Despite considerable evidence showing thalamus anatomy and connectivity abnormalities in schizophrenia, how these abnormalities are reflected in thalamus function during cognition is relatively understudied. Modulation of thalamic connectivity with the prefrontal cortex (PFC) is required for higher-order cognitive processes, which are often impaired in schizophrenia. To address this gap, we investigated how thalamus function and thalamus-PFC connectivity under different levels of cognitive demand may be disrupted in schizophrenia. Participants underwent fMRI scanning while performing an event-related two-alternative forced choice task under Single and Dual task conditions. In the Single task condition, participants responded either to a visual cue with a well-learned motor response, or an audio cue with a well-learned vocal response. In the Dual task condition, participants performed both tasks. Thalamic connectivity with task relevant regions of the PFC for each condition was measured using beta-series correlation. Individuals with schizophrenia demonstrated less modulation of both mediodorsal thalamus activation and thalamus-PFC connectivity with increased cognitive demand. In contrast, their ability to modulate PFC function during task performance was maintained. These results suggest that the pathophysiology of cognitive impairment in schizophrenia is associated with thalamus-PFC circuitry and suggests that the thalamus, along with the PFC, should be a focus of investigation.
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