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

Schizophrenia (SCZ) is a serious mental disorder that affects about 1% of the Canadian population and incurs enormous personal and national health care costs. SCZ is characterized by positive symptoms (i.e., delusions and hallucinations) and negative symptoms (i.e., amotivation and apathy). While current medications are effective against positive symptoms, treatments for negative symptoms are lacking even though these symptoms account for the greatest proportion of functional impairment in SCZ. Given the desperate need for an effective treatment against negative symptoms, deep brain stimulation (DBS) represents a novel therapeutic approach that can target pathological regions of the brain though focal stimulation. DBS is highly effective in treating late stage Parkinson's disease and has been shown to be safe and effective for treatment-resistant depression. Given the neurosurgical and psychiatric expertise at the University of Toronto, a phase I, pilot trial of DBS for SCZ patients with treatment-resistant negative symptoms has recently been approved. While the main purpose of this study is to evaluate the efficacy of DBS for negative symptoms, better understanding of the mechanisms through which the treatment works will lead to more effective and personalized treatments in the future. Our group has recently reported that SCZ patients demonstrate excessive high frequency (30-50 Hz) brain activity during cognitive tasks. We also have data from severe depression patients suggesting that DBS selectively suppresses pathological high frequency activity and that such suppression was related to symptom response. Building upon our existing knowledge, we aim to evaluate the efficacy of DBS treatment for negative symptoms and whether or not excessive high frequency activity is suppressed by the treatment. Completion of this pilot study may lead to the first bona fide treatment for negative symptoms and shed light on the mechanisms and brain structures mediating them.