 Good afternoon. The WEF estimated that the annual cost by 2030 of mental illness will exceed $6 trillion. As a psychiatrist, I see first hand how illnesses such as depression, schizophrenia and post-traumatic stress disorder, sap somebody's productivity and devastate their lives. Current treatments, primarily medications and psychotherapy, are effective, but only for some people, some of the time and often only partially. Most frustrating to me is that we haven't seen any significant progress in the treatment of these conditions in the past four decades, unlike HIV or cancer treatment. This is in part because our interventions and even our diagnoses weren't based on an understanding of the brain to begin with. Using brain imaging, we're now learning about the functions and dysfunctions of the human brain. What you see here is in 3D, regions of the brain consistently implicated in mental illnesses with slices from a brain scan in the background. However, brain regions don't act alone. They function within interconnected circuits, each underlying different sets of functions. What you see here is a jumble of wiring connecting different regions of the brain. If we are to make progress, then, from mental illness, we must untangle this mess and our interventions must speak the language of brain circuits. So let's use an analogy. Imagine that the roads in Paris reflect wiring interconnecting different brain regions. This map might give you a sense of how to get from the Louvre to the Bastille, but to truly understand how the circuit of roads functions, you need to understand dynamic changes in information flow or traffic within this circuit. Let's take as an example a circuit that I'm going to call the internal world circuit. This circuit is particularly active when you think about yourself or your emotions or recall a memory. It reflects a focus on the internal self, such as last night when I sat using about what gifts to bring my kids back from Switzerland. But then I realized I need to snap out of it and focus on my talk. And so the brain turned down my internal world network and focused on the task at hand. But how does that on-off process happen seamlessly? More specifically, where are the brain circuit switches that allow us to dynamically engage in the world around us and not within us? We studied this using a tool called transcranial magnetic stimulation or TMS, which noninvasively allows us to turn on and off brain circuits using a focal magnetic field. Using brain imaging, then, we can actually see the effects on the brain while it's being stimulated and using that combination, we started to identify regions that act like those brain circuit switches. And more generally, this now allows us to manipulate brain circuits in a targeted manner. It also allows us to map information flow within and between brain circuits. What you see here is a series of events unfolding across the brain, all within less than a third of a second after stimulating a single small area above your temple. From brain imaging studies, we know that patients with depression and post-traumatic stress disorder can't turn down their internal world networks. They end up being heavily preoccupied by negative thoughts and memories. And as a cause of that can't engage meaningfully in their lives and their jobs and relationships. So what if you could artificially turn down that internal world network for them with TMS? We're now doing that in the lab, and through that, developing an entirely new approach at the treatment of mental illnesses. Let's take as another example post-traumatic stress disorder for which psychotherapy is the mainstay of treatment. Using imaging and TMS circuit mapping before treatment, we can predict who will and who will not respond to psychotherapy. It's important because if psychotherapy fails, we have no clear alternative treatment for these individuals. Our next step then is to stimulate the brains of future non-responders such that they can now respond to therapy. Same kind of approach could apply to medication treatment as well. Moreover, psychiatric diagnoses themselves are currently based on a seemingly arbitrary checklist of symptoms. We've recently discovered, however, that a common brain circuit abnormality actually rides through a broad swath of these disorders. Manipulating that circuit then may allow us to impact a broad range of illnesses. As wonderful and powerful these tools are, however, they can still only reach a small portion of the brain. We still miss key circuits important in regulation of our emotions and drives, things that are critical for mental illness. To solve that problem, we've now come together with other neuroscientists, engineers, physicists, psychologists, and others to develop tools that can reach anywhere in the human brain. Through that, our goal together is to develop novel solutions for these debilitating illnesses, map and manipulate key human brain circuits important for behavior, and through that ultimately reconceptualize mental illness and its treatment. Thank you for your attention.