The purpose of this study is to perform longitudinal high-resolution 7T MRI in participants with first-episode psychosis (FEP) enrolled in our ongoing randomized controlled clinical trial (RCT) of cognitive training. Despite the recent explosion in treatment programs for FEP, many patients still do not experience optimal outcomes, with impaired cognition in particular being a poor prognostic indicator. Indeed, we now know that the early phases of psychotic illness are characterized by progressive neural system dysfunction, including accelerated frontal and temporal gray matter loss, as well as white matter changes and neuroinflammation. In this innovative high-risk project, we seek to determine whether a 12-week course of intensive cognitive training of auditory processing in young FEP patients delivered remotely as a stand-alone treatment is neuroprotective against neural tissue loss in auditory cortex (superior temporal gyrus, STG), and possibly in other cortical regions. We will also investigate the effects of training on white matter integrity. Our prior work has shown that intensive cognitive training of auditory processing drives significant cognitive improvement in FEP patients; our unpublished data indicate that improved positive symptoms are seen 6 months later. In studies with persistently ill patients, we have demonstrated significant functional plasticity in prefrontal and auditory cortex after this form of training. Here, we integrate our findings with emerging data from basic science and ask a high-risk/ high-gain research question: Can a short course of intensive cognitive training not only improve cognition, but prevent accelerated gray matter loss in left STG, and possibly in other regions, such as prefrontal cortex? Additionally, does it mitigate white matter changes? Finally, we will explore its possible effects on a putative marker of neuroinflammation. We will answer these questions by acquiring state-of-the-art high-resolution 7T MRI longitudinal imaging data in a subset of young FEP patients who are enrolled in our current NIMH-funded RCT of cognitive training in community mental health centers. The goal of the original RCT is to investigate the clinical and cognitive effects of 30 hours of cognitive training delivered via iPads, as compared to treatment-as-usual. This R21 Exploratory/Developmental grant will permit us to leverage our unique subject population and research infrastructure in order to obtain sophisticated imaging data at two time points 12 months apart in a highly informative preliminary sample of young FEP individuals. The data we obtain will contribute to our understanding of how to develop scalable, optimally effective personalized treatments that pre-empt cognitive and neural system deterioration and promote recovery in the early phases of psychotic illness.
The purpose of this study is to perform longitudinal high-resolution 7T MRI in participants with first-episode psychosis (FEP) enrolled in our ongoing randomized controlled clinical trial (RCT) of cognitive training. We seek to determine whether a 12-week course of intensive cognitive training of auditory processing in young FEP patients delivered remotely as a stand-alone treatment is neuroprotective against neural tissue loss in auditory cortex (superior temporal gyrus, STG), and possibly in other cortical regions. We will also investigate the effects of training on white matter integrity in the brain.
