Grant: CIHR Fellowship

With the advent of more advanced diffusion-weighted magnetic resonance imaging (MRI) it is now possible to estimate more complex models of brain tissue microstructure. Neurite-orientation dispersion and density imaging (NODDI) is a recently proposed model that utilizes these advanced diffusion MRI and extends application of diffusion imaging from white matter to the gray matter tissue microstructure. NODDI indexes neuritic (axonal and dendritic) density and dispersion of neurites in the brain tissue. We have just demonstrated that gray matter microstructural indices predict functional brain activation and cognitive performance in healthy individuals. Recent studies support altered dendritic organization and morphology in postmortem brain of individuals with schizophrenia. In particular, marked dendritic deficits have been reported in dorsolateral prefrontal cortex (DLPFC) of schizophrenia patients, a region that is essential for working memory (WM, a system that actively holds multiple pieces of transitory information in the mind, where they can be manipulated). WM impairment is a core feature of schizophrenia, and predicts disability and functional outcome. However, there is presently no satisfactory treatment for WM deficits in schizophrenia. We are currently funded to conduct a larger trial to confirm the efficacy of repetitive transcranial magnetic stimulation (rTMS) treatment for WM deficits in patients with schizophrenia, following a recently published pilot study, demonstrating that rTMS applied bilaterally to DLPFC improves WM performance in patients with schizophrenia. We have recently received funding to conduct advanced diffusion-weighted MRI immediately before and after in a subset of the study participants. Our study will be the first to determine the mechanism of treatment effects of rTMS gray matter neuritic architecture, in regions important for WM performance. Moreover, our study is designed to identify biomarkers of treatment response to rTMS.