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

Public Health Relevance

Schizophrenia is the most disabling of all common brain disorders, exacting a large toll on those afflicted and large public health costs. This research program will improve our understanding how abnormal oscillatory brain activity gives rise to cognitive problems in schizophrenia. The brain stimulation methods developed during this research may also translate into a non-pharmacological intervention for improving cognitive abilities in schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH110378-04
Application #
9764494
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mcmullen, David
Project Start
2016-09-07
Project End
2021-08-31
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
965717143
City
Nashville
State
TN
Country
United States
Zip Code
37203
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Reinhart, Robert M G; Cosman, Josh D; Fukuda, Keisuke et al. (2017) Using transcranial direct-current stimulation (tDCS) to understand cognitive processing. Atten Percept Psychophys 79:3-23