Grant: Project Grant

It is estimated that approximately 50-60% of the general population will be exposed to at least one lifetime traumatic event. While most individuals recover from the experience, 10-20% develop post-traumatic stress disorder (PTSD). PTSD is a chronic and often debilitating condition characterized by an inability to extinguish fear responses and increased anxiety. While medications and psychotherapy are often effective, 20-30% of patients do not respond to conventional treatments. In patients with psychiatric conditions such as treatment-resistant depression, obsessive-compulsive disorder, and memory dysfunction, promising results have been reported with the use of electrical stimulation through implanted brain electrodes (also known as deep brain stimulation or DBS). We have shown that DBS improves fear and anxiety in a population of rodents that mimics several of the symptoms presented by patients with PTSD. The primary goal of this proposal is to understand how DBS changes the brain so that it becomes less susceptible to the development of PTSD-type behaviour. In both rodents and humans, a brain region called the amygdala is very important for stress and fear responses. We postulate that DBS exerts its anti-fear and anti-anxiety effects by inhibiting the activity of cells in the amygdala. More than a simple inhibitory response, however, we will test whether DBS leads to protracted and more permanent changes in amygdala cells, which would alter their structure at long-term to reduce fear and anxiety responses.