Showing posts with label brain. Show all posts
Showing posts with label brain. Show all posts

Tuesday, November 6, 2018

Computational Aspects of the Human Brain



As part of my lectures on the neurobiology of addiction - I digress briefly to discuss the computational aspects of the brain.  A lot of that discussion is focused on on the above graphic showing that overlaps in capacity with a list of the world's ten fastest supercomputers.  At least that is the estimate of the AI Impacts group.  It is basically a computation based on edges and nodes. I include power estimates for a brain from existing hardware to the actual power estimate of the human brain that I would guess every physical chemistry student from my era had to contemplate at one time.  And then I try to stimulate some discussion of supercomputers versus the human brain and it generally falls flat.  My Socratic process goes something like this:

"OK so we know that humans can't really beat computers on straightforward calculations so what advantages do we have?"

"I will give you a hint - why do we all go thorough residency training? Why can't you learn your specialty by reading about it in a book?"

The first lesson is pattern matching.  The human brain is designed not only to match patterns but to be trained to match a lot of them.  Some research article suggest about 88,000, but when  you consider what has to be matched that has be very a very low estimate.  I quote references from 15-20 years ago and a course I used to teach on diagnostics and diagnostic decision making.  Ophthalmologists correctly diagnosing diabetic retinopathy at a much higher rate than nonspecialists.  Dermatologists diagnosing rashes faster and correctly classifying ambiguous rashes with greater precision than nonspecialists. If I am really on a roll I might digress to talk about Infection Disease rounds at the Milwaukee VA sometime during 1982.  I was the medical student on a team of residents and fellows doing a consult for possible subacute bacterial peritonitis.  As the attending listening to the presentation he was also looking at a rash on the patient's shin.  By the time we were done he had also diagnosed a strep infection in addition to the peritonitis.  When you have significant pattern matching capacity, and you have been exposed to relevant patterns you can recognize them quickly and improve the speed and accuracy of the diagnosis.

I move on at that point to illustrate that the computers are catching up.  The simple captcha is less robust in discriminating machines from humans.  Opening an account may take more that checking the "I am not a computer" box. Now you might have to look at 8 pictures and check the one that contains an automobile or a stop sign.  Some of these photos are often difficult for humans to decipher.

At that point I touch on human consciousness - both the unique aspects and computational power it takes to generate.   About a decade ago I started saying that if there are 8 billion people on the planet - there are 8 billion unique conscious states. It makes sense at a number of levels especially when I put up hard numbers on cell types, protein types, the genetic information represented, and the typical stream of consciousness that every person experiences every day.  What is the content and flow of that activity? How does it get biased in psychiatric disorders and addictions?  How much computational power does it take to generate all of this information?

My latest step is what I like to consider The Matrix observation.  If I am standing in front of a room of 15-20 residents - what does it take to generate the physical representation of all of the people and all of the objects in that room? What does it take to make all of those representations unique? There can be a general consensus about what is happening - but just looking around it is clear that there are obvious different experiences.  One person looks very interested and one semi-interested.  One person is more focused on her Smartphone and is indifferent to my presentation.  Some people look sleepy.  Others look irritated.    They also appear to be indifferent to the context.  I know that my job is to try to get this information across and make is semi-interesting.  There is no real expectation on the residents.  It is clear from the questions I ask that they really don't know too much about the brain.  There are parallel streams of information processing that allow us all to evaluate what is occurring on the fly both the information content and emotion.  In some case there are pre-existing heuristics and in other cases associative memories and biases.  All of this represents a tremendous amount of information or computational power depending on how you may want to discuss it.

I have been preoccupied myself with the computational power and estimating it accurately. I used to try to model it in terms of electrical buses and neuronal firing rates - but the numbers I got were far too low.  There really are no good equivalents in the physical world with the possible exception of the Transversed Edges per Second (TEPS) metric used by the AI Impacts group for the above graphic.  You can't really use estimates of typical audio or visual information and concluding that is what is being processed by the brain.  I have never really seen an accurate estimate of all of the sensory information that the brain is handling in real time.

I went to bed last night and waited for sleep reverie or that period of time where you stream of thinking is jumbled and illogical just before you fall asleep.  As a chronic insomniac it is one of the few reliable cues that I am probably getting some sleep.  It happened when I had a sudden image of a baby high up on a brick wall, followed immediately by a person who seemed to be me sitting in a single seat futuristic car.  The salesperson was describing it to me and suddenly the car and everything else was being swept down what appeared to be a very sophisticated hydraulic roadway. The roadway was bright orange and the salesman shifted his pitch to tell me the advantages of this kind of a roadway with this car.  The roadway was moving at about 20 miles per hour.

I shifted briefly and remembered it was 2018 and I was in my bedroom in Minnesota.

And for a minute I thought about being able to estimate the information necessary to generate that brief full color science fiction scene and the three or four more I would encounter that night.


George Dawson, MD, DFAPA


Some additional examples as they happened:


1. Dream of 11/22/2018:  I am back on my old inpatient unit.  The layout is exactly the way it was 20 years ago (the building has since been razed).  I am working with the same staff.  I walk into the examination room to look at the templates for the day.  In those pre-EHR days I had designed a template with all of the relevant features necessary for the billing and coding requirements.  At the time we were all threatened with legal action if we did not comply with these regulations even though they were totally subjective.  In those days I worked with a physicians assistant who prepared the templates ahead of time before we started interviewing patients and completing the subjective aspects of the evaluation and documenting the progress.

The templates were all stacked in two circular patterns - ten templates in each circle.  They appeared to be the exact temples that we used right down to the blurred fonts from being photocopied too many times.  The precise handwriting of my physicians assistant in the diagnostic section was exactly the way he wrote things down.  The placement of the exam table and crash cart were exactly where they were in reality.  The table we used was circular and about 6 feet in diameter with a laminated blonde wood finish and it was also exactly the way it was in that now 20 year old reality.

I looked at the templates and asked myself: "Why are they all face down?  I can't see the patient's name or identifying data.  I will have to go through them all to find the correct template when I start interviewing patients."

I felt somewhat irritated.

And then I woke up. 

2. Dream of 11/23/2018: I am in a large modern, multi-floor medical facility. It is not one that I specifically recognize, but it seem like there are elements of many that I have been in.  I am rushing around on the ground floor. The impression I have is that I am late for a lecture. It doesn't seem to be an explicit CME lecture but everyone else there (including myself) is too old to be a medical student or resident. I run into the elevator just beating the door as it closes.

I make to to the lecture.  It is basically a large room - maybe 50' x 50' and for some reason I burst through the door running at full speed.  Just before the crash into the back wall, a guy standing on the side wall grabs my arm to slow me down and stop me.

I ask myself if that was really necessary because my plan was just to stop myself by reaching out and planting my hand on the back wall.  I notice that there are several people who I assume are physicians that are standing and sitting near the back wall and they seem a little alarmed about something.

Then I am back in the elevator and headed to the ground floor.  I am walking out of the building and realize that I am chewing something metallic.  I realize that is is a collection of machine screws, nuts, and ball bearings. I realize that is purchased them on the ground floor of this building and that they are sold for that purpose.  I also know that I cannot really chew them or I will break my teeth.  I have to cautiously move them around in my mouth.  They remind me of a chap stick product that is applied with a ball bearing device at the end of the dispenser.

I wake up with a metallic taste in my mouth.

3.  Dream of 11/24/2018:  I am back in my home town. The streets and buildings are identical to the way they look in reality.  I am with a friend of mine and we are looking at a 1960s vintage Buick.  It is large and chalky white.  He tells me that his sister recently bought it and she wants to take everyone for a ride.  He thinks I should come along, but just then I remember something that his sister said to me in the last 15 years that would make me not want to go with them. He is talking about the car as though it is a great buy, but as I walk past the tail end of the vehicle, I notice that it has a new paint job and that whoever did it just painted over the decals of the previous dealers.  You can see them faintly through the paint.

I tell my friend that I can't stay around because I have to go grocery shopping. Just then one of his friends comes out and tells me that he has a lot of groceries he can just give me so that I will not have to go to the store.  I decline but he continues to insist. I reluctantly accept free groceries and sling them over my shoulder in a large garbage bag and start to walk home.

The real path home is just 6 blocks - 4 blocks south and 2 blocks east. It is all residential. But in the dream I encounter a large modern baseball park right next to the street. The game is just completed and they are interviewing the winning pitcher. She is in her mid 20s and short and compactly built.  Her uniform and short brown hair are drenched with sweat.  Just then I notice that it is hot. The announcer asks her if the heat was a factor in the game and she says:

"The hot was so hot that when my hot fingers touched the hot ball - I could barely feel it." 

The ballpark looks real.  There are thousands of cheering fans and the announcer and the pitchers statements are amplified over the PA system.  Everything is in color.

I wake up and feel hot and flushed.










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.