Friday, March 24, 2017

What's Popular at #CNS2017?

Memory wins again!



Word cloud for 835 poster titles at CNS 2017.


The 2017 Cognitive Neuroscience Society annual meeting will start tomorrow, March 25. To no one's surprise, memory is the most popular topic in the bottom-up abstract submission sweepstakes.

In contrast, the top-down selections of the Cognosenti are light on memory, with a greater emphasis on attention, speech, mind-wandering, and reward.



Word cloud for 16 titles/abstracts in four Invited Symposia.


The member-generated Symposium Sessions are once again memory-centric, but with the key additions of speech, learning, information, and oscillations.



Word cloud for 43 titles/abstracts in nine Uninvited Symposia.


The hot area of the brain this year is OFC, the orbitofrontal cortex.

Kicking off the meeting is a new addition to the program, a symposium on Big Ideas in Cognitive Neuroscience, which will focus on language, motor control/action, and (you guessed it) memory:

Six speakers, in three pairs, will consider some major challenges and cutting-edge advances, from molecular mechanisms to decoding approaches to network computations. The presentations and debate aim to provide a tentative outline of what might be a productive and ambitious agenda for our fields.

Speakers:
  • Charles R. Gallistel (Rutgers University) and Tomás Ryan (Trinity College Dublin & MIT) on memory.
  • Angela Friederici (Max-Planck-Institute) and Jean-Rémi King (NYU) on language.
  • John Krakauer (Johns Hopkins University) and Danielle Bassett (University of Pennsylvania) on action/motor.

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Sunday, March 12, 2017

A brain-enhancement amusement park mockumentary


“There was a level of undefined brain activity, about 30% higher, than the kids who stayed on the ground.”


The Centrifuge Brain Project is an awesome short film by Till Nowak, featuring a deadpan performance by Leslie Barany.





The fictitious website of the Institute for Centrifugal Research (ICR) is one of the best since LACUNA Inc. (which lives on at archive.org):

Welcome to the homepage of ICR - the world's leading research laboratory in the highly specialized field of spinning people around.

We are proud of our history - a chronicle of passion and pioneering achievements in the realms of brain manipulation, excessive G-Force and prenatal simulations. Established in 1976 by Dr. Matthew Brenswick and Dr. Nick Laslowicz, the institute has never stopped doubting the generally accepted laws of physics.


WEDDING CAKE CENTRIFUGE
established 1985.
Number of seats: 96
G-Force: 2.3
Model no. 810XN-96922


“Some of the test results that year were a little too extreme to be published.”


STEAM PRESSURE CATAPULT
established 2003.
Number of seats: 172
G-Force: 9
Model no. 01758X-KAZT


“Unpredictability was an important aspect of our work.”



Coming soon: Derealization during utricular stimulation.

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Monday, March 06, 2017

Patent for Stimulation of Brodmann Areas 1-48 and all other structures


Fig. 1 (Roskams-Edriset al., 2017). The number of patents implicating specific brain regions has risen from 1976 to the mid 2010s. Results were obtained by searching The Lens patent database (http://lens.org/).


“What is the ethical value of awarding patent rights that implicate regions of the brain?”

Do the applicants intend to patent the function of specific brain areas? This absurd scenario was the first thing that came to mind. The murky waters of neurotech patent law were explored by a group of neuroethics and intellectual property experts (Roskams-Edriset al., 2017) who noted several problems:
The first practical challenge to patents that relate to brain regions is well known to patent law: the danger of overbroad, vague, or obvious claims.

One egregious example is US 9327069 B2, Methods and systems for treating a medical condition by promoting neural remodeling within the brain. The language is extremely vague (and redundant):
Methods of treating a medical condition include applying at least one stimulus to a stimulation site within the brain of a patient with an implanted stimulator in accordance with one or more stimulation parameters. The [sic] at least one stimulus is configured to promote neural remodeling within the brain of the patient. Systems for treating a medical condition include an implantable stimulator configured to apply at least one stimulus to a stimulation site within the brain of a patient in accordance with one or more stimulation parameters...

What kind of stimulus will “promote neural remodeling?” All of them. As stated in the Detailed Description:
The stimulus may include an electrical stimulation current, one or more drugs, gene infusion, chemical stimulation, thermal stimulation, electromagnetic stimulation, mechanical stimulation, and/or any other suitable stimulus.

What brain conditions can be treated? All of them.
Many medical conditions have been linked to faulty neural connections and/or abnormal developmental pruning of axons, dendrites, and synapses within the brain. Such medical conditions include, but are not limited to, autism, psychological disorders (e.g., schizophrenia, compulsive behaviors, and depression), neurodegenerative diseases (e.g., Huntington's disease, Alzheimer's disease, and amyotrophic lateral sclerosis), and chromosomal abnormalities (e.g., Down syndrome and Klinefelter syndrome).

Finally, what are the implicated brain regions? You guessed it.
Nearly every brain area has been implicated in the disorders listed above. In particular, it is believed that faulty neural connections and/or abnormal developmental pruning of neural structures within the temporal lobe, limbic system, pituitary gland, brainstem, cerebral cortex, and/or any other midbrain structure are at least in part responsible for the deficits of one or more of the disorders listed above.

The Claims that apply in this patent (e.g., stimulation sites and medical conditions) are slightly more specific, but still outlandish:
4. ... said stimulation site comprises at least one or more of a temporal lobe, cerebral ventricle, structure within a limbic system, pituitary gland, brainstem, and cerebral cortex.

5. ...said medical condition comprises at least one or more of autism, a psychological disorder, a neurodegenerative disease, a chromosomal abnormality, a bad habit, and an injury to said brain.
A bad habit??


100,000,000 Hz

Even better is Patent US 9,050,463 (Systems and methods for stimulating cellular function in tissue), which touts the application of electrical fields with frequencies of 100,000,000 Hz and above to the entire nervous system...
....various structures within the brain or nervous system including but not limited to dorsal lateral prefrontal cortex, any component of the basal ganglia, nucleus accumbens, gastric nuclei, brainstem, thalamus, inferior colliculus, superior colliculus, periaqueductal gray, primary motor cortex, supplementary motor cortex, occipital lobe, Brodmann areas 1-48, primary sensory cortex, primary visual cortex, primary auditory cortex, amygdala, hippocampus, cochlea, cranial nerves, cerebellum, frontal lobe, occipital lobe, temporal lobe, parietal lobe, sub-cortical structures, spinal cord, nerve roots, sensory organs, and peripheral nerves.

 ...to treat all known diseases:
Such pathologies that may be treated include but are not limited to Multiple Sclerosis, Amyotrophic Lateral Sclerosis, Alzheimer's Disease, Dystonia, Tics, Spinal Cord Injury, Traumatic Brain Injury, Drug Craving, Food Craving, Alcohol Craving, Nicotine Craving, Stuttering, Tinnitus, Spasticity, Parkinson's Disease, Parkinsonianism, Obsessions, Depression, Schizophrenia, Bipolar Disorder, Acute Mania, Catonia, Post-Traumatic Stress Disorder, Autism, Chronic Pain Syndrome, Phantom Limb Pain, Epilepsy, Stroke, Auditory Hallucinations, Movement Disorders, Neurodegenerative Disorders, Pain Disorders, Metabolic Disorders, Addictive Disorders, Psychiatric Disorders, Traumatic Nerve Injury, and Sensory Disorders.




Oddly, the specific Claims in this patent include an indication limited to Parkinson's disease. But the list of targeted brain regions (see above) is irrelevant in this disorder.


Roskams-Edriset al. (2017) conclude with a warning drawn from previous efforts to patent human genes: “brain biomaterial and brain processes cannot be invented and, like genes, they similarly ought not to be owned.” There should be no legal rights to brain regions, or else we risk losing autonomy over our own thoughts and actions.


Reference

Roskams-Edris, D., Anderson-Redick, S., Kiss, Z., & Illes, J. (2017). Situating brain regions among patent rights and moral risks. Nature Biotechnology, 35 (2), 119-121. DOI: 10.1038/nbt.3782

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Tuesday, February 28, 2017

Neurofeedback Training For Insomnia No Better Than Sham



Neurofeedback training (NFT) is a procedure that tries to shape a participant's pattern of brain activity by providing real-time feedback, often in the form of a video game combined with other sensory stimuli that provide rewards when the “correct” state is achieved. The most common form of NFT uses EEG (brainwave) activity recorded non-invasively from the scalp. The EEG is a complex mixture of neural oscillations of different frequencies. Specific frequency bands are targeted for enhancement or reduction, so the participant can learn to modulate their own brain activity.

An overview of the neurofeedback process is shown below. Signals are recorded from sensors, processed, and classified. The calculated signal is then presented to the subject via feedback in one or more sensory modalities. Participants can learn to modulate their neural function, and complete the loop when the feedback is processed.

- click on image for a larger view -

modified from Fig 1 (Sitaram et al., 2016). The methods included here are electroencephalography (EEG), magnetoencephalography (MEG) and invasive electrocorticography (ECoG). MVPA, multivariate patterns of activity. FFT, fast Fourier transformation.


In one study, participants were trained to reduce the amplitude of alpha oscillations, with a goal of increasing long-range temporal correlations (Ros et al., 2016). Here's a description of the training procedure:
For online training, the EEG signal was ... band-pass filtered to extract alpha (8–12 Hz) amplitude with an epoch size of 0.5 s. Here, subjects were rewarded upon reduction of their absolute alpha amplitude... Visual feedback was clearly displayed on a monitor via 1) a dynamic bar graph at the center of the screen whose height was proportional to real-time alpha fluctuations and 2) a “Space Race” game, where a spaceship advanced through space when amplitude was below threshold, and became stationary when above threshold. No explicit instructions were given on how to achieve control over the spaceship, and all participants were told to be guided by the visual feedback process.

In a sham condition, the participants were shown feedback recorded from another subject in an earlier session (Ros et al., 2016). Having a sham (or placebo) condition is critical for demonstrating that any gains in performance (or increases in long-range temporal correlations, in this example) are due to self-regulation of specific EEG features learned during training, and not from some generic aspect of the procedure.

In academic articles, neurofeedback is often called closed-loop brain training, perhaps to distinguish it from neurofeedback therapy (also NFT). A recent paper in Nature Reviews Neuroscience discussed experimental applications of NFT1 and theories of the underlying mechanisms. Animal studies have demonstrated that rats and monkeys are capable of modulating the firing rates of small groups of neurons. Models of neurofeedback learning include instrumental (operant) conditioning, motor learning, global workspace theory, and skill learning. Exciting and important research ventures that capitalize on NFT are applications to brain-computer interfaces (BCI) and brain-machine interfaces (BMI), which have allowed paralyzed individuals to type and move prosthetic hands.

Psychiatric applications of NFT have been more problematic. First, you have to correctly identify the frequency band(s) that are abnormal in a clinical population. Then you must have a principled method for selecting the NFT protocol. Finally, you must demonstrate that your specific NFT protocol is superior to sham feedback (in a randomized, controlled trial). Unfortunately, this is rarely done.

Neurofeedback therapy has received critical coverage from the press in recent weeks. The new U.S. Secretary of Education, billionaire Betsy DeVos, has a major financial stake in an NFT company called Neurocore. The New York Times ran two articles critical of both DeVoss's conflict of interest and of the supposed benefits of NFT.

Betsy DeVos Won’t Shed Stake in Biofeedback Company, Filings Show
. . .

Ms. DeVos and her husband promote Neurocore heavily on the website for Windquest Group, a family office the couple use to manage some of their many investments...

But the claims that Neurocore’s methods can help children improve their performance in school could present a conflict for Ms. DeVos if she is confirmed as education secretary — especially given that the company is moving to expand its national reach.

Betsy DeVos Invests in a Therapy Under Scrutiny
. . .

Neurocore has not published its results in peer-reviewed medical literature. Its techniques — including mapping brain waves to diagnose problems and using neurofeedback, a form of biofeedback, to treat them — are not considered standards of care for the majority of the disorders it treats, including autism. Social workers, not doctors, perform assessments, and low-paid technicians with little training apply the methods to patients, including children with complex problems.

And Neurocore is in no way unique. Hundreds of Neurofeedback Centers offer cures for everything from A to T by merely wearing a few electrodes and playing a computer game for 20-30 sessions (and $2,000-3,000).

ADD / ADHD
Addiction
Alzheimer’s Disease
Anger Management
Anxiety
Attachment Disorders
Autism
Bipolar Disorder
Borderline Personality Disorder
Chronic Pain
Conduct Disorders
Depression
Dyslexia
Epilepsy / Seizures
Fibromyalgia
Insomnia / Sleep Disorders
Learning Disorders
Lyme Disease
Memory Loss
Migraines
Obsessive-Compulsive Disorder
OCD / Tourrette’s
Parkinson’s
Pre-Menstrual Syndrome
Stress / PTSD
Schizophrenia
Sleep Disorders
Stroke
Substance Abuse
Tourette’s Syndrome
Traumatic Brain Injury

Pitches are often targeted to concerned parents, but there is little to no evidence that the therapy offered at most of these centers is based on sound scientific research. As mentioned, double-blind, placebo controlled clinical trials are rarely conducted. Thibault and Raz (2017) have been particularly vocal about the lack of rigor in published studies, as well as the inflated claims of successful treatment.2 
Advocates of neurofeedback make bold claims concerning brain regulation, treatment of disorders, and mental health. Decades of research and thousands of peer-reviewed publications support neurofeedback using electroencephalography (EEG-nf); yet, few experiments isolate the act of receiving feedback from a specific brain signal as a necessary precursor to obtain the purported benefits. Moreover, while psychosocial parameters including participant motivation and expectation, rather than neurobiological substrates, seem to fuel clinical improvement across a wide range of disorders, for-profit clinics continue to sprout across North America and Europe. 

Here's how Neurocore describes its Natural Sleep Disorder Therapy for insomnia:

Neurofeedback. Natural treatment for sleep disorders & insomnia.

Neurocore’s approach to treating insomnia and sleeping disorders starts by looking at the brain. Using advanced qEEG technology, we measure your brainwaves to help identify the cause of the problem. We also monitor your heart rate and evaluate how in sync it is with your breathing pattern. Your unique neurometrics yield a customized neurofeedback training program that will teach your brain to self-regulate. The result is a brain that’s calibrated for better ongoing recovery, which means better sleep for you.

But the Neurocore “neurometrics” are not obtained from a clinical sleep study (polysomnography) which measures not only brain and heart activity, but also muscle activity, eye movements, and respiration. They haven't identified the “cause of the problem”. It could be sleep apnea or another medical condition.

Brand new evidence indicates that targeted, sensorimotor-rhythm (SMR) NFT for insomnia is no better than sham feedback. Earlier work had suggested that training to increase 12-15 Hz activity over the sensorimotor cortex could improve sleep by enhancing sleep spindles, which are in the same 12-15 Hz frequency range. In the new study, Schabus et al. (2017) took 25 patients with insomnia and administered 12 sessions of real neurofeedback and 12 sessions of sham neurofeedback, also called placebo feedback training (PFT):
Importantly, during the NFT condition, participants had to enhance EEG amplitudes in the SMR range between 12 and 15 Hz, whereas during the PFT sessions participants had to enhance random frequency ranges between 7 and 20 Hz (but not the 12–15 Hz SMR range); importantly within a PFT session only one frequency was trained and rewarded. The reason for choosing this kind of placebo or sham protocol was to involve patients to a similar degree as in NFT, yet with no specific frequency being rewarded systematically. Rewarding another frequency systematically could have resulted in undesired effects on EEG and behaviour that would render the PFT control condition suboptimal.

Outcome variables were objective (EEG) and subjective measures of sleep quality. A forthcoming commentary from Thibault et al. (2017) summarizes the results in a nifty cartoon.


As expected, when participants received genuine neurofeedback, they were able to significantly increase power in the SMR frequency band. This was not the case during sham neurofeedback sessions. Genuine neurofeedback did not alter objective measures of sleep quality (nor did sham). The most important result came in the patient ratings of subjective sleep quality. Genuine SMR neurofeedback improved subjective sleep measures, BUT SO DID SHAM NEUROFEEDBACK. This suggests that any benefit obtained from NFT was due to a placebo effect. Although this was a small study with some complications (e.g., nine of the 25 patients were “misperception” insomniacs with no objective indicators of insomnia), the results were informative about the cause of subjective improvements — they were non-specific in nature and did not rely on training SMR activity.

In their commentary, Thibault et al. (2017) refer to NFT as a superplacebo:
Whether real or sham, neurofeedback demands high engagement and immerses patients in a seemingly cutting-edge technological environment over many recurring sessions. ... In this regard, neurofeedback may represent an especially powerful form of placebo intervention—a kind of superplacebo.

Amusingly, they define superplacebo as “A treatment that is actually a placebo although neither the prescribing practitioner nor the receiving patient is aware of the absence of evidence to recommend it therapeutically.” If everyone thinks neurofeedback treatment works, it is more likely to do so, even though it bears no relation to self-regulation of selective neural activity. Future studies with refined NFT protocols may yet “tune” the brain in a desired direction, but for now... buyer beware.


Further Reading

Brain training: The future of psychiatric treatment?

DeVos-Associated Company Alleges Brain-Training Autism 'Fix'


Footnotes

1 The paper also reviewed neurofeedback studies that use hemodynamic measures. NFT based on fMRI is a newer (and more expensive) development that won't be covered here.

2 Neurocore claims: “Our ADHD Outcomes*  90% report fewer or less frequent ADHD symptoms.  85% experience a clinically important reduction of ADHD symptoms.  76% achieve non-clinical status.  53% no longer meet symptomatic thresholds for ADHD. ”


References

Ros T, Frewen P, Théberge J, Michela A, Kluetsch R, Mueller A, Candrian G, Jetly R, Vuilleumier P, Lanius RA. (2016). Neurofeedback tunes scale-free dynamics in spontaneous brain activity. Cerebral Cortex. DOI: 10.1093/cercor/bhw285

Manuel Schabus, Hermann Griessenberger, Maria-Teresa Gnjezda, Dominik P.J. Heib, Malgorzata Wislowska, Kerstin Hoedlmoser (2017). Better than sham? A double-blind placebo-controlled neurofeedback study in primary insomnia. Brain: 10.1093/brain/awx011

Sitaram, R., Ros, T., Stoeckel, L., Haller, S., Scharnowski, F., Lewis-Peacock, J., Weiskopf, N., Blefari, M., Rana, M., Oblak, E., Birbaumer, N., & Sulzer, J. (2016). Closed-loop brain training: the science of neurofeedback. Nature Reviews Neuroscience, 18 (2), 86-100. DOI: 10.1038/nrn.2016.164

Thibault RT, Lifshitz M, Raz A. (2017). Neurofeedback or Neuroplacebo? Brain, in press. PDF

Thibault RT, Raz A. (2017). The psychology of neurofeedback: Clinical intervention even if applied placebo. American Psychologist, in press. PDF

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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.





Footnotes

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.


References

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!


Footnotes

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: http://www.kansascity.com/news/politics-government/article128727224.html#storylink=cpy

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.

References

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





Crystalised
   ------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.


Footnotes

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


References

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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