The goal of our research program is to identify highly specific, low-level """"""""building blocks"""""""" of cognition that are impaired in schizophrenia (SZ) and are linked both with the underlying neurobiology of the illness and with broad measures of higher cognitive function. Such cognitive processes need to be (a) simple enough to be understood neurobiologically;(b) substantially impaired in SZ;and (c) tightly linked to performance on complex cognitive tasks. We propose that the ability to simultaneously represent multiple pieces of information (e.g., multiple objects, multiple locations)-which underlies working memory capacity and plays a key role in many cognitive tasks-meets these criteria. We have developed both behavioral and electrophysiological methods for measuring the ability to represent multiple objects or locations, and have shown that this ability is impaired in SZ and is strongly correlated with performance on complex tests that predict functional outcome in SZ (MATRICS and WASI). Moreover, computational neuroscience research has shown that local circuit abnormalities in SZ may lead to exaggerated winner-take-all processing that would interfere with the ability to maintain multiple simultaneous representations. Thus, by understanding why SZ patients exhibit a deficit in this low-level cognitive building block, we will be able to build a bridge from local circuit abnormalities in SZ to the impairments in broad cognitive functioning that influence functional outcome.
Our Aims are designed to advance our understanding of the origins of reduced working memory capacity in SZ (Aim 1);test the hypothesis that exaggerated winner take all processing impacts attention across a range of tasks(Aim 2);test the hypothesis that the ability of maintain multiple representations can be linked to local circuit abnormalities may be indexed by gamma-band EEG oscillations and lateral sensory interactions(Aim 3), to develop computational models of local circuit abnormalities that can account for observed performance in patients(Aim 4) and to examine the same processes in a group of non-psychotic first degree relatives to determine if the abnormality observed in patients may represent a genetic risk factor for the illness( Aim 5). One important feature of our hypothesis is that it leads to the predictionof either fully normal or supranormal performance among patients in task environments where an excessively narrow focus of attentional selection should benefit performance, thereby potentially avoiding the interpretive problem posed by the generalized cognitive deficit that patients often demonstrate. Relevance: The working memory deficits in SZ are substantially related to impairments in complex cognitive operations that limit daily functioning. This research program is designed to increase understanding of the specific processes that are involved in the genesis of these deficits, providing the field with a computational framework to guide basic research, an important biomarker for treatment development as well as potentially valuable clinical assessment tools.

Public Health Relevance

Most patients with schizophrenia suffer from significant disability for most of their adult lives. Impairments in attention and working memory have been shown to play an important role in determining the extent of disability that patients experience. This research program is designed to increase understanding of the specific processes that are involved in these important areas of cognitive impairment in order to provide more specific targets for treatment development research.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
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Shoham, Varda
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University of Maryland Baltimore
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United States
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Kappenman, Emily S; Luck, Steven J (2016) Best Practices for Event-Related Potential Research in Clinical Populations. Biol Psychiatry Cogn Neurosci Neuroimaging 1:110-115
Erickson, Molly A; Ruffle, Abigail; Gold, James M (2016) A Meta-Analysis of Mismatch Negativity in Schizophrenia: From Clinical Risk to Disease Specificity and Progression. Biol Psychiatry 79:980-7
Leonard, Carly J; Balestreri, Angela; Luck, Steven J (2015) Interactions between space-based and feature-based attention. J Exp Psychol Hum Percept Perform 41:11-6
Erickson, Molly A; Hahn, Britta; Leonard, Carly J et al. (2015) Impaired working memory capacity is not caused by failures of selective attention in schizophrenia. Schizophr Bull 41:366-73
Miller, Claire E; Shapiro, Kimron L; Luck, Steven J (2015) Electrophysiological measurement of the effect of inter-stimulus competition on early cortical stages of human vision. Neuroimage 105:229-37
Daie, Kayvon; Goldman, Mark S; Aksay, Emre R F (2015) Spatial patterns of persistent neural activity vary with the behavioral context of short-term memory. Neuron 85:847-60
Kiwanuka, Jacqueline N; Strauss, Gregory P; McMahon, Robert P et al. (2014) Psychological predictors of functional outcome in people with schizophrenia. Schizophr Res 157:299-304
Erickson, Molly; Hahn, Britta; Leonard, Carly et al. (2014) Enhanced vulnerability to distraction does not account for working memory capacity reduction in people with schizophrenia. Schizophr Res Cogn 1:149-154
Gray, Bradley E; Hahn, Britta; Robinson, Benjamin et al. (2014) Relationships between divided attention and working memory impairment in people with schizophrenia. Schizophr Bull 40:1462-71
Luck, Steven J; McClenon, Clara; Beck, Valerie M et al. (2014) Hyperfocusing in schizophrenia: Evidence from interactions between working memory and eye movements. J Abnorm Psychol 123:783-95

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