Maria Jalbrzikowski1, Vishnu P Murty2, Patricia L Stan3, Jusmita Saifullan4, Daniel Simmonds5, William Foran2, Beatriz Luna6. 1. University of Pittsburgh, Department of Psychiatry, Pittsburgh, PA, United States. Electronic address: jalbrzikowskime@upmc.edu. 2. University of Pittsburgh, Department of Psychiatry, Pittsburgh, PA, United States. 3. University of Pittsburgh, Center for Neuroscience, Pittsburgh, PA, United States; Center for the Neural Basis of Cognition, Pittsburgh, PA, United States. 4. University of Pittsburgh, Department of Neuroscience, Pittsburgh, PA, United States. 5. Children's Hospital of Pittsburgh of UPMC, Department of Radiology, Pittsburgh, PA, United States. 6. University of Pittsburgh, Department of Psychiatry, Pittsburgh, PA, United States; University of Pittsburgh, Department of Psychology, Pittsburgh, PA, United States; University of Pittsburgh, Department of Pediatrics, Pittsburgh, PA, United States.
Abstract
INTRODUCTION: We probed the neural basis of working memory in individuals with first episode of psychosis (FEP) and assessed how these neural abnormalities are associated with behavioral performance and/or core to psychosis pathophysiology. METHODS: FEP (N=35) and matched controls (N=25) performed a visuospatial working memory task during fMRI acquisition. We isolated neural activity during the maintenance period and examined neural activity within regions typically engaged during a working memory task. Functional connectivity estimates were derived using psychophysiological interaction analysis. We examined correlations between brain function and behavioral performance and clinical symptomatology. RESULTS: FEP had reduced accuracy and slower reaction times compared to controls (p<0.05, q<0.05). During the maintenance period, FEP exhibited reduced right dorsolateral prefrontal cortex (DLPFC) activation compared to controls (p=0.007, q=0.01), even when behavioral performance was matched between groups (p=0.01, q=0.03). Unlike controls, FEP failed to show increased dorsal anterior cingulate (dACC) activity with increased load level (p=0.02, q=0.06). Compared to controls, FEP showed increased negative DLPFC-dACC coupling during the maintenance period (p=0.05). Increased DLPFC activation was significantly associated with greater negative symptoms (p<0.005, q=0.02), while greater dACC activation was significantly associated with better performance in FEP (p<0.05, q<0.17). CONCLUSION: WM impairment in psychosis may be specific to abnormalities in the ability of frontal systems processing executive commands (DLPFC) and monitoring performance (dACC) during the maintenance of information. Our results add to accumulating evidence indicating that DLPFC abnormalities may be core to psychosis psychopathology. We also provide new insights regarding how DLPFC abnormalities may undermine dACC processing during the maintenance of information.
INTRODUCTION: We probed the neural basis of working memory in individuals with first episode of psychosis (FEP) and assessed how these neural abnormalities are associated with behavioral performance and/or core to psychosis pathophysiology. METHODS: FEP (N=35) and matched controls (N=25) performed a visuospatial working memory task during fMRI acquisition. We isolated neural activity during the maintenance period and examined neural activity within regions typically engaged during a working memory task. Functional connectivity estimates were derived using psychophysiological interaction analysis. We examined correlations between brain function and behavioral performance and clinical symptomatology. RESULTS: FEP had reduced accuracy and slower reaction times compared to controls (p<0.05, q<0.05). During the maintenance period, FEP exhibited reduced right dorsolateral prefrontal cortex (DLPFC) activation compared to controls (p=0.007, q=0.01), even when behavioral performance was matched between groups (p=0.01, q=0.03). Unlike controls, FEP failed to show increased dorsal anterior cingulate (dACC) activity with increased load level (p=0.02, q=0.06). Compared to controls, FEP showed increased negative DLPFC-dACC coupling during the maintenance period (p=0.05). Increased DLPFC activation was significantly associated with greater negative symptoms (p<0.005, q=0.02), while greater dACC activation was significantly associated with better performance in FEP (p<0.05, q<0.17). CONCLUSION:WM impairment in psychosis may be specific to abnormalities in the ability of frontal systems processing executive commands (DLPFC) and monitoring performance (dACC) during the maintenance of information. Our results add to accumulating evidence indicating that DLPFC abnormalities may be core to psychosis psychopathology. We also provide new insights regarding how DLPFC abnormalities may undermine dACC processing during the maintenance of information.
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