Diverse evidence suggests that deficits in working memory and long-term memory in patients with schizophrenia reflect deficits in at least two putatively distinct cognitive domains. Furthermore, deficits in working memory have typically been linked to an underlying disturbance in prefrontal cortex function, while deficits in long-term memory (i.e., encoding and/or retrieval) have typically been associated with medial temporal/hippocampal deficits. The investigator proposes to test an alternative hypothesis that deficits in both working memory and long-term memory in patients with schizophrenia reflect a single underlying disturbance in prefrontal cortex function. This hypothesis would be tested by a neuroactivation analysis of cognitive tasks using functional magnetic resonance imaging (fMRI) techniques and an event-related neuroimaging design. The investigator proposes to define the distributed patterns of cortical function and dysfunction associated with the performance of both working memory and long-term memory tasks during the same imaging session and the same patients with schizophrenia and in matched normal comparison subjects. This design is novel in that it represents the first functional neuroimaging study in schizophrenia attempting to simultaneously assess multiple cognitive domains and thus could impact strongly the current understanding of the precise nature and mechanisms underlying cognitive impairments associated with schizophrenia. A related specific aim of the proposal would compare the task-related lateralized brain activation for working memory and long-term memory tasks using verbal versus non-verbal (non-nameable faces) stimuli in patients with schizophrenia and healthy comparison subjects. Cognitive impairments are increasingly recognized as core features of schizophrenia. Demonstrating that deficits in both working memory and long-term memory in schizophrenia stem from a single underlying disturbance in prefrontal cortex function would both simplify and clarify the conceptualization of cognitive dysfunction in schizophrenia. These studies could also provide the groundwork for the development of powerful new behavioral, as well as neuroimaging, probes of cognitive and neurobiological function in schizophrenia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Small Research Grants (R03)
Project #
5R03MH060887-02
Application #
6330348
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Project Start
1999-12-01
Project End
2002-11-30
Budget Start
2000-12-01
Budget End
2002-11-30
Support Year
2
Fiscal Year
2001
Total Cost
$73,635
Indirect Cost
Name
Washington University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Delawalla, Zainab; Csernansky, John G; Barch, Deanna M (2008) Prefrontal cortex function in nonpsychotic siblings of individuals with schizophrenia. Biol Psychiatry 63:490-7
Barch, Deanna M; Smith, Ed (2008) The cognitive neuroscience of working memory: relevance to CNTRICS and schizophrenia. Biol Psychiatry 64:11-7
Bonner-Jackson, Aaron; Csernansky, John G; Barch, Deanna M (2007) Levels-of-processing effects in first-degree relatives of individuals with schizophrenia. Biol Psychiatry 61:1141-7
Barch, Deanna M; Csernansky, John G (2007) Abnormal parietal cortex activation during working memory in schizophrenia: verbal phonological coding disturbances versus domain-general executive dysfunction. Am J Psychiatry 164:1090-8
Barch, D M (2006) What can research on schizophrenia tell us about the cognitive neuroscience of working memory? Neuroscience 139:73-84
Brahmbhatt, Shefali B; Haut, Kristen; Csernansky, John G et al. (2006) Neural correlates of verbal and nonverbal working memory deficits in individuals with schizophrenia and their high-risk siblings. Schizophr Res 87:191-204
Andrews, Jessica; Wang, Lei; Csernansky, John G et al. (2006) Abnormalities of thalamic activation and cognition in schizophrenia. Am J Psychiatry 163:463-9
Delawalla, Zainab; Barch, Deanna M; Fisher Eastep, Jennifer L et al. (2006) Factors mediating cognitive deficits and psychopathology among siblings of individuals with schizophrenia. Schizophr Bull 32:525-37
Haut, Kristen M; Barch, Deanna M (2006) Sex influences on material-sensitive functional lateralization in working and episodic memory: men and women are not all that different. Neuroimage 32:411-22
Bonner-Jackson, Aaron; Haut, Kristen; Csernansky, John G et al. (2005) The influence of encoding strategy on episodic memory and cortical activity in schizophrenia. Biol Psychiatry 58:47-55

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