It has been a busy summer so far as NIMH Director. I’ve now seen plenty of sticky, scorching summer days in the nation’s capital, enough to develop a newfound appreciation for air-conditioned Metro cars. But actually not as many days as you might think, because I’ve been doing a bit of traveling. And what goes better with summer traveling than a little light summer reading? In the spirit of the back-to-school season, and at the risk of lapsing into cliché, I thought I would share with you what I’ve been up to this summer.
It has been a fascinating summer of travel, starting off with a trip across the pond to Geneva to attend an engagingly titled meeting called OptoDBS 2017. This conference takes on an ambitious agenda—to bring together two separate but related fields in order that each might teach the other something useful—in the name of improving upon novel treatments for neuropsychiatric illnesses. About half of the speakers were from the world of optogenetics, a brand new technology that has revolutionized basic neuroscience over the past decade. Optogenetics relies on genetic engineering techniques to introduce molecules from light-sensing bacteria into neurons, making it possible to activate or inhibit those neurons with light. As I’ve written about before, this technique allows us to study how specific neurons in specific parts of the brain drive behaviors such as anxiety and cognition in animal models. The other half of the speakers study the effects of deep brain stimulation (DBS), which uses indwelling electrodes to stimulate neurons deep in the human brain. DBS is an effective treatment for the symptoms of Parkinson’s disease and obsessive-compulsive disorder, and is being studied in treatment-resistant depression.
It turns out that the two groups of scientists have a lot to say to each other, and a lot to learn from each other. DBS works, but even when it does, we don’t really know why. As a result, much of the effort in this field is aimed at measuring the effects of successful DBS on the brain to figure out which are key to providing clinical benefits. This is hard to do in humans, but with the aid of increasingly sophisticated technologies, including some being developed by the NIH BRAIN Initiative, we’re beginning to make some headway. We are, for example, developing the ability to measure the indirect effects of stimulating one brain region on activity in far-away brain regions. Yet these techniques are not particularly helpful at identifying precisely which circuit elements near the tip of the electrode are driving these changes, nor can these techniques clarify whether DBS increases or decreases activity in these circuit elements. Meanwhile, optogenetic techniques enable such precise activation that those of us who use them think we know exactly what we’re doing—changing the activity of only a specific element, and turning activity in that element up or down with considerable precision. Yet what we are beginning to learn is that, just like with DBS, even very specific manipulations can alter brain activity throughout an extended network. Optogenetic techniques, therefore, can help the DBS researcher understand which particular element of the circuit she is manipulating and how DBS affects that element. Meanwhile, techniques and results from the DBS side can help the optogenetics researcher understand the totality of what she is doing throughout the brain, as well as helping to clarify clinically relevant effects.
My next “trip” was to Bethesda, a staycation. I was pleased to host a meeting on computational psychiatry, which readers of my messages will recognize as a priority. There were considerable similarities with OptoDBS: two different groups of people, each with a lot to teach each other. The two groups were different, of course, than at OptoDBS; for this meeting, we had computational neuroscientists and psychiatric scientists. But the outcome was the same: a conversation, where each group shared their expertise with the other, and the NIMH—as well as the field—benefited. We came away from that meeting with a clear sense of a way forward for how to best apply theoretical and computational approaches to the problems psychiatry faces. We are now hard at work implementing the ideas raised at the meeting. First and foremost among them was the recognition that we need to foster opportunities for both training and collaboration in order to encourage greater integration of computation in psychiatric research.
Also convening in Bethesda was the NIMH Outreach Partnership Program (OPP) annual meeting. The OPP is a key NIMH program that helps the Institute disseminate the latest research findings to consumers, families, providers, and other stakeholders. The reach of this program is truly national. NIMH Outreach Partners—primarily state affiliates of national mental health organizations like the National Alliance on Mental Illness and Mental Health America—represent all 50 states plus the District of Columbia and Puerto Rico. At the annual meeting, representatives of these organizations learned from experts about the latest research findings in areas such as suicide prevention, deep brain stimulation for depression, and post-traumatic stress disorder. Partner representatives also met to brainstorm about how to communicate around issues related to volunteer participation in research, such as human subjects protections and the experience of participating in a study.
Finally, a visit to the National Center for Biological Sciences (NCBS) in India beckoned. A friend and colleague had asked if I would participate in a meeting there on “Neurobiology Across Scales.” An oasis of greenery on the outer edges of the sprawling tech city of Bangalore in southern India, the NCBS campus houses many fine neuroscience labs, with a particular focus on stress neurobiology and computational neuroscience. Luminaries from Europe and the U.S. participated along with investigators from across India. It was a wonderful opportunity to exchange ideas with these colleagues, but the real treat was interacting with young Indian scientists in training. I taught a class to summer students in their computational neuroscience program, and their enthusiasm and optimism was infectious. I also learned of a nascent collaboration between NCBS scientists and a new stem cell institute aimed at understanding the neurobiology of autism spectrum disorder. Using a combination of human stem cell and animal models, they hope to explore the role of learning and memory mechanisms in the development of social deficits.
On these various trips there was plenty of time for some reading. In my next message, I’ll report on some of what I came across. In the meantime, by way of a summer commercial message, I’d like to call your attention to the Discovery Channel series in August, First in Human, in which filmmakers followed pioneering clinical studies in the National Institutes of Health’s research hospital. The series offers an inside view of the scientific and human sides of clinical research, so key to what we do here.