Restoring oscillations underlying adaptive control in schizophrenia with direct current

项目总结 精神分裂症是一种严重的、使人衰弱的疾病，全球约有510亿人受到影响， 美国每年超过600亿美元(所罗门等人，2013年)。尽管更壮观的是 精神分裂症的精神症状(如幻觉)，是认知障碍在很大程度上推动了 疾病造成的不良后果，例如，由于患者不能 有效治疗这些认知障碍的药物(Gold和Weinberger，1995；Green，1996； Elvevag和Goldberg，2000)。自适应控制的失败是认知障碍的一个标志 精神分裂症。自适应控制允许健康的个人遵守规则，并超越令人信服的竞争 回应。自适应控制的缺陷会导致错误和在负值之后无法改变 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年；van Driel等人，2012年；Anguera等人，2013；Narayanan等人，2013；Cavanagh和Frank，2014)，以及 振荡动力学的某些模式可能有助于理解认知障碍 精神分裂症(福特和马特隆，2008年；乌尔哈斯和辛格，2010年；莱什等人，2011年)。在这个项目中，我们 建议使用一种因果神经科学技术，非侵入性脑刺激，结合 测量脑电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 鼓励和表明我们可以有选择地操纵振荡活动的阶段和原因 精神分裂症患者在适应性控制方面的改善。我们研究的目标是 使用基础神经科学的工具和见解来更深入地了解认知障碍 精神分裂症，并在非药物治疗方面取得具体的翻译进展 提高精神分裂症患者的认知功能。 第1条

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