Military brain-chips to cure psychiatric disorders?

Sounding like something straight out of science fiction, DARPA recently announced grants to fund research and development of implantable brain-stimulation chips aimed to relieve, or even cure, mental disorders.  The Defense Advanced Research Projects Agency thinks big, and it has the money, i.e., our tax dollars, to back it up.  Decades ago, DARPA brought us the internet.  In comparison, revolutionizing psychiatry ought to be a walk in the park — right? Find a need and fill it: "Current approaches — surgery, medications, and psychotherapy — can often help to alleviate the worst effects of illnesses such as major depression and post-traumatic stress, but they are imprecise and not universally effective."  You can say that again.  So DARPA created a program called SUBNETS (Systems-Based Neurotechnology for Emerging Therapies) "to generate the knowledge and technology required to deliver relief to patients with otherwise intractable neuropsychological illness."   SUBNETS aims to create an "implanted, closed-loop diagnostic and therapeutic system for treating, and possibly even curing, neuropsychological illness."  In other words, computer chips in the brain.

SUBNETS will pursue the capability to record and model how these systems function in both normal and abnormal conditions, among volunteers seeking treatment for unrelated neurologic disorders and impaired clinical research participants. SUBNETS will then use these models to determine safe and effective therapeutic stimulation methodologies. These models will be adapted onto next-generation, closed-loop neural stimulators that exceed currently developed capacities for simultaneous stimulation and recording, with the goal of providing investigators and clinicians an unprecedented ability to record, analyze, and stimulate multiple brain regions for therapeutic purposes.

SUBNETS is hedging its bets.  With an overall budget of $70 million, it is funding both a diagnosis-based arm, in the manner of the DSM5 of the American Psychiatric Association (APA), as well as a “trans-diagnostic” approach, in the manner of the Research Domain Criteria (RDoC) of the National Institute for Mental Health (NIMH).   The ideological rift between the APA and NIMH last year was awkward and impolitic; fortunately,  SUBNETS has the resources to avoid choosing sides.  A research team at the University of California San Francisco (UCSF) will receive up to $26 million to study diagnostic groups, specifically post-traumatic stress, major depression, borderline personality, general anxiety, traumatic brain injury, substance abuse and addiction, and fibromyalgia/chronic pain.  Another team at Massachusetts General Hospital (MGH) will receive up to $30 million to tackle trans-diagnostic traits, such as increased anxiety, impaired recall, or inappropriate reactions to stimuli.  Both groups will include public and private partnerships, including with device manufacturers Medtronic, Draper Laboratory, and the start-up Cortera Neurotechnologies.

What to make of this?  Well, it's certainly ambitious.  As I read it, the effort relies on several unproven premises.  First, that psychiatric diagnoses, as currently construed, can be differentiated by monitoring activity in specific brain pathways.  This has been tried before without success, and it isn't clear that sensor technology was the reason.  An alternative model would suggest that mental states are an emergent property of widely integrated brain states.  If so, chips implanted in specific areas could no more capture this complexity than carefully listening to the trombone section could capture a symphony.

Another assumption is that carefully focused electrical stimulation can treat a variety of mental disorders.  The efficacy of transcranial magnetic stimulation (TMS) to treat depression provides some support for this idea.  In contrast, typical comparisons to deep brain stimulation to treat seizures and severe obsessive-compulsive symptoms only go so far.  Analogous stimulators may quell a panic state or chronic pain.  It is less clear how complex interpersonal patterns, such as those seen in borderline personality or substance abuse, could respond to this type of intervention.  Of course, we shall see.

A central tenet of SUBNETS is that implanted technology can promote healthy (or curative) neural plasticity.  Plasticity is a popular concept at the moment, highlighting the fact that brain wiring is not static, as was previously assumed.  "Neurons that fire together wire together" — that is, synaptic connections change dynamically in response to input, i.e., life experience.  This property underlies the hope that implanted stimulators may change the activity of neural pathways in a permanent way, "firing" the pathway together to make it "wire" together, and allowing the device eventually to be removed.  Again, we shall see.

Of course, there are many stumbling blocks ahead.  Implanting brain chips is no small matter, and this approach is unlikely to be used in the foreseeable future for anything short of the most severe, treatment-resistant disorders.  Initial public commentary immediately honed in on the "military mind control" aspect of the project, with visions of soldier drones being controlled on the battlefield via implanted chips.  The potential abuse of such technology is manifest and terrifying, and careful controls and standards are needed to assure freedom, not to mention safety.

At the most mundane level, the technology will only work if the science behind it is sound, and that remains to be seen.  Nonetheless, if even a portion of the SUBNETS agenda comes to pass, it would represent a monumental leap for psychiatric treatment.

Psychiatric uncertainty and the neurobiological buzzword

A few years ago I wrote that uncertainty is inevitable in psychiatry.  We literally don't know the pathogenesis of any psychiatric disorder.  Historically, when the etiology of abnormal behavior became known, the disease was no longer considered psychiatric.  Thus, neurosyphilis and myxedema went to internal medicine; seizures, multiple sclerosis, Parkinson's, and many other formerly psychiatric conditions went to neurology; brain tumors and hemorrhages went to neurosurgery; and so forth.  This leaves psychiatry with the remainder: all the behavioral conditions of unknown etiology.  Looking to the future, my fervent hope that researchers will soon discover causes and definitive cures for schizophrenia, bipolar disorder, and other psychiatric disorders comes with the expectation that these conditions will then leave psychiatry for other specialties.  We will always deal with what is left.  At minimum we psychiatrists should accept this reality about our chosen field.  After all, there appears to be no alternative.  Some of us go beyond this to embrace uncertainty as intellectually attractive.  We like that the field is unsettled, in flux, alive. Yet many of us clutch at illusory certainty.  Decades ago, psychoanalysis purportedly held the keys to unlock the mysteries of the mind.  It later lost favor when many conditions, particularly the most severe, were unaffected by this lengthy, expensive treatment.  Now the buzzword is that psychiatric disorders are "neurobiological."  This is said in a tone that implies we know more than we do, that we understand psychiatric etiology.  It's a bluff.

Patients are told they suffer a "chemical imbalance" in the brain, when none has ever been shown.  Rapid advances in brain imaging and genetics have yielded an avalanche of findings that may well bring us closer to understanding the causes of mental disorders.  But they haven't done so yet — a sad fact obscured by popular and professional rhetoric.  In particular, functional brain imaging (e.g., fMRI) fascinates brain scientists and the public alike.  We can now see, in dramatic three-dimensional colorful computer graphics, how different regions of the living brain "light up," that is, vary in metabolic activity.  Population studies reveal systematic differences in patients with specific psychiatric disorders as compared to normals.  Don't such images prove that psychiatric disorders are neurobiological brain diseases?

Not quite.  Readers of these exciting reports often overlook two crucial facts.  First, these metabolic differences only appear in group studies and cannot be used to diagnose individual patients.  As of this writing there is no lab test or brain scan to diagnose any psychiatric disorder.  Attempting to do so would be like diagnosing malnutrition based on height.  While malnourished people are shorter than the well-nourished on average, there is wide overlap and height is not diagnostic.  Second, etiology — the cause of these differences in brain function — remains unknown.  Differences in brain function (and structure) are not necessarily inborn.  Brain anatomy can change as a result of life experience, and metabolic activity (function) from experimental manipulation of cognitive effort, induced mood, guided imagery, etc.  Just as multiple factors affect a subject's height, multiple biological and psychological factors affect brain findings as well.  Thus, learning that patients with borderline personality show decreased metabolism in the frontal lobes (hypofrontality) is neither surprising nor indicative of a neurobiological etiology.  We already know the frontal lobes inhibit impulsive activity, and we already know borderline personality is characterized by impulsivity.  What else would we expect?

Genetic studies consistently show both heritable and environmental factors at play in psychiatric disorders.  Since the 1960s, psychiatry has called this combination the diathesis-stress model: an inborn predisposition meets an environmental stress, leading to an overt disorder.  The model helped shift the field from "nature versus nurture" to "nature and nurture" — and no research discovery or neurobiological rhetoric so far has shifted it back.  Patients and their doctors still contend with diathesis and stress: recreational drug use tips one patient into psychosis, sudden abandonment tips another into borderline rage.  Indeed, clinicians remain much more able to influence stress than diathesis.  A dispassionate assessment of what we currently know should lead to humble agnosticism about psychiatric etiology.  Genetics, biology, and environment all play a role, but beyond that there isn't much we can say.  This is why all current psychiatric medications treat symptoms and are not curative.

In this light, the popularity and zeal of neurobiological language is startling.   The American Psychiatric Association (APA) subtly changed the wording in its new Diagnostic and Statistical Manual, DSM-5, to imply that all psychiatric conditions are biological in nature.  The National Institute of Mental Health (NIMH) assumes that "Mental disorders are biological disorders...."  The National Alliance on Mental Illness (NAMI) says, "A mental illness is a medical condition...."

A more ground-level version is expressed by editor-in-chief Henry A. Nasrallah, MD in the latest edition of Current Psychiatry.  In an editorial not-so-subtly titled, "Borderline personality disorder is a heritable brain disease," Dr. Nasrallah proclaims BPD a "neurobiological illness" and "a serious, disabling brain disorder, not simply an aberration of personality" — as though these were distinct alternatives rather than two terms for the same thing.  After citing a number of biological findings which fail to prove etiology (e.g., the hypofrontality mentioned above) and which show partial heritability, Dr. Nasrallah concludes that "the neuropsychiatric basis of BPD must guide treatment."

Of course, it already does.  We already treat borderline personality disorder the best we know how, with psychotherapy (shown by functional imaging to modify brain metabolism, by the way) and often with adjunctive medication to treat symptoms.  What more do breathless declarations of brain disease buy us, other than reduced credibility?  It's not as though any of us currently withhold neurobiological treatment as a result of outmoded ideology.  On the contrary, the moment the FDA approves a cure for borderline personality disorder based on an established neurobiological etiology, I will gladly refer my patients to the neurologist, virologist, or genetic counselor who would thereafter treat such patients.

Psychiatry as behavioral neuroscience — Sloppy thinking in psychiatry 3

This third installment in my series on sloppy thinking in psychiatry addresses something a little more subtle than "chemical imbalance" or polypharmacy.  It is the growing vision, well represented by this recent editorial in Current Psychiatry, that the only salvation for the field lies in embracing the language and practice of neuroscience.  With "chemical imbalance" discredited, attention has turned to functional brain imaging and genetics as our last and best hope to retain a shred of dignity as a medical specialty.  Dr. Nasrallah's editorial goes further than most, arguing that we need a new name for psychiatry:  Psyche is an "archaic concept" that "has outlived its usefulness and needs to be shed."  Likewise, our "brilliant future anchored in cutting-edge neuroscience" will be hastened by renaming the major mental illnesses, calling psychotherapy “verbal neurotherapy," and by embracing the language of "brain repair."  But it's not all a matter of terminology: "The disastrously dysfunctional public mental health bureaucracy must be abandoned and transformed into 'brain institutes,' in all states, similar to cancer centers or cardiovascular institutes, where state-of-the-art clinical care, training, and research are integrated." I share the sentiment, really I do.  Wouldn't it be great to see shiny Brain Institutes cropping up all over, replacing those sad, underfunded public mental health clinics?  Wouldn't we hold our heads higher if our business cards promised "verbal neurotherapy" and "brain repair"?  We could call ourselves medical doctors without a hint of doubt or insecurity, sit proudly at the hospital cafeteria table  with the other doctors — you know, the surgeons and cardiologists and such — and charge higher fees as a premier medical specialty instead of our current status as mental health "primary care."  There's a lot to recommend this vision; where do I sign up?

Unfortunately, there is nowhere to sign up.  This is a pipe dream.  Psychiatry isn't clinging to archaic language about the psyche out of nostalgia.  It's the best we have.  "Verbal neurotherapy," while technically a valid description of psychotherapy, is absurd hand-waving.  By the same token, taking a vacation is "locational neurotherapy."  We aren't going to gain anyone's respect by dressing up our current practices in pseudoscientific jargon.

Nor are we withholding "behavioral neuroscience" from our patients now.  In addition to the verbal neurotherapy, i.e., psychotherapy, that forms the mainstay of my practice, I also offer pharmaceutical neurotherapy, advice regarding nutritional and exercise neurotherapies, discussion of various occupational and relational neurotherapies — I even suggest an occasional locational neurotherapy.  I simply lack the hubris, or perhaps it's the marketing genius, to call it that.

When scientists develop safe, effective psychiatric treatments based on neuroplasticity and neuroprotection I'll happily offer them to patients (or refer patients to centers where such treatments are available).  When my Election Day ballot includes a measure to upgrade public mental health facilities to state-of-the-art Brain Institutes, you can count on my vote.  I'm not holding my breath.

Kidding aside, there is nothing sloppy or ill-advised about incorporating neuroscience into psychiatry.  Nor is it a new idea.  From prehistoric trepanning to Freud's 1895 "Project for a Scientific Psychology" (pdf of a 2004 review), from the introduction of neuroleptics in the 1950s (modern commentary here) to the "decade of the brain" in the 1990s, psychiatry has nearly always paid homage to the neural underpinnings of behavior.  The only obvious exception was the heyday of psychoanalysis, from about 1950 to 1980.  Otherwise, we use the best neuroscience we have at the time.  The real problem, of course, is that we ask more of our neuroscience than it can deliver.  Trepanning probably didn't help, Freud abandoned his "project," neuroleptics caused major side-effects and failed to allow patients to return to the community, and the "decade of the brain" turned many psychiatrists into drug-doling technicians.  Science keeps improving, and I'm sure we'll see good things emerge in the coming years.  However, progress will occur at its own pace, and no amount of wishing or envisioning will make it happen any faster.

It is sloppy thinking to imagine that behavioral neuroscience is something new and revolutionary.  The real revolution in psychiatry, if it ever happens, will be the integration of careful neuroscience, psychology, sociology, and other disciplines to elucidate and benefit our lived experience.  This integration will incorporate, not supplant, our higher level understandings of psychology and psychodynamics.  When psychiatry is ripe for the "creative destruction" of polarized thinking and choosing sides, it will be stronger than the sum of its parts, and will have finally reinvented itself  into something we can unequivocally be proud of.

And yet again, photo courtesy of Petr Kratochvil.