Restoring oscillations underlying adaptive control in schizophrenia with direct current

项目摘要 精神分裂症是一种严重的、使人衰弱的疾病，影响着全世界约510亿人， 美国每年超过600亿美元（Salomon等人，2013年）。尽管有更壮观的 精神分裂症的精神病症状（例如，幻觉），这是认知障碍，在很大程度上推动了 疾病带来的不良后果，例如由于患者无法工作， 有效治疗这些认知障碍的药物（Gold和Weinberger，1995;绿色，1996; Elvevag和Goldberg，2000年）。适应性控制失败是认知障碍的标志 精神分裂症自适应控制允许健康的人遵守规则并超越强制性竞争 应答自适应控制的缺陷导致错误和无法改变以下负面影响 反馈在系统神经科学中，越来越多的证据表明，自适应控制过程 由健康大脑中的振荡活动支持（Luu等人，2003; Wang等人，2005; Cavanagh等人， 2009;货车德里尔等人，2012; Anguera等人，2013; Narayanan等人，2013; Cavanagh和Frank，2014），以及 某些振荡动力学模式可能有助于理解认知障碍， 精神分裂症（福特和Mathalon，2008; Uhlhaas和Singer，2010; Lesh等，2011年）。本课题 建议使用因果神经科学技术，非侵入性脑电刺激，结合 测量脑电图振荡，以确定是否修改某些振荡 精神分裂症患者的节律可以改善认知能力。我们的初步数据显示 令人鼓舞，并表明我们可以选择性地操纵振荡活动的相位， 精神分裂症患者表现出的适应性控制的改善。我们研究的目标是 使用基础神经科学的工具和见解，以更深入地了解认知障碍 在精神分裂症，并取得具体的转化进展，以非药物治疗， 增强精神分裂症患者的认知功能 1

PROJECT SUMMARY Schizophrenia is a severe and debilitating disorder that affects about 51 billion people worldwide, and costs more than $60 billion annually in United States (Salomon and al., 2013). Despite the more spectacular psychotic symptoms of schizophrenia (e.g., hallucinations), it is the cognitive impairments that largely drive the poor outcomes from the illness, such as preventing patients from keeping jobs, due to the inability of medications to effectively treat these cognitive impairments (Gold and Weinberger, 1995; Green, 1996; Elvevag and Goldberg, 2000). Failures of adaptive control are a hallmark of the cognitive impairments in schizophrenia. Adaptive control allows healthy individuals to follow rules and to override compelling competing responses. Impairments of adaptive control result in errors and an inability to change following negative feedback. In systems neuroscience, a growing body of evidence demonstrates that adaptive control processes are supported by oscillatory activity in the healthy brain (Luu et al., 2003; Wang et al., 2005; Cavanagh et al., 2009; van Driel et al., 2012; Anguera et al., 2013; Narayanan et al., 2013; Cavanagh and Frank, 2014), and that certain patterns of oscillatory dynamics might be useful for understanding the cognitive impairments in schizophrenia (Ford and Mathalon, 2008; Uhlhaas and Singer, 2010; Lesh et al., 2011). In this project, we propose to use a causal neuroscientific technique, noninvasive electrical brain stimulation, combined with measurements of electroencephalographic oscillations to determine whether modifying certain oscillatory rhythms in patients with schizophrenia can improve cognitive abilities. Our preliminary data are highly encouraging and indicate that we can selectively manipulate the phase of oscillatory activity and cause improvements in the adaptive control exhibited by patients with schizophrenia. The goals of our research are to use the tools and insights from basic neuroscience to gain a deeper understanding the cognitive impairments in schizophrenia, and achieve concrete translational progress toward a non-pharmacological therapy for boosting cognitive function in schizophrenia.  1