The goal of this 5-year project is to discover the specific mechanisms that underlie the attention and working memory deficits that are central features of schizophrenia. These impairments contribute to the functional disability of the disorder, are likely related to genetic risk for the illness, and are largely unaffected by antipsychotic treatment. This translational research program involves collaboration between a clinical research laboratory and a team of basic cognitive scientists with expertise in attention and working memory. Our approach is to use the concepts and methods of contemporary cognitive neuroscience to subdivide the constructs of attention and working memory into individual subcomponents so that specific, falsifiable hypotheses can be constructed. The proposal includes 4 interrelated specific aims.
In Aim 1, we examine the hypothesis that the illness compromises the ability to use goals to control attention, leading to deficits in perception, working memory and response selection.
In Aim 2, we examine the interactions of attention and working memory and examine how impairments in each impact the other system.
In Aim 3, we test the hypothesis that the illness compromises the ability to rapidly form precise working memory representations, thereby degrading behavioral performance.
In Aim 4, we address individual differences in working memory and attentional performance among patients in order to determine whether patients vary along a single severity of impairment continuum or instead, differ in kind. Behavioral and neurophysiological experimental paradigms were chosen for their ability to isolate specific attention and working memory processes, yielding large, distinctive patterns of results in normal subjects, thereby increasing the opportunity to observe specific, interpretable deficits in SC. These data will provide new insight into the cognitive/neural systems that are impaired in SC, potentially clarifying the nature of the phenotype, and provide new targets for pharmacological treatment.

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH065034-10
Application #
8240083
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Shoham, Varda
Project Start
2001-09-27
Project End
2013-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
10
Fiscal Year
2012
Total Cost
$666,846
Indirect Cost
$156,861
Name
University of Maryland Baltimore
Department
Psychiatry
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201
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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