Sunday, November 17, 2013

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.

S├╝dhof 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.

1 comment:

  1. I would add Mark Solms to the list. Here's a link to an article I haven't read yet, but that we might consider for the journal club.

    Also, here's a link to his talk, The Conscious Id.
    It's from last year, but I heard him give what I assume is the same talk (same title) just a couple weeks ago. He's got some interesting things to say.