Neural circuitry in psychotic disorders
Roscoe Brady, MD, PhD, Assistant Professor of Psychiatry at Harvard Medical School
The goal of our laboratory is to better understand the neural circuit basis of symptomatology in psychotic disorders. In the psychiatric clinic, the near-term goal of treatment is frequently to help patients with chronic mental illness move from a symptomatic state into an asymptomatic state of health. Despite the ubiquity of this treatment goal, we have a poor understanding of the neural basis of how disease states differ in patients with chronic disorders.
We have used functional Magnetic Resonance Imaging (fMRI) in human participants with psychotic disorders to understand how neural circuits mediate different symptomatic states. In studies of participants with bipolar disorder, we have demonstrated that bipolar mania is distinguished from euthymia by the disruption of circuits of emotion regulation. We have subsequently replicated these findings in an independent cohort of subjects with bipolar disorder who have undergone fMRI imaging longitudinally across states of mania and euthymia. We have also performed the first studies exploring the connectomics of bipolar mania to understand how other symptoms of bipolar mania (e.g. increased activity) are reflected in large scale brain networks. Ongoing work seeks to extend these studies of circuit pathology to bipolar depression.
A separate focus of our work has been to understand the neural circuits that mediate medication refractory symptoms of schizophrenia. In this disorder, negative symptoms (amotivation, anhedonia, and expressive deficits) and impairments in social cognition are the strongest predictors of poor functional outcomes such as homelessness and unemployment. We have used recent innovations in data-driven functional neuroimaging to elucidate how these deficits are reflected in brain network pathology. We have replicated these findings across multiple sites and, through collaboration with Mark Halko, PhD (BIDMC Neurology), we are empirically testing these circuit-symptom relationships by selectively modulating circuit activity using repetitive Transcranial Magnetic Stimulation (rTMS).