Causal contributions of deep prefrontal-amygdala circuits to social cognition

As humans, we constantly interact with - or think about - other people: social cognition. Social connections are important for mental and physical wellbeing. The impact of loneliness on health is on par with the dangers of smoking and alcohol consumption. Psychiatric disorders have dramatic effects on how we act socially and how we think about the social world. The inability to distinguish one's own thoughts from those of another person is an extreme example seen in psychosis, of how intact social cognition can fail. Understanding how the brain normally produces and controls our thinking and behaviour in social situations is therefore likely to be important for improving health in the longer term. Here, I develop new ways to study how the brain navigates social situations. A collection of brain cells and connections located deep inside the brain is important for social cognition. The circuit comprises the prefrontal cortex and a small structure called the amygdala which I call the deep prefrontal-amygdala circuit (DPA circuit). Abnormalities in this circuit are thought to produce several mental disorders. Although we know that the DPA circuit is important for social cognition, we don't know exactly (1) in what way and (2) to what degree it actually controls how people act socially. These are the two questions I will address. (1) Using brain imaging, it is possible to identify where and when in the brain a mental process takes place. I will use brain imaging to test my theory that it is the DPA circuit that is important for understanding social relationships. We know that this circuit is important for understanding spatial relationships like where my car is relative to my house and a lot about how it works. I will extend this idea and test whether the DPA circuit is important for understanding social relationships like how our own beliefs are related to someone else's, or understanding what alliances exist in a social group. Such processes might go awry in conditions like psychosis. Very recently, new theoretical models and analysis techniques taken from artificial intelligence have become available that will allow me to test this idea in a brand-new way. (2) It is one thing to observe what is happening in the brain when a person performs a task, but it is much more revealing when we manipulate the brain and cause new things to occur. We can do this temporarily and safely using brain stimulation techniques. If we manipulate activity and, in parallel, measure the consequences on people's engagement in social behaviour we can derive causal conclusions about the manipulated brain circuit. So far, it was not possible to manipulate activity in the DPA circuit safely in humans, because it is so deep in the brain that normal brain stimulation methods cannot reach it. However, we have been able to overcome this obstacle in macaque monkeys by using a new non-invasive and safe brain stimulation technique that uses sound waves. Here, I will use this technique in humans to test whether the DPA circuit is causally important for controlling social behaviour under experimental conditions, as well as what else it does and doesn't do. In summary, my project will (1) suggest a new perspective on the way that the DPA circuit supports natural social behaviour. It will do so with precise measures of brain activity and by using new, formalised mathematical models. This will lay the foundation for understanding problems in social cognition leading to conditions like social anxiety and psychosis. (2) I will introduce a new, non-invasive, and safe deep brain stimulation method. By targeting the DPA circuit, I will causally manipulate activity in the brain network that is most frequently associated with mental illness. This provides the first step towards one day establishing a new suite of interventions using neuromodulation techniques which could be used to evaluate and perhaps even treat patients with mental health conditions.