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.