Restoring oscillations underlying adaptive control in schizophrenia with direct current

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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