The Balanced Rhetoric Against Neuroscience

The New York Times editorial pages continue to be a place where anti-neuroscience rhetoric can be expressed primarily as decreased funding or more accurately portion of the available NIMH funding.  Maybe there has been some pro-neuroscience opinion expressed there and if there was I have missed it.  I recently posted an exciting development in neuroscience teaching for psychiatrists and psychiatric residents.  In that post I reference an opinion piece by Richard Friedman, MD a psychiatrist (1).  Dr. Friedman makes several arguments for psychotherapy as if it is unrelated to neuroscience and based on that premise concludes that there is no substitute for psychotherapy, that people are more than a brain in a jar, and that anyone benefiting from psychotherapy seems to prove  that.  I found that to be an incredible statement considering that (according to Koch in above graphic):  "The brain is the single most complex object in the universe." There is also the fact that with 7.4 billion people on earth - there are 7.4 billion unique conscious states - the vast majority of which are not accurately described by any DSM or psychodynamic diagnosis/formulation.  All the time that Dr. Friedman is mounting this critique he also discusses the importance of clinical research and suggests shifting the funding balance away from neuroscience.

In the recent case John C. Markowitz a professor of clinical psychiatry at Columbia has a more subtle form of the argument.  In this case and the previous opinion piece the authors both endorse the importance of neuroscience to a point.  In this case the argument is - yes neuroscience is important but let's reestablish balance between neuroscience and clinical studies such as looking at the efficacy of psychotherapies.  Breaking it down, Dr. Markowitz makes the following points:

 1.  Under the directorship of Thomas Insel, the NIMH clinical research budget was "strangled" and the resources were diverted to neuroscience research.  The author acknowledges both the need for neuroscience research and the primitive stage of psychiatric diagnostics based on clusters of signs and symptoms.  This was really the basis for Insel's RDoC initiative looking at more reliable markers of psychiatric syndromes.  Any practicing psychiatrist who has seen all of the iterations of the DSM realizes that we are as far as we can go with this manual.  That includes from the standpoint of validity but also in terms of the clinical examination by psychiatrists.  As long as we are all contained by this manual, the clinical method of psychiatry will remain stuck somewhere in the 1940s.  That should be extremely disconcerting to the profession and future psychiatrists.

DSM technology is extremely limiting in terms of the usual clinical trials.  The NIMH sponsored Star*D study is a decade and a half old at this point.  It has defined the response rates for both antidepressant therapies and provided a discussion point for psychotherapy trials of depression.  Clinical trials of antidepressants provide an equally varied result.  Any practicing clinician knows that these studies are all seriously flawed out of the gate by using DSM diagnoses and also an intent-to-treat analysis that does not resemble clinical practice.  The variation in diagnoses from depression to anxiety to depression plus anxiety as seen in clinical practice should point to the fact, that patient selection into clinical trials currently results in very heterogenous patient populations in terms of both therapeutic effects and medication tolerability.  We can continue to spend large sums of money on these trials of mixtures of patient populations and post modest positive results or we can attempt to identify patients who will respond specifically and not experience side effects from a particular therapy.  That is the real promise of neuroscience based research.

2.  The patients who need help are poorly served by current neuroscience research.  The helpful psychotherapies listed by the author like interpersonal psychotherapy (IPT), cognitive behavioral therapy (CBT), and other psychotherapies have been around for decades.  I happen to have copies of Interpersonal Psychotherapy by Klerman, Weissman, Rounsaville, and Chevron and Cognitive Therapy of Depression by Beck, Rush, Shaw, and Emery.  The publication date of the former is 1984 and the latter is 1979.  Both therapies have been out there for over 30 years.  At this point both have been studied hundreds of times.   Looking at clinical trials on Medline yields 1711 for CBT and 261 for IPT.  Not only that but some of the clinical trials that were successful (like IPT for cocaine use) have never made  it into clinical practice.  In fact, in most places getting a therapist who actually practices any of the specific research proven psychotherapies is impossible.  The problem does not seem to be a lack of psychotherapy research but a lack of access to practitioners who use research proven psychotherapies.  Mental health treatment is the most highly rationed treatment resource and additional studies that continue to prove that existing psychotherapies work seems superfluous at this point.  Any current studies are often compared to existing therapies and with the DSM problem contributing to diagnostic heterogeneity.  Any new trials should only be funded for serious conditions where the therapy might be useful.  There is no reason to expect that a new therapy applied using the current diagnostic system or clinical trials technology will lead to any enhanced treatment effects.

3.  Existing treatments are not "good enough".  The author attributes this "good enough" statement to Insel himself.  I understand the point he is trying to make.  The author points to continued suffering, treatment failures and suicides as evidence that more is needed now.  The problem is that there is no assurance that clinical research will add any more at this time.  Certainly a focus on suicide as a stand alone problem (not suggested at all by DSM) and on serious disorders with no treatment like adult anorexia nervosa is warranted.  But even then we are left with a clinical trials technology that consistently produces modest results at best.  More multimillion dollar trials of psychotherapy that we already know is somewhat effective when patients have no chance of ever receiving it against a backdrop of "is this really depression or anxiety" seems like a waste of time and money to me.  It seems like a much better idea to develop a neuroscience method to determine who needs psychotherapy and who might benefit from medications.  But even then, the only treatments that will be readily available will be the medications and even then less than half of the affected patients will get access to treatment.  Good luck trying to find a psychotherapist and an insurance company willing to cover the cost of the number of sessions used in the psychotherapy research. Research proven therapies are only as good as the number of practitioners using them and access to those practitioners.

4.  The placing all of your eggs in one basket argument.  This is basically saying that if the ratio of clinical to neuroscience funding is 10% to 90% the risk is missing something big in the clinical research and not getting any useful results from neuroscience.  Given the history that I have provided, there needs to be a clear advance on the clinical side in order to fund large trials.  It does not make any sense to continue to  fund more of the same  or slight modifications of treatment for common disorders.  Our eggs have been all in one basket and I would call that treatment as usual.  In the 30 years that I have been in practice, there is nothing that I would call a major breakthrough.  Clinical research results come and go.  Effective psychiatrists are effective psychiatrists not based on breakthroughs but how they approach clinical practice.  Even that mode of treatment is threatened by widespread support for "collaborative care" that is being justified using the same kind of research that justified managed care in the first place.  In the end there has been nothing more destructive in terms of access to care for mental disorders than managed care.

In many ways these ongoing arguments resemble the arguments of the biological psychiatrists and psychotherapy psychiatrists that I trained under in the 1980s.  Many programs were split under this artificial division with the residents left to identify with biological or psychotherapy faculty.  It is interesting to note that this division occurred at a time when Kandel wrote a paper on how psychotherapy is neuroscience in action (3).  That may have been missed because the biologically based psychiatrists at the time were really focused on pharmacology and neuroendocrinology rather than a comprehensive neuroscience.  Neuroscience and the old diagnostic technology and clinical methods seem to be the current points of division.

A lot of the criticism is directed at Insel.  I have heard him talk about the initiatives and the rationale sounded clear to me.  I think that rationale is very similar to what I have discussed so far, but for clinical psychiatrists it is also the realization that as long as we live in an approximate world - we will get approximate results.  The inertia to stay in that place is always puzzling to me.

But - it is time to move out of the 1950s.

Clinical psychiatry the way it is currently researched and practiced holds no promise for understanding the most complex known object in the universe.  Neuroscience is one of the big ways out of that predicament.



George Dawson, MD, DFAPA      



References:

1:  Friedman RA. Psychiatry's Identity Crisis. New York Times July 17, 2015. p SR5.

2:  Markowitz JC.  There’s Such a Thing as Too Much Neuroscience.  New York Times October 14, 2016. p A21.

3:  Kandel ER. Psychotherapy and the single synapse. The impact of psychiatric thought on neurobiologic research. N Engl J Med. 1979 Nov 8;301(19):1028-37. PubMed PMID: 40128.

              

Neuroscience In Psychiatry Now - It Is A Lot Easier Than It Looks

I read the article "The Future of Psychiatry as Clinical Neuroscience. Why Not Now?" by Ross, Travis, and Arbuckle in JAMA Psychiatry and found little to disagree with.  I was in one of the venues a few years ago when Thomas Insel, Director of the NIMH talked about a clinical  neuroscience rotation for neurology, neurosurgery, and psychiatry residents to bring neuroscience to the clinical side of things.  Unfortunately he was a lot less enthusiastic about it when I sent him a follow up e-mail and at that time suggested it would probably have to wait for some time in the future.  

As a long time neuroscience enthusiast,  I have always found the reluctance to head in this direction puzzling.  On a historical basis, neuroscience has always has a prominent role in psychiatric theory.  One of the arguments against neuroscience has been that there are no clinical applications.  Even back in the day with Alzheimer, Nissl, Kraepelin and other German neuropsychiatrists were studying brain anatomy of patients in asylums, there were important correlations - most notably those consistent with both Alzheimer's Disease and Binswanger's Disease.  About two decades later, Constantin von Economo penned his treatise Encephalitis Lethargica - Its Sequelae and Treatment and described conditions that were relevant right up to the point that I started my training in the 1980s.

Being a practicing psychiatrist with an interest in neuroscience presents a variety of CME events ranging from behavioral neurology and developmental pediatric conferences in Boston to the annual Movement Disorders conference in Aspen.  There were the occasional very unique courses, like the brain dissection course run by the late Lennart Heimer, MD and a faculty of outstanding neuroanatomists.  But most of the neuroscience in psychiatry is typically packed into a course that focuses on the specialized diagnosis and treatment of specific disorders.  A good example would be the American Association of Geriatric Psychiatry (AAGP) courses that would include a detailed discussion of Alzheimer's pathology and vascular dementia and how they might not be that disparate at the microscopic level (that was also an ongoing debate in the movement disorder conferences).  In an AAGP event there would be 1 lecture out of 7 for that day devoted to neuroscience.  On the teaching level, neuroscience has always been there in the form of neurotransmitters, localization of cognitive and neuropsychiatric disorders associated with various brain lesion and insults, cell signaling, and plasticity.  In the past 20 years there has been an unprecedented integration of neurotransmitters and specific brain structures as seen in this diagram of the ventromedial prefrontal cortex.  

I have been fantasizing about a foundation and several years ago came up with the idea that it should fund neuroscience education in psychiatry.  This would be my preliminary plan:


1.  Contract with the top neuroscientists in psychiatry to come up with the syllabus.  

From the reviews in review edition of Academic Psychiatry (reference 4) there are already residency training programs that have come up with a systematic approach to this training.  There should be a place for all programs to post what neuroscientists and researchers consider the top areas for focus.  From the reviews mentioned in the above narrative it is very likely that there are fairly complete syllabi at this point but looking at the reviews in Academic Psychiatry they seem to be fairly disparate in terms of what faculty see as the most relevant.  The vignettes prepared by the NIMH (reference 2 and 3) are illustrative of what is possible.  If I was designing a curriculum, I would want every possible concept that could be illustrated in these vignettes and build the course work around that.


2.  Develop neuroscience teaching as a specialty.

I doubt that there are enough neuroscientists around to teach the subject to psychiatry residents.  A group dedicated to teaching neuroscience and neuroscientific formulations would be a logical approach.  There are currently plenty of nonscientist faculty with an interest and more than a passing knowledge of neuroscience.


3.  Develop a repository of graphics and teaching materials. 

There is no area of psychiatry that could benefit more from high quality graphics for teaching.  Current faculty engaged in teaching need to run a gauntlet of copyright related issues ranging from implicit copyright permission (yes you can use for teaching without going through Copyright Clearance Center) to repetitive licensing fees that are difficult to track.  All of those problems are from publishers controlling these rights and in some cases charging unrealistic amounts for reuse of some of these works.  Open access work is a potential solution but it is doubtful that enough graphics currently exist to illustrate key neuroscience principles.  A coalition of residency programs can potentially contract for the production of custom figures for a central repository that could be used in residency programs across the country.  There is already a precedent for this process with the psychopharmacology course available to residency programs from the American Society of Clinical Psychopharmacology (ASCP) who produce a large number of PowerPoints that are available to residency programs for a very reasonable fee.


5.  Don't forget about addiction science.

The field of addiction has contributed immensely to understanding how the brain functions.  In many cases psychiatry residents have minimal exposure to the treatment of substance use disorders and the associated syndromes and that could potentially strengthen both those areas in any residency program.



6.  Hold annual review courses. 

The field as it applies to psychiatry contains neuroscience spread across gatherings for psychopharmacology, geriatric psychiatry, general psychiatry, child and adolescent psychiatry, sleep medicine, addiction medicine and behavioral neurology.  There should be meetings across the country that focus on the necessary neuroscience and formulations presented by the top experts in the world with that focus.


7.  Suggested readings.

I try to keep up with Nature, Science, and Neuron and the Science Signaling series as a cost effective approach to learning new developments about neuroscience and whatever open access journals that seem to have the best content.  There are top journals that are too expensive or require memberships where the threshold is set for researchers and not teachers.  A good general approach to how to approach the literature would be very useful for most of the teachers and some of the expensive journals might offer packages for teachers rather than researchers.  I can recall that when I interviewed for residency positions and asked about department recommended reading lists there was only one department who provided one in those days.  I will let readers guess about which department that was.


8.  Reviewing imaging studies and teaching files.

Some of the best neuroanatomical preparation and training in my career came from reviewing imaging studies with radiologists, neuroradiologists, neurologists and neurosurgeons.  Current electronic medical records make viewing imaging studies easier than at any time in the past.  There is no better learning procedure than to organize findings, order the test, and confirm the problem.  That is possible currently if you treat a lot of patients with apparent lesions on imaging but functional imaging is becoming more available it has the potential to revolutionize psychiatric practice.  As an example, listen to the story called How To Cure What Ails You and an enthusiastic Eric Kandel talk about the importance of the anatomical substrate (reference 5) in psychiatric disorders.

These are some of my current ideas.  I look forward to the day that a neuroscientific formulation about what might be relevant is contained in the same paragraph that includes social and psychological formulations.  It will also put psychiatrists back where most of us belong - seeing people with the most difficult problems rather giving out advice on how to prescribe antidepressants.


George Dawson, MD, DFAPA




References:

1: Ross DA, Travis MJ, Arbuckle MR. The Future of Psychiatry as ClinicalNeuroscience: Why Not Now? JAMA Psychiatry. 2015 Mar 11. doi: 10.1001/jamapsychiatry.2014.3199. [Epub ahead of print] PubMed PMID: 25760896

2:  National Institute of Mental Health neuroscience and psychiatry modules. 2012a. Available at http://www.nimh.nih.gov/neuroscience-and-psychiatry-module/index.html. Accessed on March 16, 2015.

3:  National Institute of Mental Health neuroscience and psychiatry modules: 2012b. Available at http://www.nimh.nih.gov/neuroscience-and-psychiatry-module2/index.html. Accessed on March 16, 2015.

4:  Coverdale J, Balon R, Beresin EV, Louie AK, Tait GR, Goldsmith M, Roberts LW. Teaching clinical neuroscience to psychiatry residents: model curricula. Acad Psychiatry. 2014 Apr;38(2):111-5. doi: 10.1007/s40596-014-0045-7. Epub 2014 Feb 4. Review. PubMed PMID: 24493360.

5:  How To Cure What Ails You.  Radiolab  Accessed on March 17, 2015.


Supplementary:

The header to this article is all of my copies of The Biochemical Basis of Neuropharmacology and the book I consider to be its successor  Introduction to Neuropsychopharmacology.  New editions of BBN came out in 1970, 1974, 1978, 1982, 1986, 1991, 1996, and 2003.  The copy with the white cover in the middle (a little faded) was the first copy I owned.  In those days I wrote the year I purchased books in the front jacket and that year was 1984.  This book with its elegant little drawings and low purchase price served as an introductory neuroscience text to many classes of psychiatry residents.

A Molecular Basis for Gateway Drugs

The Gateway Drug hypothesis proposes that using a particular drug increases the likelihood that there will be a progressions to using other drugs of abuse.  The competing hypothesis is that there is a general predisposition to using more than one drug in people susceptible to addiction and that it does not depend on any sequence of exposures.  In this Shattuck Lecture in the New England Journal of Medicine, Eric and Denise Kandel examine the epidemiology and molecular biology of nicotine use and the development of addictions.  Most addiction treatment centers recognize the importance of nicotine cessation in improving abstinence rates from the primary drugs of choice.  Most of that depends on series of cases discharged from treatment centers.  The idea of nicotine also has importance because one of the approaches to nicotine cessation depends on nicotine substitution and it is important to know if that treatment intervention might lead to increased risk for ongoing substance use problems.  It also has implications for electronic cigarettes (e-cigarettes).  There is a general idea that any form of nicotine that does not involve exposure to combustible or chewed tobacco components is preferred because of all of the conditions associated with the physical and combustible products of tobacco.  If nicotine alone places one at risk for using another drug like cocaine, the risk/benefit decision will need to be reconsidered.

The authors briefly reviewed the epidemiology showing of all US adults who had ever used cocaine, the vast majority of them (87.9%) smoked cigarettes before using cocaine.  Only 3.5% used cocaine first.   The rate of cocaine dependence was highest (20.2%) among those who smoked cigarettes before using cocaine.  They proceed to use an animal model to examine the possible priming effects of nicotine and to possible elucidate the mechanism.  The animal models of addiction in mice included locomotor sensitization and  conditioned place preference.  In both of these models, micd primed with nicotine first and then treated with nicotine and cocaine showed the expected addicted response with heightened locomotor sensitization and place preference.  Mice primed with cocaine did not.

They proceed to look at the effect on synaptic plasticity and the model used was long term potentiation (LTP) in the nucleus accumbens (NAcc).   The  predominate neurons in the NAcc are medium spiny neurons (MSNs) and they are innervated by dopaminergic neurons projecting from the ventral tegmental area (VTA) and glutamatergic neurons from the prefrontal cortex and the amygdala.  Reducing excitatory (glutamatergic) input to the NAcc reduces inhibitory output to the VTA leading to more dopaminergic input to the NAcc or greater reward.  Repeated cocaine administration leads to reduced LTP in the excitatory synapses of the NAcc.  A single injection of cocaine in a mouse primed with 7 days of nicotine exposure leads to marked reduction in LTP.  Nicotine alone, or nicotine after cocaine had no effect on LTP.  Priming with nicotine causes a change in neuronal plasticity that increases cocaine associated reward.

The authors turned to known gene expression markers of addiction in the striatum specifically the expression of FosB.  They demonstrated that nicotine alone for seven days increased FosB expression and adding cocaine led to a further 25% expression.  The next step was to examine if nicotine alters the chromatin structure  at FosB promotor of the gene and they looked at the acetylation of histones H3 and H4 at the FosB promotor.  Nicotine alone increased the acetylation of both histones, cocaine alone increased the acetylation of H4 only.  They went on to demonstrate that the acetylation was widespread after nicotine exposure throughout the striatum.  Cocaine alone had no similar effect.  They went on to clarify that increase acetylation was due to inactivation of histone deacetylase activity (HDAC) and not activation of acetylases.  They carried out additional pharmacological studies to confirm that the hypoacetylated state (caused by nicotine) leads to depression of LTP associated with cocaine and that further it cannot be rapidly reversed.  The authors investigated if nicotine enhanced cocaine induced LTP in the amygdala and hippocampus and found that it did.

This fairly intensive research program and series of experiments allowed the authors to conclude that nicotine has a unidirectional priming effect and it works through an acetylation mechanism by affecting HDAC activity.  The mechanism explains what is seen in human populations at the epidemiological level and in mice at the experimental level.   That has obvious implications for treatment as well as drug development.  It  also points out that e-cigarettes are potentially as much of a potential gateway drug as combustible cigarettes.  In clinical practice it is also fairly common to see patients with addiction who are continuing to use nicotine substitutes (gum, lozenge, patch) long after they have stopped smoking.  If the mechanism elucidated by Kandel and Kandel is accurate it will be important to discuss the implications of continued nicotine exposure.

Kandel's work is always compelling because of his broad view of science and psychiatry.  He is as comfortable discussing psychoanalysis and Freud as he is talking about molecular biology.  In this case he combines views on epidemiology and molecular biology in a very compelling story and suggests it might be a broader model for how gateway drugs work.  As he is drawing his conclusions there is still room for the competing hypothesis and he makes this explicit.  His work is always a breath of fresh air compared to the current zeitgeist of political arguments about science and psychiatry often from people who know very little about either subject.  Go to the article at the link below and read this paper and compare it to his 1979 article Psychotherapy and the Single Synapse.  That covers at least 34 years of studying synaptic plasticity and it is a remarkable accomplishment.


George Dawson, MD, DFAPA


1: Kandel ER, Kandel DB. Shattuck Lecture. A molecular basis for nicotine as agateway drug. N Engl J Med. 2014 Sep 4;371(10):932-43. doi: 10.1056/NEJMsa1405092. PubMed PMID: 25184865. (free full text).

Supplementary 1:  Drawing depicts nicotine inhibiting HDAC leading to increased acetylation of histones per the above discussion.  CREB-1 = cyclic AMP response-element-binding protein; CBP = CREB-binding protein (acetylates histone H4);  PKA= protein kinase A; A=acetyl groups, P=phosphate groups; H2a, H2b, H3, H4 = histone proteins in chromatin; Pol II = RNA polymerase II (catalyzes synthesis of DNA to mRNA).

Riding The "L" Train

My wife and I went to the Edward Hopper exhibit at the Walker Arts Museum last Saturday.  Hopper is one of my favorite artists because I consider him to be the artist of chronic insomniacs.  I am a chronic insomniac.  By that I mean, many of his most favorite paintings depicted scenes that were seen either directly through a window at night or the perspective of seeing a room illuminated by two or three lighting sources at night.  Reading the informational displays next to the art, I learned that may have been from riding the "L" train in New York City late at night and peering into offices where people were still working.  Some of his paintings are very natural night time occurrences like his famous painting of a diner at night called Nighthawks.  In some of his paintings displayed in this exhibit there were annotated drawings with clear attention to the light and sources of light in his paintings.  In Office At Night for example is a notation about light coming in (at night) from the window, from an overhead office light, and from a lighted adjacent room.

Nighthawks has always interested me just in terms of its form and attention to lighting details.  It interests me even more after reading Kandel's book on art and what the viewer brings to the viewing situation.  I suppose there are a lot of people just seeing a diner at night.  But if you are an insomniac, night is an entirely different proposition for you.  Many insomniacs dread the night because they equate it with no sleep.  But many of us see it as the most exciting part of the day.  It is like a different world where your perceptions are much clearer.  I have actually cataloged some of my nighttime experiences, and they remain as vivid today as they did decades ago.  For example, I remember one night, I was wide awake at 10 PM and decided I was probably not going to sleep that night.  What better time than to go to the chemistry lab where I was working at the time and continue some experiments I was working on?  It was about -5 degrees and a three mile walk.  About two inches of snow had fallen and it crunched and squeaked every time I took a step.  I was past an old decrepit sandstone block hotel at the half way point and more snow started to come down.  Across the street was a large white marble bank building flashing the time and temperature.  There were at least four lighting sources, the flashing time and temperature, the street lights, light coming out of the shops and rooms in the hotel, and light reflecting up off the fresh snow.   I walked for three miles in these unusual lighting circumstances hearing and feeling that crunching and squeaking under my boots the entire way.  It was thoroughly invigorating.  I reached the lab, did a few experiments.  As the sun came up, I found a couch in the building and fell asleep.  That may not sound like much to someone who is used to sleeping at night, but it is what I bring to viewing a Hopper painting of a diner at night.  I find myself very excited about it, when it probably does not have that effect on others.  I could easily walk into that diner at night and talk with my fellow insomniacs.  We would all be in a fairly good mood.

All of this also reminded me of Kandel's recent book  The Age of Insight and his focus on beholder's experience.  The main idea is that viewer experience is critical to the completion of the work of art.  This idea originated with Alois Reigl, an art historian who developed a formal method for analyzing works of art.  The corollary is that each new generation of artists has the implicit task of educating the public about new ways to view art.  Some of Kandel's focus was on Viennese modernist painters - Klimt, Kokoschba, and Schiele and their role in educating the public about unconscious instinctual urges through their paintings during the time that psychoanalysis was being developed.  The theory of the viewer's experience also looked at the issues of inner and external coherence.  In the case of inner coherence, the painting has a clear narrative that does not require the viewer to complete the story.  In the case of less clear narratives the viewer may respond to the physical or emotional space of the painting, social equality with the people in the painting, and emotional and empathic equality with the people in the painting.  According to Kandel: "The ambiguity in the image elicits both a conscious and an unconscious process of recognition in the viewer, who responds emotionally and empathically to the image in terms of his own life experiences and struggles."  This is a critical but rarely recognized aspect of art.  I have been out of college for some time at this point, but recall no classes that were either specifically art classes or liberal arts courses on the interpretation of art that discussed the response of the viewer as necessary to complete the art, even though that idea had been out there for over 50 years.

These considerations also highlight the artistic aspects of other media - like photography.  There are many common criticisms of photography as art.  Many consider the creative process to be too truncated: "It's just a picture after all anybody can do it."  Some consider it to be a predictable way to elicit an emotional response, such as the Humane Society and Save the Children commercials that are broadcast on late night television.  But photography is a lot more than that.  As an example, I posted this sequence of pictures of 4 sisters over a span of 37 years years to my Facebook feed.  I found these pictures especially in sequence to be emotionally stunning and I wanted to see what some of my friends who were photographers thought.  To my surprise, I got two responses: "wow" and "very cool" from friends who do not seem particularly interested in photography - at least based on what they post on Facebook.  In this case the only narrative is implicit and partial and that is sisters as they age.  The body language and facial expressions seem to change over time.  I think it would be very difficult for the average viewer to not respond emotionally, empathically and construct their own theory of the mind interpretation for what is going on.  Photography can clearly be as compelling as painting or other forms of visual art.

Being a neuroscientist, Kandel is a wealth of information on the neurobiology of the beholder's experience.  On the chapter focused on that issue, he talks about unconscious determinants of beauty and attractiveness.  He discusses activation of the reward system both at the level of the ventral tegmental area and orbitofrontal cortex (OFC) in response to attractive faces, especially smiling faces and beautiful images.  He points out that one experiment showed that beautiful pictures activate the OFC more than the motor cortex and with ugly pictures it is the opposite suggesting that seeing ugly or fearful faces sets up the brain to prepare for a fleeing response.

Kandel's approach to the discussion of the artist and the beholder and their necessary relationship to complete the art and now the underlying neuroscience makes a lot of sense to me.  The most compelling aspect of this story (apart from loving the art) is the idea that you can look at this problem from the perspective of neuroscience and not get carried away.  Kandel is as comfortable discussing the neuroscience as his is the qualitative and subjective aspects of the creation and perception of art.  One does not necessarily explain the other.  At some point in psychiatry subjective became a dirty word and the illusion was created that in the extreme our unique brains can be measured and characterized by a simple collection of symptoms.  Any student of consciousness knows that it is absurd to think that 7 billion unique people with unique brains can be broken down to a relatively few disorders or personalities or executive functions or IQs or however else we might want to approximate their neurobiology.  Art and the beholders experience is a great example of that.  I have a good idea of why I like Hopper's work.  My theory of the mind is that he was a fellow insomniac who did not mind being an insomniac.  I have other speculation about his work, especially the people he included that I will hold for now.  Another thing I have learned over the years is that people are not necessarily interested in one anothers interpretations of art.

My favorite art and the art that I collect is pure abstract art and I hope to develop a detailed post about that in the not too distant future.

George Dawson, MD

References:

Eric R. Kandel.  The Age of Insight: A Quest To Understand the Unconscious in Art, Mind, and Brain, From Vienna 1900 To The Present.  Random House, New York City, 2012.

Gustav Klimt Page -  This artist is prominent in Kandel's book and his works are on display at this web site.

Neuron Perspectives in Neuroscience

Eric Kandel's thought, research, and writing have been a major source of inspiration to me ever since I read his neuroscience text and his classic article Psychotherapy and the Single Synapse in the New England Journal of Medicine nearly 34 years ago.  I was very pleased to see that he wrote the lead article in Neuron's   25th Anniversary edition entitled "The New Science of the Mind and the Future of Knowledge."  I read the article in the same spirit that I read the original NEJM article, guidance from a world class neuroscientist who was also trained as a psychiatrist.  At that level the article is quite exciting because somewhere along the line Dr. Kandel has clearly been following concepts that are far removed from the synapse and does a good job of summarizing the major points and the current deficiencies.  He also comes back to the idea that psychotherapy is a biological treatment as he proposed in the original 1979 article.

One of the most interesting aspects of the article is that Kandel does not apologize for psychoanalysis.  He is also not excessively critical.  I read an article about his residency class at Harvard and psychoanalysis was certainly prominent at the time.  Although it is fashionable these days to throw Freud under the bus, he points out that Freud and subsequent analysts were right about a number of issues that neuroscience has caught up with including:

1.  Unconscious mental processes pervade conscious thought.
2.  The importance of unconscious thought in decision making and adaptability.

The probable link here is that Freud, psychoanalysis, and current neuroscience is focused on the mind rather than descriptive psychiatry.  At some point the majority of the field got sidetracked on the issue of identifying a small number of pathological conditions by objective criteria.  The mind was completely lost in that process and those few psychiatrists who were focused on it were engaged in generating theories.  He criticizes the field for a lack of empiricism but recognizes that has changed with clinical trials of psychodynamic psychotherapy and recent interest in testing psychoanalytical theories with the available neuroscience.  He also points out that Aaron Beck was a psychoanalyst when he developed cognitive behavior therapy focused on conscious thought processes and became a leading proponent for an evidence based therapy.

It was good to see a discussion of the hard problem of consciousness.  I was on the ASSC listserv for many years until it eventually lost a home and was shut down.  Many of the experts in consciousness studies posted on that thread but there was very little neuroscience involved but plenty of discussion of the neural correlates of consciousness.

Information flow through the brain has always been one of my interests.  The idea that information flows through biological systems at both chemical and electrical levels is a relatively recent concept.  At the clinical level behavioral neurologists like Mesulam and Damasio discussed it based on cortical organization and information flow primarily at cortical levels.  I taught a course for many years that talked about the basic information flow through primary sensory cortex, association cortex and then heteromodal cortices.  The model had good explanatory power for any number of syndromes that impacted on this organizational model.  For example, achromatopsia made sense as a lesion in pure sensory cortex and posterior aphasia made sense as a lesion of heteromodal cortex.

Using this model, overall information flow from the sensory to the motor or output side could be conceptualized, but there were plenty of open boxes in the flowchart along the way.  The theory of how consciousness is generated from neural substrates was still a problem.  Social behavior was another.  Despite decades of descriptive psychiatry, the diagnostic criteria for major psychiatric disorders still depended on symptoms.  In many cases aberrant social behavior was a big problem and often a more accurate reflection of why patients were disabled, unable to work and had limited social networks.  Even though there were scales to rate positive and negative symptoms in schizophrenia, aberrant social behavior cut across a number of major psychiatric disorders.  In my first job as a community psychiatrist, we rated social behavior of the people in our community support program and it was a better predictor of disability than diagnosis or ratings of positive symptoms.  The neuroscience of social behavior remained resistant to analysis beyond the work done on cortical lesions and obvious comparisons to those syndromes.  But people with schizophrenia had no obvious frontal lesions.

Dr. Kandel points out the developments in these areas ranging from de novo point mutations affecting circuitry in the frontal cortex to mirror neurons to the neuroendocrinology and genetics of social behavior.  The review of Thomas Insel's work with voles and the extension of that work by Bargmann in C. elegans highlights the importance of specific systems in social behavior and how these systems are preserved across species.

One of the most interesting areas outlined by Dr. Kandel was the issue of art and the neuroscience of its creation and perception.  I have just posted on abstract art and was able to locate a quote from Kandinsky:

"The abstract painter derives his "stimulus" not from some part or other of nature, but from nature as a whole, from its multiplicity of manifestations which accumulate within him and led to the work of art.  This synthetic basis seeks its most appropriate form of expression which is called "nonobjective".  Abstract form is broader, freer, and richer in content than objective [form]." (Kandinsky Complete Writings on Art - p 789)

Kandel develops a narrative based on Viennese art historians and the importance of the aesthetic response to art.  That response is an emotional one based on the life experience of the viewer and the neuroscience of that response can be studied.  He looks at the inverse optics problem, facial recognition, and comes up with a flow diagram of the processes involved in viewing visual art.  I did not realize it until I read this article but he has a new book on the subject and ordered a copy to review at a future date.

Some of the conclusory remarks about neuroscience and what it means to society are the most important.  It is easy to be cynical about any scientific endeavor and it is also very easy to be political.  Neuroscience has to endure (although to a much lesser degree) than what psychiatry endures.   There are people out there commenting on neuroscience who don't seem to know much about it.  In many cases they are not scientists.  Even in the case of scientists, it is often easy to forget that the public will probably not hear the most objective and the most scientific.  They will typically hear from the experts who unambiguously support one side of the scientific argument as opposed to the other.  Kandel is cautious in his suggested applications of neuroscience to society.  He does not view it as a panacea or an explanation for behavior necessarily.  An example:

"Attributing love simply to extra blood flow in a particular part of the brain trivializes both love and the brain.  But if we could understand the various aspects of love more fully by seeing how they are manifested in the brain and how they develop over time, then our scientific insights would enrich our understanding of both the brain and love."    

Hopefully you will have time to read this paper.  I have highlighted a few more based on my reading about neuroscience over the past 20 years or so.  I will end with a paragraph on technical expertise.

When I was interviewing for residency positions 30 years ago, one of my questions that drew the strongest emotional reaction was: "Does your program have a reading list for residents?"  That question on average elicited shock or at least irritation from the average residency director.  The only exception was Johns Hopkins.  They handed me a neatly bound list of several hundred references that they considered key references that every psychiatric trainee should read.  I should have taken it as a sign and applied there, but my trajectory in life has been more random and circuitous than studied.  If I was a current residency director, I would have a list with a neuroscience section and the following articles from this volume of Neuron would be on it.  People often recoil when I talk about the technical expertise needed to be a psychiatrist.  Technical seems like too harsh a word for most psychiatrists.  Most of the media debate after all is essentially rhetorically based political discussions  I would say that if you read these articles, you can consider them to be a starting point for what you might need to know about neuroscience and psychiatry in the 21st century.

George Dawson, MD, DFAPA

A reading list for psychiatrists of the future (all available free online at the above link):

Kandel, Eric (2013) The New Science of Mind and the Future of Knowledge.  Neuron 80: 546 – 560

                             

McCarroll Steven A, Hyman Steven E (2013) Progress in the Genetics of Polygenic Brain Disorders: Significant New Challenges for Neurobiology. Neuron 80:578-587.

Südhof Thomas C (2013) Neurotransmitter Release: The Last Millisecond in the Life of a Synaptic Vesicle. Neuron 80:675-690.

Huganir Richard L, Nicoll Roger A (2013) AMPARs and Synaptic Plasticity: The Last 25 Years. Neuron 80:704-717.

Dudai Y, Morris Richard GM (2013) Memorable Trends. Neuron 80:742-750.

Shadlen Michael N, Kiani R (2013) Decision Making as a Window on Cognition. Neuron 80:791-806

Buckner Randy L (2013) The Cerebellum and Cognitive Function: 25 Years of Insight from Anatomy and Neuroimaging. Neuron 80:807-815.