Abstract
BackgroundNumerous 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 FindingsWe 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/SignificanceThis 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.
Highlights
Working memory refers to the temporary retention of information to solve problems or guide behavior
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 independent component analysis (ICA) within widely-distributed neural networks engaged for working memory cognition
Neuroimaging studies [1], direct intracellular recordings [2], and lesion studies support neurobiological models that [1,3] emphasize the importance of activity in prefrontal cortex and parietal brain regions [4] within a complex architecture of different anatomical regions associated with temporally distinct phases of working memory
Summary
Working memory refers to the temporary retention of information to solve problems or guide behavior. Our previous results [10] suggest that working memory deficits are prominent during encoding, especially in the dorso- and ventrolateral PFC, posterior parietal regions, cingulate and basal ganglia [11,12,13]. Several brain regions including the dorsolateral PFC, visual association, cingulate and hippocampus that have been shown to be anomalous in schizophrenia during recognition/retrieval often overlap with stimulus encoding [15,17] This might suggest that despite conceptual differences between encoding and recognition, the same networks/regions that behave abnormally during encoding in schizophrenia probably are affected during recognition. 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
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