Grant: CIHR Fellowship

Working memory deficits are a significant cognitive impairment in schizophrenia, and predict disability and functional outcome. There are currently no satisfactory treatments for working memory deficits in schizophrenia. Results from our just published randomized sham-controlled pilot study suggest that four weeks of repetitive transcranial magnetic stimulation applied bilaterally to dorsolateral prefrontal cortex significantly improves working memory performance in patients with schizophrenia. We are now funded to conduct a larger, randomized, double-blind, sham-controlled study to confirm the efficacy of transcranial magnetic stimulation treatment for working memory deficits in patients with schizophrenia. This clinical trial provides the opportunity to leverage our controlled study design to improve our understanding of the biological mechanisms of transcranial magnetic stimulation treatment. This project proposes to conduct high-resolution magnetic resonance imaging immediately before the treatment trial, and immediately after the completion of treatment to comprehensively assess how transcranial magnetic stimulation affects brain structures that are important for working memory performance. Using advanced neuroimaging approaches, we will assess changes in: a) dorsolateral prefrontal cortex gray matter morphology and b) microstructure of white matter tracts connecting to dorsolateral prefrontal cortex using diffusion tensor imaging. Our sham-controlled study design and our sophisticated neuroimaging will determine the effects of transcranial magnetic stimulation treatment on brain structure, and provide us with knowledge regarding how this treatment affects brain structures important for working memory performance. Furthermore, our study design provides us with the opportunity to discover mechanisms of this treatment that improve working memory performance, and identify biomarkers of treatment response.