tDCS Augmentation of Cognitive Remediation in Schizophrenia

描述（由申请人提供）：本项目评估了经颅直流电刺激（tDCS）和基于听觉神经可塑性的治疗方法在精神分裂症（Sz）中的疗效。听觉功能障碍是Sz的核心特征，并导致情感识别、言语工作记忆、阅读和社会认知的障碍。先前的听觉补救研究已经证明了认知的改善，以及改善神经可塑性的指标。tDCS是一种新开发的脑刺激模式，可增强大脑区域的局部神经可塑性。迄今为止，它主要用于中风康复。这将是第一项关于认知修复增强疗效的研究。我们最近已经证明，tDCS显着增强伴随事件相关电位（ERP）的产生时，在学习的情况下，允许直接测定目标的参与。对于本研究，ERP将用于监测靶点参与和治疗疗效。该项目响应RFA（PAR 11-177）在以下方面：1）这代表了一种生物学上知情的，新颖的和高度创新的方法，以改变功能性治疗目标（听觉功能障碍），与Sz的功能结局相关; 2）将使用IDE批准的器械结合先前确认的行为干预进行脑刺激（tDCS）;和3）在开始RCT之前，需要对联合方法进行原理证明。评估将在多个层面（行为、神经化学、神经生理）评估干预的影响。R21阶段是试点干预措施所必需的。R33阶段旨在试点干预措施，并证明招募、保留、评估程序和安全性的可行性，并获得效应量的初步评估，用于规划未来的最终试验。没有提出推论统计。虽然本研究的重点是慢性Sz患者的持续性听觉缺陷，在增强神经可塑性的tDCS疗效的调查将是相关的一系列疾病和神经认知结构。

DESCRIPTION (provided by applicant): 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.