Grant: Doctoral Award - Frederick Banting and Charles Best Canada Graduate Scholarships

Previous studies have shown that patients with schizophrenia (SCZ) and bipolar disorder (BD) have deficits in cortical inhibition (CI). CI can be measured through paired transcranial magnetic stimulation (TMS) of the motor cortex and recorded through surface electromyography (EMG). Through the combinations of interleaved TMS and electroencephalography (EEG), we have recently reported on methods in which CI can be recorded directly from the dorsolateral prefrontal cortex (DLPFC), a cortical region that is more closely associated with the pathophysiology of SCZ. In this study, therefore, we aim to measure CI in the motor cortex and DLPFC in patients with SCZ and BD compared to healthy subjects. More specifically, we are interested in the cortical inhibition of gamma (30-50Hz) oscillations (CIgamma), as the modulation of gamma oscillations may be key to understanding mechanisms responsible for higher order cortical processing. Methods: Long interval cortical inhibition (LICI) is a TMS paradigm that is used to index CIgamma in the motor cortex and DLPFC. Preliminary Data: To date, we have studied 14 right-handed healthy subjects and 14 right-handed patients with a DSM-IV confirmed diagnosis of SCZ and found that patients with SCZ demonstrate significant deficits in CIgamma in the DLPFC compared to healthy subjects. These deficits were not present in the motor cortex. In this proposal we intend to extend our finding to a large sample of patients with SCZ and evaluate whether deficits in CIgamma are unique to SCZ or represent a more generalized pathophysiological mechanisms that occur in other neuropsychiatric disorders (i.e., BD) whose pathophysiology is also related to deficits in GABAergic circuitry of the DLPFC. If our hypotheses are correct, these findings will represent an important step in establishing the pathophysiology of SCZ and aid the development of novel treatment approaches.