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

项目概要/摘要 患有精神分裂症和相关病症的患者经历与以下相关的认知障碍： 功能性结局差。因此，至关重要的是要实现发展有效和 机械地告知治疗以改善该人群的认知。目标认知训练（TCT） 已经显示出改善精神分裂症患者认知能力的希望，但在行为上的个体差异， 和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 振荡伽马与精神分裂症患者认知能力的改善相一致。的类似增加 精神分裂症患者的前额叶伽马和认知表现已经通过使用经颅直接 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是否 可以通过将增强神经振荡节律的tDCS与 利用前额颞系统中的伽马振荡可塑性。使用一种实验性药物 在此框架下，本研究将检验中心假设，即TCT+tDCS将通过增加 前额叶振荡γ-加速和维持认知训练的行为效应， TCT+假手术本研究将追求3个具体目标：1）确定TCT+tDCS是否更快地改善 与TCT+Sham相比的认知; 2）检查认知变化与认知变化之间的关系。 TCT+tDCS后的前额振荡伽马;以及3）确定认知和功能益处是否 在TCT+tDCS之后，在3个月的随访之后，一个探索性的目标将检查交叉频率 耦合（CFC）之间的θ和γ振荡信号，并确定是否在CFC的变化 对应于认知能力的提高。为了实现这些目标，精神分裂症患者将被随机分配至 接受20小时TCT+tDCS或TCT+假手术。参与者将被评估的认知措施， 在基线、10小时训练后、20小时训练后和3个月随访时的症状和功能- 起来为了测量振荡伽马的变化，参与者将在基线时、10分钟后、15分钟后和15分钟后接受任务/静息EEG。 小时，20小时后。该方法是创新的，因为它调查了行为的综合影响， 干预和神经调节，使用实验医学框架来探测神经靶点 参与，并依赖于新的计算和神经分析。所提出的研究是有意义的 因为它将建立前额叶伽马作为精神分裂症的治疗目标，并为 个性化的治疗，可以部署在临床环境中。概述的提案还将促进 候选人的培训目标：1）tDCS管理; 2）EEG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以下方面的专家： 神经可塑性为基础的干预严重精神疾病，并使他们的竞争力R 01级资金。

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.