, fear conditioning, amygdala excitatory neurotransmission, and stress. All this could be relevant in PTSD prevention since it has previously been found that osanetant is safe in humans, although additional preclinical studies, such as those described herein, are needed first to establish the mechanisms involved. This gives our findings an exciting potential approach to translation to human patients.

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

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


References

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

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

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

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





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Sunday, June 22, 2014

Welcome to Douglas Coupland's Brain



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

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


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


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

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


100 identical Lego houses


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

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


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


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


These questions were quite salient for me because I attended another exhibition at the same gallery in 2010, called Waste Not (by artist Song Dong). This one examined hoarding overtly in the context of culture, scarcity, and loss:
Waste Not—or wu jin qi gong in Chinese—describes the philosophy of life for a generation of people in China, of which Song Dong’s mother was a part, who grew up during the Cultural Revolution with the experience of displacement, poverty and the constant shortage of goods. The installation stands as a record of his mother’s life, as well as a tribute to his father’s death.

After the artist's father died, his mother's compulsive hoarding intensified, which is not uncommon. Over 10,000 objects were on display. The exhibit was quite moving and sad:
...Carefully sorted, arranged, and displayed in the gallery, along with the wooden frame of one of the rooms of her house, these objects include everything from cracked wash basins, chipped tea cups, old radiators, and burnt-out light bulbs to flattened toothpaste tubes, yellowing newspapers, ripped nylon stockings, and empty containers of every description. And all in startling multiples.

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


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




Highways and byways of The Brain.


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




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

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

Note the aqua-colored Stroop banana.


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




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

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

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

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


Footnote

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



Coupland wall

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

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