It may seem peculiar, but it makes sense to me. As a young guy in medicine, I was pulled in two directions – research into things we don’t yet know, and the application of things we do know. The former was where my mind naturally headed, but the latter was what gave me a sense of purpose. While it’s only in retrospect, it makes perfect sense to me that I would’ve ended up being a psychoanalytically oriented psychotherapist [n=1 research with a practical application] where every case is something new. Similarly, my retirement fun has been re·search·ing the post-DSM-III psychiatric research where I’ve stayed on the practical side – psychopharmacology, clinical trials, diagnosis. I’ve shied away from the neuro·anatomy, neuro·physiology, neuro·science side of things, I think because I’m not convinced we know enough yet for there to be a practical side to the equation.
The whole of the past decade in psychiatry might be called the Decade of Jumping the Gun.The fact is that we simply don’t have good enough neuroscience tools yet to allow us to answer the clinically important questions. We just don’t. We might get there eventually but at the moment we are not there.
Given which, any attempt to ‘translate’ our primitive neuroscience into clinical practice will be an effort to jump the gun.by Neuroskeptic…
Blood-oxygen-level dependent contrast imaging, or BOLD-contrast imaging, is a method used in functional magnetic resonance imaging [fMRI] to observe different areas of the brain or other organs, which are found to be active at any given time. Its proof of concept was provided by Seiji Ogawa and colleagues in 1990, following an experiment which demonstrated that an in vivo change of blood oxygenation could be detected with MRI. Other notable pioneers of BOLD fMRI include Kenneth Kwong and colleagues, who first used the technique in human participants in 1992.Neurons do not have internal reserves of energy in the form of sugar and oxygen, so their firing causes a need for more energy to be brought in quickly. Through a process called the hemodynamic response, blood releases oxygen to them at a greater rate than to inactive neurons. This causes a change of the relative levels of oxyhemoglobin and deoxyhemoglobin [oxygenated or deoxygenated blood] that can be detected on the basis of their differential magnetic susceptibility.
In 1990, three papers published by Seiji Ogawa and colleagues showed that hemoglobin has different magnetic properties in its oxygenated and deoxygenated forms, both of which could be detected using MRI. This leads to magnetic signal variation which can be detected using an MRI scanner. Given many repetitions of a thought, action or experience, statistical methods can be used to determine the areas of the brain which reliably have more of this difference as a result, and therefore which areas of the brain are active during that thought, action or experience…from Wikipedia…
The fMRI [1992] and the mapping of the human genome [2000] had the bio-medical psychiatrists peeing in their pants filled with excitement at the turn of the century. And it was pretty exciting. Tom Insel became the Director of the NIMH and announced psychiatry was to become clinical neuroscience. The DSM-5 Task Force tooled up to add biomedical findings to their coming diagnostic manual. A new century and a new psychiatry based on solid brain science was just around the corner. They had already jumped the gun some in the Decade of the Brain [the 1990s], but this time, they forgot the adages, "look before you leap" "don’t count your chickens before they hatch", and dove into the deep end, and ended up with a long chain of disappointments fueling disillusionment and skepticism. So now we’re presented with a big NIMH Study, this time about neural circuits [see weary…].
Already we are seeing multiple approaches to identifying abnormal functional activity in the brain, from functional MRI to in vivo neurochemistry and studies of brain receptors. One approach uses functional imaging to identify differences in regional activity. For instance, evidence from several different approaches implicates circuitry involving ventral, medial prefrontal cortex [Area 25] with major depressive disorder… Individuals with the short allele of the serotonin transporter gene have reduced expression of the transporter and appear to be at a higher risk for developing depression following stressful life events. Recently, this short allele has been shown to be associated with reduced gray matter volume of Area 25 and uncoupling of an anterior cingulate-amygdala circuit necessary for extinction of negative affect, providing a model for linking genetic risk and environmental stress to a specific neural circuit implicated in depression. One might imagine that studies of this circuit could be used to predict response to treatment, just as imaging in cardiology or oncology can be used to predict treatment response.
But what I would’ve preferred from these articles would have been something solid and well referenced about the neural circuits themselves. Perhaps such things are widely talked about and known in neuroscience circles, but they’re not in the general population of practitioners, psychiatrists, or others who aren’t specifically immersed in the world of neuroimaging. The articles are so busy addressing possible translations that they give short shrift to the basics – basics that most readers [like me] don’t know much about. Since this study is essentially a data gathering exercise with the behavior of the neural circuits on the front burner, I ought to know more about that than I do after reading these papers repeatedly.
the neurobiology of “jumping the gun” is much like the adolescent brain of a pimply faced nerd wanting to get laid…underdeveloped DLPFC under the influence of strange new hormones lacking integration with the rest of the brain and reality…kind of like an eighties John Hughes comedy…file it all under “Weird Science”…except Anthony Michael Hall got the fantasy girl and Insel got nothing out the effort.
I think the biological sciences have developed an intense envy of the success of IT science…but protoplasm not cooperating with the best laid plans of mice and men upon discovery of the genome…it’s easier to dream on than try harder so I guess it’s understandable…
“Anybody have any good references that explain neural circuits more clearly?”
I’m not sure, but perhaps this could help:
Menon V. Developmental pathways to functional brain networks: emerging principles. Trends Cogn Sci. 2013 Dec;17(12):627-40.
Regarding brain circuits, all of today’s talk began with Ur-articles by Garrett Alexander and Mahlon DeLong, neurologists who went from Hopkins to Emory in the 1990s. They spelled out the general model of segregated cortico-striato-thalamo-cortical circuits – with their point of departure being the case of Parkinsonism. I have been greatly influenced by their work, which seems potentially generalizable to issues like melancholia. In fact, one of my analogies is to regard mood as “emotional tone.” Some of their seminal articles are this, and this, and this.
Anybody have any good references that explain neural circuits more clearly?
“8. Neuroscience – This is the future of the field. There will be no demand for psychiatrists in the future who don’t know brain science and how it can be applied diagnostically or therapeutically. It is the logical basis to study human consciousness, complex decision making and psychiatric disorders and contrary to what you might read on many blogs there has already been considerable progress in this area. There are many excellent psychiatrist-researchers in this area already and I encourage reading their research and some of their popular works as a starting point. There are any number of Luddites out there who seem to think that psychiatry needs to remain stagnated in the 1950s to provide any value. I don’t think there is a shred of evidence to support that contention or that neuroscience will never be of value to psychiatrists. A good starting point would be to read Kandel’s 1979 article on plasticity, his recent article on nicotine as as a gateway drug, and everything that he has written in between. If your department has a neuroscience section, asking them to compile a reading list of what they consider to be the top neuroscience papers that apply to the field would be an added bonus.”
http://real-psychiatry.blogspot.com/2015/01/advice-to-residents.html
Perhaps Dr. Dawson has some suggestions?
“I learned more neuroscience of clinical relevance in one semester from this PhD Biology professor than I have from years of attending lectures and reading papers from psychiatry researchers who are considered world experts in areas like the neurobiology of OCD, pediatric bipolar disorder neuroimaging, or how transcranial magnetic stimulation affects neural circuits in depression. For me, the most important distinction when we talk about clinical neuroscience is whether we take a broad view of neuroscience or a narrow view. The broad view would emphasize the huge effect of all of the different inputs on the brain (e.g. that six words can bring a person to tears), whereas the narrow view tends to emphasize things like genetics, neurotransmitters, biomarkers, and circuits.”
http://www.psycritic.com/2015/04/psychiatry-as-clinical-neuroscience-why.html
Perhaps Psycritic has some suggestions?
Something I came across when looking for a neurocritic quote:
http://blogs.plos.org/neuroanthropology/2013/06/25/finding-middle-ground-on-neuroscience/
I find neurocritic one of the more interesting commentators on the circuits in mental health disorders ideas:
http://neurocritic.blogspot.com/2011/10/activation-of-hate-circuit-while.html
Deisseroth is, rightly or wrongly, likely to get the nobel at some point. This might be another place to start:
http://www.cell.com/cell/pdf/S0092-8674%2816%2930345-2.pdf
We will also, for better or for ill, be seeing the same development and testing model we’ve seen with pharma
http://www.circuittx.com/team.html
It was interesting reading this
“it makes perfect sense to me that I would’ve ended up being a psychoanalytically oriented psychotherapist [n=1 research with a practical application] where every case is something new.”
jaxtaposed with this
“In our view, the FDA needs to understand the vital importance of getting first-generation devices into the field and move away from arbitrary standards like improving symptoms by 50 percent in 50 percent of the population. The notion that if we can’t help everybody we shouldn’t help anybody has no place in medical science, particularly when you consider that neuromodulation therapies are working with the hardest-case patients who have not responded to other therapies.”
From a broader perspective, the attempts to localize X mental illness (depression, suicidality, neurosis) inside the patient (specifically inside/through brain circuitry) is also a radical, cultural scapegoating of the patient. “It’s not us, it’s you,” says society, “see, you’re the one with the lesion,” pointing to the bright red dot on neuroimaging of choice.
In California, it is essentially impossible to get from Irvine to the Valley or Marin County to Silicon Valley during rush hour. No politician wants to seriously do what needs to be done to reduce traffic, which would include higher registration fees and proof of insurance in dense zip codes. Hence, unbridled enthusiasm for high speed rail (which will actually be the world’s slowest high speed train, kind of like mild major depression) from SF to LA, which is basically a hundred dollar one hour flight and not a problem at all.
In psychiatry, antidepressants and treatments cannot break the NNT of approximately 12, and therefore, unbridled enthusiasm for neuroscience. If there was a new antidepressant with few side effects and an NNT of 5, our excitement would be directed elsewhere.
It’s denial meets sleight of hand meets magical thinking meets fetish.
Anonymous, you might find the http://blogs.plos.org/neuroanthropology/2013/06/25/finding-middle-ground-on-neuroscience/ link I referenced above of interest. Part of the point it argues (though you might find unsuccessfully) is that incorporating novel tools studying the brain, and novel ways of impacting the brain, the neuro- vs psy- approach, need not be synonymous with deprioritizing the myriad issues (interpersonal, systemic,environmental,…etc) at play.
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This reminds me of what medicalizing problems has come to mean. It need not necessarily mean a focus on a very few aspects of a situation. However, as we have created a system where only certain things get paid for as “medical” and anything else isn’t (at least by insurance – cue Dr. O’Brien) then classifying something as a medical problem does have that impact. E.g. The spectrum of pre-diabetes, type II diabetes,…etc where highly effective multi-pronged approaches die for unsustainable funding reasons.
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That societies will often attempt to locate in the individual pathologies they might be more appropriately located in the society itself seems difficult to deny. And, they often do this with whatever are the tools most readily at hand. So it will be with novel neuroscience findings. Perhaps some neuroscience findings lend themselves well to such use. But I agree with psycritic, and others, who argue that that is more the fault of the hucksters, the showmanship, around the findings, than the work itself.
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I found Dr. Carroll’s references helpful to me (at least at first glance) in framing this discussion. At the se time it’s interesting that the examples are within motor control. A topic that is in many ways considered one of the most tractable in neuroscience. So it doesn’t necessarily speak to how close we are to acheiving similar results for higher order issues, but it does point to why continued work in these areas is important. If anything, I think it is Insel’s embrace of the “in 10 years this will be translated into clinical practice”, rinse and repeat, model, that has been more damaging. The work is important. The jumping the gun, while throwing what we actually can do under the bus,… not so much.
Of course I haven’t read them all yet, but I’ve read some and scanned the others. I’m hardly on a quest to become a world expert on neural circuits, but looking over the gathered material has focused me on what I was really after in this post [the Decade of “Jumping the Gun“….] and weary… in the first place.
I hate to recycle old sayings because they lose their umpf with everyday use, but…
“To a man with a hammer, everything looks like a nail.”
… pretty much sums up a lot of what this blog is about. As a psychoanalytic candidate, I used to cringe when the elders who should have known better started talking authoritatively when they were actually speculating, and the critics were right – that was an epidemic problem. I feel the same way about a lot of the KOL level biological psychiatrists. But there’s an added cringe in their case – the industry alliances that are, in my humble opinion, a cancer on the land. And that’s not the only COI around. Like a lot of the psychoanalysts, the behaviorists, and the anti-psychiatrists of the 1970s, there’s an ideological narcissism in the KOL set that complicates the problems too.
But there’s something else that I think really complicates our modern science that can be summarized in one word – Translation. "From the bench to the bedside" are the watchwords for any and every research grant proposal. Reading the two papers by Williams et al, you would think that the science of neural circuits viv-a-vis psychiatric disorders was well down the road, and that neuroimaging, specifically the fMRI [BOLD] is a finely tuned tool for working with these well established "circuitopathies." And further, that we are on a royal road to a dimensional diagnostic scheme – a goal of the Research Domain Criteria [RDoC]. Precision Medicine is just around the corner.
After thirty years of "just around the corner", we ought to be wary, even skeptical. We ought to be on the lookout for exaggeration, commercial intrusion, hype. So that’s what my next post is going to be about. Those papers set my nose "a-twitching" as did the NIMH grant description. After reading these papers, I’m not slightly convinced that these neural circuits are so well established or that the fMRI is so precise an instrument that practical application is even the point. That the neural circuit hypotheses are interesting and need to be studied makes sense. But the way these things are written up gives new life to my old saying [To a man with a hammer, everything looks like a nail] and Neuroskeptic’s [… any attempt to ‘translate’ our primitive neuroscience into clinical practice will be an effort to jump the gun]. So When I pick up this thread, I’m probably going to be changing topics in midstream to Translational Medicine.
I’m not saying the pure science research is useless or uninteresting, but that jumping the gun actually worsens the problem when the science isn’t ready for prime time. I’ve been reading about DNA methylation in child neglect and epigenetic effects but until I have a way to safely reverse the process (which might not even do the trick years later) it’s not useful to me from a practical standpoint.
There’s a difference between pure science and applied science and a goal and a plan and a lot of people who should know better have forgotten about this or using happy talk to distract away from lack of clinical advances.
http://www.psychiatrictimes.com/blogs/history-psychiatry/most-exciting-time-history-psychiatry
I had a few comments about this…
1BYW: Those links are fantastic. Thank you for them. I will read further. I will readily acknowledge that both basic science and sociological perspectives are important in this conversation, but I am just afraid that, when push comes to shove (such as legal battles, suits over patient suicides, etc), the basic-sciences-based explanations will win the day because all of society (in the example of a patient’s suicide: family, friends, the lawyers and courts themselves, the financial racket involved) will want to ensure that all explanation of etiology is clean and simple and worry-free; the easiest way to do this is to be sure all etiology is localized within a person. I am not saying that that there aren’t etiological factors within a person, it’s just that society has an interest in making sure that all factors are perceived to be within a person.
Anonymous:
That is certainly true in the case of a 10-year old boy bored in a boring class going to a school that provides no recess. Let’s talk about the neuroscience of ADHD instead of creating a better learning environment.
Very thought-provoking post and discussion. Thanks to 1boringyoungman for the mention. The term “neural circuit” is buzzword that has taken on different meanings in systems neuroscience (highly specific neuronal connections defined by cell type) and cognitive/affective human neuroscience (blobs of hemodynamic activity that are statistically coupled during resting state fMRI). The Rajasethupathy, Ferenczi, and Deisseroth “Leading Edge Perspective” paper is indeed a good place to start.
I tried to address the disconnect a couple years ago in A Neural Circuit for Voracious Overeating in Mice: Translation to Humans:
http://neurocomplimenter.blogspot.com/2013/09/a-neural-circuit-for-voracious.html
The advances in optogenetics and chemogenetics are far outpacing any conceivable current application to psychiatry, but Rajasethupathy et al. sketch a possible future (hint: Neurology and Parkinson’s Disease once again lead the way as a model).