Can tDCS accelerate and sustain the cognitive benefits of targeted cognitive training in schizophrenia

项目摘要/摘要 患有精神分裂症和相关障碍的患者经历与以下方面相关的认知障碍 功能结果不佳。因此，实现发展有效和可持续发展的长期目标至关重要。 机械知情治疗，以改善这一人群的认知。定向认知训练(TCT) 已经显示出改善精神分裂症患者认知的希望，但行为上的个体差异 神经靶点的参与限制了这种治疗的效率和可持续性。TCT增强前额叶 与精神分裂症患者认知改善相一致的振荡伽马。类似的增长 精神分裂症患者的前额叶伽马和认知功能已通过经颅直接成像证实。 电流刺激(Tdcs)。目前的研究将确定精神分裂症患者的认知增强 可以通过将增强神经振荡节律的tDCs与 利用前额颞部系统中的伽马振荡可塑性。使用一种实验药物 框架，这项研究将检验TCT-TDC将-通过增加的机制的中心假设 前额叶振荡伽马加速和维持认知训练的行为效应 TCT Sham。这项研究将追求3个具体目标：1)确定TCT tdcs是否更快地改进 认知与TCT Sham的比较；2)检验认知变化和TCT Sham变化之间的关系 TCT TDC后的前额叶振荡伽马；以及3)确定认知和功能方面的益处 TCT术后3个月随访持续TDCs。一个探索性的目标将检查交叉频率 Theta和Gamma振荡信号之间的耦合(Cfc)，并确定cfc是否发生变化 这与认知能力的提高相对应。为了实现这些目标，精神分裂症患者将被随机分配到 接受20小时的TCT-tdcs或TCT-Sham。参与者将接受认知测量的评估， 症状和功能在基线、10小时训练后、20小时训练后和3个月的随访中- 向上。为了测量振荡伽马的变化，参与者将在10点后在基线上进行任务/静息脑电 几个小时，20个小时后。这种方法是创新的，因为它调查了一种行为的综合影响 干预和神经调节，使用实验医学框架探测神经靶点 参与，并依赖于新的计算和神经分析。这项拟议的研究具有重要意义 因为它将建立前额叶伽马作为精神分裂症的治疗靶点，并为 可以在临床环境中部署的个性化治疗。概述的建议也将有助于 应聘者培训目标：1)TDC的管理；2)脑电的管理和分析；3)学习 计算精神病学方法。完成这些目标将使候选人成为一名 以神经可塑性为基础的严重精神疾病干预措施，并使它们在R01级资金方面具有竞争力。

Project Summary/Abstract Patients suffering from schizophrenia and related disorders experience cognitive disruptions associated with poor functional outcomes. It is therefore critical to achieve the long-term goal of developing efficacious and mechanistically informed treatments to improve cognition in this population. Targeted cognitive training (TCT) has shown promise for improving cognition in patients with schizophrenia, but individual differences in behavioral and neural target engagement limit the efficiency and sustainability of this treatment. TCT enhances prefrontal oscillatory gamma that coincides with improved cognition in patients with schizophrenia. Similar increases in prefrontal gamma and cognitive performance in schizophrenia have been demonstrated using transcranial direct current stimulation (tDCS). The current study will determine whether cognitive enhancement in schizophrenia can be achieved more efficiently by combining tDCS that enhances neural oscillatory rhythms with TCT that harnesses gamma oscillatory plasticity in prefronto-temporal systems. Using an experimental medicine framework, this study will test the central hypothesis that TCT+tDCS will—via the mechanism of increased prefrontal oscillatory gamma—accelerate and sustain the behavioral effects of cognitive training over TCT+Sham. This study will pursue 3 specific aims: 1) Determine whether TCT+tDCS more rapidly improves cognition compared to TCT+Sham; 2) examine the relationship between change in cognition and change in prefrontal oscillatory gamma following TCT+tDCS; and 3) determine whether cognitive and functional benefits following TCT+tDCS are sustained after a 3-month follow-up. An exploratory aim will examine cross-frequency coupling (CFC) between theta and gamma oscillatory signals and determine whether changes in CFC corresponds to improved cognition. To carry out these aims, patients with schizophrenia will be randomized to undergo either 20 hours of TCT+tDCS or TCT+Sham. Participants will be assessed on measures of cognition, symptoms, and functioning at baseline, after 10 hours of training, after 20 of training, and at a 3-month follow- up. To measure changes in oscillatory gamma, participants will undergo task/resting EEG at baseline, after 10 hours, and after 20 hours. The approach is innovative as it investigates the combined effects of a behavioral intervention and neuromodulation, uses an experimental medicine framework to probe neural target engagement, and relies on novel computational and neural analyses. The proposed research is significant because it will establish prefrontal gamma as a treatment target in schizophrenia, and lay the groundwork for personalized treatments that could be deployed in a clinical setting. The outlined proposal will also facilitate the candidate’s training goals: 1) Administration of tDCS; 2) Administration and analysis of EEG; 3) learning computational psychiatry methods. Completion of these goals will establish the candidate as an expert on neuroplasticity-based interventions for serious mental illness, and make them competitive for R01-level funding.