Saturday, February 18, 2017

Using Discourse Analysis to Assess Cognitive Decline

Figure from Gauthier et al. (2005).

Alzheimer's Disease (AD) and other dementias are progressive neurodegenerative conditions that unfold over time. Subtle symptoms such as forgetfulness and word finding problems may progress to mild cognitive impairment (MCI), and then escalate to full-blown dementia. Recent efforts to classify prodromal states have included automated analysis of spontaneous speech, which loses complexity as the disease progresses.

In one study, Frazier et al. (2015) applied machine learning methods to speech transcripts and audio files from the DementiaBank database. The participants were 167 patients with probable AD and 97 controls. The authors considered a total of 370 linguistic features, and found that a subset of 35 was able to classify patients vs. controls with 82% accuracy.1 While an advance over previous studies, this is not yet useful for diagnostic purposes. Another limitation was the relatively short length of the speech samples.2

Using factor analysis, the researchers found that four dimensions of speech3 were most indicative of dementia:
  • Semantic impairmentusing overly simple words
  • Acoustic impairment e.g., speaking more slowly
  • Syntactic impairment  using less complex grammar
  • Information impairment not clearly identifying the main aspects of a picture they were told to describe

Public figures who give repeated interviews leave a searchable record of spontaneous speech that can be analyzed for changes over time. Presidential press conferences provide another rich source of data for linguistic analysis.

Berisha et al. (2015) examined transcripts from the press conferences given by Ronald Reagan (1981-1989) and George H.W. Bush (1989-1993). We know that President Reagan received a formal diagnosis of Alzheimer's disease in 1994, five years after leaving office. And as far as we know, the elder Bush is still cognitively intact for his age (he's 92 now).

The quantified linguistic features included:
  • Number of unique words
  • Non-specific nouns – e.g., thing, something, anything
  • Filler words – well, so, basically, actually, literally, um, ah
  • Low-imageability, high frequency verbs – e.g., get, give, go, have, do

Reagan showed a significant decline in the number of unique words over the course of his presidency, but Bush did not.

Likewise, Reagan showed a significant increase in the use of non-specific nouns and fillers, but Bush did not.

There are several caveats here. Reagan was 69 when he was elected, while Bush was 64. Reagan was president for eight years and Bush for only four years; yet Bush held over twice as many press conferences as Reagan. Nonetheless, the results are consistent with a decline in cognitive function (which is not uncommon when aging from 69 to 77). Can we can classify Reagan as having MCI on the basis of these results? I don't think so. We'd really need comparable data from a population of demographically matched elderly participants.

President Donald Trump

After his Feb. 16 press conference, the public debate over whether President Trump is mentally unbalanced has intensified. Much of the current and past discussion has centered on the possibility of Narcissistic Personality Disorder (NPD), as speculated in The Atlantic and Vanity Fair and The Guardian. Sure, Trump has many of these qualities (that predate his actual grandiose status as POTUS):
  1. Grandiosity with expectations of superior treatment from others
  2. Fixated on fantasies of power, success, intelligence, attractiveness, etc.
  3. Self-perception of being unique, superior and associated with high-status people and institutions
  4. Needing constant admiration from others
  5. Sense of entitlement to special treatment and to obedience from others
  6. Exploitative of others to achieve personal gain
  7. Unwilling to empathize with others' feelings, wishes, or needs
  8. Intensely envious of others and the belief that others are equally envious of them
  9. Pompous and arrogant demeanor
And we can call him narcissistic in the generic sense of the word. But do we need to diagnose him with a quasi-psychiatric disorder, as in this NY Times letter signed by 35 mental health professionals?4
Mr. Trump’s speech and actions demonstrate an inability to tolerate views different from his own, leading to rage reactions. His words and behavior suggest a profound inability to empathize. Individuals with these traits distort reality to suit their psychological state, attacking facts and those who convey them (journalists, scientists).

In a powerful leader, these attacks are likely to increase, as his personal myth of greatness appears to be confirmed. We believe that the grave emotional instability indicated by Mr. Trump’s speech and actions makes him incapable of serving safely as president.

Dr. Allen Frances, chair of the DSM-IV task force, has forcefully argued that Trump does not meet criteria for NPD, because he is not distressed by his behavior:
Mr. Trump causes severe distress rather than experiencing it and has been richly rewarded, rather than punished, for his grandiosity, self-absorption and lack of empathy. It is a stigmatizing insult to the mentally ill (who are mostly well behaved and well meaning) to be lumped with Mr. Trump (who is neither).

Discourse Analysis

Here I'll suggest a different approach: can we quantify age-related neurological change using spontaneous speech?

“You know what uranium is, right?  It's this thing called nuclear weapons and other things.  Like, lots of things are done with uranium, including some bad things.  Nobody talks about that.  I didn't do anything for Russia.  I've done nothing for Russia.”

This is the most egregious example in the one hour, 17 minute train wreck. But there are other signs. He used the construction “very, very” 20 times. The word “thing” (and its variants) was uttered 102 times.

Am I going to diagnose him with anything? Of course not. That's unethical! But I will say that since Mr. Trump has been a public figure for nearly 40 years, we can objectively analyze his spontaneous speech and quantify any changes over time. I must emphasize that there is no magical scale to use for classification or comparison purposes (at least not yet). We don't know what's normal age-related decline and what's pathological.

I suggest that the best corpus of spontaneous speech data is the collection of Trump interviews/conversations with David Letterman. I believe they're unscripted, and there are many of them on YouTube (I've linked to eight below). Letterman has aged too, so you might as well analyze his speech as well.


1 The authors performed...
...a 10-fold cross-validation procedure in which a unique 10% of the data (i.e., the ‘test set’) are used in each iteration for evaluation, and the remaining 90% (i.e., the ‘training set’) are used to select the most useful features (of the 370 available as described in “Features” above) and construct our models. The reported accuracy is an average across the 10 folds. In a given fold, data from any individual speaker can occur in the test set or the training set, but not both.
2 A show-stopping limitation is that the two groups were not matched for age or education. The mean age was 71.8 for AD vs. 65.2 for controls, and years of education 12.5 vs. 14.1 yrs.

3 See also Alzheimer’s Disease Markers Found in Speech Patterns (link via @aholdenj).

4 BTW, they're not supposed to diagnose non-patients, that's unethical.


Berisha V, Wang S, LaCross A, & Liss J (2015). Tracking discourse complexity preceding Alzheimer's disease diagnosis: a case study comparing the press conferences of Presidents Ronald Reagan and George Herbert Walker Bush. Journal of Alzheimer's Disease, 45 (3), 959-63 PMID: 25633673

Fraser, K., Meltzer, J., & Rudzicz, F. (2015). Linguistic Features Identify Alzheimer’s Disease in Narrative Speech. Journal of Alzheimer's Disease, 49 (2), 407-422 DOI: 10.3233/JAD-150520

Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, Belleville S, Brodaty H, Bennett D, Chertkow H, Cummings JL. (2006). Mild cognitive impairment. The Lancet  367:1262-70.

Thomas, C., Keselj, V., Cercone, N., Rockwood, K., & Asp, E. (2005). Automatic detection and rating of dementia of Alzheimer type through lexical analysis of spontaneous speech. IEEE International Conference, 3, 1569-1574. doi: 10.1109/ICMA.2005.1626789

Donald Trump on the David Letterman Show

11-10-1988 Letterman Donald Trump

Donald Trump Interview on Letterman Show (1997)

Donald Trump Interview on David Letterman Show (1998)

Donald Trump on David Letterman Show (2008-08-08)

Donald Trump talks business and banks on David Letterman Show (2009-02-18)

Donald Trump on David Letterman Show (2010)

Donald Trump on David Letterman 17 October, 2013 Full Interview

Donald Trump on David Letterman January 8th 2015 Full Interview

You can find them all here.

other Trump

The Trump Archive - over 900 televised speeches, interviews, debates, and other news broadcasts related to President Donald Trump. See post at Internet Archive.

Donald Trump 1980 Interview (Brokaw)

Ronald Reagan videos

The President's News Conference - 1/29/81

The President's News Conference - 8/12/86

Iran/Contra Excerpt from 11/19/86

The President's News Conference - late Oct 1987

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Saturday, January 28, 2017

Distortions of Reality

President Trump this week repeated an assertion he made shortly after his election: that millions of ballots cast illegally by undocumented immigrants cost him the popular vote. If true, this would suggest the wholesale corruption of American democracy.

Not to worry: As far as anyone knows, the president’s assertion is akin to saying that millions of unicorns also voted illegally.

- In a Swirl of ‘Untruths’ and ‘Falsehoods,’ Calling a Lie a Lie

Reality has been more than a little trippy lately. Two different versions of current events are being presented to Americans: one based on the quantification of data and the historical record, and the other relying on “alternative facts”, a manufactured reality that supports the President's agenda. My last two posts have dealt with the nature of blatant lying and the difficulty of understanding one's political opponents. I've tried to frame my worries about the future in terms of the neuro/psychological influences on political behavior. After all, this is The Neurocritic and not The Politicritic. But the divide keeps getting worse and worse: the executive order banning Syrian refugees and restricting immigrants from Muslim countries, the baseless claim that millions of “illegals” voted for Clinton,1 the ugly wall and who will pay for it. White House/Breitbart Strategist Steve Bannon told the media to “keep its mouth shut and just listen for a while” (a violation of the First Amendment). Supporters of science are also concerned about possible censorship of the EPA, USDA,2 and National Park Service.

What a Long Strange Trip It's Been

Yesterday was the 11th anniversary of my blog. As I move forward into the 12th year, I wonder how The Neurocritic will stay relevant. Last year I wanted to revisit several posts and ask, “Was I Wrong?” I haven't done that yet. Lately, my standard critiques of cog neuro papers and DARPA projects have seemed unimportant in comparison to the cruelty of recent executive orders (and other threats). These policies are an embarrassment. Shameful. Unamerican. The US is sliding into the ill-fitting suit of an isolationist, authoritarian regime and it's frightening. We must stay engaged and fight via direct action: lobby our representatives, speak out in support of those without a voice, protest against unconstitutional changes — in defense of liberty and justice for all.

Figure from Wacker et al. (2017).

Hallucinogenic Highlights

But sometimes we need a break from reality. The alternative reality tenaciously pursued by aficionados of psychedelic drugs (e.g., mind-blowing perceptual distortions, insight into a universal consciousness, entering a portal into another dimension, etc.) is vastly different, of course, than the dystopian sociopolitical construct of  “alternative facts” (i.e., a web of lies).

On that note, two new papers on LSD were published this week. The first study provided insight into why LSD trips last so long (Wacker et al., 2017). LSD binds to the human 5-HT2B receptor (one in a large family of serotonin receptors) in a peculiar way that prolongs its signaling kinetics. The authors created a crystal structure of 5-HT2B bound to LSD and found an “unexpected binding configuration in the orthosteric site.”3

Close-up view of LSD and the orthosteric binding site of the receptor from: (B) the membrane, and (C) the extracellular space.

Wacker et al. (2017) consider this a model system for the 5-HT2A receptor, thought to be the main site of action for LSD's psychedelic properties.

In fact, the second paper linked the “fabric of meaning” to the activation of 5-HT2A receptors (Preller et al., 2017). “Meaning” was defined as the attribution of meaning to musical excerpts that were not previously significant for the participant. This “meaningless” condition was compared to musical excerpts that had been selected as personally significant, and to neutral passages. The Swiss researchers also collected pharmacological fMRI data from the 22 volunteers, 16 of whom had never taken hallucinogens before. This was surprising to me.4

The within-subject drug conditions were: (1) Placebo pre-treatment + Placebo; (2) Placebo pre-treatment + LSD; and (3) Ketanserin pre-treatment + LSD. Ketanserin is a 5-HT2A receptor antagonist and as expected, it neutralized the subjective effects of LSD (although the authors were somewhat surprised by the magnitude of this effect).

Subjective Drug Effects

Mood Ratings

LSD also increased meaningfulness ratings for the meaningless musical passages, an effect that was reversed by ketanerin as well. This overattribution of personal relevance was accompanied by increased activation of medial and lateral frontal regions for the LSD condition, compared to ketanserin + LSD.
...the results provide evidence that this alteration in relevance attribution is related to increased activity of brain areas that are typically involved in self-referential processing and are of clinical importance in psychiatric disorders characterized by altered self-processing.

But it would be an exaggeration to say that all the implicated structures are specific for self-relevant processing, since the SMA, dACC, and vlPFC are important for motor and cognitive processes. Another key issue in fMRI studies of LSD and other psychoactive drugs is motion artifact. Three participants were excluded for excessive head movement (>3 mm) during a scan, but this criterion may be too liberal.

Nonetheless, the complete reversal of LSD's mind-blowing effects by ketanserin was fascinating. Now if we could eliminate more nefarious distortions of reality with a drug, that would really be something.

As always, thank you for reading!


1 “You have people that are registered who are dead, who are illegals, who are in two states. You have people registered in two states. They’re registered in a New York and a New Jersey. They vote twice,” Trump said, adding that none of the illegal votes were cast for him.

Read more here:

But but... Trump's daughter, son-in-law, and press secretary are registered to vote in two states.

2 That order was rescinded. Others have said this is not unusual during transitions. We shall see...

3 Wacker et al. (2017):
To obtain structural insights into LSD’s actions at human serotonin receptors, we crystallized an engineered 5-HT2BR construct bound to LSD by extensively modifying our previous approach (Wacker et al., 2013). We eventually obtained crystals and solved the X-ray structure of the 5-HT2BR/LSD complex to a resolution of 2.9 Å.

4 Preller et al. (2017):
No substantial side effects were recorded during the study. Four participants reported transient headaches after drug effects had worn off. One participant reported transient sleep disturbances for the first two nights after drug administration. Participants were contacted again three months after the last drug administration. No further side effects were recorded.


Preller, K., Herdener, M., Pokorny, T., Planzer, A., Kraehenmann, R., Stämpfli, P., Liechti, M., Seifritz, E., & Vollenweider, F. (2017). The Fabric of Meaning and Subjective Effects in LSD-Induced States Depend on Serotonin 2A Receptor Activation. Current Biology DOI: 10.1016/j.cub.2016.12.030

Wacker, D., Wang, S., McCorvy, J., Betz, R., Venkatakrishnan, A., Levit, A., Lansu, K., Schools, Z., Che, T., Nichols, D., Shoichet, B., Dror, R., & Roth, B. (2017). Crystal Structure of an LSD-Bound Human Serotonin Receptor Cell, 168 (3), 377-2147483647 DOI: 10.1016/j.cell.2016.12.033

   ------The xx

You've applied the pressure
To have me crystalised
And you've got the faith
That I could bring paradise

I'll forgive and forget
Before I'm paralyzed
Do I have to keep up the pace
To keep you satisfied

Things have gotten closer to the sun
And I've done things in small doses
So don't think that I'm pushing you away
When you're the one that I've kept closest

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Sunday, January 22, 2017

Why Do Political Figures Lie So Blatantly?

Are They Pathological Liars? Narcissists? Psychopaths? “Masterful Manipulators”? 

Trump Spokesman’s Lecture on Media Accuracy Is Peppered With Lies

Nearly all American politicians lie, but few as blatantly as those affiliated with the present administration. How do they do it? Are they lacking a conscience? Do they believe their own lies? Do they start with small falsehoods, stretch the truth, reinterpret events, and finally graduate to verifiably false statements?

“This was the largest audience to ever witness an inauguration, period,” Spicer said, contradicting all available data.

Crowds on the National Mall just before Donald Trump’s inauguration in 2017 (left) and Barack Obama’s in 2009.
Photograph: Reuters.

Here are three major points from an astute analysis of why the first press conference of the Trump administration was such a bizarre sham:
1. Establishing a norm with the press: they will be told things that are obviously wrong and they will have no opportunity to ask questions.  ...

2. Increasing the separation between Trump's base (1/3 of the population) from everybody else (the remaining 2/3).  ...

3. Creating a sense of uncertainty about whether facts are knowable, among a certain chunk of the population...   ...

I recommend you read the entire statement, it's very insightful.

How Do People Reach the State of Shameless Lying?

Is there a “slippery slope”? The notorious academic fraudster Diederik Stapel describes his descent from respectable social psychologist to data fabricator:
After years of balancing on the outer limits, the grey became darker and darker until it was black, and I fell off the edge into the abyss. I’d been having trouble with my experiments for some time. Even with my various “grey” methods for “improving” the data, I wasn’t able to get the results the way I wanted them. I couldn’t resist the temptation to go a step further. I wanted it so badly. I wanted to belong, to be part of the action, to score.
. . .

I opened the file with the data that I had entered and changed an unexpected 2 into a 4; then, a little further along, I changed a 3 into a 5. It didn’t feel right. I looked around me nervously. The data danced in front of my eyes.
. . .

No. I clicked on “Undo Typing.” And again. I felt very alone. I didn’t want this. I’d worked so hard. I’d done everything I could and it just hadn’t quite worked out the way I’d expected. It just wasn’t quite how everyone could see that it logically had to be. I looked at the door of my office. It was still closed. I looked out the window. It was dark outside. “Redo Typing.”

Most of us never reach the abyss of Diederik Stapel or Sean Spicer. Or the average politician:
"People want their politicians to lie to them. The reason that people want their politicians to lie them is that people care about politics," said Dan Ariely, a professor of psychology and behavioral economics at Duke University. "You understand that Washington is a dirty place and that lying is actually very helpful to get your policies implemented." 

But we all lie to some extent. “Why yes, that outfit looks great on you” when we really mean to say, “Well, it's not the most flattering ensemble.” White lies like these are meant to spare another person's feelings, and can be considered a norm of politeness. But do small lies desensitize us to any negative feelings that may ensue, and make it easier to tell more substantial lies in the future?

Lying may be your brain's fault, honestly

Of course it is...

A recent neuroimaging study tracked brain activity while participants were given repeated opportunities to lie for financial gain (Garrett et al., 2016). The goal was to follow the escalation of dishonest behavior over time, and to determine its neural correlates. One of the authors of this paper was Dan Ariely, who is famous for his popular books and his TED talks and his work in behavioral economics. He runs the Center for Advanced Hindsight, the (Dis)Honesty Project, and wrote The (Honest) Truth About Dishonesty: How We Lie to EveryoneEspecially Ourselves. If there's anyone who understands lying, it's Ariely.

In the study, the subjects viewed pictures of jars filled with pennies. The experimental set-up involved the subjects in the role of 'Advisor' and confederates in the role of 'Estimator'. The Advisors got a better and longer look at the jars and relayed their estimated count to the confederates, who in turn guessed the number of pennies in each jar. The players were told that at the end of the experiment, one trial would be randomly selected and both parties would be paid according to how accurate the Estimator had been on that trial. Then the Advisor was privately told that the final payment did not depend on accuracy, but the Estimator didn't know this.

The Advisor was also told that the incentive structure would be manipulated, but the Estimator didn't know this, either. Dishonesty about the amount of money in the jar (overestimation) could benefit the participant at the expense of their partner (self-serving/other-harming), benefit both (self-serving/other-serving), benefit the partner at the expense of the participant (self-harming/other-serving), or a baseline condition where it would benefit neither. There were 60 trials of each, in four separate blocks, to track any changes in dishonesty over time.

A total of 55 volunteers performed the task, with 25 of them participating in the fMRI portion of the study. The behavioral results were collapsed across all 55 participants and were not reported separately for the fMRI subjects. As expected, dishonesty escalated across the course of the blocks that were self-serving, to a greater extent for self-serving/other-harming (green) than for self-serving/other-serving (purple).

But in general, this wasn't an overly selfish bunch of people. The participants started at a dishonesty level of £4 when out for only themselves, compared to £12 when it benefited them as well as their partners. Altruistic dishonesty, you might say.

Fig. 1 (Garrett et al., 2016). (ce) Averaging mean dishonesty across participants on every trial and correlating with trial number (N = 60 trials) in each condition revealed significant escalation when dishonesty was self-serving but not otherwise (Self-serving–Other-harming: r58 = 0.66, P < 0.001; Self-serving–Other-serving: r58 = 0.83, P < 0.001; Self-harming–Other-serving: r58 = −0.23, P = 0.08).

What about the neuroimaging results? Were there brain regions that tracked the subtle increase in dishonesty? The authors selected their regions of interest (ROI) via Neurosynth, an online meta-analytic framework based on words that appear in a huge database of articles. The search term they used was “emotion”, which is rather general now isn't it. The rationale for this choice was that (1) people show increased emotional arousal when dishonest; and (2) responses to emotional stimuli diminish with repeated presentation (variously known as habituation, repetition suppression, or adaptation).

It wasn't clear to me why the authors didn't conduct a whole-brain analysis in the first place; they treated it as an “exploratory analysis”.1 And the emotion ROI was basically the amygdala.
My Cousin Amygdala had an opinion about this.

One of the authors explained the results in a press release:
"When we lie for personal gain, our amygdala produces a negative feeling that limits the extent to which we are prepared to lie," explains senior author Dr Tali Sharot (UCL Experimental Psychology). "However, this response fades as we continue to lie, and the more it falls the bigger our lies become. This may lead to a 'slippery slope' where small acts of dishonesty escalate into more significant lies."

Would I Lie to You About Lie Adaptation?

But it's not that simple. Amygdala activity negative feeling. The senior author certainly knows this, since her previous work linked amygdala activity to optimism, of all things (Sharot et al., 2007). 2  The CNN report on the study had a silly eye-rolling title, but they did interview an independent expert, to their credit.
[Lisa Feldman Barrett] says focusing on the amygdala as the brain's source of emotion may be misguided.

Hand-selected, meta-analyses of brain mapping data, as opposed to results spit out by Neurosynth, she says, have shown that the amygdala is not necessarily critical for emotion.
. . .

Barrett said she also wonders if the research results would hold outside a laboratory's doors.

"They did not reward or punish for lying, whereas there is always a payoff or risk in real life," she said. "That might cause the amygdala to maintain its engagement."

All of this said, Barrett said she doesn't doubt that habituation plays a part in lying. She just isn't sure this new research, pointing to the amygdala as the source of emotion, focuses on the correct cause.

A very high-stakes real life experiment would put the most egregious public liars in a scanner during a simulated press conference or a late night bout of tweeting to see what happens when the falsehoods get more and more preposterous.

There is no such thing as “alternative facts.” Do not become desensitized to bald-faced lies.

White House press secretary attacks media for accurately reporting inauguration crowds
. . .

"This was the largest audience to ever witness an inauguration, period," Spicer said, contradicting all available data.

UPDATE (Jan. 27, 2017): Trump just gave a remarkable new interview. Here’s a tally of all his lies.


1 This wasn't always the case, apparently.

2 I was quite critical of that study at the time:

My Amygdala Is Very Optimistic Today...

...But My Subgenual Cingulate Is Sad


Garrett, N., Lazzaro, S., Ariely, D., & Sharot, T. (2016). The brain adapts to dishonesty. Nature Neuroscience DOI: 10.1038/nn.4426

Sharot T, Riccardi AM, Raio CM, Phelps EA. (2007). Neural mechanisms mediating optimism bias. Nature 450(7166):102-5.

A Good Piece in Politico

Trump's Lies vs. Your Brain

The Neurocritic Archives of Lie Detection

Would I Lie to You?

More Lies... Damn Lies...

Would I Lie To You Yet Again?

Lie To Me on the Autobiographical Implicit Association Test

Brain Scans and Lie Detection: True or False?

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Sunday, January 15, 2017

Neuroscience Can't Heal a Divided Nation

Brain activation during challenges to political vs. non-political beliefs (Figure modified from Kaplan et al., 2016).

Lately I've been despairing about the state of America.

I'm not sure how denying access to affordable health care, opposing scientific facts like global warming and the benefits of vaccines, alienating our allies, banning Muslims, building a wall, endorsing torture, and reviving nuclear proliferation are supposed to “make American great again” (as if the U.S. is a backward, put-upon, and defeated nation).

Cancer survivor (and former Republican Jeff Jeans) 1

Why do so many Americans believe that a corrupt, lying billionaire will improve their economic standing?

This way of thinking is alien to me. Is there anything that could change my mind about even one of these issues? What happens when you challenge an opponent's strongly held political views?  Typically, he will double down and affirm his closely held beliefs even more strongly. Why?

As a general slogan, The Personal Is Political is not limited to white radical feminists of the 1960s.2 Much to the dismay of fundamentalist Christians and male white supremacists in the alt-right, their respective personal identities are also closely entwined with their political views. And in turn the “political” is based on a religious/moral/ethical mindset (or an anti-religious/amoral/unethical worldview, as the case may be).

Although Trump supporters (and privileged Liberals gnashing their teeth) would like you to believe that the term “identity politics” is divisive and limited to groups like the LGBT community, the Black Lives Matter movement, Tumblr feminists, SJWs, hard-working undocumented immigrants, and 1.6 billion Muslims who live in hundreds of different countries, they too cling to their groups' identity politics. Across the political spectrum, then, an attack on your core beliefs is taken an attack on you personally. All this arguing about politics with someone on the internet is pointless, because the opponents hold an unimaginably different worldview, or else they delight in outrage.

Appealing to an ideological opponent using an argument based on one's own moral framework is doomed to failure. To briefly generalize, conservatives value in-group loyalty, respect for authority, and purity. Liberals, on the other hand, favor fairness and reciprocity, caring, and protection from harm. Talking to the other camp in terms of your own values is ineffective. But that's what we always do anyway. According to Feinberg and Willer (2015):
(a) political advocates spontaneously make arguments grounded in their own moral values, not the values of those targeted for persuasion, and (b) political arguments reframed to appeal to the moral values of those holding the opposing political position are typically more effective.

In one study, conservatives were slightly more likely to support the Affordable Care Act (ObamaCare) when the arguments in favor were framed in a “purity” context compared to a “fairness” context (Feinberg & Willer, 2015):

Purity.The absence of universal healthcare in the United States practically ensures that we will have unclean, infected, and diseased Americans walking among us.

Fairness.In its current state healthcare in the U.S. is inherently unfair and unjust.”

The purity argument went to outrageous lengths, however:

Purity.  “These diseases [of poverty] are disgusting infestations that invade the human body and leech out needed nutrients to survive. Many of these diseases have grotesque symptoms like yellowing of the skin and eyes, coughing up bloody mucus, itchy rashes, and lesions. These diseases are contagious and spread through the population infecting many, including those who are not poor.”

Other arguments included Gay Americans are Proud and Patriotic Americans (to promote conservative support for gay marriage) and The Military Provides a Fair Chance for Minorities and the Poor (to promote liberal support for military spending). Are there specific areas of the brain associated with greater (or lesser) willingness to change one's beliefs when presented with persuasive opposing evidence? This is one aim of the newly emerging field of political neuroscience.

Can Neuroimaging Heal a Divided Country?

Press Release: When political beliefs are challenged, a person’s brain becomes active in areas that govern personal identity and emotional responses to threats, USC researchers find

This study examined what happened in the brain when the political views of 40 liberals were challenged (Kaplan et al., 2016). What can we learn from this fMRI study, beyond what we already know from political psychology? Jumping ahead, the major conclusions were...
  • The political is personal.
  • When political beliefs are challenged, people get emotional.
...which we already knew. And this quote from the first author strengthened my bias against the study:
“...Kaplan says a good way to make facts matter is to remind people that who they are and what they believe are two separate things.”

Identity politics be damned! Good luck with that! But then I read another quote from Kaplan:
“Political beliefs are like religious beliefs in the respect that both are part of who you are and important for the social circle to which you belong ... To consider an alternative view, you would have to consider an alternative version of yourself.”

This seemed much more insightful, so I took a closer look at the paper. From the outset, one notable limitation is that no conservatives were included in the study. The only participants were politically avid young people who identified as strong liberals. They read eight political statements and eight non-political statements they strongly agreed with (as rated in a pre-scan questionnaire). Each statement was followed by five “challenges” that presented a counter-argument. Then they rated their belief in each statement on a scale of 1 (strongly disbelieve) to 7 (strongly believe).

Fig S1 (Kaplan et al., 2016).

Here are some examples.

Political statements

The U.S. should reduce its military budget.

The laws regulating gun ownership in the United States should be made more restrictive.

Welfare and food stamp programs offer necessary help to the poor.

Nonpolitical statements

Long term exposure to second-hand smoke is a significant health concern.

Lowering one's consumption of foods that are high in cholesterol is a good way to prevent heart disease.

People tend to feel the most trust for those who are most like them racially, culturally, economically, etc.

To be as compelling as possible, the challenges were often exaggerations or distortions of the truth. For the military budget example, one of the challenges was “Russia has nearly twice as many active nuclear weapons as the United States” (which is untrue; the number is 1,740 vs. 2,150 for the US). We can ask, is it really fair to lie to persuade someone to change their opinions? Then again, this is a mild distortion compared to some of the whoppers thrown out during the 2016 Presidential Race (and beyond).

Alas, the challenges weren't all that successful in persuading participants to change their minds about political statements. Ratings dropped by only .3, going from 6.8 to 6.5. And there was virtually no variability across subjects. Belief strength in non-political statements showed greater flexibility, dropping by 1.3 (with slightly more variability across subjects). This becomes important when we look at the brain-behavior correlations below.

For the fMRI data, three task periods were modeled (Statement, Challenge, and Rating) and compared for political vs. non-political trials. Activation maps were reported for the Challenge phase (Fig. 2 below). However, the statistical analysis used a cluster threshold that was overly liberal (see Cluster Failure), which raises the possibility of inflated false positive findings.3

Fig. 2 (Kaplan et al., 2016). In red/yellow, brain regions that showed increased signal while processing challenges to political beliefs (P > NP). In blue/green, brain regions that showed increased signal during challenges to non-political beliefs (NP > P).

At any rate, the authors argued that the big yellow blobs in the default mode network (precuneus, posterior cingulate, medial prefrontal cortex, inferior parietal lobe, and anterior temporal lobe) indicate that participants were accessing their self-identity during challenges to political beliefs: “Given the personal importance of political beliefs for the subjects enrolled in this study, we expected our stimuli to evoke cognition related to social identity.” But just as easily, they could have been disengaging from the task of reading the challenges (mind wandering), which is also associated with the DMN.4 Perhaps the participants found the political challenges more far-fetched than the non-political challenges.

Since it was impossible to correlate brain activity with political belief change across individuals (due to low variance), belief change in the impersonal, non-political condition was examined. But here, in contrast to the other whole-brain analyses, regions of interest (ROIs) in the amygdala and the insula were selected because of their status as “emotion” areas. The finding was that...
...participants who changed their minds more showed less BOLD signal in the insula and the amygdala when evaluating counterevidence. These results highlight the role of emotion in belief-change resistance and offer insight into the neural systems involved in belief maintenance, motivated reasoning, and related phenomena.

But this result has no direct relationship to emotional responses or belief change in the political condition, which is what some pop neuro articles claimed.

Overall, the fMRI data can be interpreted to fit a known narrative. The authors are quite correct that “the inability to change another person’s mind through evidence and argument, or to have one’s own mind changed in turn, stands out as a problem of great societal importance.” But they haven't persuaded me that neuroimaging can further our knowledge of how to go about this. Our collective well-being and survival may depend on the ability to change others' minds, now more than ever.

Further Reading: these two Vox pieces are pretty good.

A new brain study sheds light on why it can be so hard to change someone's political beliefs

Most people are bad at arguing. These 2 techniques will make you better.


1 In one night, the GOP voted to take away these 6 essential health benefits
  1. Protect people with pre-existing conditions
  2. Let young adults stay on their parents’ plan
  3. Maintain access to contraceptive coverage
  4. Ensure Medicaid expansion stays in place
  5. Protect children on Medicaid or CHIP
  6. Protect veterans’ health care
2 Did you know the core argument of this radical manifesto by Carol Hanisch? I didn't either. It's that women are really neat people!! How outrageous, how scandalous and offensive!
This is part of one of the most important theories we are beginning to articulate. We call it “the pro-woman line.” What it says basically is that women are really neat people. The bad things that are said about us as women are either myths (women are stupid), tactics women use to struggle individually (women are bitches), or are actually things that we want to carry into the new society and want men to share too (women are sensitive, emotional).

3 Kaplan et al. used a Z threshold of 2.3 and a cluster size probability threshold of p < 0.05. Although they used FSL FLAME1, which fared well in the Cluster Failure paper (Eklund et al., 2016), a post in the OHBM blog questioned whether this was true for task activation data:
The resting state data have a low true between-subject variance, leading to lower FWE than we might see with task data where systematic differences in task performance might indeed yield the predicted large between-subject differences. This is supported by a secondary simulation using task fMRI data with randomly assigned groups that found FLAME1 to have error rates comparable to FSL’s OLS [which were high].

4 Although the relationship between DMN activity and mind wandering isn't as straightforward anymore (Kucyi et al., 2016; Mittner et al., 2016)...


Feinberg, M., & Willer, R. (2015). From Gulf to Bridge: When Do Moral Arguments Facilitate Political Influence? Personality and Social Psychology Bulletin, 41 (12), 1665-1681 DOI: 10.1177/0146167215607842

Kaplan, J., Gimbel, S., & Harris, S. (2016). Neural correlates of maintaining one’s political beliefs in the face of counterevidence. Scientific Reports, 6. DOI: 10.1038/srep39589

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Monday, December 26, 2016

Penn's Restoring Active Memory dataset freely available

Image from an earlier DARPA news story

Restoring Active Memory (RAM) is a DARPA research program that aims to enhance memory in military personnel who have suffered traumatic brain injuries. The goal is to design an implant, or “memory prosthesis,” that will treat memory loss via electrical stimulation.

Although the failure to replicate a previous study that showed a beneficial effect of entorhinal stimulation was considered “Bad News” by The Neurocritic, among the pieces of good news is the public release of an extensive human intracranial recording dataset.

Penn’s Restoring Active Memory Project Releases Extensive Human Brain Dataset

. . .
Two years into the DARPA-funded Restoring Active Memory or RAM program, lead researcher Daniel Rizzuto, director of cognitive neuromodulation, and Michael Kahana, Penn psychology professor and RAM principal investigator, along with colleagues, have enrolled more than 200 patients and collected more than 1,000 hours of data from patients performing memory tasks. They have now released the largest human intracranial brain recording and stimulation dataset to date, and it’s available for public use, for free.

This data release (from 149 subjects collected during Phase I of RAM) includes:
  • Electrocorticographic (ECoG) recordings
  • Individual electrode contact atlas location and coordinates for localization
  • Session notes, behavioral event data, and iEEG recording data (split by channel) for the following RAM Phase 1 experiments:
    • FR1/2: Verbal Free Recall
    • CatFR1/2: Categorized Verbal Free Recall
    • PAL1/2: Verbal Paired Associates Learning
    • YC1/2: Yellow Cab Spatial Navigation

see RAM Public Data for more.

Also of interest are at least 10 posters that were presented at the 2016 meeting of the Society of Neuroscience. The abstracts for these include:

Targeted brain stimulation to modulate memory in humans (and poster).

Large-scale assessment of the effects of direct electrical stimulation on brain network activity (and poster).

Studying the effects of direct subdural electrical stimulation in human subjects during a verbal associative memory task.

Human memory enhancement through stimulation of middle temporal gyrus
In total, 40 patients implanted with intracranial electrodes for seizure monitoring were stimulated during encoding of word lists for subsequent recall in two verbal memory tasks.  ...  50Hz continuous bipolar stimulation was delivered during epochs of word presentation...

We report memory enhancement in two out of two cases of stimulation in the left posterior middle temporal gyrus, which resulted in significantly increased number of remembered words on stimulated versus non-stimulated lists (p<0.05, permutation test) with subjective experience of improved remembering of words in one of the patients. The effect of stimulation was correlated with univariate changes in spectral power, coherence and phase synchrony, as well as by a multi-variate classifier analysis of spectral power changes characterizing successful word recall. There was no positive effect found in any other of the structures tested in this study, which included areas of the prefrontal cortex, hippocampus and the associated medial temporal neocortex.

The Computational Memory Lab at Penn has been a commendable model for the Open Science movement.

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Friday, December 23, 2016

Bad news for DARPA's RAM program: Electrical Stimulation of Entorhinal Region Impairs Memory

The neural machinery that forms new memories is fragile and vulnerable to insults arising from brain injuries, cerebral anoxia, and neurodegenerative diseases such as Alzheimer's. Unlike language, which shows a great deal of plasticity after strokes and other injuries, episodic memory memory for autobiographical events and contextual details of past experiences doesn't recover after permanent damage to the hippocampus and surrounding structures.1 Is it possible to improve memory by directly stimulating specific regions in the medial temporal lobes (MTL), even in damaged or diseased brains?

Restoring Active Memory (RAM) is a DARPA research program that aims to enhance memory encoding and retrieval in military service members who have suffered traumatic brain injuries. The approach is to design an implant, or “memory prosthesis,” that will treat memory loss via electrical stimulation.
The end goal of RAM is to develop and test a wireless, fully implantable neural-interface medical device for human clinical use ... DARPA will support the development of multi-scale computational models with high spatial and temporal resolution that describe how neurons code declarative memories—those well-defined parcels of knowledge that can be consciously recalled and described in words, such as events, times, and places. Researchers will also explore new methods for analysis and decoding of neural signals to understand how targeted stimulation might be applied to help the brain reestablish an ability to encode new memories following brain injury.

Initial Funding

The first RAM awards went to teams led by investigators at University of California Los Angeles (Dr. Itzhak Fried, PI) and University of Pennsylvania (Dr. Michael Kahana, PI). DAPRA's contributions to the White House BRAIN Initiative are known for their ambitious overreach.2  The modest call for proposals requested the following:
Proposers should develop a computational model of human neural and behavioral function underlying declarative memories that can be explicitly recalled.  [sure, no problem!]
. . .

Researchers must propose a method for validating their model by demonstrating that the model can be used to restore declarative memories through neural stimulation (i.e., electrical, optical, chemical, etc). ... Efficacy of the model must be validated by demonstrating that human patients can explicitly retrieve the restored memories after at least 14 days.
Piece of cake, right?

from Fig 1A (Jacobs et al., 2016). Stimulation in the left entorhinal region did not improve memory in this patient.

Maybe not...

Initial Findings

The first step in this noble quest has been to stimulate the MTL in epilepsy patients who have electrodes implanted for another clinical reason: to monitor the location of their seizures. The UCLA group reported that stimulation of the entorhinal region improved spatial memory (Suthana et al., 2012), a finding that predated the RAM program. Let's take a closer look.

Human entorhinal cortex (Schröder et al., 2015)

The entorhinal cortex (EC), located deep within the temporal lobes, projects to the hippocampus, a key region for the formation of episodic memories.3 EC plays an important role in spatial navigation and is famous for containing a spatial map. The EC and its neighbors in the parahippocampal region also receive projections from neocortical association areas, thus serving as a convergence site for cortical input and a distribution center for cortical afferents to the hippocampus.4

from Fig. 1 (Eichenbaum, 2000). The anatomy of the hippocampal memory system.

Suthana et al. (2012) began by reviewing all the potential benefits of entorhinal stimulation:
In rodents, electrical stimulation of the perforant pathway, which originates in the entorhinal cortex and projects into the hippocampus, results in long-term potentiation, release of acetylcholine, and resetting of the theta phase, all of which are associated with improved memory. It has also been shown that electrical stimulation can enhance neurogenesis in the hippocampus. Whether direct stimulation of this entorhinal output to the hippocampus enhances learning is not known.

In the study, seven individuals with epilepsy performed a spatial task where they learned destinations within virtual environments. There were four blocks, each containing six different destinations (that repeated across blocks). In half the trials of blocks 1-3, electrical stimulation (at 50 Hz) was delivered to the EC or hippocampus. No stimulation was given in block 4.

Spatial learning was quantified by determining the actual path traveled by the participant, relative to the shortest possible path. This variable was called excess path length, with shorter “excess” path length indicating better performance. Latency to reach a destination was measured as well.

The graph below shows the results averaged across six patients with entorhinal stimulation. During the three “learning” blocks, stimulation made no difference for (A) latency or (C) excess path length. During the identically structured “retention” block (when no stimulation was actually given), there seemed to be a small difference, with shorter latency and smaller excess path length for the destinations that had been learned with stimulation. No differences in performance were found when the hippocampus was stimulated, which is a little odd. Previous studies have shown that direct stimulation of the hippocampus impairs memory.

Basically, it looks as if the participants were not learning at all without EC stimulation. But the benefits of stimulation were quite modest (p=.03 for both measures), and the error bars were large for non-stimulation trials. Will these findings replicate in a larger sample of patients?

New Findings

Jacobs et al. (2016) tested 49 patients across seven different hospitals and found that 50 Hz electrical stimulation of the entorhinal region during encoding impaired memory in both spatial and verbal tasks. The effects were modest (and not always significant), yet surprising in light of the results from Suthana et al. (2012):
Across all patients and both tasks, entorhinal stimulation impaired memory accuracy (as measured by MS) by an average of 9% (permutation p < 0.02; t[15] = 2.3, p < 0.02). Entorhinal stimulation impaired memory in both the spatial task (permutation p = 0.03; t[5] = 1.7, p = 0.08) and the verbal task (permutation p = 0.09; t[9] = 1.49, p < 0.09).

You can get an idea of the individual variability in the spatial task below, where p < 0.1 and p < 0.05 (one-sided rank-sum test).

The impairments appeared to be more robust with hippocampal stimulation, in contrast to the lack of effect in Suthana et al.:
Stimulation in the hippocampus significantly impaired performance by 8% overall across both tasks (permutation p = 0.002; t[42] = 2.97, p < 0.003). This impairment was present separately in both the spatial task (permutation p < 0.05; t[22] = 1.94, p < 0.05) and the verbal task (permutation p < 0.001; t[19] = 2.3, p < 0.02).

You might notice from the df above that not all patients had electrodes located in the regions of interest: 28 subjects for hippocampus (43 sites) and only 12 subjects for entorhinal (16 sites).

Nothing is Ever Simple

Why the discrepancy between studies?? Jacobs et al. (2016) discussed some potential differences: number of participants, number of independent observations (i.e., greater statistical power in their study), a better test of MTL-based spatial memory, and duration of stimulation (fixed at 10 seconds per trial vs. longer and variable). They also ran a simulation of Suthana et al.'s statistical methods using similar data and reported that “an effect at least as big as the 64% EPL reduction they observed is found in 19% of randomly shuffled data” (meaning that the result is not statistically significant).

What does this mean for the RAM of the future? In an extensive review of the brain stimulation literature, Kim et al. (2016)...
...tentatively suggest that stimulating multiple memory nodes in concert could enhance cognitive processes supporting memory.

Thus, the stimulation studies published so far make the point that for effective modulation of memory performance to be achieved, a network perspective rather than a purely focal stimulation approach should be considered. Declarative memory relies on a distributed network of multiple neocortical and medial temporal regions that serve cohesive roles in memory processes...

ADDENDUM (Dec 24 2016): DARPA has responded, and they're still bullish on closed-loop stimulation for memory restoration. 

One promise of this technology is that when you forget where you went for lunch on Thursday, and what you ate, and where you sat, and what you wore, your implant will kick in and retrieve the memories for you. 

And in response to a reader question, an extended quote from the Kim et al. (2016) network approach is in the comments below.


1 For an extreme example, see Patient H.M.

2 see these posts by The Neurocritic: A Tale of Two BRAINS: #BRAINI and DARPA's SUBNETS and DARPA allocates $70 million for improving deep brain stimulation technology.

3 Synaptic connections in the hippocampus and entorhinal cortex.

from Fig. 1 of Dobrunz (1998). Lateral perforant path (dotted green) and medial perforant path (solid green) provide inputs from the entorhinal cortex to the dentate gyrus of the hippocampus. Perforant path axons form synapses onto dentate granule cells (lateral in yellow, medial in red). Axons from the CA3 region of hippocampus form synapses onto cells in CA1 (purple).

4 Functional overview of the extended hippocampal-diencephalic memory system.


Jacobs, J., Miller, J., Lee, S., Coffey, T., Watrous, A., Sperling, M., Sharan, A., Worrell, G., Berry, B., Lega, B., Jobst, B., Davis, K., Gross, R., Sheth, S., Ezzyat, Y., Das, S., Stein, J., Gorniak, R., Kahana, M., & Rizzuto, D. (2016). Direct Electrical Stimulation of the Human Entorhinal Region and Hippocampus Impairs Memory. Neuron, 92 (5), 983-990. DOI: 10.1016/j.neuron.2016.10.062

Kim, K., Ekstrom, A., & Tandon, N. (2016). A network approach for modulating memory processes via direct and indirect brain stimulation: Toward a causal approach for the neural basis of memory. Neurobiology of Learning and Memory, 134, 162-177. DOI: 10.1016/j.nlm.2016.04.001

Suthana, N., Haneef, Z., Stern, J., Mukamel, R., Behnke, E., Knowlton, B., & Fried, I. (2012). Memory Enhancement and Deep-Brain Stimulation of the Entorhinal Area. New England Journal of Medicine, 366 (6), 502-510. DOI: 10.1056/NEJMoa1107212

Further Reading

Restoring Active Memory Program Poised to Launch (July 9, 2014)
DARPA has selected two universities to initially lead the agency’s Restoring Active Memory (RAM) program, which aims to develop and test wireless, implantable “neuroprosthetics” that can help servicemembers, veterans, and others overcome memory deficits incurred as a result of traumatic brain injury (TBI) or disease.

UCLA and Penn will each head a multidisciplinary team to develop and test electronic interfaces that can sense memory deficits caused by injury and attempt to restore normal function. Under the terms of separate cooperative agreements with DARPA, UCLA will receive up to $15 million and Penn will receive up to $22.5 million over four years...
. . .

Unique to the UCLA team’s approach is a focus on the portion of the brain known as the entorhinal area. UCLA researchers previously demonstrated that human memory could be facilitated by stimulating that region, which is known to be involved in learning and memory. Considered the entrance to the hippocampus—which helps form and store memories—the entorhinal area plays a crucial role in transforming daily experience into lasting memories. Data collected during the first year of the project from patients already implanted with brain electrodes as part of their treatment for epilepsy will be used to develop a computational model of the hippocampal-entorhinal system that can then be used to test memory restoration in patients.
. . .

The Penn team’s approach is based on an understanding that memory is the result of complex interactions among widespread brain regions. Researchers will study neurosurgical patients who have electrodes implanted in multiple areas of their brains for the treatment of various neurological conditions. By recording neural activity from these electrodes as patients play computer-based memory games, the researchers will measure “biomarkers” of successful memory function—patterns of activity that accompany the successful formation of new memories and the successful retrieval of old ones. Researchers could then use those models and a novel neural stimulation and monitoring system ... to restore brain memory function.

DARPA Project Starts Building Human Memory Prosthetics (August 27, 2014)
“They’re trying to do 20 years of research in 4 years,” says Michael Kahana in a tone that’s a mixture of excitement and disbelief. Kahana, director of the Computational Memory Lab at the University of Pennsylvania, is mulling over the tall order from the U.S. Defense Advanced Research Projects Agency (DARPA). In the next four years, he and other researchers are charged with understanding the neuroscience of memory and then building a prosthetic memory device that’s ready for implantation in a human brain.

Work Begins on Brain Stimulator to Correct Memory (April 3, 2015)
If the Penn team is able to identify markers of memory formation, it will try to influence them by stimulating the brain with low doses of electricity. The goal is to test whether it’s possible to coax the brain’s circuitry into whatever state represents a specific patient’s best possible memory function.

Kahana, who is director of the university’s Computational Memory Lab, says it’s too soon to say whether the idea will work. “We want the brain to exhibit a certain pattern of electrical activity,” he says. “It’s a big leap [to say] we can somehow nudge it into that state by giving it a little push.”

Targeted Electrical Stimulation of the Brain Shows Promise as a Memory Aid (September 11, 2015)
. . .

Just over one year into the effort, the novel approach to facilitating memory formation and recall has already been tested in a few dozen human volunteers, said program manager Justin Sanchez. ...

The study aims to give researchers the ability to “read” the neural processes involved in memory formation and retrieval, and even predict when a volunteer is about to make an error in recall. The implanted electrodes also provide a means of sending signals to specific groups of neurons, with the goal of influencing the accuracy of recall.

Initial results indicate that it is indeed possible to capture and interpret key signals or “neural codes” coming from the human brain during memory encoding and retrieval, and improve recall by providing targeted electrical stimulation of the brain.

Top image (from Penn): Illustration showing placement of deep brain electrodes in an epilepsy patient.

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