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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH065034-12
Application #
8594260
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Kozak, Michael J
Project Start
2001-09-27
Project End
2018-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
12
Fiscal Year
2014
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Psychiatry
Type
Schools of Medicine
DUNS #
City
Baltimore
State
MD
Country
United States
Zip Code
21201
Luck, Steven J; Gaspelin, Nicholas (2017) How to get statistically significant effects in any ERP experiment (and why you shouldn't). Psychophysiology 54:146-157
Kreither, Johanna; Lopez-Calderon, Javier; Leonard, Carly J et al. (2017) Electrophysiological Evidence for Hyperfocusing of Spatial Attention in Schizophrenia. J Neurosci 37:3813-3823
Erickson, Molly A; Albrecht, Matthew A; Robinson, Benjamin et al. (2017) Impaired suppression of delay-period alpha and beta is associated with impaired working memory in schizophrenia. Biol Psychiatry Cogn Neurosci Neuroimaging 2:272-279
Beck, Valerie M; Luck, Steven J; Hollingworth, Andrew (2017) Whatever You Do, Don't Look at the . . .: Evaluating Guidance by an Exclusionary Attentional Template. J Exp Psychol Hum Percept Perform :
Erickson, Molly A; Albrecht, Matthew; Ruffle, Abigail et al. (2017) No association between symptom severity and MMN impairment in schizophrenia: A meta-analytic approach. Schizophr Res Cogn 9:13-17
Gaspelin, Nicholas; Leonard, Carly J; Luck, Steven J (2017) Suppression of overt attentional capture by salient-but-irrelevant color singletons. Atten Percept Psychophys 79:45-62
Leonard, Carly J; Robinson, Benjamin M; Hahn, Britta et al. (2017) Altered spatial profile of distraction in people with schizophrenia. J Abnorm Psychol 126:1077-1086
Sawaki, Risa; Kreither, Johanna; Leonard, Carly J et al. (2017) Hyperfocusing of attention on goal-related information in schizophrenia: Evidence from electrophysiology. J Abnorm Psychol 126:106-116
Bengson, Jesse J; Luck, Steven J (2016) Effects of strategy on visual working memory capacity. Psychon Bull Rev 23:265-70
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

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