tDCS Augmentation of Cognitive Remediation in Schizophrenia

描述(申请人提供)：本项目评估联合经颅直流电刺激(Tdcs)和基于听觉神经可塑性的治疗精神分裂症(Sz)的疗效。听觉功能障碍是Sz的一个核心特征，并导致情绪识别、言语工作记忆、阅读和社会认知方面的障碍。以前的听觉矫正研究已经证明，结合神经可塑性改善的指标，认知能力有所改善。TDCS是一种新开发的脑刺激方式，可以增强大脑各区域的局部神经可塑性。到目前为止，它主要用于中风的康复。这将是第一次关于增强认知补救的有效性的研究。我们最近证明，当在学习情景中应用tDCs时，显著增强伴随事件相关电位(ERP)的产生，从而允许直接分析目标参与。在本研究中，事件相关电位将被用来监测目标参与和治疗效果。该项目以以下方式响应RFA(PAR 11-177)：1)这代表了一种从生物学上了解情况的、新颖的和高度创新的方法，以改变与Sz的功能结果相关的功能治疗目标(听力障碍)；2)将使用IDE批准的设备结合先前验证的行为干预措施进行脑刺激(TDC)；以及3)在启动随机对照试验之前，需要对组合方法进行原则证明。评估将在多个层面(行为、神经化学、神经生理学)评估干预的影响。R21阶段是试点干预措施的必要阶段。R33阶段旨在对干预措施进行试点，并论证招募、保留、评估程序和安全性的可行性，并获得效果大小的初步评估，以用于规划未来的最终试验。没有提出任何推论统计数据。虽然目前的研究集中在慢性Sz患者的持续性听力障碍上，但tdcs在增强神经可塑性方面的有效性的研究将涉及一系列障碍和神经认知结构。

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.