This project evaluates the efficacy of combined transcranial direct current stimulation (tDCS) and auditory neuroplasticity based remediation in Schizophrenia (Sz). Auditory dysfunction is a core feature of Sz and contributes to impairments in emotion recognition, verbal working memory, reading and social cognition. Prior studies of auditory remediation have demonstrated improvements in cognition, in combination with indices of improved neuroplasticity. tDCS is a newly developed brain stimulation modality that enhances local neuroplasticity across brain regions. To date it has been used primarily for stroke rehabilitation. This will be the first study of efficacy for augmentation of cognitive remediation n Sz. We have recently demonstrated that tDCS significantly enhances concomitant event-related potential (ERP) generation when applied during learning situations, permitting direct assay of target engagement. For the present study, ERP will be used to monitor target engagement and treatment efficacy. The project is responsive to the RFA (PAR 11-177) in the following ways: 1) This represents a biologically informed, novel and highly innovative approach to alter a functional treatment target (auditory dysfunction) which is relevant to functional outcome in Sz; 2) brain stimulation (tDCS) will be conducted using an IDE-approved device in combination with a previously validated behavioral intervention; and 3) proof-of-principle for the combination approach is required prior to initiation of an RCT. Assessments will assess impact of the intervention at multiple levels (behavioral, neurochemical, neurophysiological). The R21 phase is necessary to pilot the interventions. The R33 phase is designed to pilot the interventions and demonstrate feasibility of recruitment, retention, assessment procedures and safety, and to obtain an initial assessment of effect-size for use in planning a future, definitive trial. No inferential statistics are proposed. Although the present study focuses on persistent auditory deficits in chronic Sz patients, investigation of tDCS efficacy in enhancement of neuroplasticity will be relevant across a range of disorders and neurocognitive constructs.
Cognitive dysfunction is a core feature of schizophrenia and a primary predictor of poor long term outcome, such that deficits in basic auditory function contribute to impairments in higher order functions such as auditory emotion recognition, verbal working memory, and social function. Transcranial direct current stimulation (tDCS) is a recently developed brain stimulation modality that increases the ability of the brain to learn new information and respond to training exercises ('plasticity'). This study will assess the ability of tDCS to enhance the effectiveness of auditory remediation in schizophrenia, as well as the ability of auditory retraining to improve overall aspects of cognitive function in schizophrenia.
