TY - JOUR
T1 - Evidence for anomalous network connectivity during working memory encoding in Schizophrenia
T2 - An ICA based analysis
AU - Meda, Shashwath A.
AU - Stevens, Michael C.
AU - Folley, Bradley S.
AU - Calhoun, Vince D.
AU - Pearlson, Godfrey D.
PY - 2009/11/19
Y1 - 2009/11/19
N2 - Background: Numerous neuroimaging studies report abnormal regional brain activity during working memory performance in schizophrenia, but few have examined brain network integration as determined by "functional connectivity" analyses. Methodology/Principal Findings: We used independent component analysis (ICA) to identify and characterize dysfunctional spatiotemporal networks in schizophrenia engaged during the different stages (encoding and recognition) of a Sternberg working memory fMRI paradigm. 37 chronic schizophrenia and 54 healthy age/gender-matched participants performed a modified Sternberg Item Recognition fMRI task. Time series images preprocessed with SPM2 were analyzed using ICA. Schizophrenia patients showed relatively less engagement of several distinct "normal" encoding-related working memory networks compared to controls. These encoding networks comprised 1) left posterior parietal-left dorsal/ ventrolateral prefrontal cortex, cingulate, basal ganglia, 2) right posterior parietal, right dorsolateral prefrontal cortex and 3) default mode network. In addition, the left fronto-parietal network demonstrated a load-dependent functional response during encoding. Network engagement that differed between groups during recognition comprised the posterior cingulate, cuneus and hippocampus/parahippocampus. As expected, working memory task accuracy differed between groups (p<0.0001) and was associated with degree of network engagement. Functional connectivity within all three encoding-associated functional networks correlated significantly with task accuracy, which further underscores the relevance of abnormal network integration to well-described schizophrenia working memory impairment. No network was significantly associated with task accuracy during the recognition phase. Conclusions/Significance: This study extends the results of numerous previous schizophrenia studies that identified isolated dysfunctional brain regions by providing evidence of disrupted schizophrenia functional connectivity using ICA within widely-distributed neural networks engaged for working memory cognition.
AB - Background: Numerous neuroimaging studies report abnormal regional brain activity during working memory performance in schizophrenia, but few have examined brain network integration as determined by "functional connectivity" analyses. Methodology/Principal Findings: We used independent component analysis (ICA) to identify and characterize dysfunctional spatiotemporal networks in schizophrenia engaged during the different stages (encoding and recognition) of a Sternberg working memory fMRI paradigm. 37 chronic schizophrenia and 54 healthy age/gender-matched participants performed a modified Sternberg Item Recognition fMRI task. Time series images preprocessed with SPM2 were analyzed using ICA. Schizophrenia patients showed relatively less engagement of several distinct "normal" encoding-related working memory networks compared to controls. These encoding networks comprised 1) left posterior parietal-left dorsal/ ventrolateral prefrontal cortex, cingulate, basal ganglia, 2) right posterior parietal, right dorsolateral prefrontal cortex and 3) default mode network. In addition, the left fronto-parietal network demonstrated a load-dependent functional response during encoding. Network engagement that differed between groups during recognition comprised the posterior cingulate, cuneus and hippocampus/parahippocampus. As expected, working memory task accuracy differed between groups (p<0.0001) and was associated with degree of network engagement. Functional connectivity within all three encoding-associated functional networks correlated significantly with task accuracy, which further underscores the relevance of abnormal network integration to well-described schizophrenia working memory impairment. No network was significantly associated with task accuracy during the recognition phase. Conclusions/Significance: This study extends the results of numerous previous schizophrenia studies that identified isolated dysfunctional brain regions by providing evidence of disrupted schizophrenia functional connectivity using ICA within widely-distributed neural networks engaged for working memory cognition.
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U2 - 10.1371/journal.pone.0007911
DO - 10.1371/journal.pone.0007911
M3 - Article
C2 - 19936244
AN - SCOPUS:70949085574
SN - 1932-6203
VL - 4
JO - PloS one
JF - PloS one
IS - 11
M1 - e7911
ER -