Alterations of fronto-temporal connectivity during word encoding in schizophrenia

Abstract

Cognitive deficits, including impaired verbal memory, are prominent in schizophrenia and lead to increased disability. Functional neuroimaging of patients with schizophrenia performing memory tasks has revealed abnormal activation patterns in prefrontal cortex and temporo-limbic regions. Aberrant fronto-temporal interactions thus represent a potential pathophysiological mechanism underlying verbal memory deficits, yet this hypothesis of disturbed connectivity is not tested directly with standard activation studies. We performed within-subject correlations of frontal and temporal timeseries to measure functional connectivity during verbal encoding. Our results confirm earlier findings of aberrant fronto-temporal connectivity in schizophrenia, and extend them by identifying distinct alterations within dorsal and ventral prefrontal cortex. Relative to healthy controls, patients with schizophrenia had reduced connectivity between the dorsolateral prefrontal cortex (DLPFC) and temporal lobe areas including parahippocampus and superior temporal gyrus. In contrast, patients showed increased connectivity between a region of ventrolateral prefrontal cortex (VLPFC) and these same temporal lobe regions. Higher temporal-DLPFC connectivity during encoding was associated with better subsequent recognition accuracy in controls, but not patients. Temporal-VLPFC connectivity was uncorrelated with recognition accuracy in either group. The results suggest that reduced temporal-DLPFC connectivity in schizophrenia could underlie encoding deficits, and increased temporal-VLPFC connectivity may represent an ineffective compensatory effort.

Association of Dorsolateral Prefrontal Cortex Dysfunction With Disrupted Coordinated Brain Activity in Schizophrenia: Relationship With Impaired Cognition, Behavioral Disorganization, and Global Function

“…Enhanced functional connectivity during the B cue condition relative to the A cue condition was observed in healthy comparison subjects, while there was a marked inability to enhance dorsolateral prefrontal cortex connectivity in schizophrenia patients. Previous studies have also shown altered interactions between cortical regions, suggesting the presence of disordered connectivity in schizophrenia (22)(23)(24)(25). Accordingly, not only are our results consistent with the hypothesis that connectivity is impaired in individuals with schizophrenia, but they suggest that there is a potential fundamental neural mechanism by which dorsolateral prefrontal cortex dysfunction leads to cognitive impairment (i.e., top-down modulation through impaired connectivity with the dorsolateral prefrontal cortex).…”

Superior temporal lobe dysfunction and frontotemporal dysconnectivity in subjects at risk of psychosis and in first-episode psychosis

“…Functional neuroimaging studies in schizophrenia report abnormal activation of STG during performance of a range of cognitive tasks (Fletcher et al, 1996;Gur et al, 2007), and activity in this regions has been linked to the severity of auditory hallucinations (McGuire et al, 1995;Allen et al, 2007) and formal thought disorder (McGuire et al, 1998;Kircher et al, 2001). …”

Fronto-temporal Interactions during Overt Verbal Initiation and Suppression

“…For example, aberrant fronto-temporal connectivity is postulated to underlie many of the cognitive deficits associated with schizophrenia (Wolf et al, 2007;Ragland et al, 2001;McGuire & Frith, 1996;. Furthermore, the analysis of fMRI data in terms of connectivity, in addition to standard activations, allows for a more detailed picture of disturbances in neural circuitry underlying group differences between patients and healthy controls.…”