Network dysfunction during associative learning in schizophrenia: Increased activation, but decreased connectivity: An fMRI study

Schizophrenia (SCZ) is characterized by disordered activation and disordered connectivity, yet few fMRI studies have convergently investigated both. Here, we compared differences in activation and connectivity between SCZ and controls (HC). Twenty-two subjects (18 ≤ age ≤ 35 yrs) participated in a paired-associative learning task, a behavioral domain particularly dependent on fronto-hippocampal connectivity and of relevance to the schizophrenia diathesis. Activation differences were assessed using standard approaches. Seed-based connectivity differences were compared using Psychophysiological Interaction (PPI) with a hippocampus-based seed. SCZ evinced significantly increased activation, but significantly decreased connectivity with the hippocampus across a cortical-striatal learning network. These results assess potentially complementary patterns of network dysfunction in schizophrenia: increased activation suggests inefficient responses relating to functional specialization; decreased connectivity suggests impaired integration of functional signals between regions. Inefficiency and dysconnection appear to collectively characterize functional deficits in schizophrenia.