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Distortions of Reality

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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

Using Discourse Analysis to Assess Cognitive Decline

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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

Neurofeedback Training For Insomnia No Better Than Sham

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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

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

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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

A brain-enhancement amusement park mockumentary

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“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.

What's Popular at #CNS2017?

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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.

What are the Big Ideas in Cognitive Neuroscience?

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This year, the Cognitive Neuroscience Institute (CNI) and the Max-Planck-Society organized a symposium on Big Ideas in Cognitive Neuroscience. I enjoyed this fun forum organized by David Poeppel and Mike Gazzaniga. The format included three pairs of speakers on the topics of memory, language, and action/motor who “consider[ed] some major challenges and cutting-edge advances, from molecular mechanisms to decoding approaches to network computations.”

Co-host Marcus Raichle recalled his inspiration for the symposium: a similar Big Ideas session at the Society for Neuroscience meeting. But human neuroscience was absent from all SFN Big Ideas, so Dr. Raichle contacted Dr. Gazzaniga, who “made it happen” (along with Dr. Poeppel). The popular event was standing room only, and many couldn't even get into the Bayview Room (which was too small a venue). More context:
“Recent discussions in the neurosciences have been relentlessly reductionist. The guiding principle of this symposium is that there is no privileged level of analysis that can yield special explanatory insight into the mind/brain on its own, so ideas and techniques across levels will be necessary.”

The two hour symposium was a welcome addition to hundreds of posters and talks on highly specific empirical findings. Sometimes we must take a step back and look at the big picture. But since I'm The Neurocritic, I'll start out with some modest suggestions for next time.

  • There was no time for questions or discussion.
  • There were too many talks.
  • It would be nice for all speakers to try to bridge different levels of analysis.
  • This is a small point, but ironically the first two speakers (Gallistel, Ryan) did not talk about human neuroscience.

So my idea is to have four speakers on one topic (memory, let's say) with two at the level of Gallistel and Ryan1, and two who approach human neuroscience using different techniques. Talks are strictly limited to 20 minutes. Then there is a 20 minute panel discussion where everyone tries to consider the implications of the other levels for their own work. Then (ideally) there is time for 20 minutes of questions from the audience. However, since I'm not an expert in organizing such events, allotting 20 minutes for the audience could be excessive. So the timing could be restructured to 25 min for talks, 10-15 min panel, 5-10 min audience. Or combine the round table with audience participation.

Last year, Symposium Session 7 on Human Intracranial Electrophysiology (which included the incendiary tDCS challenge by György Buzsáki) had a round table discussion as Talk 5, which I thought was very successful.

Video of the Big Ideas symposium is now available on YouTube, but in case you don't want to watch the entire two hours, I'll present a brief summary below.


Big Box Neuroscience

Here's an idiosyncratic distillation of some major points from the symposium.

  • The brain is an information processing device in the sense of Shannon information theory.
  • The brain does not use Shannon information.
  • Memories (”engrams”) are not stored at synapses.
  • We learn entirely through spike trains.
  • The engram is inter-spike interval.
  • The engram is an emergent property.
  • Emergent properties are for losers.
  • Language is genetically predetermined.
  • There is something called mirror neural ensembles.
  • Recursion is big.
  • Architectures are important.
  • Build a bridge from networks to models of behavior.
  • Use generative models to construct theories.
  • Machine learning will save us.
  • Go back to behavioral neuroscience.

Maybe I'll explain what this all means in the next post. You can also check out the official @CogNeuroNews coverage.


Footnote

1 Controversy is always entertaining, and these two had diametrically opposed views.




The Big Ideas in Cognitive Neuroscience, Explained

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Are emergent properties really for losers? Why are architectures important? What are “mirror neuron ensembles” anyway? My last post presented an idiosyncratic distillation of the Big Ideas in Cognitive Neuroscience symposium, presented by six speakers at the 2017 CNS meeting. Here I’ll briefly explain what I meant in the bullet points. In some cases I didn't quite understand what the speaker meant so I used outside sources. At the end is a bonus reading list.

The first two speakers made an especially fun pair on the topic of memory: they held opposing views on the “engram”, the physical manifestation of a memory in the brain.1 They also disagreed on most everything else.


1. Charles Randy Gallistel (Rutgers University) What Memory Must Look Like

Gallistel is convinced that Most Neuroscientists Are Wrong About the Brain. This subtly bizarre essay in Nautilus (which waswidelyscorned on Twitter) succinctly summarized the major points of his talk. You and I may think the brain-as-computer metaphor has outlived its usefulness, but Gallistel says that “Computation in the brain must resemble computation in a computer.” 

Shannon information is a set of possible messages encoded as bit patterns and sent over a noisy channel to a recipient that will hopefully decode the message with minimal error. In this purely mathematical theory, the semantic content (meaning) of a message is irrelevant. The brain stores numbers and that's that.

  • Memories (“engrams”) are not stored at synapses.
Instead, engrams reside in molecules inside cells. The brain “encodes information into molecules inside neurons and reads out that information for use in computational operations.” A 2014 paper on conditioned responses in cerebellar Purkinje cells was instrumental in overturning synaptic plasticity (strengthening or weakening of synaptic connections) as the central mechanism for learning and memory, according to Gallistel.2 Most other scientists do not share this view.3

  • The engram is inter-spike interval.
Spike train solutions based on rate coding are wrong. Meaning, the code is not conveyed by the firing rate of neurons. Instead, numbers are conveyed to engrams via a combinatorial interspike interval code. Engrams then reside in cell-intrinsic molecular structures. In the end, memory must look like the DNA code.

  • Emergent properties are for losers.
“Emergent property” is a code word for “we don't know.”



2. Tomás Ryan (@TJRyan_77) Information Storage in Memory Engrams

Ryan began by acknowledging that he had tremendous respect for Gallistal's speech which was in turn powerful, illuminating, very categorical, polarizing, and rigid. But wrong. Oh so very wrong. Memory is not essentially molecular, we should not approach memory and the brain from a design perspective, and information storage need not mimic a computer.

  • The brain does not use Shannon information.
More precisely, “the kind of information the brain uses may be very different from Shannon information.” Why is that? Brains evolved, in kludgy ways that don't resemble a computer. The information used by the brain may be encoded without having to reduce it to Shannon form, and may not be quantifiable as units.

  • Memories (“engrams”) are not stored at synapses.
Memory is not stored by changes in synaptic weights, Ryan and Gallistel agree on this. The dominant view has been falsified by a number of studies including one by Ryan and colleagues that used engram labeling. Specific “engram cells” can be labeled during learning using optogenetic techniques, and later stimulated to induce the recall of specific memories. These memories can be reactivated even after protein synthesis inhibitors have (1) induced amnesia, and (2) prevented the usual memory consolidation-related changes in synaptic strength.

  • We learn entirely through spike trains.
Spike trains are necessary but not sufficient to explain how information is coded in the brain. On the other hand, instincts are transmitted genetically and are not learned via spike trains.

  • The engram is an emergent property.
And fitting with all of the above, “the engram is an emergent property mediated through synaptic connections” (not through synaptic weights). Stable connectivity is what stores information, not molecules.


Angela Friederici (Max Planck Institute for Human Cognitive and Brain Sciences) Structure and Dynamics of the Language Network

Following on the heels of the rodent engram crowd, Friederici pointed out the obvious limitations of studying language as a human trait.

  • Language is genetically predetermined.
The human ability to acquire language is based on a genetically predetermined structural neural network. Although the degree of innateness has been disputed, a bias or propensity of brain development towards particular modes of information processing is less controversial. According to Friederici, language capacity is rooted in “merge”, a specific computation that binds words together to form phrases and sentences.

  • The “merge” computation is localized in BA 44.
This wasn't one of my original bullet points, but I found this statement rather surprising and unbelievable. It implies that our capacity for language is located in the anterior ventral portion of Brodmann's area 44 in the left hemisphere (the tiny red area in the PHRASE > LIST panel below).



The problem is that acute stroke patients with dysfunctional tissue in left BA 44 do not have impaired syntax. Instead, they have difficulty with phonological short-term memory (keeping strings of digits in mind, like remembering a phone number).

  • There is something called mirror neural ensembles.
    I'll just have to leave this slide here, since I really didn't understand it, even on the second viewing.



    “This is a poor hypothesis,” she said.


    Jean-Rémi King (@jrking0) Parsing Human Minds

    King's expertise is in visual processing (not language), but his talk drew parallels between vision and speech comprehension. A key goal in both domains is to identify the algorithm (sequence of operations) that translates input into meaning.

    • Recursion is big. 
    Despite these commonalities, the structure of language presents the unique challenge of nesting (or recursion): each constituent in a sentence can be made of subconstituents of the same nature, which can result in ambiguity.


    • Architectures are important. 
    Decoding aspects of a sensory stimulus using MEG and machine learning is lovely, but it doesn't tell you the algorithm. What is the computational architecture? Is it sustained or feedforward or recurrent?

      Each architecture could be compatible with a pattern of brain activity at different time points. But do the classifiers at different time points generalize to other time points? This can be determined by a temporal generalization analysis, which“reveals a repertoire of canonical brain dynamics.”


      Danielle Bassett (@DaniSBassett A Network Neuroscience of Human Learning: Potential to Inform Quantitative Theories of Brain and Behavior

      Bassett previewed an arc of exciting ideas where we've shown progress, followed by frustrations and failures, which may ultimately provide an opening for the really Big Ideas. Her focus is on learning from a network perspective, which means patterns of connectivity in the whole brain. What is the underlying network architecture that facilitates the spatial distributed effects?



      What is the relationship between these two notions of modularity?
      [I ask this as an honest question.]

      Major challenges remain, of course.

      • Build a bridge from networks to models of behavior.
      Incorporate well-specified behavioral models such as reinforcement learning and the drift diffusion model of decision making. These models are fit to the data to derive parameters such as the alpha parameter from reinforcement learning rate. Models of behavior can help generate hypotheses about how the system actually works.

      • Use generative models to construct theories. 
      Network models are extremely useful, but they're not theories. They're descriptors. They don't generate new frameworks for understanding what the data should look like. Theory-building is obviously critical for moving forward.


      John Krakauer (@blamlab Big Ideas in Cognitive Neuroscience: Action

      Krakauer mentioned the Big Questions in Neuroscience symposium at the 2016 SFN meeting, which motivated the CNS symposium as well as a splashy critical paper in Neuron. He raised an interesting point about how the term “connectivity” has different meanings, i.e. the type of embedded connectivity that stores information (engrams) vs. the type of correlational connectivity when modules combine with each other to produce behavior. [BTW, is everyone here using “modules” in the same way?]

      • Machine learning will save us. 
      Krakauer discussed work on motor learning using adaptation paradigms and simple execution tasks. But there's a dirty secret: there is no computational model, no algorithmic theory of how practice makes you better on those tasks. Can the computational view get an upgrade from machine learning? Go out and read the manifesto by Marblestone, Wayne, and Kording: Toward an Integration of Deep Learning and Neuroscience. And you better learn about cost functions, because they're very important.4



      • Go back to behavioral neuroscience.
      This is the only way to work out the right cost functions. Bottom line: Networks represent weighting modules into the cost function.4 


      OVERALL, there was an emphasis on computational approaches with nods to the three levels of David Marr:

      computation – algorithm – implementation



      We know from from Krakauer et al. 2017 (and from CNS meetings past and present) that co-organizer David Poeppel is a big fan of Marr. The end goal of a Marr-ian research program is to find explanations, to reach an understanding of brain-behavior relations. This requires a detailed specification of the computational problem (i.e., behavior) to uncover the algorithms. The correlational approach of cognitive neuroscience and even the causal-mechanistic circuit manipulations of optogenetic neuroscience just don't cut it anymore.



      Footnotes

      1Although neither speaker explicitly defined the term, it is most definitely not the engram as envisioned by Scientology: “a detailed mental image or memory of a traumatic event from the past that occurred when an individual was partially or fully unconscious.” The term was first coined by Richard Semon in 1904.

      2This paper (by Johansson et al, 2014) appeared in PNAS, and Gallistel was the prearranged editor.

      3For instance, here's Mu-ming Poo: “There is now general consensus that persistent modification of the synaptic strength via LTP and LTD of pre-existing connections represents a primary mechanism for the formation of memory engrams.”

      4 If you don't understand all this, you're not alone. From Machine Learning: the Basics.
      This idea of minimizing some function (in this case, the sum of squared residuals) is a building block of supervised learning algorithms, and in the field of machine learning this function - whatever it may be for the algorithm in question - is referred to as the cost function. 


      Reading List

      Everyone is Wrong

      Here's Why Most Neuroscientists Are Wrong About the Brain. Gallistel in Nautilus, Oct. 2015.

      Time to rethink the neural mechanisms of learning and memory. Gallistel CR, Balsam PD. Neurobiol Learn Mem. 2014 Feb;108:136-44.

      Engrams are Cool

      What is memory? The present state of the engram. Poo MM, Pignatelli M, Ryan TJ, Tonegawa S, Bonhoeffer T, Martin KC, Rudenko A, Tsai LH, Tsien RW, Fishell G, Mullins C, Gonçalves JT, Shtrahman M, Johnston ST,  Gage FH, Dan Y, Long J, Buzsáki G, Stevens C. BMC Biol. 2016 May 19;14:40.

      Engram cells retain memory under retrograde amnesia. Ryan TJ, Roy DS, Pignatelli M, Arons A, Tonegawa S. Science. 2015 May 29;348(6238):1007-13.

      Engrams are Overrated

      For good measure, some contrarian thoughts floating around Twitter...


      “Can We Localize Merge in the Brain? Yes We Can”

      Merge in the Human Brain: A Sub-Region Based Functional Investigation in the Left Pars Opercularis. Zaccarella E, Friederici AD. Front Psychol. 2015 Nov 27;6:1818.

      The neurobiological nature of syntactic hierarchies. Zaccarella E, Friederici AD. Neurosci Biobehav Rev. 2016 Jul 29. doi: 10.1016/j.neubiorev.2016.07.038.

      Really?

      Asyntactic comprehension, working memory, and acute ischemia in Broca's area versus angular gyrus. Newhart M, Trupe LA, Gomez Y, Cloutman L, Molitoris JJ, Davis C, Leigh R, Gottesman RF, Race D, Hillis AE.  Cortex. 2012 Nov-Dec;48(10):1288-97.

      Patients with acute strokes in left BA 44 (part of Broca's area) do not have impaired syntax.


      Dynamics of Mental Representations

      Characterizing the dynamics of mental representations: the temporal generalization method. King JR, Dehaene S. Trends Cogn Sci. 2014 Apr;18(4):203-10.

      King JR, Pescetelli N, Dehaene S. Brain Mechanisms Underlying the Brief Maintenance of Seen and Unseen Sensory InformationNeuron. 2016; 92(5):1122-1134.


      A Spate of New Network Articles by Bassett

      A Network Neuroscience of Human Learning: Potential to Inform Quantitative Theories of Brain and Behavior. Bassett DS, Mattar MG. Trends Cogn Sci. 2017 Apr;21(4):250-264.

      This one is most relevant to Dr. Bassett's talk, as it is the title of her talk.

      Network neuroscience. Bassett DS, Sporns O. Nat Neurosci. 2017 Feb 23;20(3):353-364.

      Emerging Frontiers of Neuroengineering: A Network Science of Brain Connectivity. Bassett DS, Khambhati AN, Grafton ST. Annu Rev Biomed Eng. 2017 Mar 27. doi: 10.1146/annurev-bioeng-071516-044511.

      Modelling And Interpreting Network Dynamics [bioRxiv preprint]. Ankit N Khambhati, Ann E Sizemore, Richard F Betzel, Danielle S Bassett. doi: https://doi.org/10.1101/124016


      Behavior is Underrated

      Neuroscience Needs Behavior: Correcting a Reductionist Bias. Krakauer JW, Ghazanfar AA, Gomez-Marin A, MacIver MA, Poeppel D. Neuron. 2017 Feb 8;93(3):480-490.

      The first author was a presenter and the last author an organizer of the symposium.



      Thanks to @jakublimanowski for the tip on Goldstein (1999).


      Looking for Empathy in All the Wrong Places: Bizarre Cases of Factitious Disorder

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      Factitious disorder is a rare psychiatric condition where an individual deliberately induces or fabricates an ailment because of a desire to fulfill the role of a sick person. This differs from garden variety malingering, where an individual feigns illness for secondary gain (drug seeking, financial gain, avoidance of work, etc.). The primary goal in factitious disorder is to garner attention and sympathy from caregivers and medical staff.

      The psychiatric handbook DSM-5 identifies two types of factitious disorder:
      • Factitious Disorder Imposed on Self (formerly known as Munchausen syndrome when the feigned symptoms were physical, rather than psychological).
      •  
      • Factitious Disorder Imposed on Another: When an individual falsifies illness in another, whether that be a child, pet or older adult (formerly known as Munchausen syndrome by proxy).

      Since the desire to elicit empathy is one of the main objectives in this disorder, it is odd indeed when the “patient” feigns a frightening or repellent condition. A recent report by Fischer et al. (2016) discussed a particularly flagrant example: the case of a middle-aged man who falsely claimed to be a sexually sadistic serial killer to impress his psychotherapist. Not surprisingly, his ruse was a complete failure.

      The case report noted that Mr. S had been a loner his entire life:
       ... He described having anxiety growing up, mainly in social situations. ... Mr. S had a history of alcohol abuse starting in his mid-twenties and continuing into his early forties. He denied any significant medical history. He denied legal difficulties, psychiatric hospitalizations, and suicide attempts. He was single, had never been married, had no children, and reported having only one close friend for most of his life. He never had a close long-term romantic relationship and stated a clear preference for living a solitary life. 

      Mr. S had served in the military but did notsee combat, and afterwards worked the graveyard shift as a security guard (all the better to avoid people).
      One year prior to his admission to the psychiatric hospital, Mr. S sought outpatient therapy for depression and engaged in weekly supportive psychotherapy with a young female psychology intern. His psychiatrist started an SSRI antidepressant and a low dose of antipsychotic medication for “depression with psychotic features.” Mr. S's alleged psychosis consisted of “voices” of crowds of people saying things that he could not make out, which he experienced while working the night shift. He consistently attended his therapy sessions and was noted to be making progress. However, several months into his therapy, Mr. S told his therapist that he had been involved in of military combat and described himself as a decorated war hero. After several therapy sessions in which he [falsely] recounted his combat experiences, Mr. S was queried as to whether he ever killed anyone, to which Mr. S replied, “During the military or after the military?” He then told his therapist that he had followed, raped, and killed numerous women during the 20 years since leaving the military.

      He recounted his imaginary crimes to the young female intern:
      Mr. S reported that he would follow a potential female victim for several months before raping and strangling her to death with a rope. Although he claimed to rape and kill the women, he did not describe any sexual arousal from the subjugation, torture, or killing of his alleged victims. He refused to disclose how many women he had killed, where he had killed them, or how he had disposed of their bodies. He described having purchased various supplies to aid in abduction, which he kept in the back of his van while cruising for victims. These supplies included rope and two identical sets of clothes and shoes to help evade detection by the police. He described using various techniques to track his victims, as well as evade surveillance of his activities. He informed his therapist that he was actively following a woman he had encountered in a local public library several days earlier. Mr. S acknowledged that he studied the modus operandi of famous sexually sadistic serial killers by reading books. The patient's therapist, feeling frightened and threatened by these disclosures, transferred his case to her supervisor, who then saw the patient for a few therapy sessions. Mr. S reported worsening depression, hearing more “voices,” and attempting to self-amputate his leg using a tourniquet. Consequently, Mr. S was involuntarily detained as a “danger to self” and “danger to others” for evaluation in the local psychiatric hospital.

      He was diagnosed with major depressive disorder, single episode, unspecified severity, with psychotic features. His routine physical, neurological exam, and lab work all yielded normal results.
      ...The inpatient treatment team contacted the District Attorney's office in order to file for continued involuntary hospitalization due to the patient's homicidal ideation and history of violence. Subsequent police investigation and review of records could not substantiate any of the patient's claims of committing multiple homicides in the Pacific Northwest.
      . . .

      After the District Attorney accepted the application for the prolonged involuntary civil commitment (180-day hold), Mr. S was confronted with the inconsistencies between his self-reported symptoms and objective findings and the failure to corroborate his claims of prior homicides. In response, Mr. S then confessed that he “had made the whole thing up…about the killings…all of it” because he “wanted attention.” He said that he had never followed, raped, or killed anyone and never had an intention to do so. He said that he did not know why he claimed this, other than an “impulse came over me and I acted on it.”

      His false identity as a serial killer backfired, and he couldn't understand why his therapist had discontinued their sessions:
      He had believed that his feigned history and symptomatology would make him a “more interesting” patient to his therapist. He reported feeling rejected when his therapist transferred his care to her supervisor. He had little insight into why his therapist may have been frightened by his behavior. Mr. S revealed that following his initial fabrications, and despite his initial involuntary hospitalization, he had felt too embarrassed to admit the truth.

      His original diagnosis was revised to “factitious disorder with psychological symptoms, and cluster A traits (particularly schizoid and schizotypal traits) without meeting criteria for any one specific personality disorder.” Because of these personality traits, he had no insight into why his therapist might feel threatened by his terrifying stories.

      There are at least two other papers describing cases of factitious disorder with repugnant feigned symptoms: one reported a case of factitious pedophilia, and the other reported a case of factitious homicidal ideation.


      Thanks to Dr. Tannahill Glen for the link.


      References

      Fischer, C., Beckson, M., & Dietz, P. (2017). Factitious Disorder in a Patient Claiming to be a Sexually Sadistic Serial Killer. Journal of Forensic Sciences, 62 (3), 822-826 DOI: 10.1111/1556-4029.13340

      Porter, T., & Feldman, M. (2011). A Case of Factitious Pedophilia. Journal of Forensic Sciences, 56 (5), 1380-1382 DOI: 10.1111/j.1556-4029.2011.01804.x

      Thompson CR, & Beckson M (2004). A case of factitious homicidal ideation. The journal of the American Academy of Psychiatry and the Law, 32 (3), 277-81. PMID: 15515916



      Appendix

      What are the symptoms of Factitious Disorder?

      • Dramatic but inconsistent medical history
      • Unclear symptoms that are not controllable, become more severe, or change once treatment has begun
      • Predictable relapses following improvement in the condition
      • Extensive knowledge of hospitals and/or medical terminology, as well as the textbook descriptions of illness
      • Presence of many surgical scars
      • Appearance of new or additional symptoms following negative test results
      • Presence of symptoms only when the patient is alone or not being observed
      • Willingness or eagerness to have medical tests, operations, or other procedures
      • History of seeking treatment at many hospitals, clinics, and doctors’ offices, possibly even in different cities
      • Reluctance by the patient to allow health care professionals to meet with or talk to family members, friends, and prior health care providers

      Gaslighting in the Medical Literature

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      Have you felt that your sense of reality has been challenged lately? That the word “truth” has no meaning any more? Does the existence of alternative facts make you question your own sanity? In modern usage, the term gaslighting refers to “a form of psychological abuse in which false information is presented to the victim with the intent of making him/her doubt his/her own memory and perception”.
      Gaslighting is a form of manipulation that seeks to sow seeds of doubt in a targeted individual or members of a group, hoping to make targets question their own memory, perception, and sanity. Using persistent denial, misdirection, contradiction, and lying, it attempts to destabilize the target and delegitimize the target's belief.

      In December 2016, the amazing Lauren Duca1wrote a widely shared piece for Teen Vogue, Donald Trump Is Gaslighting America. In it, she argued that Trump won the election by normalizing deception. Duca noted that the term gaslighting originated from the 1938 play Gas Light by Patrick Hamilton, and explained it in this way:
      "Gas lighting" is a buzzy name for a terrifying strategy currently being used to weaken and blind the American electorate. We are collectively being treated like Bella Manningham in the 1938 Victorian thriller from which the term "gas light" takes its name. In the play, Jack terrorizes his wife Bella into questioning her reality by blaming her for mischievously misplacing household items which he systematically hides. Doubting whether her perspective can be trusted, Bella clings to a single shred of evidence: the dimming of the gas lights that accompanies the late night execution of Jack’s trickery. The wavering flame is the one thing that holds her conviction in place as she wriggles free of her captor’s control.

      Gaslighting in the Medical Literature

      Barton and Whitehead (1969) were the first to report cases where a patient's mental state was manipulated for material (or situational) gain, calling it the “Gas-Light Phenomenon”. If these incidents sound like something straight out of domestic noir or a TV crime drama, you'd be right.


      Case 148 year old mechanic, married for 10 years, with three children
      Mr. A. was admitted one evening to a psychiatric hospital as an emergency. His general practitioner, when asking for his admission, had said he was mentally ill and had attacked his wife. ...

      On admission the patient said he had felt tense and depressed for about six months and related this to his wife’s changed attitude towards him. He said she had become "cold", and he thought she might have been seeing another man. He denied he had been violent and thought he had been sent into hospital because of his "nerves".
      His wife had concocted an elaborate tale of abuse, saying he had become “irritable, bad-tempered, and liable to unprovoked violent outbursts in which he sometimes hit her and once struck her with a hatchet.” She also claimed his memory was deteriorating, and she categorically denied having an affair. Mr. A was hospitalized for 12 days with no obvious physical or psychiatric disorder and left feeling more relaxed.

      However, he returned to hospital two weeks later: “He said his wife had started taunting him, saying he was mad and should be in a mental hospital. His wife said that his mental condition had considerably worsened and that he had attacked her twice.”

      Fortunately for Mr. A, his boss overheard a conversation between two men in the local tavern. One of the men was Mrs. A's lover, discussing how the two of them had plotted to get rid of Mr. A using the false claims of mental illness and abuse. The hospital staff confronted Mrs. A with her lies:
      She finally agreed that she had plotted with her boy-friend to get rid of her husband, but claimed she had been led on by him and now very much regretted her behaviour. Following some family counselling Mr. and Mrs. A. became reconciled and five years later were still living happily together.


      Case 245 year old pub owner married for 14 years

      Mr. B was admitted based on his wife's story about her husband’s “heavy drinking, erratic behaviour, and aggressive outbursts.”
      On admission to the unit Mr. B. gave a history of domestic difficulties and described mild symptoms of anxiety and depression. ...  He agreed that he was irritable but said that he had never been aggressive and did not acknowledge any of the common symptoms of alcoholism. ... recently ... his wife had lost interest in him and had started associating with younger men. She often stayed out all night, and when he asked her about this behaviour she told him not to be silly and accused him of being a drunk who should be put away.
      A member of the staff eventually found out about Mrs. B's fabrication and her intent to get rid of her husband, keep the pub, and “then really start living.” Unlike the outcome of Case 1, Mr. B left his wife and was quite happy without her five years later.


      Case 372 year old widow

      This case is unique, because it goes beyond mere mental manipulation. Mrs. C. was referred to a psychiatric hospital because of a "confusional state" and "fecal incontinence" that made her unfit for the old persons' home where she resided. She had moderate Parkinson's disease and slight dementia, but she was fairly well oriented and pleasant in demeanor. She stayed in the hospital for six weeks and showed no signs of fecal incontinence while there. And indeed it turned out that her incontinence had been cruelly induced by large doses of laxatives:
      The lady running the home had been unable to develop a good relationship with Mrs. C. and considered "she was a naughty old thing making life difficult for me, my staff, and other folk on purpose".

      For some weeks before admission to hospital Mrs. C. had been receiving ’Dulcolax’ tablets one three times a day. This had produced the expected effect with occasional "accidents" due to Mrs. C.’s mobility difficulties. The evidence suggested that Mrs. C. was not wanted in the home and induced incontinence was used as a method of getting her removed to hospital.


      Case 4 Another example is an incident reported by Lund and Gardiner (1977), where the staff of the mental hospital conspired to keep a patient there so that one of them could live in her flat. The elderly woman had suffered from paranoid episodes in the past that were successfully treated with medication. But this time “they” were really out to get her:
      Miss A., an 80-year-old retired professional lady, was first admitted to a mental hospital in connection with this incident under Section 31 of the Mental Health (Scotland) Act 1960, from her pleasant flat in a residential establishment. The admission notes stated that she had complained that there were people on the premises who had no business there, that they had spoken outside her door saying that they were going to throw her into the river and that she further believed that these people were 'after my flat'...
      Miss A was shuttled in and out of hospital several times until the evil plot was finally foiled:
      She was admitted for the third time some four months later with a depressingly similar story. Her general practitioner had been called to the home where the patient had allegedly ' barricaded her room'; she had simply put a chair against the door. She was again admitted under an Emergency Order and once more settled down very rapidly, showing no sign of disturbed behaviour. She was generally pleasant and witty, showing some evidence of valuing her independence and mildly resenting the help of the nursing staff, which she regarded as unnecessary interference.

      At this point, suspicion about the motives of the staff at the institution were aroused. Discreet inquiries revealed that the rooms which Miss A occupied had been earmarked for a proposed additional member of staff...

      [And the rental market has only gotten worse in the last 40 years!! So it's not surprising to see many stories emerging from trendy urban areas (and South Carolina). For starters, you can read these anecdotes of landlord gaslighting and harassment from tenants in New York, San Francisco, Santa Monica, and elsewhere.]


      Case 5 Let's conclude with one final report from the Canadian Journal of Psychiatry. Kutcher (1982) described the sad case of Mrs. N, a 59 year old financially successful woman who was referred to a psychiatrist at her husband's insistence. Marital problems were clearly the source of her distress.
      About two years into the marriage she established Mr. N in a business as he had entered the relationship without a secure financial basis. She then noted he would stay away from home, be unavailable when she tried to contact him, tell her he was visiting with friends even though they denied any visits, and so forth. When she confronted him with these issues he denied any extramarital activity.  ...
      Mr. N. wasn't terribly creative; his ruse was ripped from the pages of Gaslight. An outside party described him as "a 60 year old Cassanova who thinks he's 25."
      Numerous friends often intimated that he was involved with another woman and Mrs. N eventually saw this for herself. When confronted, he denied it, then said it was all over and refused to discuss the matter further. He then complained about her "saggy breasts" and when she had surgery for reduction he ridiculed her. He hid her jewelry and accused her of losing it, often changed times they were to meet without notifying her and berated her for being late; and told their acquaintances that she was "going a little strange."
      Unfortunately, Mrs. N's case was not a success story: “Currently she is still in therapy and as yet is unable to resolve the issue.”


      Let's hope the U.S. can collectively (and individually) regain its grip on the truth so it will not suffer a similar fate.


      Footnote

      1I think she's amazing for her persistence as a guiding voice on social media despite the grotesque harassment she's received.


      Further Reading

      On the Origins of “Gaslighting” (by Rosemary Erickson Johnsen)

      A Few Notes on Gaslighting (by Tressie McMillan Cottom)


      References

      Barton R, & Whitehead JA (1969). The gas-light phenomenon. Lancet (London, England), 1 (7608), 1258-60. PMID: 4182427

      Kutcher SP (1982). The gaslight syndrome. Canadian journal of psychiatry. Revue canadienne de psychiatrie, 27 (3), 224-7 PMID: 7093877

      Lund CA, & Gardiner AQ (1977). The gaslight phenomenon--an institutional variant. The British journal of psychiatry : the journal of mental science, 131, 533-4. PMID: 588872

      Smith CG, & Sinanan K (1972). The "gaslight phenomenon" reappears. A modification of the Ganser syndrome. The British journal of psychiatry : the journal of mental science, 120 (559), 685-6 PMID: 5043219 [although Milo Tyndel (1973) pointed out those cases were nothing like Ganser syndrome].






      You can watch the entire film for free at archive.org.

      Terrorism and the Implicit Association Test

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      Induced Stereotyping?

      Imagine that you're riding on a very crowded bus in a busy urban area in the US. You get on during a shift change, when a new driver takes over for the old one. The new driver appears to be Middle Eastern, and for a second you have a fleeting reaction that the situation might become dangerous. This is embarrassing and ridiculous, you think. You hate that the thought even crossed your mind. There are 1.8 billion Muslims in the world. How many are radical Islamist extremists? For example, in the UK at present, the number comprises maybe 0.00000167% of all Muslims? 1


      Language matters.

      Theresa May:
      “First, while the recent attacks are not connected by common networks, they are connected in one important sense. They are bound together by the single, evil ideology of Islamist extremism that preaches hatred, sows division, and promotes sectarianism. 

      It is an ideology that claims our Western values of freedom, democracy and human rights are incompatible with the religion of Islam. It is an ideology that is a perversion of Islam and a perversion of the truth.”

      Donald Trump:
      “That means honestly confronting the crisis of Islamist extremism and the Islamist terror groups it inspires. And it means standing together against the murder of innocent Muslims, the oppression of women, the persecution of Jews, and the slaughter of Christians.
      . . .

      DRIVE THEM OUT OF THIS EARTH.”

      In both of these cases, the world leaders did acknowledge that Islamist extremism is not the same as the religion of Islam. Nonetheless, in terms of statistical co-occurrence in the English language, the root word Islam- is now associated with all that is bad and evil in the world. Could the constant exposure to news about radical Islamist terrorism and Trump's proposed Muslim Ban result in an involuntary or “forced” stereotyping in the bus scenario above?

      A recent study found that semantics derived automatically from language corpora contain human-like biases, which means that machines (which do not have cultural stereotypes) become “biased” when they learn word association patterns from large bodies of text, such as Google News. The authors used a word embedding algorithm called Global Vectors for Word Representation (GloVe) to improve the performance of the machine learning model. As a measure of human bias, they used the popular implicit association test (IAT), from which they developed the Word-Embedding Association Test (WEAT). Instead of response times (RTs) to a specific set of words, WEAT used the distance between a set of vectors in semantic space. The authors were able to replicate the associations seen in every IAT they tested (Caliskan et al., 2017), suggesting:
      The number, variety, and substantive importance of our results raise the possibility that all implicit human biases are reflected in the statistical properties of language.

      Arab-Muslim Implicit Association Test

      Because of the relationship between word associations and implicit bias, I decided to take the Arab-Muslim IAT at Project Implicit, an organization interested in “implicit social cognition — thoughts and feelings outside of conscious awareness and control.” This definition seemed to fit with the bus scenario, which involved an impulse to profile the driver based on a rapid evaluation of perceived ethnicity.

      In the Arab-Muslim IAT, the participant classifies words as good (e.g, Fantastic, Fabulous) or bad (e.g, Horrible, Hurtful), and proper names as Arab Muslim (e.g., Akbar, Hakim) or “Other People” (e.g, Ernesto, Philippe, Kazuki).2 The bias is revealed when you have to sort both of these categories at the same time. Are you slower when Good/Arab Muslim are mapped to the same key, compared to when Bad/Arab Muslim are mapped to the same key? (and vice versa).

      My results are below.

      - click on image for a larger view -


      I showed a moderate automatic preference for Arab Muslims over Other People. But this wasn't completely unique compared to the population of 327,000 other participants who have taken this test:

      The summary of other people's results shows that most people have little to no implicit preference for Arab Muslims compared to Other People - i.e., they are just as fast when sorting good words and Arab Muslims than sorting good words and Other People.”


      The aggregate results above covered a period of 11.5 years ending in December 2015. The strength of semantic associations between words can vary over time and contexts, so we can wonder if this has shifted any in the last year. In addition, different results have been observed when faces were used instead of names, and when a better list of “Other People” names was used to specify ingroup vs. outgroup (see explanation in footnote #2).

      A Muslim-Terrorism test has in fact been developed by Webb et al. (2011). They used a variant of the IAT (the GNAT) with Muslim names (e.g., Abdul, Ali, Farid, Khalid, Tariq), Scottish names (e.g., Alistair, Angus, Douglas, Gordon, Hamish), terrorism-related words (e.g., attack, bomb, blast, explosives, threat) and peace-related words (e.g., friendship, harmony, love, serenity, unity). In an interesting twist, the authors varied “implementation intentions” to flip the Muslim-Terrorism test to the Muslim-Peace test in half of the subjects:
      Following the practice trials, one-half of the participants (implementation intention condition) were asked to form an implementation intention to help them to respond especially quickly to Muslim names and peace-related words. Participants were asked to tell themselves ‘If Muslim names and peace are at the top of the screen, then I respond especially fast to Muslim words and peace words!’. Participants were asked to repeat this statement several times before continuing with the experiment. The other half of the participants (standard instruction condition) were given no further instructions.

      I actually discovered this strategy on my own in 2008, when my IAT results revealed I was Human AND Alien and NEITHER Dead NOR Alive.

      And indeed, the Muslim-Peace instructions neutralized the strong Muslim-Terrorism association seen in the control participants Webb et al. (2011).



      Calvin Lai and colleagues conducted a high-powered series of experiments showing that instructions such as implementation intentions and faking the IAT can shift implicit racial biases (Lai et al., 2014), but these interventions are short-lived (Lai et al., 2016).

      I wrote about the former study in 2014: Contest to Reduce Implicit Racial Bias Shows Empathy and Perspective-Taking Don't Work. Failed interventions all tried to challenge the racially biased attitudes and prejudice presumably measured by the IAT. These interventions are below the red line in the figure below.

      - click on image for a larger view -


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


      The major message here is that top-down cognitive control processes can affect thoughts and feelings that are purportedly outside of conscious awareness — and can apparently override semantic associations that are statistical properties of language obtained from a large-scale crawl of the Internet (containing 840 billion words)!

      Now whether the IAT actually measures implicit bias is another story...


      ADDENDUM (June 11 2017):Prof. Joanna J. Bryson, a co-author on the machine learning/semantic bias paper, wrote a very informative blog post about this work: We Didn't Prove Prejudice Is True (A Role for Consciousness).


      Footnotes

      1 I cannot imagine what it's like to be a survivor of the recent Manchester and London attacks, and my deepest condolences go out to the families who have lost loved ones

      2 Notice I put “Other People” in quotes. That's because the names are not all from the same category (country/ethnicity)  Latino, French, and Japanese in the examples above. This lack of uniformity could slow down RTs for the “Other People” category. A better alternate category would have been all French names, for instance. Or use common European-American names to differentiate ingroup (Michael, Christopher, Tyler) vs. outgroup (Sharif, Yousef, Wahib)


      References

      Caliskan A, Bryson JJ, Narayanan A. (2017). Semantics derived automatically from language corpora contain human-like biases. Science 356(6334):183-186.

      Lai CK, Marini M, Lehr SA, Cerruti C, Shin JE, Joy-Gaba JA, Ho AK, Teachman BA, Wojcik SP, Koleva SP, Frazier RS, Heiphetz L, Chen EE, Turner RN, Haidt J, Kesebir S, Hawkins CB, Schaefer HS, Rubichi S, Sartori G, Dial CM, Sriram N, Banaji MR, Nosek BA. (2014). Reducing implicit racial preferences: I. A comparative investigation of 17 interventions. J Exp Psychol Gen. 143(4):1765-85.

      Lai CK, Skinner AL, Cooley E, Murrar S, Brauer M, Devos T, Calanchini J, Xiao YJ, Pedram C, Marshburn CK, Simon S, Blanchar JC, Joy-Gaba JA, Conway J, Redford L, Klein RA, Roussos G, Schellhaas FM, Burns M, Hu X, McLean MC, Axt JR, Asgari S, Schmidt K, Rubinstein R, Marini M, Rubichi S, Shin JE, Nosek BA. (2016). Reducing implicit racial preferences: II. Intervention effectiveness across time. J Exp Psychol Gen. 145(8):1001-16.

      Webb TL, Sheeran P, Pepper J. (2012). Gaining control over responses to implicit attitude tests: Implementation intentions engender fast responses on attitude-incongruent trials. Br J Soc Psychol. 51(1):13-32.

      The Big Bad Brain

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      I’m high, staring at the ceiling
      Sending my love, what a wonderful feeling
      What comes next, I see a light
      I’m along for the ride as I’m taking flight




      Plus a cool brain tattoo to boot. AND the song is an earworm (at least it is for me).


      It feels good to be running from the devil
      Another breath and I'm up another level
      It feels good to be up above the clouds
      It feels good for the first time in a long time now







      A monument to love unspoken
      Carved into stone “Unwilling to come undone”


      Here's what singer Landon Jacobs had to say about those specific lyrics:
      “in the face of what I incorrectly assumed was an impending brain aneurysm, I decided that the best way to spend my final moments was to push my love through the universe to the people I cared about. I was terrified of dying, but that’s not reason to squander a potential death bed situation.”

      (he had gotten way too high on one occasion and had a panic attack... he thought he was dying)






      What Is Thought?

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      Is that some sort of trick question? Everyone knows what thought is. Or do they...  My questions for you today are:

      • How do you define “a thought” (yes, a single thought)? Where is the boundary from one thought to the next?
      • What is “thought” more generally? Does this cognitive activity require conscious awareness? Or language? We don't want to be linguistic chauvinists, now do we, so let's assume mice have them. But how about shrimp? Or worms?

      What is “a thought”?

      Can you define what a discrete “thought” is?  This question was motivated by a persistent brain myth:
      You have an estimated 70,000 thoughts per day.
      Where did this number come from? How do you tally up 70,000 thoughts? Do some thoughts last 10 seconds, while others are finished in one tenth of a second?

      Over 24 hours, one thought per second would yield 86,400 thoughts. If “thoughts” are restricted to 16 waking hours, the number would be 57,600. But we're almost certainly thinking while we're dreaming (for about two hours every night), so that would be 64,800 seconds, with an ultimate result of one thought every 0.9257 seconds, on average.

      LONI®, the Laboratory of Neuroimaging at USC, included this claim on their Brain Trivia page, so perhaps it's all their fault.1

      How many thoughts does the average person have per day?
      *70,000

      *This is still an open question (how many thoughts does the average human brain processes in 1 day). LONI faculty have done some very preliminary studies using undergraduate student volunteers and have estimated that one may expect around 60-70K thoughts per day. These results are not peer-reviewed/published. There is no generally accepted definition of what "thought" is or how it is created. In our study, we had assumed that a "thought" is a sporadic single-idea cognitive concept resulting from the act of thinking, or produced by spontaneous systems-level cognitive brain activations.

      Neuroskeptic tried to find the origin of The 70,000 Thoughts Per Day Myth five years ago. He found a very bizarre post by Charlie Greer (“Helping Plumbing, HVAC, and Electrical service contractors Sell More at Higher Profits”):
      Several years ago, the National Science Foundation put out some very interesting statistics. We think a thousand thoughts per hour. When we write, we think twenty-five hundred thoughts in an hour and a half. The average person thinks about twelve thousand thoughts per day. A deeper thinker, according to this report, puts forth fifty thousand thoughts daily.

      If this “NSF report” exists, no one can find it (NSF is a funding agency, not a research lab). Were the LONI® researchers funded by NSF?  No one knows...





      Maybe we're approaching this in the wrong way. We shouldn't be relying on descriptions of mental events to define a thought, but rather discrete brain states.


      Using this definition, “a thought” is what you can capture with your fancy new imaging technique. Therefore, a thought conveniently occupies the available temporal resolution of your method:
      “A thought or a cognitive function usually lasts 30 seconds or a minute. That’s the range of what we’re hoping to be able to capture,” says Kay Tye, an assistant professor in the Department of Brain and Cognitive Sciences at MIT.
      In this case, the method is FLARE, “an engineered transcription factor that drives expression of fluorescent proteins, opsins, and other genetically encoded tools only in the subset of neurons that experienced activity during a user-defined time window” (Wang et al., 2017).


      But what if your method records EEG microstates, “short periods (100 ms) during which the EEG scalp topography remains quasi-stable” (Van De Ville et al., 2010). In this case, thoughts are assembled from EEG microstates:
      One characteristic feature of EEG microstates is the rapid transition from one scalp field topography into another, leading to the hypothesis that they constitute the “basic building blocks of cognition” or “atoms of thought” that underlie spontaneous conscious cognitive activity.

      And for good measure, studies of mind wandering, spontaneous thought, and the default mode network are flourishing. To learn more, a good place to start is Brain signatures of spontaneous thoughts, a blog post by Emilie Reas.

      What is “thought”?

      What is called thinking? The question sounds definite. It seems unequivocal. But even a slight reflection shows it to have more than one meaning. No sooner do we ask the question than we begin to vacillate. Indeed, the ambiguity of the question foils every attempt to push toward the answer without some further preparation.

      - Martin Heidegger, What Is Called Thinking?

      Philosophers have filled thousands of pages addressing this question, so clearly we're way beyond the depth and scope of this post. My focus here is more narrow, “thought” in the sense used by cognitive psychologists. Is thought different from attention

      Once we look at the etymology and usage of the word, no wonder we're so confused...

      Does Beauty Require Thought?

      Speaking of philosophy, a recent study tested Kant's views on aesthetics, specifically the claim that experiencing beauty requires thought (Brielmann & Pelli, 2017).




      Participants in the study rated the pleasure they felt from seeing pictures (IKEA furniture vs. beautiful images), tasting Jolly Rancher candy, and touching a soft alpaca teddy bear. In one condition, they had to perform a working memory task (an auditory 2-back task) at the same time. They listened to strings of letters and identified when the present stimulus matched the letter presented two trials ago. This is distracting, obviously, and the participants' ratings of pleasure and beauty declined. So in this context, the authors effectively defined thought as attention or working memory (Brielmann & Pelli, 2017).2 


      Alternate Titles for the paper (none of which sound as exciting as the original Beauty Requires Thought)

      Aesthetic Judgments and Pleasure Ratings Require Attention

      Judgments of Beauty Require Working Memory and Cognitive Control

      ...or the especially clunky Ratings of “felt beauty” Require Attention — but only for beautiful items.


      Dual task experiments are pretty popular. Concurrent performance of the n-back working memory task also disrupts the execution of decidedly non-beautiful activities, such as walking and timed ankle movements. So I guess walking and ankle movements require thought...



      Footnote

      1This claim was still on their site as recently as March 2017, but it's no longer there.

      2They did, however, show that working memory load on its own (a digit span task) didn't produce the same alterations in beauty/pleasure ratings.


      References

      Brielmann, A., & Pelli, D. (2017). Beauty Requires Thought. Current Biology, 27 (10), 1506-1513.

      Van de Ville D, Britz J, Michel CM. (2010). EEG microstate sequences in healthy humans at rest reveal scale-free dynamics. Proc Natl Acad Sci 107(42):18179-84.

      Wang W, Wildes CP, Pattarabanjird T, Sanchez MI, Glober GF, Matthews GA, Tye KM, Ting AY. (2017). A light- and calcium-gated transcription factor for imaging andmanipulating activated neurons. Nat Biotechnol. Jun 26.



      gif from palerlotus

      Role of the Vestibular System in the Construction of Self

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      How do we construct a unified self-identity as a thinking and feeling person inhabiting a body, separate and unique from other entities? A “self” with the capacity for autobiographical memory and complex thought? Traditionally, the field of cognitive science has been concerned with explaining the mind in isolation from the body.

      The growing field of embodied cognition, on the other hand, seeks to rejoin them. One major strand has focused on grounding higher-order semantics and language understanding in perceptual and sensory-motor representations. This view is distinct from theories of knowledge based on abstract, amodal representations divorced from sensory-motor experience. Another wing of the embodied approach is concerned with how interoception the inner sense of your physical state grounds your feelings and emotions in the body. Interoceptive awareness of visceral functions such as heartbeat has been related to core consciousness and awareness of self, including body image.

      A relatively neglected yet critical aspect of any grand theory of the embodied self is the vestibular system. The vestibular system is the set of sensory organs responsible for maintaining our balance and keeping our visual field in a stable position while our head moves around. These organs are located in the inner ear and include...
      ...two otolith organs (the saccule and utricle), which sense linear acceleration (i.e., gravity and translational movements), and the three semicircular canals, which sense angular acceleration in three planes. The receptor cells of the otoliths and semicircular canals send signals through the vestibular nerve fibers to the neural structures that control eye movements, posture, and balance.

      The quote above is from Kathleen Cullen and Soroush Sadeghi (2008), who have an excellent review on the vestibular system in Scholarpedia.



      We take the vestibular system for granted until something goes wrong, like motion sickness (a mismatch of movement perceived by the vestibular and visual systems) or a rare disorder of the inner ear such as Menière’s disease. But how can a dysfunction of the inner ear influence our sense of self?

      Song, Jáuregui-Renaud, and colleagues (2008) looked at symptoms of depersonalization (a feeling of detachment from oneself) in 50 patients with peripheral vestibular disease and 121 healthy controls. The participants were given the Depersonalization/Derealization Inventory of Cox and Swinson (2002) to assess symptoms of these conditions:
      1. Depersonalization: Experiences of unreality, detachment, or being an outside observer with respect to one's thoughts, feelings, sensations, body, or actions (e.g.,perceptual alterations, distorted sense of time, unreal or absent self, emotional and/or physical numbing.)" 
      2. Derealization: "Experiences of unreality or detachment with respect to surroundings (e.g., individuals or objects are experienced as unreal, dreamlike, foggy, lifeless, or visually distorted."

      Beyond the expected high frequency of dizziness, the patients were much more likely to experience feelings of Shifting Ground, Spaced Out, Body Feels Strange, and Not Being in Control of Self than were controls (see bottom half of the figure below).



      The authors suggest that abnormal vestibular signals disrupt the relationship of the self to the environment, leading to strange feelings of detachment:
      Vestibular disease causes primary symptoms of vertigo and feelings that the ground is unstable ... which are more marked in distinct, acute episodes. These immediate symptoms are, by definition, unreal experiences since the body is not spinning and the ground is not heaving, but they are readily understandable as perceptions derived directly from abnormal sensory signals. Vestibular dysfunction could also compromise more general precepts of stable relationships between the self and the environment...

      Symptoms of depersonalization/derealization can be induced experimentally in healthy people via caloric stimulation. This procedure is used medically to check the vestibulo-ocular reflex, which stabilizes the visual image while the head is moving. The test involves delivering warm or cold water into the ear canal and observing the resultant eye movements (or lack thereof).

      Song et al. (2008) administered caloric stimulation to 20 of their vestibular patients and 20 controls. After stimulation, many healthy participants reported feelings of detachment/separation from their surroundings (40%), and that their body feels strange/different (50%). These were novel experiences for most. Conversely, the patients reported no such changes after stimulation because they already experience these symptoms.

      An even more extreme way to stimulate the vestibular system is through unilateral centrifugation (i.e., spinning around in a specialized chair). NOTE: this has nothing to do with the fictional Centrifuge Brain Project. See more about that here.



      (I don't think I'd be smiling)


      A recent study subjected 100 healthy participants to unilateral centrifugation to stimulate the utricles (Aranda-Moreno & Jáuregui-Renaud, 2016). The target of this test differs from the caloric procedure, which stimulates the semicircular canals. The utricles and the semicircular canals detect different types of motion (linear acceleration and angular acceleration, respectively), and the authors wanted to see if unilateral centrifugation would produce the same effects as caloric stimulation. And indeed, after centrifugation, symptoms of depersonalization and derealization were reported with increased frequency e.g., Surroundings seem strange and unreal; Time seems to pass very slowly; Body feels strange or different in some way (see Table below for details).


      - click on image for a larger view -


      modified from Table 2 (Aranda-Moreno & Jáuregui-Renaud, 2016). Frequency (Freq) and severity (score range) for each of the symptoms of the Cox and Swinson (2002) depersonalization/derealization inventory reported by 100 subjects.


      These results provide further evidence that the vestibular system contributes to the construction of the self. The sense of inhabiting one's body is assembled from many different inputs, of course. These can go awry in epilepsy, migraine, focal brain injury, psychiatric disturbances, and under extreme stress. Although rare, out-of-body experiences are more frequent in persons who suffer from dizziness due to vestibular disorders (Lopez & Elzière, 2017). In these instances, the vestibular system is unable to ground the self within the body.


      References

      Aranda-Moreno C, Jáuregui-Renaud K. (2016). Derealization during utricular stimulation. Journal of Vestibular Research 26(5-6):425-431.

      Cullen K, Sadeghi S (2008). Vestibular system. Scholarpedia, 3(1):3013.

      Lopez C, Elzière M. (2017). Out-of-body experience in vestibular disorders - A prospective study of 210 patients with dizziness.Cortex Jun 8.

      Sang FY, Jauregui-Renaud K, Green DA, Bronstein AM, Gresty MA. (2006). Depersonalisation/derealisation symptoms in vestibular disease. Journal of Neurology, Neurosurgery & Psychiatry 77(6):760-6.


      Further Reading

      Research Topic: The Vestibular System in Cognitive and Memory Processes in Mammalians (collection edited by Besnard et al., 2015)

      Personality changes in patients with vestibular dysfunction (review by Smith & Darlington, 2013)

      Feeling Mighty Unreal: Derealization in Kleine-Levin Syndrome (blog post by The Neurocritic)

      A Detached Sense of Self Associated with Altered Neural Responses to Mirror Touch (blog post by The Neurocritic)

      Theme issue ‘Interoception beyond homeostasis: affect, cognition and mental health’ (edited by Manos Tsakiris and Hugo D. Critchley).

      The poverty of embodied cognition (Goldinger et al., 2016).

      Arguments about the nature of concepts: Symbols, embodiment, and beyond (Mahon & Hickok, 2016).

      Olfactory Deterrence

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      A military aide carries the “nuclear football” aboard the Marine One helicopter in which President Trump was waiting to depart the South Lawn of the White House on Feb. 3. (Michael Reynolds/European Pressphoto Agency). via Washington Post.


      August 6, 1945 President Harry S. Truman, announcing the bombing of Hiroshima:

      “If they do not now accept our terms they may expect a rain of ruin from the air, the like of which has never been seen on this earth.” (video)
      [Trump was less than a year old.]


      August 8, 2017 President Donald Trump:

      “North Korea best not make any more threats to the United States. They will be met with fire and fury like the world has never seen... he has been very threatening beyond a normal state[ment]. They will be met with fire, fury and frankly power the likes of which this world has never seen before.” (video)

      Issuing a threat of nuclear war is not something to cheer about (“We're number one! We're number one!”). Jesus does not condone such an action, despite what pastor Robert Jeffress says.

      “The mixture of foreign policy, golf and veiled threats about nuclear war is unprecedented and jarring,” said BBC reporter Tara McKelvey.

      I would like to think that most Americans are horrified by the prospect of nuclear war. But many are pleased with the blunt, bracing talk and feel “protected by the vastness of America” “It doesn’t concern me,” said [a guy] at the Morgan County Fair in Brush, Colo. “We live in the safest part of the whole country.”

      WHAT IS WRONG WITH YOU?!! I shout to myself.1 The people interviewed for that article were between the ages of 45 and 76 (mean = 64.5 yrs), so they were all alive during the Cold War and probably watched The Day After on TV (now on YouTube). Mushroom clouds, incineration, radiation sickness, utter devastation. In Kansas. The apocalyptic wasteland of suffering encouraged by a younger generation of trolls immune to actual footage of melting bodies and acute radiation syndrome.


      Olfactory VR

      The callous Gamergate set requires a more visceral and disgusting approach to the gravity of the Trump-Kim Jong-un escalation. My near-future sci-fi solution to nuclear trolling would involve delivering odorants that carry the stench of death (e.g., cadaverine, putrescine) each and every time these jokers spread anxiety and discord. This would require immersive virtual reality (or some preposterous way to deliver odorants via smart phone) and real-time monitoring of social media streams for key phrases. Exposure to the nauseating, inescapable smell of rotting flesh might be punishing enough to initiate a change in behavior...




      ...but this could ultimately backfire in the event of an actual Zombie Apocalypse, because they would be protected from the marauding undead hoards. And that's not what we want.






      For a very different view on ironic amusement, see this essay:
      Today, the younger generations that will determine our future did not experience terrifying emotions as part of their nuclear education. For them, the gigantic mutant ants and degenerate war survivors that stalk the memories of their grandparents are obvious myths, evoking only the kind of ironic amusement that young people find in video games, TV shows and superhero movies. These post-Cold War generations should therefore be more ready than their elders to face nuclear missiles dispassionately, not as supernatural prodigies but as plain machinery.


      Footnote

      1But wait. Don't Conservatives Scare More Easily Than Liberals? (“Say Scientists” so it must be true). Or not. There were a lot of problems with that study, see Conservatives Are Neurotic and Liberals Are Antisocial.


      Smell as a Weapon, and Odor as Entertainment

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      The use of smell as a weapon, or a deterrent, was explored in a fanciful way in my previous post on nuclear threats. While poking around the literature, I found a fascinating unclassified document from the Army Research Laboratory, Olfaction Warfare: Odor as Sword and Shield (PDF). The authors provide a sweeping overview of odor, from chemical tactics in the natural world to the use of scents in the beauty and entertainment industries. The primary military application discussed by Schmeisser et al. (2013) is the use of odor in stealth operations. These are designed to deceive the enemy by masking current location or projecting smells to a false location. Although the document does not propose putrid odor as an offensive weapon, the authors discuss the history of such efforts.


      Stink Bombs

      Stink bombs are “devices designed to create an unpleasant smell forcing people to leave an area or protecting off-limits areas against being entered.”

      One unsavory application during WWII was used to make German officers smell like rotten meat, but unfortunately, “this substance was so volatile that it could not be confined to specific targets and contaminated everything in the area.”

      Another unsuccessful project from 1966 tried to develop “culturally specific stink bombs, which would affect Vietnamese guerillas, leaving the U.S. troops unaffected. The project was abandoned due to technical barriers.”

      But a more contemporary program reached the pinnacle of olfactory deterrence:
      In 2001 the U.S. announced the development of the ultimate stink bomb aimed at driving away hostile forces by a stench so foul that it results not only in disgust or aversion but also fear. The odorant used in the bomb has been developed by a team of researchers led by Dr. Pamela Dalton at the Monell Chemical Senses Center in Philadelphia and is a mixture of two agents: the U.S. Government Standard Bathroom Malodor (a mixture of eight chemicals with a stench similar to human feces but much stronger) and the Who-Me?, a sulphur-based odorant that smells like rotting carcasses...

      Scratch-and-Sniff

      Schmeisser et al.'s technical report makes for surprisingly entertaining reading. It's highly unlikely that any other military document praises Polyester, John Waters' 1981 multimodal film event that provided viewers with scratch-and-sniff cards.
      The cards had 10 numbered spots (1.roses, 2.flatulence, 3.model airplane glue, 4.pizza, 5.gasoline, 6.skunk, 7.natural gas, 8.new car smell, 9.dirty shoes, and 10.air freshener) that the audience scratched and sniffed when the appropriate number flushed at the corner of the screen. This system, called Odorama, solved the problem with hanging odors that was the main problem of the early smell-distributing systems.

      Waters' Odorama succeeded where the older scent distributions systems had failed. Smell-O-Vision (1939) and AromaRama (1959) were financial disasters for movie theaters, because “the odors were weak, the smells persisted longer than was desired, and the molecules were distributed by noisy systems.”


      OloramaTM

      Present day technology for odor delivery has advanced beyond scratch-and-sniff, of course, and Olorama offers an enhanced cinematic experience (“the smells jump off the screen”). The kits feature “very compact, hidden aromatization devices that are installed under seats (1 device for every 5-7 seats, depending on their size).”

      They also sell a product for home use. Olfactory enhancement of virtual reality is not a new development, but this VR system looks stylish, at the very least.





      The company stocks over 70 scents in categories such as Fantasy, Food, Wild, and...

      ACTION

      FIRE - RAIN - FOREST

      (AND COMING SOON...):
      GUNPOWDER - BLOOD - BURNING RUBBER


      Reference

      Schmeisser E, Pollard KA, Letowski T. Olfaction warfare: odor as sword and shield. ARMY RESEARCH LAB. ABERDEEN PROVING GROUND MD. HUMAN RESEARCH AND ENGINEERING DIRECTORATE; 2013 Mar.

      Survival and Grief

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      There is no transcendent moment of growth or meaning in watching a childhood friend die of cancer. There is no learning experience that will somehow make me stronger. Only horror, helplessness, loss, and grief. I am deriving no spiritual uplift from this experience, only depression and despair. If someone wants to talk to me about post-traumatic growth, I will spray paint their car.

      Others disagree with me, I'm sure of it. For religious reasons. And I will respect their beliefs. There is no point in being a skeptical asshole to a grieving family.

      The most important point here is that dying patients should not have to suffer this much. I wrote about this and related issues seven years ago, as my father was dying of cancer.

      Ketamine for Depression: Yay or Neigh?

      Limbaugh/Palin "death panels" extend the lives of terminally ill patients

      2009 Lie of the Year Redux: Palin's so-called Death Panels

      Update on Ketamine in Palliative Care Settings


      I had more of a voice back then. Today I feel hopeless about the state of the world and my ability to have any impact on it. But I will try to keep my happy memories alive.



      I love you.
      RIP.


      Neuroexistentialism: A Brain in Search of Meaning

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      [image from Huth et al., 2016]

      No, not “meaning” in the semantic sense... 


      “Neuroexistentialism” is the angst that some humans feel upon realizing that the mind and spirit have an entirely physical basis. At a personal level I don't understand all the hubbub, because I accepted that mind = brain when I entered graduate school to study neuroscience. But for others:
      “Coming to terms with the neural basis of who we are can be very unnerving. It has been called “neuroexistentialism”, which really captures the essence of it. We’re not in the habit of thinking about ourselves that way” (Churchland, 2013). 

      It's very 2013.




      Neuroexistentialism is also the title of a forthcoming volume of essays edited by Caruso and Flanagan. In their introductory chapter, Flanagan and Caruso define this philosophical variant in the progression of existentialisms to the present third-wave:
      “There are three kinds of existentialism that respond to three different kinds of grounding projects—grounding in God’s nature, in a shared vision of the collective good, or in science. The first-wave existentialism of Kierkegaard, Dostoevsky, and Nietzsche expressed anxiety about the idea that meaning and morals are made secure because of God’s omniscience and good will. The second-wave existentialism of Sartre, Camus, and de Beauvoir, was a post-holocaust response to the idea that some uplifting secular vision of the common good might serve as a foundation. Today, there is a third-wave existentialism, neuroexistentialism, which expresses the anxiety that even as science yields the truth about human nature it also disenchants. The theory of evolution together with advances in neuroscience remove the last vestiges of an immaterial soul or self that can know the nature of what is really true, good, and beautiful.”

      But I don't understand why the neuroscientific view must be so disenchanting. (But then again I'm a neuroscientist.) I knew fellow students who went to church yet easily reconciled their cell culture day jobs with their religious beliefs.

      Professor Patricia Churchland is the best at explaining the “Don't Worry, Be Happy” response to neuroexistential terror:
      Q - Some might say the idea that you are just your brain makes life bleak, unforgiving and ultimately futile. How do you respond to that?
      A - It’s not at all bleak. I don’t see how the existence of a god or a soul confers any meaning on my life. How does that work, exactly? Nobody has ever given an adequate answer. My life is meaningful because I have family, meaningful work, because I love to play, I have dogs, I love to dig in the garden. That’s what makes my life meaningful, and I think that’s true for most people.


      Word cloud for the 18 chapter titles in Neuroexistentialism


      The Scope of Neuroexistentialsim

      In brief, it's about free will, morality, meaning, and purpose. And of course neuroscience.

      Back to my puzzlement about who suffers from a modern-day ailment caused by science spoilers. I found the below sentence to be both condescending and hyperbolic (Flanagan and Caruso):
      But for most ordinary folk and many members of the nonscientific academy, the idea that humans are animal and that the mind is the brain is destabilizing and disenchanting, quite possibly nauseating, a source of dread, fear and trembling, sickness unto death even.

      Perhaps the authors overascribe the illness and exaggerate the depth of ennui experienced by “most ordinary folk” who are too busy to grapple with the scientific implications of social neuroscience.

      Honestly, I don't mean to be overly snarky but right now I'm grappling with Survival and Grief, and with second-wave existential crises caused by crazed leaders with bad hair who wave around their phallic symbols of nuclear destruction, and with persisting racism that divides the country, and with the hypocrisy of anti-immigration Christians, and with a future of toxic air and coastal regions underwater. Maybe what I'm experiencing is actually fourth-wave existentialism...




      Medicating Neuroexistential Angst

      If neuroexistentialism is a narrow form of generalized anxiety or even panic, can't we use our scientific knowledge to sooth these troubled brains? Why not apply psychopharmacological principles (and/or psychotherapy) to calm the fearful and trembling mind? We have already presupposed that mind = brain (which brought us “sickness unto death even”), and that medications can alter brain function in psychiatric disorders.

      But this is not the correct way forward (see Flanagan and Caruso).
      “...Are there naturalistic resources that can quell the anxiety produced by the ascendancy of the scientific image generally, and specifically, the picture that comes from combining neo-Darwinism with neuroscience, which produces the new and nerve-wracking anxiety associated with neuroexistentialism?

      One promising approach is to pursue a kind of descriptive-normative inquiry into the causes and conditions of flourishing for material beings living in a material world, whose self-understanding includes the idea that such a world is the only kind of world that there is and thus that the meaning and significance of their lives, if there is any, must be found in such a world. We can call such an inquiry eudaimonics (Flanagan 2007, 2009).”

      So the solution to third-wave existentialism is positive psychology (as opposed to despair).1


      Footnote

      1Despair:
      What sets the existentialist notion of despair apart from the conventional definition is that existentialist despair is a state one is in even when he isn't overtly in despair. So long as a person's identity depends on qualities that can crumble, he is considered to be in perpetual despair. And as there is, in Sartrean terms, no human essence found in conventional reality on which to constitute the individual's sense of identity, despair is a universal human condition.


      Further Reading



      Existential Neuroscience: a field in search of meaning

      Earlier in 2013, the field of Existential Neuroscience (distinct from Neuroexistentialism) took the journal SCAN by storm, with neuroimaging studies focused on terror management theory (which describes how we deal with the inevitability of death). At the time,
      I asked:
      But what is Existential Neuroscience, exactly? A group of French intellectuals discussing brain research in a cafe while smoking and sipping espresso? An authentic neuroscience of utter freedom that embraces a state of perpetual despair1 over the meaninglessness of existence? Or independent groups of German-speaking neuroscientists who scan subjects while they ponder death?

      BROADEN Trial of DBS for Treatment-Resistant Depression No Better than Sham

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      Website for the BROADEN™ study, which was terminated by
      the sponsor.


      A multi-site, randomized, double-blind, placebo-controlled clinical trial of deep brain stimulation (DBS) for treatment-resistant depression has failed, according to a new article in Lancet Psychiatry. The targeted brain region was bilateral subcallosal cingulate white matter, which had been called the “Depression Switch” based on acute stimulation studies at Emory. These disappointing results were not surprising, since they were covered by Neurotech Business Report in December 2013 and then in depth by my posts here and here. The new paper followed the patients for a longer period of time, up to 24 months for some in the cohort.

      The main portion of the trial was six months in length. All patients received implantation surgery. Two weeks later, they were randomized to either the treatment group (n=60), who received stimulation right away, or the “sham” control group (n=30), who did not. After six months, the blinding was uncovered and both sham and treatment groups were offered open label DBS for another six months.

      In the figure below, Control (red line) and Stimulation (blue line) groups both showed slight improvements over time, with no significant difference in depression severity measured by the Montgomery-Åsberg Depression Rating Scale (MADRS). This was the primary endpoint. We don't see a difference between groups at six months or any other time.


      - click on image for a larger view -


      Fig. 2. (Holtzheimer et al., 2017).At months 9 and 12, the control group was receiving active stimulation; therefore, for the control group, 9 months refers to 3 months of active stimulation, and 12 months refers to 6 months of active stimulation. Error bars indicate standard deviations.


      Concerning the endpoint more specifically (Holtzheimer et al., 2017):
      The primary efficacy endpoint for the study was defined as difference in proportion of patients achieving a response between the stimulation and control groups. Response was defined as a 40% or greater reduction in MADRS and no worsening in GAF from baseline (average of three baseline MADRS assessments) to the average scores at months 4, 5, and 6.


      Table 3 (modified from Holtzheimer et al., 2017).


      Here's the full scoop for the futility analysis that put an end to the trial (because of the low probability of success). I had erroneously stated in January 2014 that the trial was halted by the FDA. It wasn't. It was stopped by the sponsor, St. Jude Medical (Holtzheimer et al., 2017):
      For the futility analysis, based on the first 6 months' data, the proportion of patients with response for the stimulation group was predicted to be 40%, and for the control group was predicted to be 18·5%. In the actual futility analysis, these figures were 20% for the stimulation group and 17% for the control group. It was concluded that the study had a 17% chance of success if continued. Although this did not meet the prespecified definition for futility (<10% chance of success), the sponsor chose to end study enrolment following the futility analysis.

      Although “These findings are disappointing given the encouraging data from earlier open-label studies of subcallosal cingulate DBS,” all was not lost, according to the authors. They offered a number of possible explanations (which can be summarized as long duration of illness, suboptimal stimulation parameters, and lack of tractography):
      • “participants in this study had an average current episode duration of about 12 years, which is much longer than the average duration of current episode in previous studies of subcallosal cingulate DBS (approximately 5 years) and might have contributed to the low overall proportion of patients achieving a response.”
      • “possible that stimulation contacts and parameters were suboptimal during the first 12 months of this study, given the somewhat restrictive programming algorithm used. Greater improvement in depression occurred after the 12-month endpoint when more flexibility in stimulation contacts and parameters was allowed.”
      • “Neurosurgical placement of the DBS electrodes, based on this algorithm, was highly accurate and did not differ between eventual responders and non-responders.”
      [NOTE: placement was verified by at least two of three experts: HSM, CH, PEH. Nonetheless, the authors argue that placement could improve with more detailed tractography, e.g. Riva-Posse et al. 2017. This refinement of protocol has been discussed for the last 10 years; see Johansen-Berg 2007 and ...But My Subgenual Cingulate Is Sad.]
      • “for maximal efficacy, the active electrode for subcallosal cingulate DBS must be placed such that it affects a crucial network of white matter tracts connecting key brain regions, including the forceps minor, cingulum bundle, and uncinate fasciculus. Therefore, it is possible that prospective targeting on the basis of individual diffusion tensor imaging tractography could optimise electrode placement in subcallosal cingulate DBS.”

      In an earlier paper, a group of DBS investigators and ethics experts advised other researchers, industry mavens, and even bloggers on “Being open minded about neuromodulation trials: Finding success in our 'failures'.” (Finns et al., 2017)
      “Similarly, another randomized double blind clinical trial comparing active versus sham stimulation for the treatment of severe depression targeting Brodmann Area 25 was also halted for futility prior to completion of the planned study (St Jude Medical sponsored BROADEN trial). While there are neither publications nor official industry statements, uninformed speculations as to causes of the failure are in the public domain [28,29] to the detriment of the scientific process and progress.

      In each of these instances, different combinations of variables can lead to disappointing results. For example, patient characteristics, surgical variability, stimulation algorithms, outcome metrics, and institutional variance, can all contribute to negative outcomes in complex trials that initially seem promising. Further, once a negative report is published, the work can become ‘toxic’, and there is little incentive to engage in small subset analyses that have a limited market.
      Finally,
      “We believe that investigators, industry, regulators and society need to fully understand what is casually described as success and failure in order to maximize return on investment, all the more so when opportunities for additional knowledge generation remain in place. To do otherwise, would be irresponsible.”

      So to call the BROADEN trial a failure is “irresponsible”? Personally, I am aware that a multi-site trial using invasive new technology to treat intractable psychiatric patients with a terrible and (ultimately) ill-defined syndrome is a massive undertaking. And very, very, very expensive. I have no problem with the investigators trying to glean what they can from individual differences to move forward with better targets/parameters/etc. I wanted to see this procedure help a majority of patients.

      The bottom line here is that the primary preregistered endpoint was as follows: 12/60 (20%) improved with stimulation, 5/30 (17%) improved with no stimulation, 8/60 (12%) patients with stimulation reported an increase in depressive symptoms (this was not defined or quantified), and 1/30 (3%) patients with no stimulation reported an increase in depressive symptoms.

      Let's take a look at the registered clinical trial. Oh we can't.


      Clinical Trial NCT00617162

      [Trial of device that is not approved or cleared by the U.S. FDA]




      However, we can look at other clinical trials using the same device (Libra Deep Brain Stimulation System) with the same sponsor (St. Jude Medical) in Europe and Canada. Oh by the way, an April 2016 news release announced: Abbott to Acquire St Jude Medical (DBS was not mentioned). In January 2017 Abbott Completes the Acquisition of St. Jude Medical (no DBS here, either). I won't speculate any further. I'm too tired.


      I'd like to conclude with an upbeat tweet from a prominent neuroscientist who studies pain and the placebo effect.



      References

      Choi KS, Riva-Posse P, Gross RE, Mayberg HS. (2015). Mapping the "Depression Switch" During Intraoperative Testing of Subcallosal Cingulate Deep Brain Stimulation. JAMA Neurol. 72(11):1252-60.

      Fins JJ, Kubu CS, Mayberg HS, Merkel R, Nuttin B, Schlaepfer TE. (2017). Being open minded about neuromodulation trials: Finding success in our "failures". Brain Stimul. 10(2):181-186. 

      Holtzheimer PE, Husain MM, Lisanby SH, Taylor SF, Whitworth LA, McClintock S, Slavin KV, Berman J, McKhann GM, Patil PG, Rittberg BR. (2017). Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial. The Lancet Psychiatry. 2017 Oct 4.

      Riva-Posse P, Choi KS, Holtzheimer PE, Crowell AL, Garlow SJ, Rajendra JK, McIntyre CC, Gross RE, Mayberg HS. (2017). A connectomic approach for subcallosal cingulate deep brain stimulation surgery: prospective targeting in treatment-resistant depression. Mol Psychiatry. 2017 Apr 11. [Epub ahead of print].


      Further Reading

      BROADEN Trial of DBS for Treatment-Resistant Depression Halted by the FDA
       NOTE: the trial was actually halted by the sponsor, not the FDA

      Update on the BROADEN Trial of DBS for Treatment-Resistant Depression

      Deep Brain Stimulation for Bipolar Depression

      Modern Tract-Tracing for Historical Psychosurgery

      ...But My Subgenual Cingulate Is Sad

      The Sad Cingulate

      Sad Cingulate on 60 Minutes and in Rats

      The Devilish Side of Psychiatry

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      The devil always experienced malicious pleasure in imposing himself in neuropsychiatric nosology


      Olry and Haines (2017) published a mischievous article in the Journal of the History of the Neurosciences:
      Having an inquiring mind by nature, the Devil always managed to interfere in all spheres of human activity, including the sciences. ... Biologists use an enzyme called “luciferase” — Lucifer has been described as the “light-bearing” fallen angel, hence the bioluminescence — to spot certain proteins by chromogenous reactions (Lodish et al., 2005, p. 92). ...

      But how did the Devil get a foot — of course cloven (!) — into the door of the neurosciences?

      Demonic possession plays an important role, of course, even in modern day psychiatric nosology (see the debate over Possession Trance Disorder in DSM-5). Does it make any sense to use DSM-5 (or DSM-IV) criteria to diagnose spirit possession across cultures? Transcultural psychiatry takes a much more inclusive and sensitive approach to such phenomena, which are often precipitated by trauma.

      Olry and Haines (2017) avoid this literature entirely and suggest that:
      The concept of demonic possession has been mainly of theological (Omand, 1970; Balducci, 1975; Rodewyk, 1988; Amorth, 1999, 2002; Bamonte, 2006; Fortea, 2006, 2008) and/or historical concern (Villeneuve, 1975; Pigin, 1998; Kelly, 2010; Kiely & McKenna, 2007).  ...

      Although conservative theologians might not question the reality of diabolical possession (see Haag, 1969; Cortès & Gatti, 1975, for the few exceptions), many psychiatrists and psychologists admit being interested in the concept though, of course, not declaring themselves in favor of a supernatural etiology...

      But being diabolical sorts themselves, the authors namedrop and show off their autographed copy of The Exorcist.



      Figure 1. Title page of William Peter Blatty’s The Exorcist, with signed dedication by the actress Linda Blair. Author’s (R.O.) copy.



      They continue:
      However, literature and the movie industry — let’s remember William Peter Blatty’s The Exorcist (Blatty, 1971) (see Fig. 1) and the sociological impact of William Friedkin’s screen adaptation two years later (Bozzuto, 1975) — not only generated impassioned movie critics ... but also brought back scientific discussions involving neurosciences and, more specifically, psychology, neurology, and psychiatry (Montgomery, 1976).



      Häxan (1922)entire film available at archive.org


      Deadly exorcisms have been reported recently in the medical literature, including several cases of Fatal Hypernatraemia from Excessive Salt Ingestion During Exorcism. One 20-year-old woman received a prescription for Prozac to treat her postpartum depression, but her family also advised her to undergo an exorcism. She reportedly drank six glasses of a mixture of 1 kg table salt in a liter of water.

      The Church itself involved physicians many centuries ago in the differential diagnosis between possession and mental disease, as exemplified by the 1583 Rheims National Synod:

      [Before he undertakes to exorcize, the priest has to inquire diligently about the life of the possessed [. . .], of his health [. . .], because melancholics, lunatics often need much more cures of the physician than the ministry of exorcists.] (Tonquédec, 1948, p. 330)

      Physicians, and in actual fact, clinical neuroscientists, then had to name a phenomenon — nosology oblige — about which most did not believe.


      The Devil's Influence Over Neuropsychiatry – “some lexicological compromises”
      ...neuropsychiatrists sometimes allow themselves the use of theological concepts (e.g., possession, diabolical, demonological), provided that an additional term — medical or not — grants them a little more scientific credibility. This addition may be “neurosis” (demonological neurosis: Hélot, 1898; Freud, 1923), “psychosis” (diabolical possession psychosis: Lhermitte, 1944), “delirium” (diabolical possession delirium: Gayral, 1944; Delay, 1945), “syndrome” (possession syndrome: Yap, 1960), “phenomenon” (phenomenon of possession: Bron, 1975), “state” (possession state: Wittkower, 1970), or “experience” (possession experience: Pattison, 1969, p. 323).

      Or sometimes the patient may feel like they are literally in hell.



      Self-Portrait in Hell, by Edvard Munch (1903)



      Reference

      Olry R, Haines DE. (2017). The devil always experienced malicious pleasure in imposing himself in neuropsychiatric nosology. J Hist Neurosci. 26(3):329-335.


      Further Reading

      Possession Trance Disorder in DSM-5

      Spirit Possession as a Trauma-Related Disorder in Uganda

      "The spirit came for me when I went to fetch firewood" - Personal Narrative of Spirit Possession in Uganda

      Possession Trance Disorder Caused by Door-to-Door Sales

      Fatal Hypernatraemia from Excessive Salt Ingestion During Exorcism

      Diagnostic Criteria for Demonic Possession



      The Wailing (aka 곡성, , Gokseong)


      ...and to make your Halloween nightmares complete...



      Although it's certainly not for everybody, The Wailing is an amazing film.
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