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Date: Monday, 21 Apr 2014 08:03

Dr. Suzanne Corkin on H.M.

One of the highlights of this year's Cognitive Neuroscience Society Meeting was Dr. Corkin's keynote address about Henry Molaison the person and his lasting contribution to the neurobiology of memory. In her more timely recap of the meeting, Daisy Yuhas included this moving quote from H.M., who could not remember meeting Corkin even after decades of testing:
Corkin also discussed the man behind the initials, describing his gentle and remarkably upbeat disposition, given that he was repeatedly confronting a confusing, context-free present. Her talk included a poignant and powerful audio recording of Corkin and H.M. chatting in 1992. In the excerpt, H.M. professes to “not mind” all of the tests and studies, saying simply, “I figure what’s wrong about me helps you help others.”

Henry Molaison died on December 6, 2008. Corkin described the post-mortem handling of H.M.'s brain, which was first scanned before autopsy. Then the brain was removed and preserved in formaldehyde for 10 weeks, and later scanned in a 7T magnet (see Annese et al., 2014 for details).1

H.M.'s brain flew Jet Blue

H.M.'s brain was transported across the country, where it underwent lengthy processing prior to sectioning into 2,401 slices on a heavy duty frozen microtome (Annese et al., 2014).2 This event was webcast live at the Brain Observatory, which she said was “like watching paint dry.”  I beg to differ.  I thought the live coverage was like the Stanley Cup of Neuroscience, as mesmerizing as watching the Zamboni clean the ice at a hockey game.

At the time, I noted that “H.M.'s ventricles are quite enlarged. Then again, he was 82 when he died (so that's not unexpected).”

H.M. was, in fact, demented when he died. His cerebellum was severely atrophied after years on the anticonvulsant drug Dilantin. Cerebellar dysfunction on its own can be associated with explicit memory deficits (Baillieux et al., 2008). And finally, his amygdalae were gone bilaterally (Annese et al., 2014): 
The excision of the anterior hippocampus, together with the bulk of the amygdala, may explain H.M.’s dampened expression of emotions, poor motivation and lack of initiative19. The fact that he was impaired in reporting internal states such as pain, hunger and thirst and his apparent lack of initiative was ascribed to the almost complete removal of the amygdala...

Dr. Corkin has long said that “H.M.'s amnesia was pure.” But these additional issues, along with some reports that his language production and visual cognition were not entirely normal, raise questions about his status as the definitive hippocampal amnesic. Nonetheless, there's no denying the immense importance of what H.M. so generously taught us about memory. “It’s a funny thing,” he said, “you live and learn. I’m living and you’re learning.”


1 H.M's brain was...
...fixed in standard buffered formalin (4% formaldehyde; postmortem interval of ∼14 h). The brain was fixed for 10 weeks at 4 °C with three changes of fixative during that time; it was suspended upside down, hung by the basilar artery. When the tissue was firm enough, the brain was immersed in fixative laying on a cushion of hydrophilic cotton. Subsequently, multiple series of MRI scans of the fixed specimen were acquired in 3T and 7T scanners.

2 Annese et al., 2014:
The results of our examination are based on 2,401 digital anatomical images and selected corresponding histological sections that were collected at an interval of 70 μm over the course of an uninterrupted 53-hour procedure. The series of digital images of the block’s surface was obtained using a digital camera mounted directly above the microtome stage. Volumetric reconstruction from these images was the basis for subsequent visualization and 3D measurements along arbitrary planes. The dissection of the brain was video-recorded and streamed live on the web to permit scientific scrutiny and to foster public engagement in the study.
Author: "noreply@blogger.com (The Neurocritic)"
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Date: Friday, 18 Apr 2014 05:07

My, that title sure is a mouthful, isn’t it? That's because in the span of a few short days, we’ve seen the following:

(1) An invited review in Neuron on the role of blogs, Twitter, Facebook, and online forums such as PubPeer, PubMed Commons, and journal comments in shaping discussions about published research papers.

(2) A commentary in PNAS about the sad structural state of biomedical research in the U.S. and  suggestions for change.

(3) A MAJOR revision in how NIH (National Institutes of Health) reviews research grants.

These communiques intersect because of how rapidly we can discuss them, who is allowed to comment, and where the debate takes place. Let me take these in turn.

The Vacuum Shouts Back: Postpublication Peer Review on Social Media

(1) An invited review in Neuron covered the role of blogs, Twitter, Facebook, and online forums such as PubPeer, PubMed Commons, and journal comments (like at PLOS ONE) in shaping discussions about published research papers (by Dr. Zen Faulkes):
Postpublication peer review through traditional scientific publishing is like kabuki theater: a slow, rehearsed drama in which the viewer must recognize the subtle profundities of performers wearing deliberately ambiguous masks.

Postpublication peer review on social media is like the mosh pit at a punk rock show. It’s fast, uncoordinated, a lot less subtle, more in your face, and involves a few more risks.

I thank Dr. Faulkes (“Dr. Zen”) for mentioning this blog and its cousin, The Neurocomplimenter.  I started the latter in response to overt dismissals of neuroscience as providing anything useful to our understanding of human cognition (and to emphasize the importance of studying brain function, more broadly). I see it as “a new project designed to counter gratuitous anti-neuroscience sentiment. It’s part of my campaign to combat pop neurobashing profiteers.”

Lately, the compliments have been sparse (perhaps due to my pessimistic nature) but I will try to highlight the positives anon. Meanwhile, the critical element soldiers on. Dr. Zen nailed my reason for starting an anonymous blog right on the head: professional peer review is anonymous, so why should bloggers identify themselves? Many do, of course, and some researchers sign their reviews.
Regardless, there are strong traditions for using both anonymity and pseudonyms in science (Neuroskeptic, 2013), not the least of which is journal peer review itself. It is a little audacious for authors and editors to decry the negative effects of “anonymous bloggers” when essentially every journal practices anonymous peer review. Bloggers are often easier to identify than journal reviewers. We still don’t know who reviewed Wolfe-Simon et al. (2011)) for Science. But we know Rosie Redfield critiqued it on her blog (http://rrresearch.fieldofscience.com/2010/12/arsenic-associated-bacteria-nasas.html), which ultimately led to a paper that failed to replicate key claims of the original paper (Reaves et al., 2012).

The voodoo correlations neuroimaging brouhaha is another major example of post-publication peer review (that went a little pre-publication due to a preprint going public), much to the dismay of the journal editor and some of the implicated researchers (see The Voodoo of Peer Review).

Dr. Zen also made the important distinction between completely anonymous commenters and those who identify as a pseudonym, a point that I often fail to make, e.g. Anonymous Peer Review Means Never Having to Say You're Sorry: “The Neurocritic is happy to provide a new form of anonymous peer review, free of charge.”

Rescuing US biomedical research from its systemic flaws

(2) A commentary in PNAS relayed the sad structural state of biomedical research in the U.S. and made [some unrealistic, some potentially helpful] suggestions for change (by four distinguished scientists in positions of power):
There is a no more worrisome consequence of the hypercompetitive culture of biomedical science than the pall it is casting on early careers of graduate students, postdoctoral fellows, and young investigators.

The commentary discusses the unsustainable growth of the biomedical research enterprise and the overly competitive yet conservative culture it has spawned. This win-at-all costs mentality squelches creativity and collaboration, and concentrates resources in the hands of fewer and fewer investigators. The average age for landing one’s first tenure-track position has risen to 37. And some estimates project that fewer than 8% of new PhDs will get tenure, with the figure an abysmal 0.45% according to one report.

The “post-doc apocalypse”1 has been widely discussed on social media (and in the popular press) for some time now. Potential solutions have been expressed by researchers at all levels, but these voices have been scattered. Those of us who are not in certain informal social circles may overlook a site of discussion somewhere, but who has time to search for it.

On the other hand, specific responses to the Alberts et al. PNAS article have already appeared on PubPeer (which allows anonymity) and PubMed Commons (which does not). Professor Dorothy Bishop made some trenchant points on the three major solutions proposed by the authors. You can read these at PubMed Commons and click on links to blog posts, where she expands on the topics of academic workload, grant review, and evaluation.

Here's my worthless $0.02 on the matter, from a position of no power and no influence: I agree with Prof. Bishop that the “Predictable and Stable Funding of Science” solution is a pipe dream...
We encourage Congressional appropriators and the executive branch to consider adding a 5-y projected fiscal plan to the current budgetary process. This plan would be updated each year, at the same time that annual appropriation bills are written.

Ha ha ha ha ha! Have they forgotten the Great Budget Sequestration of 2013 already? Getting the political parties to agree (or factions within parties) seems impossible to me. Even if all four authors win plum positions in Congress or the White House, good luck with that.

Perhaps more plausible are recommendations for downsizing the future workforce to reduce the glut of under- and unemployed junior scientists. However, they have to persuade graduate programs to admit fewer students and ban principal investigators from funding students through research grants (rather than through training grants). Some funding sources/agencies already forbid PIs from paying student stipends, and Alberts et al. propose that NIH should move towards this model.

They also suggest “Broadening the career paths for young scientists” so they're not looked down upon as failures if they don't become a clone of their advisor at MIT. This would also require changing the minds of Bob Graybeards everywhere. Good luck with that.

Another modest proposal is to force universities to pay their faculty. Here, however, they have to convince Chancellors and Deans of medical schools to forgo the “perverse incentives” of “soft money” positions, where the institution benefits from the indirect costs awarded to the university in conjunction with salary money paid by NIH. This would do away with a whole army of productive researchers. What a great idea.

Perhaps these unemployed “soft money” faculty could apply for the proposed Staff Scientist positions, displacing all the post-docs who are supposed to be in line for them. What a great idea. Good luck with that.

To be fair, let's see if the proposed Staff Scientist position might be a good idea. Post-post-docs could move into higher paying jobs that would better prepare them to run their own labs. This is because they will actually run their supervisor's lab, at much lower pay and with no prestige:
We believe that staff scientists can and should play increasingly important roles in the biomedical workforce. Within individual laboratories, they can oversee the day-to-day work of the laboratory, taking on some of the administrative burdens that now tend to fall on the shoulders of the laboratory head; orient and train new members of the laboratory; manage large equipment and common facilities; and perform scientific projects independently or in collaboration with other members of the group. Within institutions, they can serve as leaders and technical experts in core laboratories serving multiple investigators and even multiple institutions.

Or here's an idea: there could actually be a place in the system for individuals who may not want to run their own lab! These people could conduct their own independent research and help with the grant application process, if so inclined. We'd call them Staff Scientists. We'd hire different people to take on the administrative burdens and call them Lab Managers. Still others could be hired as “technical experts in core laboratories serving multiple investigators and even multiple institutions.” We'd call them Technical Experts.

But this would be prohibitively expensive. Back to cheap graduate student labor...

The most important point is that I can lobby all I want for the Snarky Policy Consultant position, since this is my blog.

NIH and AHRQ Announce Updated Policy for Application Submission

(3) A MAJOR, MAJOR revision in how the NIH reviews research grants was released today (April 17, 2014). At first I thought it was an April Fool's joke (and that I must have been dreaming for the last 16 days, which would explain a lot of things).
Effective immediately … following an unsuccessful resubmission (A1) application, applicants may submit the same idea as a new (A0) application for the next appropriate due date. The NIH and AHRQ will not assess the similarity of the science in the new (A0) application to any previously reviewed submission when accepting an application for review.

In essence, this does away with the “two strikes” rule – which meant that rejected proposals were barred from being submitted again sans a complete overhaul.

Within minutes of this announcement, Drug Monkey had 159 tweets and a blog post on this new policy, which would allow investigators to submit multiple revisions of basically the same grant (hence the R01 A7, a grant funded on the eighth try). But it wouldn't really be considered the same grant, so the numbers only go up to A1 (one amendment), thereby avoiding the stigma of A7. Thank you, NIH, that's very considerate.

And here we are again on social media, providing immediate feedback and discussion of important issues that impact the biomedical research enterprise. Can I get a full-time job doing that? We'd call it Blogger-in-Residence.


1 I refuse to use the neologism because of what Google will turn up. And this is nothing new; it's been brewing since the early 90s: “From the early 1990s, every labor economist who has studied the pipeline for the biomedical workforce has proclaimed it to be broken.”
Author: "noreply@blogger.com (The Neurocritic)"
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Date: Saturday, 12 Apr 2014 03:04

Another CNS meeting, another series of delayed blog posts from The Neurocritic. Long in the vanguard of the slow blogging movement, these conference recaps have attained the cult status of unplanned obsolescence.

Without further ado, let's begin our walk down memory lane...

The 21st Annual Cognitive Neuroscience Society Meeting was held in Boston from April 48, 2014. We'll kick off our recapping festivities with a contest of "Name that Soundbyte!" from an invited symposium on how developmental cognitive neuroscience can (and cannot) inform policy.

Invited Symposium Session 1
Sunday, April 6 3:00 - 5:00 pm, Grand Ballroom Salon A-F

The Broader Applicability of Insights from Developmental Cognitive Neuroscience

Chair: Silvia Bunge, UC Berkeley
Speakers: John D. E. Gabrieli, Margaret Sheridan, Martha J. Farah, Helen J. Neville

The burgeoning field of developmental cognitive neuroscience is yielding important insights into how the human brain develops and changes with experience. These findings are proving to be of great interest not only to other scientists, but also to practitioners and policymakers from various corners of society. What have we learned so far that warrants consideration by those in a position to shape policy and practice in education, healthcare, or the judicial system? In this symposium, leading cognitive neuroscientists will discuss the potential applications of their research.

Given the list of symposium speakers, can you name who said each of these quotes? [or close paraphrases?]  Be sure to chime in by leaving your best guesses in the comments.

(1) “I am not a neurochauvinist”

(2) “U.S. Prison Experiment”

(3) “evidence-based politics”

(4) “IMHO still premature to dictate policy based on neuro”

(5) “Here's where going ‘neuro’ earns its keep”

(6) ‘descriptive’ often considered derogatory in science

Author: "noreply@blogger.com (The Neurocritic)"
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Date: Sunday, 30 Mar 2014 22:46

NCAA college basketball isn't the only hot competition involving a team from the University of Virginia.  UVa Psychology Professor Brian Nosek is one of three founders of Project Implicit, a collaborative nonprofit dedicated to the study of implicit social cognition — how unconscious thoughts and feelings can influence attitudes and behavior.

Prof Nosek is also heavily involved in the Open Science and Replication movements. Along with graduate student Calvin Lai, he led a multinational group of 22 other researchers in a competition to see who could devise the best intervention to reduce racial bias scores on a widely administered implicit test, the race IAT (Lai et al, 2014).

The Implicit Association Test (IAT) is a mainstay of social psychology research that assesses implicit (unconscious) attitudes towards outgroups (based on race, sexual orientation, body size, age, etc.), stereotypes (e.g., men are in science, women are in arts/humanities), opposing ideologies (e.g, Democrat vs. Republican), and a staggering array of other binary preferences (Classical-Hip hop IAT, Astrology-Science, Britney Spears-50 cent, Boxers-Briefs, Harry Potter-Lord of the Rings and on and on). 

Or does it... ? There have been some vocal critics of the IAT over the years who have questioned what the test actually measures. I'll return to this point later, but for now let's look at the impressive aspects of the new paper.

Performance on the Black-White IAT was compared after 17 brief interventions aimed at changing pro-White bias (and a "faking" condition) relative to a control condition of no pre-test intervention. Participants were over 20,000 non-Black individuals registered at the Project Implicit website, randomized into groups of 300-400. Most of the interventions were tested in four different studies. The contest rules allowed changes to the design between studies. The goal was to lower pro-White bias scores to the point of no preference between Blacks and Whites.

In the IAT, participants classify faces as Black or White and words as good or bad. Some blocks contain only faces or only words. The two critical conditions are shown in the figure above. The stimulus-response mappings are rotated in different blocks to either reinforce stereotypes (bottom) or go against stereotype (top). In the Stereotype condition, participants press the same key when they see White faces or “good” words. They press the other key when they see Black faces or “bad” words. Most White participants (and many African Americans) show a pro-White “preference” or bias, with faster responses when White/good and Black/bad are mapped to the same key (than vice versa).

Conversely, in the Against Stereotype condition, Black faces and positive words are mapped to one key, and White faces and negative words are mapped to the other key. In essence, this induces a response conflict similar to that seen in many classic cognitive psychology tasks such as the color-word Stroop task, e.g. BLUE (say “red”) and the Eriksen flanker task, e.g. ← ← → ← ← (press right button). Slower response times in the IAT conflict conditions has been interpreted as an implicit bias against Black people (Greenwald et al., 2009), although one could argue that executive control abilities play a role here, just as they do in the Stroop task (Siegel et al, 2012).1

The Interventions

The interventions were divided into six different descriptive categories. Although the descriptions were based on existing hypotheses in the literature, they do not imply the operation of any specific psychological mechanism. The interventions had to be brief in length (5 min or less), yield interpretable scores, and have a low attrition rate. See Appendix 1 at the end of this post for a detailed list.

(1) Engage with others’ perspectives: imagine the thoughts, feelings, and actions of Black individuals (Interventions #1–3).

(2) Exposure to counterstereotypical exemplars: assigned to fictional groups with positive Black ingroup members and/or negative White outgroup members; OR think about famous Black people and infamous White people (Interventions #4–8).

(3) Appeals to egalitarian values: activate egalitarian goals (e.g., thinking about failures to be objective or egalitarian); OR think about multicultural values (Interventions #9–13).

(4) Evaluative conditioning: strengthen counterstereotypical associations by pairing White faces with Bad words and Black faces with Good words (Interventions #14 and #15).

(5) Inducing emotion: the positive emotion of elevation (Intervention #16).

(6) Intentional strategies to overcome biases: provide strategies to override or suppress the influence of automatic biases, rather than trying to shift associations directly (Interventions #17 and #18).

To reveal my own a priori biases regarding these descriptive categories, I favor (6) Intentional strategies to overcome biases, which I have written about previously (in 2008). These were interventions #17 Using Implementation Intentions, and #18 Faking the IAT as proposed by Calvin K. Lai, the first author of the manuscript.

Results indicated that nine of the interventions were effective, and nine were ineffective. The interventions that tried to change attitudes (Appeals to egalitarian values), increase empathy or perspective-taking (Engage with others’ perspectives), or elicit an elevated sense of morality (Inducing emotion - Haidt) were completely ineffective.

I note here that the failed interventions all tried to challenge the racially biased attitudes and prejudice purportedly measured by the IAT. These interventions are below the red line in the figure below.

- click on image for a larger view -

Figure 1 (modified from Lai et al, 2014). Effectiveness of interventions on implicit racial preferences, organized from most effective to least effective. Cohen’s d = reduction in implicit preferences relative to control; White circles = the meta-analytic mean effect size; Black circles = individual study effect sizes; Lines = 95% confidence intervals around meta-analytic mean effect sizes. IAT = Implict Association Test; GNAT = go/no-go association task.

Some of the most effective interventions showed variability across studies, because the parameters were altered between studies (which was allowed). Importantly, some of the interventions included multiple manipulations. The top three, Vivid Counterstereotypic Scenario, Practicing an IAT With Counterstereotypical Exemplars, and Shifting Group Boundaries Through Competition all employed Implementation Intentions in addition to the primary intervention.

What are Implementation Intentions? [in brief, think “Black = good”]
The mechanism connects an environmental cue with the goal intention, making associations between the behavior and the cue more accessible in memory. ... The task gave participants a short tutorial on how to take the IAT and informed them about the tendency for people to exhibit an implicit preference for Whites compared with Blacks. Participants were then asked to commit themselves to an implementation intention by saying to themselves silently, “I definitely want to respond to the Black face by thinking ‘good.’” 

On its own, this manipulation was effective in reducing bias scores (p = .032, d = .19). The effect size was enhanced by allowing participants to practice the task before the instructions were given (p = .00037, d = .32). In other words, once subjects were even superficially familiar with the task, being told to think “Black = good” significantly reduced pro-white sentiment (i.e., IAT scores).

This intervention is remarkably similar to my previous anecdotal findings (n=1) for the Human or Alien? test and the Dead or Alive? test. My 2008 results are below. I showed similar effects for the Black-White test and the Women in Science test, but I couldn't find the results for those.

The Neurocritic is Human AND Alien. Coming soon: “Tips for Manipulating the IAT.”

You have completed the study.
Your Result

Your data suggest little to no automatic identification with Human compared to Alien.

If your results, provided above, indicate a stronger identity with alien relative to human, then you are probably an alien.

The Neurocritic is NEITHER Dead NOR Alive. Or both Dead AND Alive. Plus, as promised, today we'll cover “Tips for Manipulating the IAT.”

You have completed the study.
Your Result

Your data suggest little to no automatic identification with Alive compared to Dead.

Your results, summarized above, are an implicit indicator of whether you are alive or dead. Implicit measures are superior to self-report because the latter is notoriously unreliable. People may report being alive because social pressures suggest that it is more desirable to be alive. Also, people may not have introspective access to their animate-status, making such self-report untrustworthy.

Super Secret Tip for Manipulating the IAT
My “faking” strategy was simple, and relied on neither deliberate slowing of response times nor a long-standing affiliation with aliens. When SELF and ALIEN were mapped to the same key, I merely said to myself, “I'm an alien.” This strategy was transient, applied only when those stimulus-response mappings were the same, not when SELF and ALIEN were mapped to different keys. I used the same strategy for the Dead or Alive IAT. In both cases, I responded as quickly and as accurately as possible.

Here, what I'm calling “faking” is the Using Implementation Intentions instructions (and not the Faking the IAT intervention of Lai et al, 2014). Again, the top three contest winners combined this strategic feature with another manipulation, as noted by the authors:
The three most effective interventions appear to leverage multiple mechanisms to increase their impact on implicit preferences...  The most effective intervention, Vivid Counterstereotypic Scenario, involved the participant as the subject of the story, had the participant imagine his- or herself under a highly threatening life-or-death situation, exposed participants to counterstereotypical exemplars (malevolent White villain, dashing Black hero), and provided strategies to overcome bias (goal intentions to associate good with Black and bad with White) to reduce implicit preferences.

This vivid intervention is illustrated by using a TV example in Appendix 2. [Note: participants in the actual experiment read a story; they did not watch an episode of Criminal Minds.] The strategy was receiving the instruction that “the task following the story (i.e., the race IAT) was supposed to affirm the associations: White = Bad, Black = Good.”

The conclusion I draw from this impressive project is that performance on the IAT is subject to strategic control, supporting the notion that the IAT is not a pure measure of implicit attitudes. Even a brief training session is sufficient to reduce (or reverse) stereotypical preferences and associations that are supposed to be unconscious in nature (also see Hu et al., 2012; Siegel et al, 2012).

Further Reading

Open Science Framework entry on Reducing Implicit Racial Preferences: I. A Comparative Investigation of 17 Interventions

Project Implicit

"The Disturbing World of Implicit Bias..."

Human or Alien?

Human, All Too Human (AND Alien)

I'm Alive I'm Dead

Lie To Me on the Autobiographical Implicit Association Test

The Lovely Dr. ARINA K. BONES, PhD Strikes Again!


1 Another common paradigm in cognitive psychology, semantic priming, can explain a goodly portion of the effect as well. In one study, the bias shown in IAT scores was based on statistical co-occurrence of words and concepts in the ambient culture and not on prejudiced attitudes. A discussion of those findings is beyond the scope of this post.


Greenwald AG, Poehlman TA, Uhlmann EL, Banaji MR. (2009). Understanding and using the Implicit Association Test: III. Meta-analysis of predictive validity. J Pers Soc Psychol. 97:17-41.

Hu X, Rosenfeld JP, Bodenhausen GV. (2012). Combating automatic autobiographical associations: the effect of instruction and training in strategically concealing information in the autobiographical implicit association test. Psychol Sci. 23:1079-85.

Lai CK, Marini M, Lehr SA, Cerruti C, Shin JE, Joy-Gaba JA, Ho AK, Teachman BA, Wojcik SP, Koleva SP, Frazier RS, Heiphetz L, Chen EE, Turner RN, Haidt J, Kesebir S, Hawkins CB, Schaefer HS, Rubichi S, Sartori G, Dial CM, Sriram N, Banaji MR, & Nosek BA (2014). Reducing Implicit Racial Preferences: I. A Comparative Investigation of 17 Interventions. Journal of Experimental Psychology. General PMID: 24661055

Siegel EF, Dougherty MR, Huber DE (2012). Manipulating the role of cognitive control while taking the implicit association test. Journal of Experimental Social Psychology 48: 1057–1068.

Appendix 1

(1) Engaging with others’ perspectives
  • Training Empathic Responding
  • Perspective Taking
  • Imagining Interracial Contact 

(2) Exposure to counterstereotypical exemplars
  • Vivid Counterstereotypic Scenario
  • Practicing an IAT With Counterstereotypical Exemplars
  • Shifting Group Boundaries Through Competition
  • Shifting Group Affiliations Under Threat
  • Highlighting the Value of a Subgroup in Competition

(3) Appeals to egalitarian values
  • Priming Feelings of Nonobjectivity
  • Considering Racial Injustice
  • Instilling a Sense of Common Humanity
  • Priming an Egalitarian Mindset
  • Priming Multiculturalism

(4) Evaluative conditioning
  • Evaluative Conditioning
  • Evaluative Conditioning With the GNAT

(5) Inducing emotion
  • Inducing Moral Elevation

(6) Intentional strategies to overcome biases
  • Using Implementation Intentions
  • Faking the IAT

Appendix 2 - Vivid Counterstereotypic Scenario
...participants read an evocative story told in second-person narrative in which a White man assaults the participant and a Black man rescues the participant ( “With sadistic pleasure, he beats you again and again. First to the body, then to the head. You fight to keep your eyes open and your hands up. The last things you remember are the faint smells of alcohol and chewing tobacco and his wicked grin”).

In the therapist's office.

Escaped and running down the hallway.

Stalked by evil white sadist.

Caught and choked by evil white sadist.

FBI Profiler Derek Morgan to the rescue.

Perp in custody at the station.

The end.
Author: "noreply@blogger.com (The Neurocritic)"
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Date: Monday, 24 Mar 2014 04:00

In 1987, over 100 Canadians became ill after eating cultivated mussels from Prince Edward Island. Symptoms included the typical gastrointestinal issues, but serious neurological findings such as disorientation, confusion, and memory loss were also observed (Perl et al., 1990). In the worst cases, the patients developed seizures or went into coma. Three elderly people died. The cognitive changes were persistent, and had not resolved within a two year follow-up.

The toxin was identified as domoic acid, which received the well-deserved moniker of Amnesiac Shellfish Poison. Domoic acid is a potent excitatory amino acid that activates kainate and AMPA receptors, the binding sites for the ubiquitous excitatory neurotransmitter glutamate. It acts as an excitotoxin by overstimulating these receptors, causing a flood of calcium ions into the cells. Particularly vulnerable are neurons in medial temporal lobe structures such as the amygdala and the hippocampus, which is critical for memory.

Postmortem examination of four brains revealed hippocampal pathology that could account for the clinically significant anterograde amnesia seen in other (still living) patients (Teitelbaum et al., 1990). The pattern of neuronal loss was consistent with the damage observed in kainic acid animal models of epilepsy.

Fig. 3 (modified from Teitelbaum et al., 1990).  Panel A: Section of hippocampus from a patient who died 24 days after mussel-induced intoxication, showing severe loss of neurons in all fields except CA2 (arrow), and tissue collapse is evident in part of field CA1 (double arrow).  Panel B: Control Subject.

What was the source of the Amnesiac Shellfish Poison that had accumulated in the mussels?  A "red tide" of phytoplankton created a harmful algal bloom that produced domoic acid, which accumulates not only in shellfish but also in fish such as anchovies and sardines.
This is where the California sea lions make their noisy entrance...

click here to play mp3

Bonus! Live Sea Lion Web Cam at Pier 39 in San Francisco.

Domoic Acid Toxicity in California Sea Lions

The Marine Mammal Center in Sausalito, California rescues and rehabilitates sick, stranded, and malnourished marine mammals, including seals, sea lions, and cetaceans. An up-to-date list of their current patients is available here. They are the premiere institution for the diagnosis, treatment, and scientific study of domoic acid toxicity in California sea lions:
The Marine Mammal Center was the first group to definitively diagnose DA posioning in marine mammals because of a large outbreak in California sea lions in 1998. In September 2004, the Center received a grant from the Oceans and Human Health Initiative to study the long term effects of domoic acid in sea lions. This project studied the impact of DA on health, survival, and reproduction. Part of this project focused on the neurological effects of DA. Effects were evaluated using magnetic resonance imaging (MRI), cognitive behavior tests (how the animal behaves), and histopathology (tissue samples from dead animals).

Their website on the topic is highly recommended, and contains links to published papers such as Magnetic resonance imaging quality and volumes of brain structures from live and postmortem imaging of California sea lions with clinical signs of domoic acid toxicosis [PDF].

Most recently, a team of researchers from Stanford University collaborated with the Marine Mammal Center to conduct a detailed neuropathological investigation of the brains of sea lions who suffered from seizures due to domoic acid toxicity (Buckmaster et al., 2014). Unfortunately, this is not an uncommon occurrence, since the current census of pinniped patients includes five sea lions diagnosed with acute domoic acid toxicity. In the chronic state, the animals can experience recurrent seizures, leading to a failure to thrive and poor prognosis. The authors hypothesize that the animals develop temporal lobe epilepsy, which can serve as an unfortunate accidental model of temporal lobe epilepsy in humans.

The researchers examined the brains of 14 domoic acid-exposed (DA) animals and 9 control animals. Five of the affected sea lions were admitted in status epilepticus, a state of continual seizure that can cause severe brain damage and even death. The study expanded on earlier work by using stereological methods to obtain an unbiased estimate of the total number of neurons in each hippocampus (left and right hemispheres).

In control sea lions, Buckmaster and colleagues (2014) estimated that each hippocampus contains over 6 million neurons! For the comparative hippocampal anatomy aficionados, sea lions had a relatively small proportion of neurons in the dentate gyrus granule cell layer relative to other mammals (i.e., macaque monkeys, squirrel monkeys, dogs, rats, and mice), and the granule cell layer was thinner than in other species.

Importantly, the authors observed significant neuronal loss in the DA-exposed animals, with substantial variation across the hippocampal subfields (see Fig. 3). And interestingly, the damage was unilateral in most cases: the left hippocampus in four, the right hippocampus in seven, and bilaterally in only three.

Fig. 1 (modified from Buckmaster et al., 2014). Nissl-stained cell bodies in the hippocampi from (A) control and (B-D) chronic domoic acid sea lions. Note the increasing levels of neuron loss in the three chronic DA cases. All were admitted in status epilepticus with DA toxicity. In (A), lines indicate border between the hilus (h) and CA3 field. g, granule cell.

In addition, the authors compared the pattern of neuronal loss in sea lions to that observed in human patients with temporal lobe epilepsy, using tissue obtained at autopsy or after temporal lobe resection (for seizure control):
Substantial neuron loss was evident in all hippocampal subfields of patients with temporal lobe epilepsy and chronic DA sea lions compared with controls (Fig. 3B). In sea lions neuron loss was more severe in the hilus, CA3, and CA2 subfields compared with humans. In humans neuron loss was more severe in CA1. Sea lions and humans displayed similar levels of granule cell loss.

Fig. 3 (modified from Buckmaster et al., 2014). Neuron loss in hippocampal subregions. (B) Neurons per affected hippocampus for chronic DA sea lions (mean + SEM) and neuron densities reported in 11 previously published studies for patients with temporal lobe epilepsy. Symbols indicate results from individual studies. Bars indicate averages.

As we saw in the earlier cases of Amnesiac Shellfish Poisoning in Canada, the CA1 region of the hippocampus was especially vulnerable, and this is also true in cases of hypoxia or anoxia. However, it's notable that significant neuron loss was observed throughout the hippocampus.

Why the difference from sea lion CA1? The reasons are unclear. Nonetheless, when examining the brain as a whole, it is remarkable that the hippocampus shows such qualitatively similar pathology in sea lions and humans poisoned by domoic acid, and humans with temporal lobe epilepsy. The authors speculate that the misfortune of chronic DA sea lions may yield an opportunity to test new anti-seizure treatments, for the benefit of both marine and terrestrial mammals.


Buckmaster, P., Wen, X., Toyoda, I., Gulland, F., & Van Bonn, W. (2014). Hippocampal neuropathology of domoic acid-induced epilepsy in California sea lions. Journal of Comparative Neurology, 522 (7), 1691-1706 DOI: 10.1002/cne.23509

Perl, T., Bédard, L., Kosatsky, T., Hockin, J., Todd, E., & Remis, R. (1990). An Outbreak of Toxic Encephalopathy Caused by Eating Mussels Contaminated with Domoic Acid. New England Journal of Medicine, 322 (25), 1775-1780 DOI: 10.1056/NEJM199006213222504

Teitelbaum, J., Zatorre, R., Carpenter, S., Gendron, D., Evans, A., Gjedde, A., & Cashman, N. (1990). Neurologic Sequelae of Domoic Acid Intoxication Due to the Ingestion of Contaminated Mussels. New England Journal of Medicine, 322 (25), 1781-1787 DOI: 10.1056/NEJM199006213222505
Author: "noreply@blogger.com (The Neurocritic)"
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Date: Saturday, 15 Mar 2014 05:42
Everyone knows the hazards of bringing metal objects into the MRI scanner room (right?). Now we have a lovely musical reminder of why this is such a bad idea...

In the Scanner is an entry in the Brains on Film contest, a Brain Awareness Week event sponsored by the UCL Institute of Cognitive Neuroscience. The film was made by Sophie Meekings, Dana Boebinger and Nadine Lavan.

Featuring Lucy's amazing voice, a spoken word introduction by Professor Sophie Scott, and a cameo appearance by none other than the Atlantic salmon — of “oh yes you better do corrections for multiple comparisons” fMRI fame (Bennett et al. 2009 - PDF).

Author: "noreply@blogger.com (The Neurocritic)"
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Date: Wednesday, 05 Mar 2014 10:55

The dissociative anesthetic and ravey club drug ketamine has been hailed as a possible “miracle” cure for depression. In contrast to the delayed action of standard antidepressants such as SSRIs, the uplifting effects of Special K are noticeable within an hour. “Experimental Medication Kicks Depression in Hours Instead of Weeks,” says the National Institute of Mental Health. NIMH has been bullish on ketamine for years now. Prominent researchers Duman and Aghajanian called it the “the most important discovery in half a century” in a recent Science review.

But in 2010, I pondered whether this use of ketamine was entirely positive:
Drawbacks include the possibility of ketamine-induced psychosis (Javitt, 2010), limited duration of effectiveness (aan het Rot et al., 2010), potential long-term deleterious effects such as white matter abnormalities (Liao et al., 2010), and an inability to truly blind the ketamine condition due to obvious dissociative effects in many participants.

Ketamine can also cause memory impairments, and abuse of the drug can result in severe bladder damage. There's even a model of schizophrenia based on antagonism of glutamate NMDA receptors, ketamine's main mechanism of action.

Now, in the latest issue of the American Journal of Psychiatry, Dr. Alan F. Schatzberg of Stanford University School of Medicine has a commentary entitled, A Word to the Wise About Ketamine. He first acknowledges the excitement about acute ketamine for refractory depression, then raises several cautionary notes and warns:
“This unbridled enthusiasm needs to be tempered by a more rational and guarded perspective.”

He notes that the drug is administered off-label in free-standing private psychiatry clinics without regulation by the FDA. Some leading proponents have advocated for strictly inpatient use, but that cat is already out of the bag.

Another potential issue is abuse liability.  The antidepressant effects of ketamine are short-lived (less than a week), which means that repeated infusions are required. The published literature suggests a relatively safe profile over two weeks in a hospital setting, but patients at commercial clinics are unlikely to be monitored as closely.

The commentary also suggests that “We Need To Know More About the Mechanism of Action of the Mood-Elevating Effects” but that is true of all drugs with antidepressant properties.

The Slippery Ketamine Slope

In response to the question, “Should Clinicians Prescribe Ketamine for Patients With Refractory Depression?” Dr. Schatzberg answers:
Without more data on what ketamine can do clinically, except to produce brief euphoriant effects after acute administration, and knowing it can be a drug of abuse, it is difficult to argue that patients should receive an acute trial of ketamine for refractory depression. ... The recent ketamine studies are exciting, and they open up important avenues for investigation that should be supported; however, until we know more, clinicians should be wary about embarking on a slippery ketamine slope.

However, in the midst of all this naysaying, it's important to note that Dr. Schatzberg has extensive ties to the pharmaceutical and biotech industries. He receives consulting fees from 19 different companies and has equity in 16 different companies, including one for which he is a co-founder. Ketamine of course is not under patent and is cheap to purchase. Perhaps not coincidentally, he does not receive fees from AstraZeneca, which (until recently) was developing a “low-trapping” NMDA antagonist that does not cause the hallucinogenic effects of ketamine (AZD6765, aka lanicemine).

In the past, I have suggested that short-term use for immediate relief of life-threatening symptoms (i.e. suicidal ideation) or end-of-life depression seem to be the best indications. Neuroskeptic has argued for the use of an active placebo condition (i.e, a non-dissociative comparison drug) in clinical trials, which has happened only rarely (Murrough et al., 2013), and for better assessment of dissociative behavioral effects.

At this point, the long-term ramifications of ketamine use for treatment-resistent depression remain to be seen...

In a future post I'll investigate the potential side effects in more detail.


I have no financial conflicts to declare. But if some company wants to employ a critic for some bizarre reason, I'll take this under advisement.

Further Reading

Ketamine for Depression: Yay or Neigh?

Chronic Ketamine for Depression: An Unethical Case Study?

While I Was Away... (more on ketamine for depression)

Update on Ketamine in Palliative Care Settings


Schatzberg AF (2014). A word to the wise about ketamine. The American journal of psychiatry, 171 (3), 262-4 PMID: 24585328

Author: "noreply@blogger.com (The Neurocritic)"
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Date: Sunday, 23 Feb 2014 04:34

Social Neuroscience power couple, John T. Cacciopo and Stephanie Cacciopo

This, my friends, is a belated Valentine's Day tale that went oh so wrong...

On Feb 14, Scientific American ran a piece about When Scientists Are Mad about Each Other. The cutesy narrative on the Cacciopos described a wonderful story of love at first sight:
He was studying loneliness and isolation. She was studying love and desire. When they found themselves together, they gravitated toward her end of the continuum of social connection.

John Cacioppo was living in Chicago and Stephanie Ortigue in Geneva when they met—in Shanghai. ... On the last night of the conference, they happened to be seated next to one another at an official dinner, and soon became absorbed in conversation. “She was wonderful and brilliant and funny and I was completely taken by her,” Cacioppo says.

They both felt the chemistry but had to return to their respective homes the next day. Before parting ways they walked out of the restaurant together and noticed a beautiful moon hanging over the city. He snapped a picture of it. “A couple weeks later, she e-mailed me and asked if I could send her the picture,” Cacioppo says—a request his wife now confesses was just an excuse to strike up another conversation.

Within weeks they arranged to meet again, and from there their love unfurled. ... Within eight months they were engaged, and a season later they had married.

Their romantic story and collaborative work has been covered by a number of professional and popular media outlets, including the press office at the University of Chicago. The newsroom issued a press release on February 13, 2014 to coincide with Valentine's Day:
Researchers find brain’s ‘sweet spot’ for love in neurological patient

A region deep inside the brain controls how quickly people make decisions about love, according to new research at the University of Chicago.

The finding, made in an examination of a 48-year-old man who suffered a stroke, provides the first causal clinical evidence that an area of the brain called the anterior insula “plays an instrumental role in love,” said UChicago neuroscientist Stephanie Cacioppo, lead author of the study.

The study (Cacioppo et al., 2013) showed no such thing (in my opinion), and I'll return that in a moment. But for now I'll point out the Cacioppo spin didn't translate so well to other reports about this neurological patient. According to the Fox News affiliate in Little Rock, AK:
Love at first sight does not exist, claim researchers in the Current Trends in Neurology journal.

A stroke patient had a damaged anterior insula -- which is the part of the brain which controls how quickly we fall for someone.

They found that he could make decisions about lust normally but needed longer to think about love.

The researchers say this finding "makes it possible to disentangle love from other biological drives".

The Chicago researchers never said that love at first sight is a myth. But that didn't stop the British tabloid Metro from running that headline, while the Times of India declared:
'Love at first sight' doesn’t exist!
Feb 18, 2014, 04.52 PM

A new study suggests that love at first sight is a myth and it does not exist.

According to the study, the speed at which we fall for someone is controlled by a region in the brain called the anterior insula, Metro.co.uk reported.

All this curt tabloid fodder contradicts the meet-cute trope of the Cacciopo's own relationship. But their study itself is also quite problematic. It doesn't support the authors' contention, in my view, and here's why.

The Martin Lindstrom School of Anterior Insula Studies

Remember this classic op-ed piece in the New York Times?
You Love Your iPhone. Literally.

Published: September 30, 2011

WITH Apple widely expected to release its iPhone 5 on Tuesday, Apple addicts across the world are getting ready for their latest fix.

But should we really characterize the intense consumer devotion to the iPhone as an addiction? A recent experiment that I carried out using neuroimaging technology suggests that drug-related terms like “addiction” and “fix” aren’t as scientifically accurate as a word we use to describe our most cherished personal relationships. That word is “love.”
. . .

...most striking of all was the flurry of activation in the insular cortex of the brain, which is associated with feelings of love and compassion. The subjects’ brains responded to the sound of their phones as they would respond to the presence or proximity of a girlfriend, boyfriend or family member.

Here Lindstrom committed the logical fallacy of reverse inference – one cannot directly infer the participants' cognitive or emotional state from the observed pattern of brain activity in neuroimaging experiments. 1 Fortunately, Russ Poldrack and Tal Yarkoni (and I) wrote posts about the debacle: NYT Editorial + fMRI = complete crap and the New York Times blows it big time on brain imaging and Neuromarketing means never having to say you're peer reviewed. We all corrected the completely erroneous assumption that activation of insular cortex = love.

As Dr. Poldrack said:
In Tal Yarkoni’s recent paper in Nature Methods [PDF], we found that the anterior insula was one of the most highly activated part of the brain, showing activation in nearly 1/3 of all imaging studies!

Here's where the Cacciopos and their anterior insulae come in...

The Common Neural Bases Between Sexual Desire and Love

That was the title of a review article that conducted a statistical meta-analysis of the neuroimaging literature on "love" compared to "lust" (Cacioppo et al., 2012). The emphasis was on the similarity of brain regions activated by purported experimental elicitors of these complex behavioral and cognitive states (e.g., "look at a picture of your spouse" vs. close friend, or "watch porn" vs. non-porn). However, they did report a "gradient" of differential activation from the anterior "love" insula to the posterior "lust" insula, as shown below.

Fig. 1 (modified from Cacioppo et al., 2012). Brain networks related to sexual desire (blue) vs. love (red). (B) Lateral view of regions uniquely activated by desire based on the quantitative multilevel kernel density analysis. (C) Regions uniquely activated by love.

In their more recent paper, Cacioppo et al. (2013) wanted to move beyond correlational data by testing a neurological patient with damage in the anterior insula. This is generally a good strategy to evaluate whether your highly vaunted theory based on fMRI data can hold up to causal manipulations, or in this case an accident of nature. If a person with anterior insula damage cannot feel love, then you'd say that region is necessary for feelings of love. If their ability to love is unaffected, then you'd say the anterior insula is not very important.

We can go even further and ask if that patient with damage to anterior insula – but sparing of posterior insula – can still feel lust but not love. In that case, you'd say there's a dissociation between love and lust in the anterior vs. posterior insula. 2 

But that's not what the study was about!! Instead, it was about a speeded response task: look at pictures and quickly decide whether the person evokes feelings of love (or desire, in separate blocks). From the outset, I'll say that reaction times (RTs) in this task really have nothing to do with love, even as it was conceived in the fMRI experiments (i.e., "look at a picture of your spouse" and even "look at a picture of your child" - !!)

The participant in the study was a 48 year old heterosexual man who had a stroke affecting a fairly large portion of the right insula [I think], which is good for the investigators because "lust" seems to "localize" to the left posterior insula in their schematic above. We don't know a whole lot about this man (like, how long ago was his stroke?), other than that "At the moment of evaluation, the patient showed no symptoms and his neurological exam was normal." We'll just have to trust them on that...

Oh, and he was cognitively normal on some brief screening tests, not depressed or anxious, and fine in two social cognition tasks (including empathy for pain, a task where other persons with anterior insular lesions show deficits).

On to the task. The patient and 7 age- and sex-matched controls viewed 40 pictures in blocks of 20. In two of the blocks, the participants decided whether the sexily dressed girl/young woman (aged 18-30) in the photo was "relevant to sexual desire" (yes/no) or "relevant to love" (yes/no). Each image was viewed twice. Only the RTs on "yes" responses were evaluated, for some unknown reason, so we don't know if the patient was faster/slower than controls to reject a photo.

The patient behaved similarly to controls in the "lust" task. It took him just under a second, 926 milliseconds (ms), to respond "yes" when he desired the sexy young girl in the picture, compared to 959 ms for controls [remember, these guys are 48 and the girls are as young as 18], which did not differ. The patient said "yes" to lust 58% of the time vs. 61% for controls. The authors write (PDF):
The anamnesis indicated that the patient was unaware of any differences in his feelings of love or desire, whereas behavior testing revealed a selective deficit for love (but not sexual desire).

In the "love" task, the patient said "yes" to love 35% of the time vs. 43% for controls (which again did not differ). For RT, the patient took 1279 ms to say "yes" to love vs. 1020 ms for controls. And this constitutes his selective deficit for love!! It took him 259 ms longer to decide that a stranger in a photo in a laboratory task was "relevant to love." And we don't know how long it took him to say "no." And he reported no subjective change in his feelings of love, and no significant others or family or friends were queried about this.

The patient could have been slower to make that decision for any number of reasons that have nothing to do with “playing an instrumental role in love.” I won't belabor the point, but this particular region of the brain is implicated in many different functions.

With all due respect to the authors, I don't understand how this paper was published in its current form.3 

Might as well do fMRI and neuropsychological studies of Celebrity "F#@k, Marry, Kill"...


1 See papers by Aguirre (2003) and Poldrack (2006) for detailed explanations.

2 To complete the package with a double dissociation, a posterior insula lesion that affects lust but not love would confirm the hypothesis.

3 Current Trends in Neurology isn't exactly a stellar journal... it's published by Research Trends of India (not the prestigious Cell Press Trends series), and noted as "questionable" by scholarly publishing watchdog Jeffrey Beall. The paper is not listed in PubMed, nor can it be found at the journal website. A Google Scholar search only turns up a PDF at the authors' own labs.


Cacioppo S, Bianchi-Demicheli F, Frum C, Pfaus JG, & Lewis JW (2012). The common neural bases between sexual desire and love: a multilevel kernel density fMRI analysis. The journal of sexual medicine, 9 (4), 1048-54 PMID: 22353205

Cacioppo S, Couto B, Bolmont M ... Cacciopo JT (2013). Selective decision-making deficit in love following damage to the anterior insula Current Trends in Neurology, 7, 15-19 PDF

Dedication: For my wife.

> I love you
> Now and always
> Across space and time
Author: "noreply@blogger.com (The Neurocritic)"
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Date: Monday, 10 Feb 2014 00:53

Can neuroscience illuminate the nature of human relationships? Or does it primarily serve as a prop to sell self-help books? The neurorelationship cottage industry touts the importance of brain research for understanding romance and commitment. But any knowledge of the brain is completely unnecessary for issuing take-home messages like tips on maintaining a successful marriage.

In an analogous fashion, we can ask whether successful psychotherapy depends on having detailed knowledge of the mechanisms of “neuroplasticity” (a vague and clichéd term). Obviously not (or else everyone's been doing it wrong). Of course the brain changes after 12 sessions of psychotherapy, just as it changes after watching 12 episodes of Dexter. The important question is whether knowing the pattern of neural changes (via fMRI) can inform how treatment is administered. Or whether pre-treatment neuroimaging can predict which therapy will be the most effective.

However, neuroimaging studies of psychotherapy that have absolutely no control conditions are of limited usefulness. We don't know what sort of changes would have happened over an equivalent amount of time with no intervention. More importantly, we don't know whether the specific therapy under consideration is better than another form of psychotherapy, or better than going bowling once a week.

Enter Love Sense: The Revolutionary New Science of Romantic Relationships, a new book by Dr. Sue Johnson, the clinical psychologist who developed Emotionally Focused Therapy (EFT).1 The book is reviewed by Dr. Helen Fisher in the New York Times:

Love in the Time of Neuroscience


In “The Devil’s Dictionary,” Ambrose Bierce defined love as “a temporary insanity curable by marriage.” Enter Sue Johnson, a clinical psychologist and couples therapist who says that relationships are a basic human need and that “a stable, loving relationship is the absolute cornerstone of human happiness and general well-being.” To repair ailing partnerships, she has developed a new approach in marriage counseling called Emotionally Focused Therapy, or EFT, which she introduces in her new book, “Love Sense.”

Johnson believes EFT can help couples break out of patterns, “interrupting and dismantling these destructive sequences and then actively constructing a more emotionally open and receptive way of interacting.” She aims to transform relationships “using the megawatt power of the wired-in longing for contact and care that defines our species,” and offers various exercises to restore trust.

Most interesting to me was Johnson’s brain-scanning study. Before EFT therapy, unhappily married women participating in the study reported considerable pain from an electric shock to the ankle as they held their husbands’ hands. After 20 sessions of EFT, however, these now more securely attached women judged their pain as only “uncomfortable” and their brain scans showed no alarm response. Secure attachment appears to change brain function and reduce pain.

Initial questions:
  • Is there a “wired-in longing for contact and care that defines our species”? {my needy cat seems to long for contact and care}
  • What's with that hand-holding ankle shock brain-scanning study? {did EFT really eliminate the “alarm response” in these women?}
Then Fisher continues:
But Johnson too often focuses on attachment to the exclusion of other “megawatt” brain systems. Remarkably, she lumps romantic love with attachment, saying “adult romantic love is an attachment bond, just like the one between mother and child.” In reality, romantic love is associated with a constellation of thoughts and motivations that are strikingly different from those of attachment. My research bears out that humankind evolved distinct but interrelated brain systems for mating and reproduction: the sex drive (to seek a range of partners); feelings of romantic love (to focus one’s mating energy on a single partner); and feelings of attachment (to drive our forebears to form a pair-bond to rear their young together). Each brain system is associated with different neurochemicals; each is a powerful drive that still plays a continuing role in partnership stability.

More questions:
  • Are there distinct (but interrelated) brain systems for the sex drive, romantic love, and feelings of attachment? {I actually find this to be plausible}
  • Is each brain system associated with different neurochemicals? {i.e. testosterone, dopamine, and oxytocin, respectively. I find this to be less plausible, or at least a bit simplistic.}

It's time to correct the misperceptions and overinterpretations that have arisen from this research!!

This is a job for...


Since there are a number of issues to tackle here – too many for a single post – I'll concentrate on only one of them here.

I Wanna Hold Your Hand

In 2006, Dr. James Coan and colleagues published a neuroimaging paper suggesting that the brains of happily married women showed an attenuation of activity related to emotion and threat when they held the hands of their husbands (Coan et al., 2006). Threat was induced experimentally by presenting a stimulus which occasionally signaled that a mild electric shock would be delivered to the ankle (20% of the time). Holding the hand of a male stranger also attenuated the hemodynamic response in some of these regions, relative to a no hand-holding control condition.2

Backing up a bit, the participants in the study were 16 heterosexual couples who rated their marital satisfaction as at least 40 on the Satisfaction subscale of the 50 point Dyadic Adjustment Scale (DAS). Total scores on the DAS were 126 for husbands (on a 151 point scale) and 127 for wives.3

The experimental design is illustrated below. The red X indicated a 20% chance of shock.

Figure adapted from a 2011 presentation by Coan (PDF), part of which can be viewed here.

At the end of each block, the women rated their subjective levels of unpleasantness and arousal on a 5 point scale. The results of the hand-holding manipulation were a bit weak. Unpleasantness ratings in the husband-hand condition were indeed significantly lower than no-hand (p=.001), but only marginally so compared to the stranger-hand condition (p=.05, with p<.05 being the usual cutoff for significance). The arousal ratings for husband-hand vs. no-hand (p=.07) and stranger-hand vs. no-hand (p=.08) were not officially significant either.

This raises a question I considered in 2006: why were the wives the only ones who were scanned?
...what about married women holding their mothers' hands? married men holding their wives' hands? unmarried women holding their partners' hands? single women holding the hands of their best friends? Perhaps the authors started with the relationship that they most expected to yield significant results...

The subjective effects of spousal-handholding were not enormous in women, which might explain why we've never seen data from husbands (i.e., perhaps there were no effects on self-report and/or neural activity). The highly-touted correlations between the wife's relationship quality rating and attenuation of threat-related brain signals weren't especially impressive either: −.59, p = .02 for the left superior frontal gyrus, −.47, p = .07 (not significant) for the right anterior insula, and −.46, p = .08 (not significant) for the hypothalamus. These numbers represent the magnitude of reduction in threat-related activity when holding the husband's hand, and were interpreted to suggest that the attenuations in pain (insula) and stress (hypothalamus) were related to the strength of attachment.4

Emotionally Focused Therapy

This finally brings us to the recent paper by Johnson et al. (2013). They followed the imaging protocol of Coan et al. in a set of 35 married couples who were screened for relationship dissatisfaction and scanned both before and after 23 sessions of EFT couples counseling (range of 13 to 35 sessions over 3.25 to 8.75 months). On average, the couples were white Canadians 44-45 years of age, married for 17 years. In contrast to the happy couples described above (DAS scores of 127), these couples reported moderate levels of relationship distress, with DAS scores of 80-97. For various understandable reasons, only 23 couples completed pre- and post-EFT fMRI scans. Again, only the wives were scanned.

Still, retaining 23 couples over 6 months of treatment is no mean feat. However, I will again note that there is no control condition in this experiment, so we can't know whether any changes are specifically due to the treatment of interest.

According to Johnson et al. (2013), EFT is "a manualized treatment that conceptualizes relationship distress as reflecting emotional disconnection and unmet attachment needs [18]."
Session and therapy length varied depending on the couples' presenting concerns and their progression through EFT-defined therapeutic change events [18], [28]. Specifically, when a couple was deemed according to EFT guidelines to have achieved 1) “softening” – a state of vulnerability and sharing of attachment related needs between the partners [37] – and 2) “consolidation” – where the therapist works with the couple to review treatment gains – treatment was terminated.

I am not qualified to comment on EFT and will not discuss it further, beyond saying that post-therapy DAS scores were significantly increased (pre-EFT mean=81 and post-EFT mean=96) but still, on average, in the moderately distressed range. Unpleasantness and arousal ratings in the husband-hand fMRI condition were lower after EFT.

The fMRI results after EFT were.... complicated, as shown below, and involve what appears to be post-hoc reasoning in relation to initial marital strife. Percent signal change was assessed for all voxels in the ROIs that were reported by Coan et al., which is a good and unbiased method for analyzing an independent dataset.

Fig. 2 (Johnson et al., 2013). Point estimates of percent signal change graphed as a function of EFT (pre vs. post) by handholding (alone, stranger, partner) and DAS score. Point estimates were computed separately for individuals high (+1SD) and low (−1SD) in DAS. Point estimates reflect average percent signal change (threat – safe) from all voxels activated in the original Coan et al. handholding study.

But the results are a little hard to interpret for the wives with high DAS scores, who nonetheless still experienced relationship distress. The intervention had no effect on their global threat-related brain response when holding their husbands' hands. In contrast, those with lower DAS scores showed a post-EFT increase in the threat response in the no-hand condition, a large reduction for stranger-hand, and a very large reduction for husband-hand.

Next the authors moved towards analyzing specific ROIs. I'll skip the husband vs. alone comparisons because these are less relevant. Well, except I'll quote this bizarre finding (which isn't terribly relevant, just hard to explain):
Interestingly, participants with higher DAS scores were generally less active in the substantia nigra/red nucleus when holding hands with their partners relative to when alone, independent of EFT, F(1,49.5)=6.6, p=.01.

OK then. What about the husband vs. stranger comparisons? There were a number of brain areas that showed pre- to post-therapy decreases that did not differ for husband-hand vs. stranger-hand.5 These regions included the right insula, which was related to relationship quality in the Coan et al. (2006) study. The two regions with positive findings (i.e., threat-related reductions in husband-hand and increases in stranger-hand) are right dorsolateral prefrontal cortex (dlPFC) and left supplementary motor area (SMA). No relationships to DAS score were reported.

Fig. 5 (Johnson et al., 2013). Percent signal change (±SE) graphed as a function of EFT (pre vs. post) by handholding (stranger vs. partner) interaction effects. Row A represents activity in the supplementary motor cortex (SMG) [sic]. Row B represents activity in the right dlPFC.

What have we learned from this study, and how does it inform the practice of EFT? If we take it at face value, the one consistent finding between the two experiments is that the threat response in right dlPFC was attenuated when holding the husband's hand, relative to holding a stranger's hand. If this neural region serves to downregulate negative emotional responses expressed elsewhere (as described below), there were no downstream regions in need of downregulation:
The dlPFC in particular supports explicit, cognitive, or “reappraisal” based self-control strategies active during unpleasant emotional states [54].  ...  The relative post-EFT inactivity of the dlPFC implies further that a secure connection with an attachment figure does not help individuals to maintain equilibrium by boosting self-regulatory capabilities per se but by reducing the perception and significance of threats, thus obviating the need for self-regulation to occur [13]

Having some kind of autonomic measure of threat perception (e.g., skin conductance or heart rate) would be useful in verifying this hypothesis. The authors don't interpret their other major finding, a similar effect in the left SMA (a motor control region).

The final question remains unanswered: how does this study inform the practice of EFT? The authors state:
Ultimately, our handholding paradigm has provided a unique opportunity to test some of the proposed mechanisms of social support in general, and EFT in particular, all at the level of brain function, in vivo.  

But not all of their predictions were supported. In particular, to explain the changes in neural threat processing observed in the no-hand condition, they resorted to an alternate model of therapeutic change:
We predicted that EFT would not affect neural threat responding during the alone condition.  ... [But] threat-related activity during the alone condition actually increased as a function of EFT in regions such as the dACC and portions of the PFC. Increased reactivity in these regions suggests a possible cost to increasing one's dependence upon social resources: that it becomes more difficult to tolerate being alone.

This is not what we observed. Although positivity ratings did not change, subjective arousal actually decreased. This suggests an alternative hypothesis: that EFT either trained or motivated clients to be more effective self-regulators even when alone.  ...  Although EFT focuses strongly on interpersonal attachments and interdependence, doing so may also increase self-regulatory motivation as clients come to value fostering effective relationships in part through self-regulatory effort.

I'm not sure that I understand this formulation, or that a dissociation between behavioral self-report and dACC activity warrants a reinterpretation of EFT's therapeutic effects. Ultimately, I don't feel like a BS-fighting superhero either, because it's not clear whether Magneto has effectively corrected the misperceptions and overinterpretations that have arisen from this fMRI research.


1 Not to be confused with Emotional Freedom Techniques, or “tapping”, a rather ridiculous practice that purports to manipulate the body's energy field.

2 The specific neuroimaging results were a bit less straightforward and easily interpreted than this. Regions of interest (ROIs) were defined by determining which areas were activated by the red X threat compared to the safe signal in the no-hand condition. This threat response was attenuated in the husband-hand vs. no-hand condition in the ventral anterior cingulate cortex (vACC), left caudate, superior colliculus, posterior cingulate, left supramarginal gyrus, and right postcentral gyrus. The threat response was also specifically attenuated in husband-hand vs. stranger-hand only in right dorsolateral prefrontal cortex, considered a “cognitive control” area. Finally, the stranger-hand vs. no-hand comparison revealed attenuation in the same bold blue regions above.

3 However, the correlation between husbands' and wives' DAS scores was not significant. Hmm... Would knowledge of this finding create any discord?

4 I won't get into how those single functions were assigned to these two complex and diverse brain regions.

5 Johnson et al. (2013): “In the vmPFC, left NAcc, left pallidum, right insula, right pallidum, and right planum polare, main effects of EFT revealed general decreases from pre- to post- therapy in threat activation, regardless of whose hand was held.”


Coan JA, Schaefer HS, & Davidson RJ (2006). Lending a hand: social regulation of the neural response to threat. Psychological science, 17 (12), 1032-9 PMID: 17201784

Johnson SM, Moser MB, Beckes L, Smith A, Dalgleish T, Halchuk R, Hasselmo K, Greenman PS, Merali Z, & Coan JA (2013). Soothing the threatened brain: leveraging contact comfort with emotionally focused therapy. PloS one, 8 (11) PMID: 24278126
Author: "noreply@blogger.com (The Neurocritic)"
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Date: Tuesday, 04 Feb 2014 09:55

We all start to forget things, have word finding problems, and generally slow down cognitively once we get older, right? Wrong, says a recent paper by Ramscar et al. (2014), The Myth of Cognitive Decline: Non-Linear Dynamics of Lifelong Learning [free PDF].

Well, the real answer is more like, “it’s complicated,” as the first author explained in a blog post on the the paper. A giant in the field of cognitive aging quickly retorted, oh no it's...
...“Clever-Silly” comes irresistibly to mind, but this must be inadvertent fall-out from an elderly brain overstuffed by failure to assimilate the vast literature on cognitive aging.

The Rise of Academic Blogging

In the last post, I noted the potential Decline of Neurocriticism. At the same time, more and more people have started their own neuroscience and psychology blogs (which magnifies the channel factor, as Roger Dooley noted). And it's not only the SciCom crowd, which includes science journalists and aspiring science writers who aim to leave lab work behind. Some professional societies like the Society for Neuroscience are getting into the game (BrainFacts.org Blog in 2012), while some like APS We're Only Human (2010) and the venerable BPS Research Digest (2005) have been around a while longer.

An increasing number of academics are starting to blog as well. The Myth of Cognitive Decline provides a perfect example of the rapid (and serious) exchange of ideas that's possible in a "non-peer reviewed" format. Certainly, heavyweight academic blogs such as Language Log, and Statistical Modeling have existed for 10 years, but I think academic blogging is on the rise, perhaps even more so in psychology than neuroscience.

The latest exciting entrée is distinguished Professor Emeritus Patrick Rabbitt, a self-described “grumpy gerontologist.” A tribute volume of essays published in 2005 had this to say:
For over almost five decades, Professor Patrick Rabbitt has been among the most distinguished of British cognitive psychologists. His work has been widely influential in theories of mental speed, cognitive control, and ageing, influencing research in experimental psychology, neuropsychology, and individual differences.

So if someone makes a bold new claim about cognitive aging, they really should listen to what he says.

In his inaugural post, Age and the overstuffed mind, Prof. Rabbitt lightly and humorously skewers Ramscar et al.'s (2014) claim that cognitive decline is a myth (which received extensive coverage in the press). He unfavorably compares their model to the Homer Simpson model, summarized as, “Every time I learn something new it pushes something out”:
The Simpson model makes no prediction for decision speed because it posits finite data capacity beyond which no increment, and so no further slowing, can occur. In this respect it is more elegant than the Ramscar model which makes no allowance for stabilisation or even shrinking of the data store by data attrition (forgetting) or displacement.

However, Rabbitt makes the astute observation that the paper may have been deliberately provocative:
In conclusion: unlike the Simpson model, which was arguably first empirically tested seventy years ago and still offers a touching insight into the human condition, the Ramscar model may be intended only as a provocation and to stimulate discussion. The boundary between provocation and exasperation is narrow, and is shifted by the experiences and intellectual commitments of an audience.

Two weeks earlier, Michael Ramscar started a blog called The Importance of Being Wrong. The first post, What happens to our minds and memories in healthy ageing?, provided an in-depth explanation of his paper. I'll be curious to see if he responds to Rabbitt.

...and in the time this post has lain dormant, Prof. Ramscar has responded to Prof. Rabbitt: Cognitive Ageing or Cognitive Decline? An FAQ. The entire exchange makes for great reading, so I won't try to summarize it here.

Author: "noreply@blogger.com (The Neurocritic)"
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Date: Sunday, 02 Feb 2014 10:03
The Brain From Beyond Infinity

In the last post, I celebrated Eight Years of Neurocriticism but wistfully noted that this blog's popularity peaked in 2012. The traffic last year showed a decline to 2009-2010 levels. Why did this happen? And does it matter? No it does not, but it gives me the opportunity to comment on the state of a specialized little corner of science blogging. The sort of piece where people say things like “blogging as a chance to exercise our voices doesn’t seem to be going anywhere” and “the blog is dead.”

Except not that.

@practiCalfMRI politely suggested it's the quality of visitor that counts. In 2013 the Average Time on Site for my homepage was indeed up 25%, but I could have been inadvertently cherry picking the data...

Commenters on the post anticipated some of my thoughts. Perhaps it was related to the demise of Google Reader, said one. A drop did occur when the service stopped in July 2013, but traffic started trending downward in April-May 2013. So I don't think this can explain it. Instead, the format may have been a victim of its own success and run its course. As another commenter aptly put it:
What happened? Well, what always happens: with time, people get bored. Of anything. From marriage to cereal bar flavor. When you started Neurocritic, it was new, and people were sick of all the neurocrap published out there. Then, the neurocrap people and others, started realizing that talking crap about neuro stuff got a lot of hits! And so everybody started doing it, from Voodoo correlations to Retraction Watch. It was the fashionable thing to do. That's when it got boring.

The Decline of Neurocriticism

In the latter half of 2012, the backlash against Insula iPhone opinion pieces and the neural correlates of ______ fMRI studies was noticed in the popular press. Allegations of neurobollocks, neurodoubt, and neuroscience fiction had become fashionable. The Mainstreaming of Neurocriticism had arrived, and you know what that means: it's all downhill from there. It's like when The Sartorialist wrote about meggings in 2010, but then USA Today declared them the latest male fashion trend just the other day. So now it's time to throw yours away (or to give them to Justin Bieber).

Then Brainwashed: The Seductive Appeal of Mindless Neuroscience was published in June 2013, prompting a resurgence of dualism (e.g., “The brain is not the mind”).

As I've said before, this general trend has been useful in pointing out flawed studies, overblown conclusions, and overly hyped press releases. But some working neuroscientists thought the naysaying had gotten a little out of hand, because expert critiques are easily misinterpreted. A little neuronuance is needed here, the middle ground that acknowledges limitations yet avoids global condemnations. Around this time, I initiated my own little backlash against the anti-neuro backlash by starting a new blog, The Neurocomplimenter.

Daniel Engbar went out on a limb and proposed that “the public turned its back on neuro-hype” long ago (in 2008) and that “2008 may also have been the high point for critical neuroscience blogging.” But I place the date later than that, in 2012. Nevertheless, popular new blogs like Neurobollocks started after then, and Neuroskeptic shows no signs of slowing down. And there's plenty of blogging to be done that doesn't involve neurocriticism.

Maybe I'm just getting boring (or bored). So perhaps it's time to use a new platform like Tumblr to post animated gifs of brains from cheesy horror movies OMG Neurocritic!

Brain of Blood Trailer

"How many ways can you distort the human mind?"

Instead of blogging, people are posting to Tumblr, tweeting, pinning things to their board, posting to Reddit, Snapchatting, updating Facebook statuses, Instagramming, and publishing on Medium.  ...  Blogs are for 40-somethings with kids.

-Jason Kottke, The blog is dead, long live the blog

There are 123 independent neuroscience and psychology blogs aggregated on @neuroghetto now, and some huge number in networks. Science blogging isn't dead yet, long live science blogging.
Author: "noreply@blogger.com (The Neurocritic)"
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Date: Tuesday, 28 Jan 2014 07:57
A Mad Scientist Party Idea, from Party on Purpose.

Eight years ago, I started a blog out of sheer frustration. I decided to call it The Neurocritic. I sent out an anonymous e-mail to some of my friends to describe the project.

subject: unveiling The Neurocritic

I've started a blog to critique the most outrageous claims published in high-profile journals and discussed in the popular press:


Because The Neurocritic is not a member of the all-powerful Editorial Boards at Science, Natute, or Neuron, The Neurocritic is published under an assumed identity.  Your comments are most welcome.

Enjoy the inaugural posting! [we'll see how long it lasts.]

[I had forgotten how surprised I should be that the blog has lasted this long.]

At first, I invited others to join. Two people expressed interest in joining the party, and one was issued an account (but never posted). I soon became very proprietary and revoked that account. I had become The Neurocritic.

I didn't think anyone would read the blog. But then a funny thing happened. Several posts that discussed journal articles drew the attention of the authors, who actually commented.

Meanwhile, I tried my best to stay under the radar and hoped that no one would think of me as a real person.

Pretty colorful brains and simplified explanations of human cognition and emotion and personality had became staples of mainstream newspapers and magazines, first in the dying print media and then in purely online news sources and press release farms. Gradually, a backlash grew against studies on the neural correlates of shopping at Macy's. This blog (and others such as Mind Hacks, Neuroskeptic, and Neurobonkers) was mentioned in the same press outlets that ran outlandish opinion pieces about Loving Your iPhone:

Neuroscience: Under Attack (Nov 23, 2012)

Neuroscience Fiction (Dec 2, 2012)

Why ‘neuroskeptics’ see an epidemic of brain baloney (Apr 13, 2013)

This blog reached the height of its popularity in 2012.  Then we hit 2013... the year of decline.

What happened?? I'll explore some possible reasons in the next post, and take a glimpse into the future.
Author: "noreply@blogger.com (The Neurocritic)"
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Date: Friday, 24 Jan 2014 11:17

The Brain Radio is a long-running French radio program:

THE BRAIN are Eva & Pascal Lebrain aka Puyo puyo, they run this radioshow from 1999, it deals with freaky electro, cheesy vintage, dry rock, movie themes and oddities in general. All is stuffed with absurd aphorisms, written by themselves most of the time.

The fun archive of playlists dates back to 2003 and includes 91 of the 129 radioshows.

The “Brain Radio” is also a deep brain stimulation (DBS) device that “Records and Emits Electrical Pulses,” according to an August 9, 2013 story in the MIT Technology Review:

A new brain implant that can record neural activity while it simultaneously delivers electric current has been implanted into a patient for the first time.

The new device from Medtronic, a Minneapolis-based medical device company, can also adjust its electrical output in response to the changing conditions of the brain. This automated control could one day improve deep-brain stimulation treatment and even enable doctors to use the device to treat more conditions, say experts.

This new generation device seems like what DARPA had in mind for its SUBNETS program, part of the BRAIN Initiative. The MIT Technology Review story continues:
The patient trials launched on Wednesday will test whether Medtronic’s new device can safely record electrical activity in a patient’s brain while also delivering electric currents. These tests will explore how patients’ brains respond to deep brain stimulation therapy. However, according to lab animal tests, the device is capable of not only sensing the electrical activity of the brain tissue it sits in, but of also changing its output accordingly.

The ultimate goal for the device is to provide responsive therapy by detecting brain signals and tweaking its output accordingly, says Lothar Krinke, general manager of the company’s deep brain stimulation division.

The Activa® PC+S Deep Brain Stimulation System was first implanted in a German patient with Parkinson’s disease. But now there's a new clinical trial for treatment-resistant depression (TRD) that will implant the device in the subgenual cingulate (Brodmann area 25):
The experiment described in this application is to use a new DBS device that can record the electrical activity in the brain around the site of stimulation. The electrical activity is known as Latent [sic] Field Potential (LFP) and is a reflection of the activity if the neural network. The new DBS device is an experimental device that has not been approved by the FDA, but allows for simultaneous recording of LFP while stimulation is being delivered. The device is manufactured by Medtronics and is known as Activa Primary Cell + Sensing(PC+S), but because it can be used to record the brain electrical activity it is also known as "the Brain Radio". The Brain Radio is based on an approved device commonly used for DBS for other conditions that has the added sensor capacity. The stimulation system is identical to that in the approved device. The goal of this investigation is to use the Brain Radio to study LFP in the brains of people with TRD before and during active stimulation. 

The device used in the aborted BROADEN Trial of DBS for TRD is manufactured by another company.

As I've mentioned previously, the goal of the SUBNETS program is to develop devices that both stimulate and record neural activity, and provide real-time data that can be decoded as reflecting a particular behavioral state... basically, a futuristic implant that can adjust its own stimulation parameters based on how the patient is doing.

The new DBS trial for intractable depression (which is not yet open for participant recruitment)...
...will recruit 10 patients with advanced TRD and implant them with the Brain Radio system. The recording system will be to record LFP over 3 years, while patients reesceive stimulation. A brief discontinuation study will be conducted after 6 months of stimulation when the device will be turned off and patterns of LFP changes will be recorded. All LFP measures will be correlated with the primary clinical response outcome metric, the Hamilton Depression Rating Scale.

The Journal of Neural Engineering has just published a paper outlining the results of a two year study that tested the Activa® PC+S neurostimulator in a rhesus monkey (Ryapolova-Webb et al., 2014): Chronic cortical and electromyographic recordings from a fully implantable device: preclinical experience in a nonhuman primate.

The senior author on that paper (neurosurgeon Dr. Philip Starr) was one of the first to implant the device in a Parkinson's patient in the US.

Author: "noreply@blogger.com (The Neurocritic)"
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Date: Sunday, 19 Jan 2014 03:10
Webpage for the BROADEN™ study formerly run by St. Jude Medical

It's become mainstream these days to say that psychiatric disorders are neural circuit disorders. You can even read all about it in the New York Times! Cognitive training and neuromodulation (“electroceuticals”) are in, and pharmaceuticals are out, as explained by NIMH Director Dr. Tom Insel in a blog post about the Ten Best of 2013:
...if mental disorders are brain circuit disorders, then successful treatments need to tune circuits with precision. Chemicals may be less precise than electrical or cognitive interventions that target specific circuits.

One of the first to champion this position was Dr. Helen Mayberg and her colleagues, who conducted a small trial using deep brain stimulation (DBS) as a treatment for intractable depression (Mayberg et al., 2005). The technique has been heralded as a potential breakthrough in psychiatry, with $70 million in BRAIN Initiative funding going to DBS development. So a recent tweet announcing the failure of a major clinical trial garnered a lot of attention.

The December 13, 2013 issue of the Neurotech Business Report had the scoop:
The news that St. Jude Medical failed a futility analysis of its BROADEN trial of DBS for treatment of depression cast a pall over an otherwise upbeat attendance at the 2013 NANS meeting. Once again, the industry is left to pick up the pieces as a promising new technology gets set back by what could be many years.

It’s too early to assess blame for this failure. It’s tempting to wonder if St. Jude management was too eager to commence this trial, since that has been a culprit in other trial failures. But there’s clearly more involved here, not least the complexity of specifying the precise brain circuits involved with major depression. Indeed, Helen Mayberg’s own thinking on DBS targeting has evolved over the years since the seminal paper she and colleague Andres Lozano published in Neuron in 2005, which implicated Cg25 as a lucrative target for depression. Mayberg now believes that neuronal tracts emanating from Cg25 toward medial frontal areas may be more relevant. Research that she, Cameron McIntyre, and others are conducting on probabilistic tractography to identify the patient-specific brain regions most relevant to the particular form of depression the patient is suffering from will likely prove to be very fruitful in the years ahead.

But it was hard to find any other information about the failed trial. I can't be sure, but I think this is the study in ClinicalTrials.gov A Clinical Evaluation of Subcallosal Cingulate Gyrus Deep Brain Stimulation for Treatment-Resistant Depression. The sponsor is St. Jude Medical. The record hasn't been updated since March 2013.

BROADEN is a tortured acronym for BROdmann Area 25 DEep brain Neuromodulation.

The July 30, 2013 version of the BROADEN website is preserved at archive.org.

The BROADEN (BROdmann Area 25 DEep brain Neuromodulation) study is a study to evaluate the safety and effectiveness of deep brain stimulation in patients with a severe form of depression known as Major Depressive Disorder (MDD) who have not responded to multiple treatments. Stimulation to the brain is provided by a surgically implanted medical device called a deep brain stimulation (DBS) system. The system provides stimulation directly to an area of the brain known as Brodmann Area 25 (sometimes referred to as BA25). The study will build upon the depression work of a research team from the University of Toronto, led by neurologist Helen S. Mayberg, M.D. and neurosurgeon Andres Lozano, M.D., PhD, FRCSC.

On January 10, 2014 an Anonymous commenter at DBS Trial1 said:
Regarding the Broaden Study, I'm not writing it off entirely but things aren't looking good. The FDA has put the brakes on the study so it will not enroll any new participants.
While the study is over a year old, the results so far are not encouraging and the device manufacturer is scaling back on monitoring and programming.
It appears that a possible major misstep was made, by not including fMRI mapping prior to implanting the electrodes. 

As Neurotech Business Report (NBR) mentioned, more precise mapping of the white matter connections of the subgenual cingulate (Brodmann area 25) may be essential (e.g., Johansen-Berg et al., 2008). To determine the anatomical connectivity of the subgenual cingulate region, those authors performed tractography (using diffusion-weighted magnetic resonance imaging) to trace the pathways mediating treatment response with DBS. They compared the connections of the subgenual ACC (sACC, blue/cyan) and the perigenual ACC (pACC, red/yellow).

Fig. 3 (Johansen-Berg et al., 2008). Connectivity-based parcellation of anterior cingulate cortex (ACC) and location of electrode contacts. Effective electrode locations are mainly localized within the sACC subregion.

A July 11, 2011 News Release from St. Jude Medical announced that the FDA had approved an expansion of the BROADEN Trial so that up to 20 different sites could enroll a total of 125 patients. There were only three sites originally Chicago, New York City and Dallas. Perhaps the trial resources were getting stretched too thin.

Another possibility raised by James Cavuoto
, Editor and Publisher of NBR, is that the FDA is too darn stringent in what it considers a treatment response:
Unfortunately, much of the progress in our understanding of DBS mechanisms in depression is potentially wasted without a vibrant installed base of patients and clinicians using and perfecting DBS therapies. ... In our view, the FDA needs to understand the vital importance of getting first-generation devices into the field and move away from arbitrary standards like improving symptoms by 50 percent in 50 percent of the population. The notion that if we can’t help everybody we shouldn’t help anybody has no place in medical science, particularly when you consider that neuromodulation therapies are working with the hardest-case patients who have not responded to other therapies.

Finally, there is the unfortunate possibility that DBS treatment in this patient group doesn't work as well as initially thought...

If anyone has additional information, please leave a comment.


1 This blog [EDIT:  i.e., the DBS Trial blog] is written by an individual who for the past four years has had an implanted device for the treatment of intractible depression.


Johansen-Berg H, Gutman DA, Behrens TE, Matthews PM, Rushworth MF, Katz E, Lozano AM, Mayberg HS. (2008). Anatomical connectivity of the subgenual cingulate region targeted with deep brain stimulation for treatment-resistant depression. Cereb Cortex. 18:1374-83.

Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH. (2005). Deep brain stimulation for treatment-resistant depression. Neuron 45:651-60.

Further Reading:

A Depression Switch?

The Sad Cingulate

Sad Cingulate on 60 Minutes and in Rats

...But My Subgenual Cingulate Is Sad

Deep Brain Stimulation for Bipolar Depression
Author: "noreply@blogger.com (The Neurocritic)"
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Date: Sunday, 12 Jan 2014 00:41

Crowdfunders, get a clue! You're throwing your money away on bogus prototypes for impossible technology! Why give your hard-earned cash to the equivalent of modern-day snake oil salesman instead of funding essential projects to bring clean water and hygienic toilets to third world countries?

First we have No More Woof, which was first brought to my attention by Professor Dwayne Godwin. Writing in BrainFacts.org, a blog sponsored by the Society for Neuroscience, he considers whether an EEG-to-speech converter for dogs is plausible [HINT: of course it's not!]:
What is proposed is a gadget that on the basis of a few dry EEG electrodes will do for a creature without known speech centers what we’ve been unable to do for humans (with well-defined speech centers) using the best EEG systems yet developed.

In other words, don't you think you would have heard about a device that could translate the brain waves of a person with speech difficulties due to Broca's aphasia or ALS into fluent sentences? Gizmodo and the New York Times and even Oprah would be all over it!

Here's what the No More Woof developers have to say:
Every mammal creates and transports "thoughts" the same way, as a swarm of electrical signals through a complex neurosystem). It has long been possible to record this activity through Electroencephalogram (EEG) readings. When it comes to humans, the last decade has seen tremendous progress.

However every species uses its unique structure. You could say that all creatures speak the same language only with varying dialects. And as animal brains are less complex than humans their signal patterns are more distinct for feelings of anger, curiosity or tiredness – actually making them easier to distinguish.

There's absolutely no scientific evidence for distinguishing "anger" and "curiosity" brain signals in dogs, especially via a cheap ($65) doggie EEG headset with only one electrode.

What we really need is Professor Schwartzman's canine decoder!

The campaign has already raised $19,152 of their $10,000 goal. And there's 35 days left! So save your money!

But at least the No More Woof developers have issued a caveat. We can't say the same about our next prototype...

NeuroOn: World's first sleep mask for polyphasic sleep

Why waste any time with a trivial and unimportant activity such as sleep? The NeuroOn developers promise their device will deliver a "unique sleep schedule" that will maximizes each user's waking time... up to 22 hours a day! You'll become an efficient and brilliant productivity machine, just like Da Vinci, Tesla, Churchill and even Napoleon!
In conclusion, through great sleep efficiency, Polyphasic sleep can give you an extra 4 hours of free time every day. That’s up to 28 hours (1 day+) a week, 1460 hours a year.

That’s right - Your year now has over 420 working days!

What is polyphasic sleep? It's the division of sleep into several bouts per day, instead of the usual 8 hours or so at night. This schedule is standard in some mammals and may serve a protective purpose, according to Capellini et al. (2008):
The duration of [REM and non-REM] cycles varies extensively across mammalian species. Because the end of a sleep cycle is often followed by brief arousals to waking, a shorter sleep cycle has been proposed to function as an anti-predator strategy. Similarly, higher predation risk could explain why many species exhibit a polyphasic sleep pattern (division of sleep into several bouts per day), as having multiple sleep bouts avoids long periods of unconsciousness, potentially reducing vulnerability.

In humans, "disentrainment" protocols isolate volunteers under strict lab conditions and remove all cues to the time of day. In one study, 50 participants were allowed to eat and sleep at any desired time over a 72 hour period (Campbell & Murphy, 2007). Activity options were limited to a set playlist of recorded music, a deck of cards, and a small anthology of poetry. No strenuous exercise, TV, videos, work, study or hobbies. Why? To look at natural sleep tendencies unencumbered by that Battlestar Galactica marathon you've always wanted.

On average, the participants slept for 27.67 hrs of the 72 hour disentrainment period. That's 9.22 hrs every 24 hours, which was verified by EEG recordings (not based on self-report, as in an earlier study). There was an average of 7.6 sleep episodes per subject (instead of the standard 3 bouts each night). The mean duration of sleep episodes was 3.27 hrs but this varied wildly, with a range of 0.33-13.57 hrs. And the younger subjects (30 and under) slept longer and spent more time in REM than the middle (31-59 yrs) and older (60 and over) subjects.

What is polyphasic sleep according to the NeuroOn team?
It is a term referring to alternate sleep patterns that can reduce the required sleep time to just 2-6 hours daily. It involves breaking up your sleep into smaller parts throughout the day, which allows you to sleep less but feel as refreshed as if you slept for 8 hours or more.

Although I could be wrong, the majority of NeuroOn backers are presumably young and therefore will require more sleep than their older counterparts. Have the developers taken age differences into account?

But but,you say, these techie hipsters spend their lives on more valuable and fulfilling activities than reading poetry and playing solitaire (with an actual deck of cards)!! So of course they don't need as much sleep!

So sure, we can criticize the exaggerated claims that humans have a minimal need for sleep, with wondrous increases in productivity as a result of adopting a proprietary "unique sleep schedule". All without developing a serious psychiatric condition! While ignoring the necessity to medically screen users in the event that such a device would actually work.

The real impetus for writing this post, however, came from Justin Kiggins:

The ensuing discussion on Twitter included debunking of the entire technical premise of the device, which uses a limited number (one? three?) of ill-placed electrodes to purportedly record a wide variety of electrical signals.

Let's take a closer look at the prototype. Is that really only one electrode?? * That uses a magical "dedicated and extraordinary biological amplifier" and AI algorithms that can filter and distinguish the differing source generators and frequency bands for EEG, EMG, and EOG? Without a reference electrode connecting to the differential amplifier?

* ADDENDUM Jan 12 2014: No, that is “a part to generate physical vibration.” There are 3 electrodes, as shown in the prototype image further down.

PCB version 2.1

The developers claim:
Thanks to the use of the newest technologies we were able to create a device that will improve your effectiveness and concentration at work to the best possible levels. Measurements of EEG, EOG and EMG, coupled with the usage of artificial intelligence, allows us to create the world's first digital sleep-control system that provides accuracy close to professional polisomnographic clinics.

According to what criteria? Which published studies? Because here's a paper from a group of clinical EEG experts on how difficult it was to reach a consensus on Standardized Computer-based Organized Reporting of EEG (SCORE):
The interobserver agreement in electroencephalography (EEG) interpretation is only moderate (Van Donselaar et al., 1992; Stroink et al., 2006). The EEG signal has a high complexity. It depends on the intricate interplay between the activation of neural networks, localization and orientation (Wong, 1998) of the source (dipole), and its propagation throughout the brain (Lopes da Silva & van Rotterdam, 1993; Scherg et al., 1999; Flemming et al., 2005).

Current prototype (the backside view)

So those three gray squares sitting on your eyebrows are the recording electrodes that will distinguish eye movements like those during REM sleep (very large amplitude signals) from actual brain activity (very tiny signals)? And when the A to D output is transmitted wirelessly via bluetooth to a smartphone application, the app will wake you up precisely at the end of a REM sleep cycle? AND will induce lucid dreaming on demand, so you can literally control your dreams. Really??

No.  Dream on.

And the sad thing is that hundreds of people have pledged $250 to buy a device that will not deliver what's promised.

What is your dream?

Do you need more energy and to feel well - rested?
Do you want to pack even more into your day?
Do you want to have more control over your day?
Do you hate jet lag?
Do you just need that few extra hours every day?
Do you want to be a hero by day and a superhero by night?
Or maybe it's not so sad... people are always susceptible to snake oil and miracle cures, only now in a high tech faux-neuro guise. As of this writing, 1,901 backers have pledged $431,114, far surpassing the $100,000 goal.  Only 15 hours to go!

Don't you think it's more important to expand access to clean water and improved sanitation in poor, rural households in Vietnam? This Kiva microloan has raised 61% of its $4,750 goal, with $1,850 to go before Jan 27, 2014.

Further reading:

Dormivigilia (an actual sleep researcher) on sleep

Gaines on Brains on sleep tracking apps and why their premise is flawed

ADDENDUM #2 (Jan 12 2014): Since a commenter mentioned the Zeo headband (made by the now-defunct company Zeo, Inc.), I thought I'd say a few words about it here. The company published a paper in the Journal of Sleep Research (Shambroom et al., 2012) that examined the performance of their wireless system (WS) to professional polysomnography (PSG; see Gaines on Brains for more on sleep EEG). The Zeo agreed with the simultaneously recorded PSG sleep stages 75% of the time over the course of a night. However, the Zeo did poorly at the detecting onset of the first REM episode:
"The WS significantly and substantially underestimated REML compared to PSG. There were nine nights for which the WS scored REM within the first 6 min of sleep, possibly indicating a tendency for the technology to score REM in the early lightest stage of sleep."
The headband has 3 electrodes on the forehead like NeuroOn and used an Fp1-Fp2 bipolar recording montage (two standard left and right frontopolar sites on the forehead). EEG recorded here is particularly prone to artifacts from eye movements and muscle activity and is thus a mixture of all these signals. Analytic techniques such as independent component analysis (ICA) try to separate the sources. The Zeo group used some sort of training algorithm that used "a combination of time and frequency dependent features derived from the signal to create a best estimate of sleep stage." Interestingly, they had to filter out the very low frequencies (below 2 Hz) that comprise much of the delta wave activity seen during slow wave sleep. This was because of contamination by excessive noise in the low frequency range.

I have no idea of how any of Zeo technology relates to that used by NeuroOn, but the published paper presented some of the challenges involved in developing such a system.

ADDENDUM #3 (Jan 12 2014): While I'm at it, I should mention another neurocrap Kickstarter project -- Aurora: The Dream-Enhancing Headband, which was brought to my attention by Micah Allen. Save your money! If you want to support a worthwhile project, try OpenBCI: An Open Source Brain-Computer Interface For Makers, recommended as legit by Neurobonkers.

ADDENDUM #4 (Jan 13 2014): New post from a sleep researcher: Nonsense neurogadgets: sleep edition, at Taking a cat apart.

Author: "noreply@blogger.com (The Neurocritic)"
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Date: Tuesday, 31 Dec 2013 03:07
** This post is meant to be read in tandem with its more complimentary cousin, Electroconvulsive Therapy Impairs Memory Reconsolidation, at The Neurocomplimenter. **

spECTrum 5000Q® ECT device (MECTA)

Bad memories haunt a significant number of people with serious mental illnesses, such as chronic major depression and post-traumatic stress disorder (PTSD). If it were possible to undergo an experimental procedure that selectively impairs your memory for an extremely unpleasant event, would you do it? If this sounds like the plot of Eternal Sunshine of the Spotless Mind, you're not alone.

A pet peeve of mine is reference to this excellent but far-fetched film in scientific journals and popular media coverage of “memory erasure.” The idea that it's possible to selectively remove a complex autobiographical memory that has become intimately entwined with the fabric of our constructed selves is utter science fiction.

At some level, even Michel Gondry knew it. One incident in Eternal Sunshine is suggestive of how memories might actually be stored. It was after one of the main characters (Joel) had his memories of his ex-girlfriend Clementine erased, and he couldn't remember who Huckleberry Hound was. He had associated the cartoon character and the song "Darling Clementine" with her. That resembles a semantic network, where an overlapping network of neurons and synapses code different but semantically related things. Take out all episodic and semantic memories of Clementine, and knowledge of Huckleberry Hound goes with it.

The latest incarnation of this particular memory erasure meme was provoked by publication of a paper (Kroes et al., 2013) that examined the process of memory reconsolidation in depressed patients administered a course of electroconvulsive therapy (ECT). Here are some of the headlines:
Zapping the brain can help to spot-clean nasty memories

Absolutely shocking: electrocuting brain can wipe unpleasant memories

Unwanted Memories Erased in Electroconvulsive Therapy Experiment

Shocking Memories Away

My companion post at The Neurocomplimenter reviews the literature on memory reconsolidation and describes the experiment of Kroes et al. (2013) in some detail. What I'd like to do here is to point out possible weaknesses in the results that could undermine the authors' conclusions. I'll also discuss a much earlier ECT study which did not support the notion that reactivated memories are especially vulnerable to disruption (Squire et al., 1976).

To briefly reiterate the methods used in the new paper (Kroes et al., 2013), the participants were 39 patients with moderate to severe major depression. They were either at the end of an acute treatment cycle or receiving maintenance ECT. The study used a between-subjects design with three different experimental conditions, with patients randomly assigned to one of the three groups (n=13 in each). The within-subjects factor was whether or not the patients received a reminder of previously learned material before treatment.

All participants learned two different emotionally charged slide stories with audio narration, each consisting of 11 images. In one, a boy is in an accident that severs his feet, which are reattached at the hospital. In the other, two sisters leave their home at night, and one is kidnapped at knife point and attacked by an escaped convict.

Memory for one of the stories was reactivated a week later by presenting part of the first slide, and then giving a test for this slide. Only four minutes later, Groups A and B were anesthetized and received ECT. Group C received their ECT treatment at a later date. The final memory test for Groups A and C was 24 hrs after the reminder, while Group B was tested as soon as they woke up from the procedure (mean = 104 min later). The final test consisted of 40 multiple choice questions about each of the stories.

The basic idea is that reconsolidation of the reactivated story isn't complete within 104 min, so Group B's test performance should be the same for the two stories. In contrast, reconsolidation is complete by 24 hrs, so for Group A the disruptive effect of ECT should selectively impair memory for the transiently reactivated story, which is in a labile state (relative to the "consolidated" story learned 7 days earlier).

Is that what was observed? Statistically speaking, yes. But two patients in Group B (out of 13 total) performed very well on the reactivated story (see purple box in the figure below).

Fig. 1 (modified from Kroes et al. 2013). ECT disrupts reconsolidation. Memory scores on the multiple choice test are expressed as percentage correct (y axis). Memory for the reactivated story shown in solid bars and non-reactivated story in open bars. Each circle is the score for an individual patient. The horizontal dotted line is chance performance. Group A is in red, Group B in blue, and Group C in orange. Edited to add: The purple box highlights 2 outliers in Group B who could be driving the major effect.

If these two individuals are omitted, would the difference between Groups A and B still be significant? This is the key finding of the paper, that memory for the reactivated story is no better than chance if ECT disrupts reconsolidation (a time-dependent process). Hence all the Eternal Sunshine / “memory erasure” headlines.

The purple boxes show that (1) the Reactivation x Group interaction squeaks in at just barely significant (p=.049); and (2) the Group A vs. Group B comparison for the reactivated story is p=.042. Clearly, it would be nice to include twice as many patients in each group. But it took the authors 3.5 years to recruit their final total of n=39.

This type of study is not easy to pull off, which is why I applaud the authors (and the patients) for such an ambitious undertaking. I thought it was a very clever idea as well, but not an original one as it turns out.

In the 1970s and 80s, Dr. Larry Squire and his colleagues published a series of papers on ECT and memory. The one I'll describe here takes a similar approach to Kroes et al. by testing previously learned material after ECT, and by giving a memory reminder just before the treatment (Squire et al., 1976).

Squire et al. (1976) used a completely within-subjects design (n=12) that manipulated the pre-ECT learning interval (14-18 hrs vs. 3-10 min). The third condition presented a memory reminder 3-10 min before ECT for material learned 14-18 hrs previously. Completely different stimuli were used each time, and the order of conditions was counterbalanced. The memory tests were recognition memory for a set of 32 previously learned items (common objects, common words, yearbook photos, and nonsense drawings), and paired associates (producing the correct target for 18 previously learned cue-target pairs). In all conditions, retention was tested 6-10 hrs after ECT (compare to 104 min and 24 hrs in Kroes et al.).

A separate group of patients (n=9) was tested on their remote memories for old TV shows under three conditions: (1) 6-10 hrs after ECT; (2) 14-18 hrs before  ECT and again with the same questions 6-10 hr after ECT; (3) Less than 10 min before ECT and again with the same questions 6-10 hrs after ECT (the reminder procedure).

The critical result is that the memory reactivation procedure did not impair performance (bar graphs A vs. R below). In both of these conditions, material was learned 14-18 hrs before ECT. This is in contrast to the findings of Kroes et al. (2013).

Fig. 1 (modified from Squire et al., 1976). Results from (A) 32-item recognition memory test, and (B) paired-associate learning test, under three conditions in conjunction with the patients' first 3 ECT sessions. Retention was significantly impaired in Condition B (initial learning 3-10 min before ECT). The reminder procedure (Condition R) caused no impairment in performance relative to Condition A.

Squire and colleagues (1976) concluded that “...the results provide no evidence that the presentation of previously learned material just prior to ECT increases its vulnerability to disruption.” Similar results were observed in the patient group tested on their knowledge of old TV shows: “the results clearly indicate that amnesia for remote memory did not occur when remote memory was evoked prior to ECT.”

The final conclusions [clairvoyantly] throw cold water on the study published 37 years later:
The present findings also have important clinical implications. The reactivation phenomenon described in experimental animals has raised the possibility that it might be therapeutically advantageous to evoke depressive ideation just prior to treatment, in order to produce amnesia for this ideation. The results reported here strongly suggest that this procedure would be ineffective.

However, you'll probably notice some differences between the two studies. Kroes et al. pointed out that their effect was observed at a 24 hr retention interval, while Squire et al. only tested at 6-10 hrs (perhaps not long enough to disrupt reconsolidation). The Squire stimuli were neutral in valence, whereas the Kroes stimuli were emotional (and perhaps more susceptible to disruption). There were also differences in the patient groups (Squire's were younger, mean=39 yrs), anesthesia used, electrode locations, and ECT parameters (likely to be way more potent in the earlier study, which would predict worse amnesia). An unfortunate side effect of ECT is memory impairment, although other studies claim the opposite.

Certainly, subjective cognitive complaints after ECT are very common. For a first hand look at some of the more devastating effects, watch the powerful video below. For a lighthearted and critically acclaimed look at fictional memory erasure, watch Eternal Sunshine of the Spotless Mind.

from Eternal Sunshine of the Spotless Mind


Kroes MC, Tendolkar I, van Wingen GA, van Waarde JA, Strange BA, & Fernández G (2013). An electroconvulsive therapy procedure impairs reconsolidation of episodic memories in humans. Nature neuroscience PMID: 24362759

Squire LR, Slater PC, & Chace PM (1976). Reactivation of recent or remote memory before electroconvulsive therapy does not produce retrograde amnesia. Behavioral biology, 18 (3), 335-43 PMID: 1016174

Liz Spikol (of The Trouble With Spikol fame) tries to explain the confusion and the loss of self she felt after waking up from ECT.

"After the ECT, I did not know how to use a toothbrush. And that lasted for months."
- Liz Spikol (at 9:28)
Author: "noreply@blogger.com (The Neurocritic)"
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Date: Friday, 27 Dec 2013 10:24

Never Forget Srebrenica, by Scott McIntyre. A Bosnian Muslim man makes his way past the caskets of those killed in the Srebrenica genocide of July 1995.

Horrible, unspeakable memories will forever haunt the psyches of many survivors of war, genocide, and other atrocities. But what is behind the systematic denial of crimes against humanity?

The Science of Hatred

What makes humans capable of horrific violence? Why do we deny atrocities in the face of overwhelming evidence? A small group of psychologists say they are moving toward answers. Is anyone listening?

By Tom Bartlett

The former battery factory on the outskirts of Srebrenica, a small town in eastern Bosnia, has become a grim tourist attraction. Vans full of sightseers, mostly from other countries, arrive here daily to see the crumbling industrial structure, which once served as a makeshift United Nations outpost and temporary haven for Muslims under assault by Serb forces determined to seize the town and round up its residents. In July 1995 more than 8,000 Muslim men, from teenagers to the elderly, were murdered in and around Srebrenica, lined up behind houses, gunned down in soccer fields, hunted through the forest.

This stunning article in The Chronicle of Higher Education focuses on studies of intergroup conflict, in particular the work of Sabina Cehajic-Clancy, a Bosnian social psychologist. “It is unbelievable the extent and amount of creativity that people possess when it comes to denying,” she said.

Sadly, this sort of research is seriously undervalued in psychology:
Studying conflict can be a draining, thankless endeavor. Government officials rarely turn to social psychologists for advice on how to end war or cool simmering tensions. Within psychology, research on intergroup conflict is not a speedy route to professional acclaim. The fieldwork can be arduous and expensive. Funds are hard to come by, and so is publication in top journals. You’d be better off surveying undergraduates about their dating preferences or dietary habits.
Author: "noreply@blogger.com (The Neurocritic)"
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Date: Sunday, 22 Dec 2013 04:49

Most of us have had frightening nightmares – someone is chasing after us trying to kill us, or the world is coming to an end. Other disturbing dreams are based on real life anxieties – our partner leaves us, we lose our job, we become homeless. One specific psychiatric condition includes nightmares as part of the diagnosis. Individuals with post-traumatic stress disorder (PTSD) often have terrible nightmares that relive the traumatic event (Pigeon et al., 2013)

We're always glad to wake up from such nightmares, whether they were of the supernatural or mundane or terrifying variety. "Thank god it was only a dream," we say.

But what if waking up from sleep was the nightmare? Hypnopompic hallucinations are unusual sensory phenomena experienced just before or during awakening. Their better known mirror image, hypnagogic hallucinations, are vivid and frightening episodes of seeing or hearing or feeling phantom sensations while falling asleep (or in early stage 1 sleep). Both are frequently associated with sleep paralysis, the terrifying condition of being half awake but unable to move. This is because the complete muscle atonia typically experienced during REM sleep has oozed into lighter stages of non-REM sleep.

Hypnagogic and hypnopompic hallucinations are usually associated with narcolepsy, but 37% of a representative community sample reported frequent hypnagogic hallucinations, and 12.5% reported hypnopompic hallucinations (Ohayon et al., 1996).1 This went well beyond the low incidence of narcolepsy in that population. Both types of hallucinations were more common in those with insomnia, excessive daytime sleepiness, anxiety disorders, and depression (according to self-report).

Night Terrors 1, by Beth Robinson

Nocturnal Episodes of Pain and Screaming

A new case study in the journal Sleep (Mantoan et al., 2013) reports on the terrifying hypnopompic hallucinations of a 43 year old woman who experiences intense limb pain when waking up, which vanishes within 30 seconds. This is a very unusual manifestation of a non-REM parasomnia, a sleep disorder involving partial arousal during the transition between non-REM and wakefulness. The phenomenology might be best characterized as a night terror.

According to the case report (Mantoan et al., 2013), the patient had...
...a history of nocturnal screaming episodes within 1–2 h of sleep onset from the age of 30 years. Her husband was habitually awoken by his wife screaming loudly, usually flapping either her right or left hand against the bed in a semi-purposeful fashion. Her husband reported that the events were sometimes heralded by an inspiratory sigh, she looked terrified and would not respond to him. The screaming would usually last 5–10 sec, and she would then complain to her husband of intense pain affecting the fingers of either hand or arm and occasionally her legs, with no associated numbness or paraesthesia. She would become fully orientated within 30 sec and would be partially amnesic for the event, but would recall an accompanying sense of “fighting to stay alive” associated with intense panic and often accompanied by fast regular palpitations. Otherwise no dream mentation or visualizations were reported in association with the episodes.

She initially had these episodes monthly, but they increased in frequency to 2-5 times a week with 1-2 episodes per night.
She was unable to identify any triggers for the episodes, and neither she nor her husband considered her to be stressed, anxious, or depressed. There was no history of sleep violence, sleep sex, sleep eating, or any other NREM parasomniac automatisms. 

The authors could not identify any standard physical source for the pain. Thoracic outlet syndrome, cervical radiculopathy, focal nerve entrapment, and median neuropathy (carpal tunnel syndrome) were all ruled out.

Pharmacological treatments were unsuccessful. A low dose (0.5–1 mg) of clonazepam was poorly tolerated (it made her feel depressed) and had no effect on her symptoms. Paroxetine was poorly tolerated (due to sedative effects), and gabapentin was also a complete failure. Trazodone, a sedating antidepressant most often prescribed for insomnia, actually made the symptoms worse.

An MRI ruled out a thalamic or hypothalamic lesion. Sleep EEG revealed sudden arousals from deep sleep, accompanied by looks of pain and/or fear on the patient's face. The episodes were consistent with a NREM parasomnia. In the example below, the patient was shaking her arm – muscle activity (EMG) is shown in the green trace.

adapted from Fig. 1B (Mantoan et al., 2013). EEG showing delta waves of stage 3 sleep before an episode of arousal with shaking of one arm and looks of fear. Channels 1-12 are EEG; channels 13 and 14 are electro-oculogram (EOG) activity; channel 15 is electromyography (EMG); channel 16 is electrocardiogram (ECG); channel 17 is oxygen saturation by pulse oximetry (SpO2).  {click on image for a larger view}

What did the doctors do to help this poor woman? Nothing, it seems. A few more musculoskeletal causes need to be ruled out.

The authors end on a vague note about the possible mechanism(s):
In conclusion, to our knowledge this is the first report of a NREM parasomnia associated with painful paroxysms, for which we postulate the following underlying pathophysiological mechanism: an internal or external stimulus triggers arousal, facilitating the activation of innate motor pattern generators in the brainstem and activating somatosensory cortical areas to produce hypnopompic hallucinatory pain.

So instead of the more typical visual hallucinations, the patient experiences pain hallucinations that originate.... where?? It seems to me that the sleep EEG could be analyzed more thoroughly, beyond merely ruling out seizure occurrence. Perhaps another imaging modality like PET could be tried (PET would be quieter than fMRI and would better tolerate movement). Identifying the neurophysiological correlates of her phantom night terror pain would provide a fascinating glimpse into a highly unusual sensory phenomenon.2

Further Reading

The Phenomenology of Pain During REM Sleep

The Neurophysiology of Pain During REM Sleep


1 The questions asked in the telephone interviews by Ohayon et al. (1996) were:
(a) Do you experience at least twice a week the following perceptions?

(i) the realistic feeling that someone or something is present in the room
(ii) a vivid experience of being caught in a fire
(iii) a vivid experience that you are about to be attacked
(iv) a vivid experience that you are flying through the air
(v) the feeling that you will soon fall into an abyss
(vi) the feeling that shadows or objects are moving and distorting.

(b) Do you experience other types of vivid perceptions?

(c) Can you specify the type of perception?

(i) auditory
(ii) visual
(iii) kinetic (involving movement)
To me, the most surprising part of the survey is that 37% reported these phenomenon at sleep onset twice a week for the past year. This contrasts sharply with only 0.04% reporting symptoms of narcolepsy.

2 I've occasionally felt pain in dreams that vanished upon awakening, but I'm pretty sure the episodes occurred during REM (or another stage of dreaming sleep), because visual narrative content was associated with the episodes. Those experiences were clearly not night terrors, and very different from what was reported in the case study.


Mantoan L, Eriksson SH, Nisbet AP, & Walker MC (2013). Adult-onset NREM parasomnia with hypnopompic hallucinatory pain: a case report. Sleep, 36 (2), 287-90 PMID: 23372277

Ohayon MM, Priest RG, Caulet M, & Guilleminault C (1996). Hypnagogic and hypnopompic hallucinations: pathological phenomena? The British journal of psychiatry, 169 (4), 459-67 PMID: 8894197

Pigeon WR, Campbell CE, Possemato K, Ouimette P. (2013). Longitudinal relationships of insomnia, nightmares, and PTSD severity in recent combat veterans. J Psychosom Res. 75:546-50.

The Sleep Paralysis Project
Author: "noreply@blogger.com (The Neurocritic)"
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Date: Wednesday, 18 Dec 2013 09:33

National Institutes of Health (NIH) has finally released detailed descriptions for six separate funding opportunities in support of the BRAIN Initiative. If you're big on cells, circuits, and/or technologies, one of these programs could be for you. NIH hopes to award $40 million by the end of the fiscal year (September 30, 2014). The application deadlines are all in March 2014.

In October, Defense Advanced Research Projects Agency (DARPA) announced that it would spend $70 million over the next five years to develop and improve deep brain stimulation (DBS) techniques. The approaches of the two agencies are quite different, as outlined in this post.

The NIH Director's BRAIN Advisory Committee issued its Interim Report (PDF) on September 16. The report focused on animal models, including improvement of technologies for recording neuronal activity and manipulating circuit function. The new Requests for Applications (RFAs) reflect the high-priority research areas for FY 2014. Here are concise summaries of the new funding opportunities from the White House:
  • Generate an inventory of the different types of cell types in the brain
  • Develop new tools to analyze the complex circuits that are responsible for brain function by delivering  genes, proteins and chemicals to particular cells
  • Develop new approaches to record the activity of large numbers of neurons in any location in the brain, and improve existing technologies so they can be widely adopted by neuroscientists
  • Understand large-scale neural circuits by integrating experimental, analytical, and theoretical approaches
  • Form teams to develop the next generation of non-invasive imaging technologies

As you can see, Cellular/Molecular and Systems/Circuits neuroscience researchers will benefit the most, along with engineers, physicists, and other technology-development types.

Here are the RFA summaries from NIH:
  • Transformative Approaches for Cell-Type Classification in the Brain (RFA-MH-14-215) – aims to pilot classification strategies to generate a systematic inventory/cell census of cell types in the brain, integrating molecular identity of cell types with connectivity, morphology, and location. These pilot projects and methodologies should be designed to demonstrate their utility and scalability to ultimately complete a comprehensive cell census of the human brain.

  • Development and Validation of Novel Tools to Analyze Cell-Specific and Circuit-Specific Processes in the Brain (RFA-MH-14-216) – aims to develop and validate novel tools that possess a high degree of cell-type and/or circuit-level specificity to facilitate the detailed analysis of complex circuits and provide insights into cellular interactions that underlie brain function. A particular emphasis is the development of new genetic and non-genetic tools for delivering genes, proteins and chemicals to cells of interest; new approaches are also expected to target specific cell types and or circuits in the nervous system with greater precision and sensitivity than currently established methods.

  • New Technologies and Novel Approaches for Large-Scale Recording and Modulation in the Nervous System (RFA-NS-14-007) – focuses on development and proof-of-concept testing of new technologies and novel approaches for large scale recording and manipulation of neural activity, with cellular resolution, at multiple spatial and/or temporal scales, in any region and throughout the entire depth of the brain. The proposed research may be high risk, but if successful could profoundly change the course of neuroscience research.

  • Optimization of Transformative Technologies for Large Scale Recording and Modulation in the Nervous System (RFA-NS-14-008) – aims to optimize existing and emerging technologies and approaches that have the potential to address major challenges associated with recording and manipulating neural activity. This FOA is intended for the iterative refinement of emergent technologies and approaches that have already demonstrated their transformative potential through initial proof-of-concept testing, and are appropriate for accelerated engineering development with an end-goal of broad dissemination and incorporation into regular neuroscience research.

  • Integrated Approaches to Understanding Circuit Function in the Nervous System (RFA-NS-14-009) – focuses on exploratory studies that use new and emerging methods for large scale recording and manipulation to elucidate the contributions of dynamic circuit activity to a specific behavioral or neural system. Applications should propose teams of investigators that seek to cross boundaries of interdisciplinary collaboration, for integrated development of experimental, analytic and theoretical capabilities in preparation for a future competition for large-scale awards.

  • Planning for Next Generation Human Brain Imaging (RFA-MH-14-217) – aims to create teams of imaging scientist together with other experts from a range of disciplines such as engineering, material sciences, nanotechnology and computer science, to plan for a new generation of non-invasive imaging techniques that would be used to understand human brain function. Incremental improvements to existing technologies will not be funded under this announcement.

Is this a call for DARPA-lite projects? Or for proposals as far-fetched as calcium imaging in humans? As the RFA explains...
The long-term objective is to develop tools for the precise imaging of molecules, cells, and circuits in the human brain.  Applications submitted in response to this R24 FOA should support the formation and development of interdisciplinary teams that will plan innovative approaches to substantively expand the ways by which brain structure and function can be imaged in humans.  These R24 awards will support planning activities such as meetings, prototype development projects and small scale pilot studies in mammals or humans that would provide proof of principle for transformative approaches to assessing human brain structure and function.  The proposed concepts are expected to be high-risk, high-impact, and disruptive (c.f. C. Christensen “The Innovator's Dilemma”, 1997; http://en.wikipedia.org/wiki/Disruptive_innovation).

What might these [post-]BOLD new BRAIN scanners of the future look like? This question was addressed by practiCal fMRI in September:
This week's interim report from the BRAIN Initiative's working group is an opportunity for all of us involved in fMRI to think seriously about our tools. We've come a long way with BOLD contrast to be sure, even though we don't fully understand its origins or its complexities. ...

I can't help but wonder what my fMRI scanner might look like if it was designed specifically for task. Would the polarizing magnet be horizontal or would a subject sit on a chair in a vertical bore? How large would the polarizing magnet be, and what would be its field strength? The gradient set specifications? And finally, if I'm not totally sold on BOLD contrast as my reporting mechanism for neural activity, what sort of signal do I really want? In all cases I am especially interested in why I should prefer one particular answer over the other alternatives.

Note that I'm not suggesting we all dream of voltage-sensitive contrast agents. That's the point of the BRAIN Initiative according to my reading of it. All I'm suggesting is that we spend a few moments considering what we are currently doing, and whether there might be a better way...

Further Reading

DARPA allocates $70 million for improving deep brain stimulation technology


New Deep Brain Stimulation System Measures Neurotransmitter Release

Anyone who is awarded one of these #BRAINI grants is free to use this nifty badge on all their promotional materials and publications.

The BRAIN Initiative badge is awarded by President Obama to research supported by his $100 million #BRAINI. This bold new research effort will include advances in nanotechnology and purely exploratory efforts to record from thousands of neurons simultaneously.
Author: "noreply@blogger.com (The Neurocritic)"
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Date: Saturday, 14 Dec 2013 21:17

German Composer Richard Wagner (1813-1883) wasn't the healthiest guy. He suffered from heart disease, skin disorders, acute infections, minor ailments, and most prominently, recurring headaches – the “main plague” of his life (Göbel et al., 2013). He complained of “Headache, ‘sick headache,’ ‘dyspepsia,’ ‘nervousness,’ melancholy, insomnia, indescribable suffering... Wagner had all of them all of the time” (Gould, 1903).

Wagner wrote many letters to his doctor, Dr. Pusinelli, over a 35 year period (Gould, 1903):
They begin with, "I have headache," and continue with complaints of bad weather and bad health; of growing old and loss of joy (aged 33 years); of increase of illness; working at composition with consequent frightful suffering; with prayers for peace, peace; moans at the uselessness of life; regrets at inability to get a good photograph; and sleeplessness. Baths and douches drive him nearly crazy. There is longing for his natural joyfulness; reiteration of physical and mental exhaustion; the thought of suicide; emphasis of his irritability and of his inability to write another line, etc.

A new article in the Christmas edition of BMJ by a trio of Göbels (Göbel, Göbel, & Göbel, 2013) focuses on Wagner's migraines and how he incorporated the attacks and auras into his operas. The specific example of interest is the opera Siegfried (1876), which is the third part of the Ring Cycle.
The first scene of act 1 of the opera Siegfried provides an extraordinarily concise and strikingly vivid headache episode. The music begins with a pulsatile thumping, first in the background, then gradually becoming more intense. This rises to become a directly tangible almost painful pulsation. While the listener experiences this frightening headache sensation, Mime is seen pounding with his hammer, creating the acoustic trigger for the musically induced throbbing, painful perception. At the climax Mime cries out: “Compulsive plague! Pain without end!”

A contemporary staging of Siegfried by Anthony Pilavachi portrays the character of Mime as a scientist in a white lab coat (see video below). Göbel et al. (2013) identify a “migraine aura leitmotif” that occurs in act 1, scene 3. It depicts the visual disturbances that accompany migraine aura. Mime sings, “Loathsome light! Is the air aflame? What is it flaring and flashing, glittering and whirring, what is swirling and whirling there and flickering around? It glistens and gleams in the sunlight’s glow. What is it rustling and humming and blustering there?”

Wagner's disabling migraines contributed to a 12 year disruption in his work on Siegfried, which was finally completed in 1871 and first staged in 1876. He wrote of his struggles in one of his many letters, this one to Franz Liszt in January 1857 (Gould, 1903):
My health, too, is once more so bad that for ten days after I had finished the sketch for the first act of Siegfried, I was literally not able to write a single bar without being driven away from my work by a most alarming headache. Every morning I sit down, stare at the paper, and am glad enough when I get as far as reading Walter Scott. The fact is I have once more overtaxed myself, and how am to recover my strength? With Rheingold I got on well enough but the Valkyrie caused me much pain. At present my nervous system resembles a pianoforte very much out of tune. 

The Göbels summarize their paper in the video below.

Here's hoping that your holiday season is headache-free!


Carl H Göbel, Anna Göbel, Hartmut Göbel (2013). “Compulsive plague! pain without end!” How Richard Wagner played out his migraine in the opera Siegfried BMJ DOI: 10.1136/bmj.f6952

George M Gould (1903). THE ILL-HEALTH OF RICHARD WAGNER. Lancet DOI: 10.1016/S0140-6736(01)34061-8 
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