Showing posts with label neuroscience. Show all posts
Showing posts with label neuroscience. Show all posts

Monday, December 26, 2016

Basic Models




In order to bring some clarity into the discussion of why neuroscience is important for psychiatrists, I thought I would get back to the basics.  I have three models in the above graphic that I think represent the basic conceptualizations of the brain in my lifetime.  They are very basic models, but I think reasonable jumping off points for further discussion.  They also serve to make my point about the importance of neuroscience.  I realize that there is a natural human tendency to be argumentative.  When I mention neuroscience or even science it seems that many psychiatrists and interestingly their detractors both get irritated.  I can understand why the detractors are irritated since many of them are at the level of Black Box thinking in the above diagram.  I will elaborate further, but many of them seem to consider the brain an amalgam of various qualities that either defy understanding or are unnecessary to understand because the brain may be involved at the very periphery of human behavior if at all.  But I don't understand any attitude on the part of brain professionals like psychiatrists that doubt the importance of neuroscience. With that let me proceed with the three levels of thought about the brain in the above diagram.

The Black Box embodies what people have thought about the brain since the beginning of time.  The brain is a mystery on the one hand and immutable on the other.  The reality of that situation could not be denied for long.  It was obvious that people with clear brain damage who survived the initial insult could have a number of changes in cognition, personality, and social behavior.  The black box view eventually gave way to mind-body dualism that held there were a number of mental phenomenon that could not be explained  by physical properties alone.  That is really the last refuge of the Black Box and that is that the conscious human state has not been explained in terms of how it arises from the neural correlates of consciousness.  It is an active area of research in the Clear Box area today.  It is always interesting in terms of who adheres to Black Box thinking these days.  I can't think of any legitimate science that occurs using this model.  Pre-modern and modern neuroscience if anything has clearly dispelled black box and most mind-body duality.  Some philosophers and antipsychiatrists are at this level.

In the Grey Box Box things got clearer.  The transition from Black to Grey to Clear is not a well defined boundary.  The best example that I can think of is German neuropsychiatry at the beginning of the 20th century.  Much of that movement was focused in asylums.  There is a famous picture of giants in the field like Kraepelin. Alzheimer, Nissl, Binswanger and others who were active at the time.  These psychiatrists made good phenomenological observations but they were also focused on gross neuroanatomy.  In the case of some illnesses like Alzheimer disease some observations could be made at autopsy.  In the case of schizophrenia and bipolar disorder, gross anatomical changes were not evident.  Although that is a negative finding. it is a finding that propelled a century of more sophisticated neuroanatomy, neurophysiology and the beginnings of a much more sophisticated molecular  biological approach to functional mental illnesses or illnesses with no gross anatomical or physiological markers.

While neuroscience was moving forward at a slow pace, there was some slight progress on the fronts of diagnosis and treatment.  The DSM is always a controversial document, largely because there is never any shortage of self-proclaimed experts in psychiatry.  Psychiatrists know the limitations, what can be tested for, what physical illnesses are important to rule out, and what states can be cause by drug or alcohol intoxication, chronic use and withdrawal.  These medical and intoxicant induced states are all clear medical illnesses by any definition as well as the associated syndromes.  There is a disclaimer in the DSM about who should be using it.  Training is required to conduct the appropriate evaluations and make the appropriate diagnosis.  Further training is required to assure that patients can be safely treated.  Associated medical conditions need to be recognized and diagnosed.  All of this came about as a result of a medical focus that was reemphasized with the advent of the DSM.  Prior to that there was an overemphasis on psychoanalysis and psychodynamic psychotherapy.  A darker Grey Box consisted of a brain full of psychoanalytic constructs and the diagnosis and treatment was overly dependent on this model.

DSM technology was a required step in refocusing psychiatry on medicine and the brain as an organ.  But that occurred 40 years ago.  During that time, psychiatrists diagnoses and treat people based on clinical experience and general patterns that they recognize in the course of their training and practice.  In some cases the DSM has very clear criteria that are very helpful - like the definition of a manic episode.  In other cases - like the difference between anxiety and depression there are problems.  The same patients can endorse predominately anxious symptoms one week and predominately depressive symptoms the next.  The severity of the illness can typically lead to a clearer diagnosis and that is most likely due to the fact that the boundary between a clinical case and normal is arbitrarily defined as impairment in functioning.  More impairment should lead to clearer diagnosis.  Better markers to classify illness and hopefully predict treatment response are needed.  The search for these markers is an active area of investigation.  Psychiatry will remain in the Grey Box without these markers and more clear-cut treatments that address the underlying biological changes.

A lot of pharmacological research was done during the DSM era.  There was a lot of discussion about neurotransmitter and receptor pharmacology and the implications for scientific treatment.  Like all science, receptor pharmacology and post synaptic cell signalling mechanisms do not stand still.  There are many theories of receptor and drug pharmacology that have stood the test of time.  With a focus on the pathological nobody could hope that drugs that were often accidentally discovered would lead to highly effective treatments or a more comprehensive theory of mental illness or normal brain  function.  Clinical trials of psychiatric drugs and studies of pharmacology and physiology are are also limited by research subject heterogeneity.  That is a problem with research on any complex polygenic illness.  In the case of pure mental  illness where any medical cause has been ruled out, the DSM criteria alone are a poor filter for selecting homogeneous populations for research.

Drug and psychotherapy research in the Grey Box have both suffered from treatments being applied to heterogeneous populations.  There is no researcher that I know who thinks that any two people with a DSM diagnosis are similar to the point that drug or medication response would be high or necessarily reproducible.  Apart from the diagnostic problem, the DSM suggests homogeneity in a context where any seasoned clinician knows differently.

The Clear Box is the goal here.  The knowledge needed to get to this box is much more comprehensive.  It recognizes brain complexity and the importance of the conscious state rather than just a collection of DSM descriptors. Despite the fact that many of the basic mechanisms were elucidated over 40 years ago neuroscience has detractors just like psychiatry.  A common strategy of neuroscience detractors is to take either a research finding or a media quote and "debunk" it with fanfare in the popular media.  Ulterior motives are often suggested for connecting neuroscience primarily with psychiatric disorders.  Many of these detractors depend on their own characterization of the original research and the cultural phenomenon of piling on with negative criticism to score what appears to be a victory with the vocal and like minded.  They use the same strategy in claiming that mental illness or addictions are "not diseases" like "real" diseases - despite the fact that the general population considers them to be equivalent.  I find nothing compelling about critiques of ongoing science and medicine by the unqualified.  The main problem is that the people truly qualified to produce the criticism are ignored in favor of what amounts to unscientific criticism.  There is a secondary problem with the proliferation of journals, especially opinion pieces rather than scientific papers.  
                                   
Another interesting thought that I had about the Clear Box is that many people have no difficulty at all in recognizing that machine intelligence is improving and that at some point it might exceed human intelligence.  They don't seem to have any problem in figuring out whether a computer may have negotiated the Turing Test and seem indistinguishable from another human being.  Many people seem to have difficulty recognizing the computational capacity of the human brain and the result of that complexity.  Despite some philosophical arguments - that is a possible reason for not seeing the Clear Box as the preferred state of brain knowledge.

I have tried to point out many times that one key element of the  mischaracterization of neuroscience in psychiatry is a basic lack of understanding of science.  Science is a process and a dialogue.  Medical science is more of a process and a dialogue than physical science - the processes involved are more complicated and the experiments involve proportionally fewer relevant variables.  There are no differential equations based on a few variables that explain how the brain works.  Entire blocks of research can end up partially true or a dead end.  That does not mean there is some grand conspiracy - that just means it is time to move on to a new paradigm.  

George Dawson, MD, DFAPA



Quotation Credit:

"The brain is the most complex object in the known universe" is a quote from Christof Koch, Chief Scientific Officer of the Allen Institute for Brain Science and well-known consciousness researcher.


Tip For The Better Graphic:

The graphic at the top is rendered with Visio.  Blogger makes it blurry and ill defined.  Click on it for the sharp Visio version.

Saturday, October 22, 2016

Coffee Shop Neuroscience




I went into my favorite coffee shop the other day for my usual mocha.  They typically post a trivia question of the day that gives you a 10 cent discount on the coffee.  After a conference with a recent focus on neuroscience it was interesting to see a question about the number of thoughts per day.  My wife ventured a guess.  I asked the barista for the source and all that she could tell me was: "We get it off the Internet like most of our questions."  No footnote or reference available.  The source was not difficult to find.  It was a typical Internet site that has never impressed me as a knowledge source, but it did have a link to the original paper.  It turns out to be a neuroscience site - The Laboratory of Neuroimaging (LONI) at UCLA.  Read the fine print at the bottom of this page for qualifiers on what counts as a thought.  I looked for any papers on this estimate on the web site as well as Medline and did not come up with anything.

Irrespective of the methodology the question poses interesting questions for clinical psychiatrists if they are comfortable outside the confines of the DSM.  How much attention is being paid the the baseline conscious state of the patient and why might that be important?  What is their stream of consciousness every day?  Is it disrupted by mental illness or addiction?  To what extent is that stream of consciousness broken up into daydreams, memories, and fantasies?  To what extent is it impacted by a process that is not even suggested by the DSM?  The best example that I can think of is boredom.  Being easily bored can be a diagnostic criterion, but it seems to be an uneasy mental state on its own.  People who are bored get driven to do things to alleviate boredom and sometimes those activities are very risky.  Are the thoughts mentioned in the coffee shop question memories, fantasies, or daydreams? Why the large number?  I am not aware of brief frequent thoughts.  My stream of conscious thought is comprised of more coherent stories or images.

I did a Grand Rounds on fantasy and daydreaming about 15 years ago.  There has never been much quantitative work on fantasy.  There were some new research approaches to daydreaming being used at the time and I incorporated some of those references into the presentation.  I don't recall the exact number of daydreams per day but they were considerably less than 100.  The only research approximating the numbers of thoughts per day may be the research on the exact number of spoken words per day.  This research has generally been a comparison between men and women and a test of which sex speaks the most words.  Those numbers across different cultures and sampling periods range from 12,867 to 24,051 words per day (5).  Standard deviation were large and the authors conclude that on the average both sexes spoke about 16,000 words per day.  To me speech and language is unconsciously processed thought, but even counting all of those words does not get us to the level of the coffee shop question.  Do the authors believe that they have a way to capture tens of thousands of unconsciously processed thoughts?  I am very interested in hearing how they arrive at these figures.

The research in this area has since moved into the area of the wandering mind.  Wandering mind is defined as a cognitive focus on information unrelated to the immediate sensory input or task on hand.   It would include daydreams, fantasies, and the typical stream of consciousness that every person experiences at times throughout the day.  The critical research questions include when is mindwandering adaptive as is the case of generative fantasies and when it is maladaptive?  Smallwood, et al (7) have written an excellent brief review of how mindwandering can negatively impact medical decision making and the cognitive performance of physicians.  They point out that fatigue, depression, and circadian rhythm disturbances can lead to increased mindwadering with negative consequences by decoupling attention to the external environment from the necessary memories, patterns and access to decision-making that are the physician's cognitive set.      
    
The question also involves neuroscience.  Is there a physical representation of this process in the brain and what is it?  Neuroscience tells us that the brain has a Default Mode Network (DMN).  It was initially noted to be a network of brain regions that remain active during functional brain imaging studies in the absence of an external task.  These studies typically involve an active task for the research subject and the resulting brain image is analyzed as a response to that stimulus.  It was determined that this DMN comprises the system that allows for internal dialogue and stimulus-independent thought.  The physical representation includes a primary system comprised of the anterior medial prefrontal cortex (aMPFC) and the medial posterior cingulate cortex (PCC) communicating with two subsystems.  The medial temporal lobe subsystem is comprised by the retrosplenial cortex (RSP), parahippocampal cortex (PHC), hippocampal formation (HF), the ventral medial prefrontal cortex (vmPFC), and the posterior inferior parietal lobule (pIPL).  The dorsal medical prefrontal cortex subsystem is comprised of the temporal pole (TempP), the lateral temporal cortex (LTC), the temporoparietal junction (TPJ), and the dorsal medial prefrontal cortex) (1).  Some groups differ on the physical representation of this system and some groups use Brodmann area designations.  I drew a slightly different model based on Sporn's text (6) with some obvious distortion due to the lack of a three dimensional representation (the rTC should be folded over to the right temporal area away for the medial view):



Subsequent research has shown that the DMN may be implicated in several psychiatric disorders (2). Several functions for the DMN have been proposed that cut across a number of disorders including mind-wandering when no specific external stimulus is present, memory consolidation, to possibly maintain a baseline level of arousal, to divide attention across tasks and for continuity across time (3).  Disruptions and functional disconnects to the DMN have been studied for a number of psychiatric disorders.  If the conceptualization is correct it is useful to think about the implications of functional or anatomic disconnects or hyperconnects to other systems.

How is all of this relevant to psychiatry?  Consider the case of two patients with severe depression.  They both have insomnia, anhedonia and decreased appetite.  They both have typical depressogenic thought patterns including abundant self criticism, hopelessness, and suicidal thoughts without intent to harm themselves.  The only difference is that one of these patients has intense rumination about a job loss.  This patient was downsized along with 50 other people.  The job loss was a straight business decision rather than any performance deficiency.  The patient without rumination is treated with standard methods and recovers.  The patient with intense rumination does not.  The depression and rumination persists despite multiple antidepressant trials.  The degree of disability persists.  There is not much guidance about how to treat this person from a biological standpoint.  It comes down to empirical drug trials and additional treatment for what has been considered anxiety, psychosis, or possible obsessive compulsive disorder.  I have seen these patients recover with detoxification from drugs or alcohol, treatment with antipsychotics, treatment with electroconvulsive therapy, but not treatment with benzodiazepines.  Will the cognitive neuroscience that incorporates models of the wandering mind and default mode network offer fast and more effective treatments?  I think that we may already be seeing that.  Mayberg's classic 2005 article (8) explicitly testing the network hypotheses about treatment resistant depression with deep brain stimulation was a start.  That literature has greatly expanded since that point.

There has been an explosion of network based theories of both psychopathology and normal conscious thought in the past decade.  These models are increasingly relevant as psychiatry is dragged out of a receptor and reuptake protein based discipline, where the practitioners may have a vague idea of where those receptors are located and what they really might be doing.  It was a necessary second step, but only neuroscience will get us to better models and models that we can apply to the treatment of unique individuals.  Psychiatrists have a critical decision to make at this point.  Are we going to remain stuck in a diagnostic and treatment paradigm that clearly applies to a minority of the people with mental illness or are we going to embrace the science that will both allow us to treat everyone better and give us a more complete understanding of human consciousness?

Learning about the Default Mode Network is a good starting point.  


George Dawson, MD, DFAPA



References:

1;  Barron, DS, Yarnell S.  Default Mode Network: the basics for psychiatrists.  Fundamentals of neuroscience in psychiatry.  National Neuroscience Curriculum Initiative.


2:  Mohan A, Roberto AJ, Mohan A, Lorenzo A, Jones K, Carney MJ, Liogier-Weyback
L, Hwang S, Lapidus KA. The Significance of the Default Mode Network (DMN) in
Neurological and Neuropsychiatric Disorders: A Review. Yale J Biol Med. 2016 Mar 
24;89(1):49-57. eCollection 2016 Mar. Review. PubMed PMID: 27505016; PubMed
Central PMCID: PMC4797836

3: Mason MF, Norton MI, Van Horn JD, Wegner DM, Grafton ST, Macrae CN. Wandering minds: the default network and stimulus-independent thought. Science. 2007 Jan 19;315(5810):393-5. PubMed PMID: 17234951; PubMed Central PMCID: PMC1821121.

4: Stafford JM, Jarrett BR, Miranda-Dominguez O, Mills BD, Cain N, Mihalas S,Lahvis GP, Lattal KM, Mitchell SH, David SV, Fryer JD, Nigg JT, Fair DA. Large-scale topology and the default mode network in the mouse connectome. Proc Natl Acad Sci U S A. 2014 Dec 30;111(52):18745-50. doi: 10.1073/pnas.1404346111. Epub 2014 Dec 15. PubMed PMID: 25512496

5: Mehl MR, Vazire S, Ramírez-Esparza N, Slatcher RB, Pennebaker JW. Are women really more talkative than men? Science. 2007 Jul 6;317(5834):82. PubMed PMID:17615349.

6: Olaf Sporns.  Networks of the Brain.  MIT Press.  Cambridge, Massachusetts, 2011.

7: Smallwood J, Mrazek MD, Schooler JW. Medicine for the wandering mind: mindwandering in medical practice. Med Educ. 2011 Nov;45(11):1072-80. doi: 10.1111/j.1365-2923.2011.04074.x. PubMed PMID: 21988623. (link to free full text).

8: Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM,Kennedy SH. Deep brain stimulation for treatment-resistant depression. Neuron. 2005 Mar 3;45(5):651-60. PubMed PMID: 15748841.

9: Christoff K, Irving ZC, Fox KC, Spreng RN, Andrews-Hanna JR. Mind-wandering asspontaneous thought: a dynamic framework. Nat Rev Neurosci. 2016 Nov;17(11):718-731. doi: 10.1038/nrn.2016.113. PubMed PMID: 27654862


Supplementary 1:

Olaf Sporn's book Networks of the Brain is an excellent resource to study this topic and to try to catch up on a decade of research:







Supplementary 2:

Default Mode Network links that are relevant for psychiatrists (unedited):

"default mode network" dementia

"default mode network" addiction

"default mode network" "bipolar disorder"

"default mode network" schizophrenia"

"default mode network" ADHD 

"default mode network" depression

"default mode network" anxiety

"default mode network" mind-wandering

"default mode network" day dreaming


Supplementary 3:

The answer to the coffee shop question is a.




Sunday, October 16, 2016

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.









              

Friday, October 14, 2016

National Neuroscience Curriculum Initiative - a brighter future for psychiatry






As any reader of this blog probably knows, I am a big proponent of neuroscience education for psychiatrists and always have been.  I have suggested in the past that it would take broad collaboration.  I posted some examples of an NIMH initiative on neuroscience  education.  I teach neuroscience (also known as neurobiology) myself and that has led me to be acutely aware of the lack of educational resources on the field.  That background is what has made this the happiest day at a CME conference that I have ever spent.  I am currently at the University of Wisconsin 4th Annual Update and Advances In Psychiatry - a conference that has really been in place for the past 41 years.  After watching a comprehensive update on eating disorders I settled in to listen to Melissa Arbuckle, MD, PhD; Professor of Clinical Psychiatry, Director of Residency Training; Department of Psychiatry, Columbia University Medical Center.  The title of her presentation was Discussing the Neuroscience of Mental Illness with Your Patients.  I turned to the section in the syllabus and there was one page with a case report on the front and a crude drawing of the brain (two views) on the back.  Being a traditional conference guy who likes a ton of technical information, no audience participation, and no role playing - I was prepared to be disappointed.

I was not prepared for what would transpire in the next 90 minutes.  I have posted here many times why I thought that every psychiatrist should know neuroscience and ways to do it, specifically the need for widespread collaboration due to a lack pf neuroscience manpower in most departments.  Dr.  Arbuckle started out explaining what the National Neuroscience Curriculum Initiative was.  It was started by a collaboration of like minded residency directors  to come up with a program to teach neuroscience to psychiatry residents.  She showed the explosion in neuroscience papers in psychiatry just over the past decade.  She referred to an article in JAMA Psychiatry (1) with her collaborators on why neuroscience needs to be integrated into psychiatry right now.  She discussed the New York Times editorial that showed up three weeks later with the criticism of their viewpoint (2).  Although she did not mention it, like a lot of articles it as written from the perspective of a psychiatric identity crisis.  Whenever I see that term it seems like the authors are firmly behind the curve and don't seem to understand what neuroscience encompasses.  Dr. Arbuckle said that the article was critical of the criticism that the brain was the basis of human behavior.  Quoting the article:

"Indeed an article in May in one of the most respected journals in our field JAMA Psychiatry echoed this view: "The diseases we treat are diseases of the brain."........ Even if this premise were true - and many would consider it reductionist and simplistic - an undertaking as ambitious as unraveling the function of the brain would likely take many years."  The author is a psychiatrist and goes on to say that he is all for neuroscience and even talks about some recent research techniques he (implicitly) just doesn't think psychiatrists should study it?  He also seems to conflate psychotherapy as being independent of neuroscience when in fact we have known just the opposite since since Kandel's 1979 seminal lecture Psychotherapy And The Single Synapse.  

I am equally incredulous when people seem to argue about the importance of neuroscience in psychiatry.  I find reductionism and reductionist approaches to be perfectly understandable and acceptable.  It is an interesting form of rhetoric to use these terms pejoratively.  Most people go into medicine because they want to know how things work.  If they did not enter with that goal, it soon becomes apparent that knowing mechanisms whether they are theoretical or not is an important aspect of studying medicine.  Some of the first mechanisms I studied in medical school involved cholera and diphtheria toxin. How is it possible to determine these mechanisms and recent significant epigenetic mechanisms without taking a reductionist approach?

The exercise that Dr. Arbuckle introduced to the audience was the diagnosis and treatment of complex cases.  The case vignette involved a young woman with borderline personality disorder.  The task for the audience was to pair up and role play discussing the relevant neuroscience concepts of treatment with the patient using the brain diagram as an aid.  Eliciting responses from 300 people in a room slows things down.  After the audience was done, she showed a film of an expert presenting this information to a patient and what presentation materials might be available.  It went very well and it presented the rationale for dialectical behavior therapy and not a medication.  It was a clear example of a neuroscience based discussion that provides a rationale for psychotherapy.  There are numerous materials on the web site (9 modules, 56 sessions, 40 authors) and wide scale participation is encouraged.

The information up to that point was quite exciting.  Dr Arbuckle had plenty of enthusiasm in her closing remarks.  In those remarks she pointed out the goal of "getting the entire field up to speed" in neuroscience.  She pointed out that everything on the site is free but at some point they may ask physicians to pay for CME.  She said that she realizes that this is literally "changing the world and that is what we are going to do."        

This was the most exciting commentary from a psychiatrist about teaching the entire field and the future of psychiatry that I have ever heard.  I have never been this impressed by any development in the field during my career.  And I am a psychiatrist who is as pro-neuroscience as anybody.  How is it that I am just hearing about this initiative right now and only because I am attending a conference?  That is why I am posting my experience here and a link to the NNCI web site and materials.

Dr. Arbuckle and her collaborators are one of the few bright spots for the future of psychiatry.

But they are very bright.


George Dawson, MD, DFAPA


References:


1:  Ross DA, Travis MJ, Arbuckle MR. The future of psychiatry as clinical neuroscience: why not now? JAMA Psychiatry. 2015 May;72(5):413-4. doi: 10.1001/jamapsychiatry.2014.3199. PubMed PMID: 25760896.

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


Attribution: 

The graphics at the top are two slides from one of my lectures.  I like to present data on the unique aspects of every individual brain and why that can happen.  The slides are not from the NNCI program and I am not affiliated with that program.  Click on each slide to enlarge.








Sunday, May 31, 2015

The NIMH Director and the RDoC - The Politics and The Science





from: Insel TR, Cuthbert BN. Medicine. Brain disorders? Precisely. 
Science. 2015 May1;348(6234):499-500.




I caught this article about the RDoC criteria for classifying mental illnesses based on various non descriptive parameters and neuroscience in the journal Science a couple of weeks ago.  As any reader of this blog can attest, there is no stronger advocate for the role of neuroscience in current psychiatric practice and the future of psychiatry than me.  There has been media controversy on this subject and it is always difficult to determine how much real controversy exists and how much of it is just made up for the sake of media self promotion like much of the DSM-5 controversy was.  Reading through the article by Thomas Insel and Bruce Cuthbert  there are statements that can be taken at face value.  I think these statements are consistent with the position that clinicians in general are not very scientific and are also outright clueless in some areas.  This is a bias that I have certainly heard from other scientists and it does not serve the cause of science very well, especially if the goal is to advance neuroscience and bring everyone up to speed on that discipline.  Dr. Insel has presented his view that all of the trainees in the clinical neurosciences of psychiatry, neurology, and neurosurgery should rotate through a year or two of a shared neuroscience.  When I first heard him present it five years ago I thought it was a great idea.  In the time since and especially after getting a response from him, I think it is less clear.  It would be great if every department of psychiatry had neuroscientists on staff to teach neuroscience.  But they don't and there is also the problem of neuroscientists being focused on research rather than teaching.  On the other hand, there are plenty of bright people in those departments who know a lot about the brain.  It is a question of reconciling these two points to come up with the necessary infrastructure yet in this article the authors make it seem as if large clinical problems are not addressed and that clinicians are fumbling around with very crude assessment methods.

They list three articles as examples of the RDoC.  The most interesting of these articles is one from the American Journal of Psychiatry that proposes that computer abstracted data from hospital notes that is converted to RDoC criteria are better predictors of hospital length of stay (LOS) than DSM criteria.  Just considering that method my first impression was that there was a lot wrong with that picture.  First of all,  LOS data is tremendously skewed based on non-clinical practices.  All it takes is hospital case managers with some success in intimidating physicians to skew the data in favor of business rather than actual medical or psychiatric discharge decisions.  Second, the quality of data from inpatient settings is incredibly bad due to the toxic combination of electronic health records and government billing and coding regulations.  As a reviewer, I have seen thousands of inpatient records, some of them hundreds of pages in length and I have found EHR records are notoriously poor in information content.  And finally, I thought the RDoC was a new system designed to be dependent more on neuroscience than the DSM-5?  How does methodology that looks at this DSM biased, sketchy clinical data result in a RDoC diagnosis?  Looking at the graphic from the Science article at the top of this post, it is pretty clear that 3 out 5 data dimensions under "Integrated Data" are basically clinical data.  There is a smugness displayed in the report similar to what might be seen in a rant by an antipsychiatrist: "For now clinicians might be best advised simply to be aware of the usefulness of dimensional models to capture psychopathology."  and "This result should provide some reassurance to clinicians that their notes do contain relevant detail for deriving dimensional measures of illness; like Molière’s Bourgeois Gentlemen speaking prose without knowing it, clinicians may already speak some RDoC."

Really?

The average person I see has chronic insomnia and has had possible sleep terrors and nightmares in childhood along with social phobia.  At some point they developed either severe anxiety or depression, but they can't recall the sequence of events and they currently have both.   They typically think that they have had "manic episodes" and may have been diagnosed with bipolar disorder even though they don't know what a manic episode is.  All they know is that their symptoms have persisted usually without remission for the past 10 to 15 years.  Of course that is complicated by the fact that they have been using marijuana, alcohol, and opioids in excessive amounts since then,  they may not have a significant family history of psychiatric and addiction problems, and they have the expected childhood adversity and adult markers of psychological trauma and abuse.  Further, I know from talking to the same people in repeated initial evaluations over the years that they don't give the same history twice and rarely remember much about their medications or psychotherapy treatment.  Should I use a "placeholder diagnosis" (pejorative term from reference 4) or should I assume that I am dealing with the social phobia that the patient may have had in childhood?  The idea that an RDoC diagnosis is going to give me an answer to that question any better than a DSM-5 diagnosis is pure folly if you ask me.  At least until we get the promised neuroscientific markers promised by the NIMH.  In fact, the description of the RDoC in these articles is reminiscent of another technology that was supposed to diagnose mental illness and that was quantitative EEG or QEEG.  I know quite a lot about QEEG, because I purchased a machine in the 1980s after a promising article on the technology came out in the journal Science.  I researched it using highly skilled EEG techs and an expert in neurophysiology to run the protocols, and concluded the diagnoses that came from the computerized analysis of the tracing were no better than chance in terms of what patients presented with.  Like RDoC diagnoses, the computerized analysis of QEEG data was highly dependent on the input of clinical data collected by the clinician.  It allowed the clinician to add and subtract clinical variables and look at how the diagnosis varied.  

The staff and researchers at the NIMH need to decide if a superior and critical attitude toward physicians who use current clinical approaches and are successful with them is the best one.  It should be obvious from the above analysis that many of us are not as naive or as ignorant about science as they expect. My proposed solution would be a more collaborative approach including the following:

1.  Recruit and train neuroscience teachers - most of them are already out there.  For example much of what I teach to trainees interested in addiction and addiction medicine is neuroscience.  It is also much more realistic than waiting for every department to have access to neuroscience researchers and then expecting those researchers to teach in addition to doing research.  My guess is that every Psychiatry department already has faculty that teach neuroanatomy, pharmacology, brain science and neuroscience already and that most of them are not officially scientists.

2.  Make the reading list available online - the article refers to over 1,000 published articles that focus on the RDoC criteria.  These should be available though the National Library of Medicine web site along with other neuroscience articles of interest to psychiatrists.  An added bonus would be CME activity available for self study.

3.  Post a list of neuroscience modules and build on that list -  In a previous post, I posted two links to neuroscience modules through the NIMH.  I would put up two lists, one containing a growing list of modules and the second with a list of the neuroscience concepts that need to be illustrated.  This would be useful for psychiatrists, psychiatrists in training, and medical school professors hoping to make their basic science lectures more relevant, since many clinicians still seem to have difficulty understanding how neuroscience is important in psychiatry.

4.  Better graphics - make high resolution graphs that illustrate detailed brain anatomy and basic science available online for teachers.  Pulling this material together is often the most difficult part of the teaching job and it requires an intensive effort to not run afoul of copyright laws.   It would be easier to recruit neuroscience teachers if there are high quality teaching materials available.

5.  A neuroscience teaching blog - In addition to the NIMH staff posting the references, concepts and modules, an open teaching blog should also be available.  I would encourage it to be a platform for discussing concepts and how to present them to trainees.  Ideally, it would be a place for active dialogue about the concepts and teaching them.

I think that all of these measures would be helpful in building an infrastructure of neuroscience teachers, neuroscience teaching, and a mechanism for the widespread dissemination of this material in residency programs and in educational programs for practicing psychiatrists.  If the RDoC is in fact worthwhile, there is plenty of brainpower outside of the NIMH to figure that out.

It is the brainpower that is currently focused on coming up with solutions and resolving problems of incredible clinical complexity.  And that happens every day.

I plan to send these recommendation to Director Insel and see what he thinks.



George Dawson, MD, DFAPA



1: Insel TR, Cuthbert BN. Medicine. Brain disorders? Precisely. Science. 2015 May 1;348(6234):499-500. doi: 10.1126/science.aab2358. PubMed PMID: 25931539.

2: Casey BJ, Craddock N, Cuthbert BN, Hyman SE, Lee FS, Ressler KJ. DSM-5 and RDoC: progress in psychiatry research? Nat Rev Neurosci. 2013 Nov;14(11):810-4. doi: 10.1038/nrn3621. Review. PubMed PMID: 24135697.

3:  NIMH.  Research Domain Criteria

4:  McCoy TH, Castro VM, Rosenfield HR, Cagan A, Kohane IS, Perlis RH. A clinical perspective on the relevance of research domain criteria in electronic health records. Am J Psychiatry. 2015 Apr;172(4):316-20. doi: 10.1176/appi.ajp.2014.14091177. PubMed PMID: 25827030.


Supplementary 1:

The above figure is licensed through the American Association for the Advancement of Science - license number 3637270124183.




Wednesday, March 18, 2015

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.




Sunday, February 15, 2015

"Junk" Neuroscience?

A recent comment on my observation that normal function of human memory could explain what he considered to be obvious lies prompted a reading suggestion.  The author suggested that I should read a book called "Junk Neuroscience" by Satel. The only book I could find with a similar title was  Brainwashed: The Seductive Appeal of Mindless Neuroscience.   I am reluctant to spend good money on a polemics when I can get as much polemic as I want by reading it for free on the internet.  It turns out I am familiar with the author's work from a Frontiers in Psychiatry series that I reviewed last year before presenting a CME course lecture on the neurobiology of addiction.  There are currently 19 papers collected there including Satel and Lilienfeld's.  It is somewhat ironic that the entire series is based on a what I would see as assumptions that have a faulty historical, medical and certainly neurobiological premise and that is:

"For much of the 20th Century, theories of addictive behavior and motivation were polarized between two models. The first model viewed addiction as a moral failure for which addicts are rightly held responsible and judged accordingly. The second model, in contrast, viewed addiction as a specific brain disease caused by neurobiological adaptations occurring in response to chronic drug or alcohol use, and over which addicts have no choice or control....."

The first few lines captures the main problem with debates about any topic but it is particularly pernicious when it comes to addiction and neuroscience.  It leads to a number of false observations that seem to be cropping up in the popular press at an increased frequency.  The observation that most addictions spontaneously remit is taken as evidence that they do not require treatment or that neurobiological factors do not need to be considered.  There is the idea that you can be a "heavy drinker" without being an alcoholic suggesting that "heavy drinking" is protective against the factors leading excessive mortality and morbidity in alcoholism.  Those same arguments lead back to the idea that addiction is either a choice or a bad habit.  Both are gross oversimplifications of how complex decision-making is affected in addictions.  One of the main diagnostic systems for addiction from the American Society of Addiction Medicine (ASAM) describes addiction as:  "Addiction is a primary, chronic disease of brain reward, motivation, memory and related circuitry".  It does not however suggest that addicts "have no choice or control".  In fact, much treatment of addiction depends on a 12-step recovery model that is designed to help learn new controls, improve social affiliation, and re-engineer living environments to remove triggers for relapse.  The learning, affiliation, cravings and relapse triggers all have neurobiological substrates.  Against that backdrop there are 19 papers offered and Satel and Lilienfeld's is one of them.

I happen to be fortunate enough to work at a residential center that specializes in treating addictions.  In addition to the clinical work I present a number of lectures to graduate students, physicians, and residents.  The residents are in primary care and psychiatry.  The two slides that follow are right out of my PowerPoint on the neurobiology of addiction.  The Theories of Addiction slide is intended as a rapid survey of addiction theories.  I put it out there as a warm up and free associate to the theories on the slide.  As an an example, I will look at the nutritional deficiency theory of alcohol or look at alcohol being considered a medicine by itself and how that correlates with per capita alcohol consumption in the US.  I can build on that point by looking at the cultural factors that affect per capita alcohol consumption int he US and the UK.  I might ask groups of physicians if Self Medication is a legitimate theory of addiction.  Practically all physicians have heard: "Listen doc, if you can't do something about my (pain, depression, anxiety, insomnia) - I know what I can do to make it go away for a few hours."  Everybody in the room also knows that in the long run, none of those symptoms/syndromes/disorders can be treated and in fact many become considerably worse as a result of the drug or alcohol use.  Even the example of availability proneness that I typically use only partially accounts for addiction.


Any approach to neurobiology has to account for pathways to recovery as well as pathways to addiction.  In treatment centers most of those pathways are based on learning interventions.  I digress to talk about the how learning occurs both in the addiction process and in the recovery process.  I start out with Kandel's example from his classic New England Journal of Medicine article on plasticity.  His original example talks about two people in a room during a psychotherapy session, and the brain changes that occur in both as a result of that session.  Both people leave the room and their brains have been changed by the discussion.  Experience dependent changes in the brain.  That brief introduction brings me to the four considerations of the neurobiology lecture.  They are listed in the second slide below.  

I think that these are all fairly basic starting points for a lectures on neurobiology and proceed to talk about a number of systems and structures that are thought to be important from a neurobiological standpoint.  I bring in the concept that nobody knows how it all works together by a brief discussion of Chalmers hard problem or the fact that we don't know how anyone's unique conscious state comes about and what that implies.  I am evolving to a new lecture that looks at complex decision making and its roots in the neuroanatomical structures that I discuss in this lecture.  Studying this field is what I consider to be fun.  It brings together a number of concepts from my previous scientific studies.  I would probably be focused on this if I was practicing clinical psychiatry or retired.  I will be the first to admit that I am not a trained neuroscientist, but I have been trained in science and worked in scientific research.

That brings me to Satel and Lilienfeld's paper.  I don't know either author.  If you read the paper it is definitely well written and it has 121 references.  There is a bolded statement before the text begins saying that this paper is excerpted from the book Brainwashed: The Seductive Appeal of Mindless Neuroscience.  As far as I know that is the book that would apparently straighten out my views about neuroscience.  The author's begin with: "The brain-disease model implies erroneously that the brain is necessarily the most important and useful level of analysis for understanding and treating addiction." and build rapidly to a second: "In short, the brain-disease model obscures the dimension of choice in addiction, the capacity to respond to incentives, and also the essential fact people use drugs for reasons (as consistent with a self-medication hypothesis)."

Working at an addiction treatment center and talking with thousands of people in my career with severe addictions leads me to have an explosion of associations whenever I see broad generalizations about the problem.  I don't know that the concept of disease means that an affected organ system is necessarily "the most important and useful level of analysis."  There seem to me to be many diseases where that is not true.  On the issue of "reasons to take drugs" it is seldom as rational as the author's suggest.  A classic example is one that I frequently use when lecturing about the current opioid epidemic.  A significant portion of the population is prone to get a hypomanic euphorigenic effect from taking opioids.  For nonpsychiatrists, that mean the person becomes extremely euphoric, energetic, productive, and socially outgoing.  On the initial night or two, they may engage in work or creative activities at a rate that surprises them.  Many will say: "I thought I had become the person I always wanted to be."  Carefully interviewing that person several months later will get the description that they developed a tolerance to that effect.  Now they were taking the opioid "just to stay well" or prevent withdrawal symptoms.  Koob has described this cycle as  "a chronic relapsing syndrome that moves from an impulse control disorder involving positive reinforcement to a compulsive disorder involving negative reinforcement."  Consistent with this definition is that the drug has both positive (euphoria) and negative (prevents withdrawal) reinforcing effects.  The reason to take the drug is an addiction or the specific match of drug effects on a specific nervous system.  Even in a case when addictive drugs are taken for other reasons (there is a long list) it often is due to the fact that the drug is perceived as having magical qualities or as a rationalization for continuing the addiction.

I could make similar arguments for all of the main points in this paper that I have laid out in the following table.  The authors provide ample details examples to support their contentions.  Part of the problem is that the concept of disease is complex.  When you try to dissect it the problems become apparent.  The other problem is that if this is a disease, it is a disease of complex decision making and very few people focus on that.  



What after all is considered a disease?  Any reader can come up with conditions that they consider diseases for many of the ten points above.  That is easiest for the points involving the clearest comparisons with disease (1, 2, 6, 10).  In other cases (4), their point seems to be somewhat arbitrary.  With any chronic illnesses it is usually possible to function with limited incapacity due to the illness until the late stages.   In some cases the critique has more to do with the unique capacity of the organ than anything else.  For example in point (3), emergent properties that are less obvious can be considered a property an any electrical tissue.  Cardiac tissue can produce electrical patterns of decreasing complexity as a heart ages or is affected by disease.  The brain can produce a very similar pattern (see Supplementary 1).  The only difference is that heart tissue is unable to produce a conscious state.  Two of the points (5, 9) minimize the role of a systems involved in complex decision-making.  This is no trivial matter because it is associated with addictive behaviors that lead most people to classify alcohol and drug use disorders as diseases.  Common examples include people who are unable to stop using drugs and alcohol despite life threatening illnesses, repeated pleas from family members, or repeated problems with relationships, employment or the law.  Deaths due to addiction are common and they impact on a large population.  You are much more likely to see a condition as a disease if you know it has killed somebody.  Point (7) is a curious argument.  In the past several years, I have attended seminars showing for example that in some trials of buprenorphine maintenance for opioid use disorders that the addition of counseling adds nothing to the outcome beyond the medication.   I don't personally believe that, but I am used to seeing people with severe addiction who cannot stop until they are taken out of their using environment.  In every residential treatment center that I am aware of, the main focus is on "personal agency" whether that is 12-step recovery (Alcoholics Anonymous, Narcotics Anonymous) or other methods for psychological change.  As part of that process there is often a focus on neurobiology not as an excuse but as an explanation for how people can become somebody that they never thought they could become and how that process can be reversed.  The other reason for a focus on neurobiology is medication assisted treatment and a discussion of how those medications might work as part of both informed consent and interest on the part of the patients.

I wonder if the best characterization of what is going on here has more to do with philosophy than neuroscience.  As I previously pointed out in a critique of a philosopher's attack on psychiatry - a straw man approach was used.  He suggested that something was true about the field and then proceeded with his attack as if it was true.  When confronted with that single fact and asked about any evidence to support the contention - the people supporting that contention drew an apparent blank.  To this day as far as I know there is no rational way to argue that the APA has an implicit position in the DSM-5 that teaches people how to live their lives.  Even as I write it on the page it is absurd and yet that was the form of the argument.   The current paper is much more sophisticated than that.   It points out the limitations of the disease concept and how that can be used rhetorically but then proceeds to eschew what they refer to as a "neurocentric view" of addiction.  I don't think that argument carries the day largely because there is very little evidence that the people who know neuroscience have the adverse effects that the authors suggest.  There is plenty of evidence that the neuroscientist-clinicians are focused on multiple levels of care.  I have a lot more to say about what is a disease and diseases of complex decision-making but I am going to stop here.  Look for those topics to be addressed in individual posts in the future.  In the meantime, read about the neuroscience of addiction.  The field has added more to brain neuroscience than just about any other discipline in the past three decades.  

I think an additional explanation of my intent in the reply is necessary.  I use the term "political" a lot when referring to editorials, rhetoric, and other polemics.  People who should know better seem to respond to a lot of these articles as though they are either the "truth" or the "facts" that happen to support their viewpoint.  I like my science very dry.  I ascribe to Pigliucci's observation that science is a process and if there is a truth it only occurs at the end of a very long process or a series of approximations.

Seeing it any other way shuts down that process and we are left with something that is ideologically based and no longer science.



George Dawson, MD, DFAPA


1: Satel S, Lilienfeld SO. Addiction and the brain-disease fallacy. Front Psychiatry. 2014 Mar 3;4:141. doi: 10.3389/fpsyt.2013.00141. eCollection 2013.   Review. PubMed PMID: 24624096


Supplementary 1:

I attached these graphics to illustrate that electrically active tissue can have emergent properties that are really unknown by either looking at the tissue or doing other kinds of biological analyses.  That is true for both the brain and the heart.  I don't have the heart graphs but could probably find them.  They are identical.  I do have the graphs of brain activity from a patient with Alzheimer's Disease and a normal control patient.  Recordings are from a single parietal electrode in the delta frequency and show the degree of variability over the same time interval.

Single Electrode EEG - Control

Single Electrode EEG - Alzheimer's Disease

Sunday, December 28, 2014

Snow Shoveling Theory and Plasticity

I drove back from my home town to the Twin Cities area yesterday  In this age of connectedness, there are times when you get a false sense of information.  My wife called her friend who was driving north to Duluth on Hwy 35.  She got the message that there was about 6 inches of snow on the freeway and numerous vehicles in the ditch.  I don't mind driving in the snow.  I used to drive north in the winter in some notoriously unreliable vehicles.   Rear wheel drive and no limited slip differential.   Poor weight distribution was an added bonus.  Some of the worst engineered cars in the world.  Most people my age all still use the brand name Positraction, rather than the generic limited slip differential.  More evidence that pharmaceutical companies don't differ much from other businesses in terms of branding of inserting themselves into the public consciousness.  Like most people, when you get to the point where more safety is affordable you buy it.  I am driving a modern four wheel drive sport utility vehicle (4WD SUV).  I was confidant that 6 inches of snow would only be a problem if there was congestion from large trucks and snow removal vehicles.  I was also confidant that would only happen close to the Twin Cities.  Competency in snow removal seems to vary directly with latitude with northern latitudes being the best.   I thought about that as I drove down Hwy 2 across northern Wisconsin.  The road was clean down to the pavement about 4 hours after white out conditions.

As we turned the corner in Duluth, the grey skies lifted and it turned out to be a bright sunny day but 10 degrees colder than the day before (about 22 ℉).  There was no bad road all the way back to the Twin Cities.  That only happened when we pulled into our neighborhood and there was 6 inches of snow in the driveway.  All of my neighbors driveways were clear and in many cases the pavement was dry and clear.  The physical chemistry of snow is always interesting.  In this case the bottom few millimeters of the snow was liquefied, but the upper 5 inches plus was medium density snow, the kind that is good for cross country skiing.  Clear it off and the liquid evaporates in the direct sunlight, even when it is well below the freezing temperature.  In some cases sublimation occurs and the snow vaporizes directly from the solid state.  But I was focused on additional theories.

People living in northern climes think a lot about moving snow.  We have had some epic snowfalls.  Some of my fantasies coming into this season included getting an enclosed tractor with climate control and the ability to move a massive amount of snow.  The image I have is a condensation of a couple of images.  The first is a cola commercial from many years ago - a set of combines cutting wheat.  All of the operators in their climate controlled cabs drinking Coke (or Pepsi?).  The second is a show about building ice castles in Norway and a small vehicle that was described an an airport runway snowblower that could move a tremendous amount of snow through a chute directly over the operators cab.  Those are my grandiose commercial induced fantasies.  Even a small tractor with a cab set up to move snow is ridiculously expensive and it needs a lot of ongoing maintenance.  I have never been able to locate the manufacturer of the Norwegian snow blower.

The reality is that I have a 15 year old Toro 2 stage snow thrower and about 200 square feet of sidewalk and 1,000 square feet of driveway to clear.  The snow thrower cuts a 24 inch path.  In many ways the strategy is mathematical and practical.  What is the most efficient way to clear away the snow?  Is it just going back and forth and turning the chute on the snow blower on every turn or is it something else?  Since moving into this house I have decided it is a right angled arc starting up the left hand side of the driveway and then turning back (and turning the chute on the snowblower) and heading back in the same direction.  This moves all of the blown snow to the eastern side of the lot, away from the sidewalk and areas where ice might accumulate.  It also results in fewer change in the chute direction that just going back and forth or the length of the driveway.

Mathematics aside - what are the practical aspects?  The first of course is the weather.  Is more snow expected?  Do you really want to concentrate the effort if there is going to be another foot?  In some cases of wet and heavy snow it is imperative.  That layer cannot be allowed to freeze and it is the most difficult to handle with a snow blower.  In this case I was left with about 1/2 inch of translucent slush that I had to scrape up with shovel before it all froze in the colder temperatures.  The second is the surface that you are clearing.  There are some web sites that recommend snowblower sizes based on whether your driveway is finished (asphalt or concrete) or not (gravel).  In my case I have two different surfaces - a concrete driveway and a textured concrete sidewalk.   I can't use the steel shovel on the textured concrete.  I use a plastic shovel very similar to the metal shovel that my father used to shovel coal into a steam engine on the 1950s.  One of my earliest recollection was being placed in the cab of a steam locomotive.  My father was a locomotive fireman at the time and the engine was hand fired.  His job was to keep coal burning to keep the steam pressure up.  He explained to me at the time how the scoop shaped shovel was designed to slide large amounts of coal off of it and into the furnace without wasting any energy.  To clear the sidewalk - I clear one edge and then cut across that using the same motion my father used to shovel coal.  Snow is a lot lighter than coal but it takes me about 50 passes to clear it using this motion.

With every pass, I am careful to extend the stroke out onto the grass by about 2-3 inches.  When my father first taught me to shovel snow, he said this was critical in the event that there was any melting of the snow.  Without that 2-3 inch margin the water pooled on the sidewalk and created ice.  With the margin the water soaked into the grass and no ice was formed.  I have tried to pass that knowledge along to other sidewalk shovelers, but it falls on deaf ears.  Either they don't believe me or they have their own theories of shoveling.

In addition to the theory of clearing snow and carrying it out, I get another thought from about 50 years ago.  I have always been an insomniac and one night back then I was waiting for my father to come home from work.  By then he was a railroad engineer and drove freight and iron ore trains.  It was about midnight.  It was snowing and drifting to a depth of about 3 or 4 feet on the street outside of our home.  He told  me that day before he left that they might need to plow snow off the tracks.  The worst case scenario would be hitting deep snow and blowing it into the diesel engine air intakes on the top of the locomotive.  That would kill the engines and result in a long restarting process that would slow him down.  I kept staring out the window.  The wind was so intense that I could not hear any trains even though we were only about 3 blocks from tracks.  I could finally see him leaning into the wind and snow.  He always wore union style clothes and none of it was really made for winter weather.  He wore a chromer cap with ear flaps that offered limited protection.  He was carrying a leather satchel that he called a "grip" that contained all of his important paperwork.  He was wading through hip deep snow, using the exaggerated hurdler motion that you had to use to travel in deep snow without snowshoes.  I was very happy to see him and even happier when he burst into the kitchen and it smelled like the fresh air version of diesel fuel, Lucky Strikes and leather.

I have a greater appreciation of these events than I used to.  Early on it was easy to grasp the psychodynamic significance, especially when it came to countertransferences toward mechanics and anyone else who might smell of diesel fuel and cigarettes in my office.  There were the associated issues of blue collar rage, exploitation of union workers, and a stronger affiliation with workers rather than management.  These days I can think of it in terms of the brain systems that are represented and the underlying mechanisms that allow for this experience.  I still feel happy when I have that image of my father pushing through deep snow toward home.  It probably accounts to some degree for my affiliation with snow and winter weather.  Every month or so I give a lecture and talk about the time frame, neuroscience and structures that are probably responsible for that experience.

Most of all I remind the students about how these structures allow for unique human experience.  I like to say that if there are 7 billion humans on Earth, there are 7 billion unique conscious states.  I suppose planning and fantasizing about clearing the snow is not that unique in the upper midwest.

But I doubt that any two of us learned to do that in the exact same way.


George Dawson, MD, DFAPA