tDCS Augmentation of Cognitive Remediation in Schizophrenia

描述（由申请人提供）：本项目评估经颅直流电刺激（tDCS）联合听觉神经可塑性治疗精神分裂症（Sz）的疗效。听觉障碍是Sz的核心特征，导致情绪识别、言语工作记忆、阅读和社会认知障碍。先前的听觉修复研究已经证明了认知的改善，并结合了改善神经可塑性的指标。tDCS是一种新发展的脑刺激方式，可以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。这将是第一次对Sz认知修复增强效果的研究。我们最近证明，当在学习情境中应用tDCS时，tDCS显著增强了伴随事件相关电位（ERP）的产生，从而可以直接分析目标参与。在本研究中，ERP将用于监测目标参与和治疗效果。该项目在以下方面响应了RFA (PAR 11-177): 1)这代表了一种生物学上的，新颖的，高度创新的方法来改变与Sz功能结果相关的功能治疗目标（听觉功能障碍）；2)脑刺激（tDCS）将使用ide批准的设备与先前验证的行为干预相结合进行；3)在RCT开始之前，需要对组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阶段对干预措施进行试点是必要的。R33阶段旨在对干预措施进行试点，并证明招募、保留、评估程序和安全性的可行性，并获得对效应大小的初步评估，以用于规划未来的确定试验。没有提出推论统计。虽然目前的研究重点是慢性Sz患者的持续性听觉缺陷，但tDCS在增强神经可塑性方面的效果的研究将与一系列疾病和神经认知结构相关。

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.