Reduced functional connectivity in brain networks underlying paired associates memory encoding in schizophrenia

Patients with schizophrenia exhibit deficits in associative learning and semantic memory. The current functional magnetic resonance imaging (fMRI) study investigated the neural correlates of successful versus unsuccessful semantic associative encoding in schizophrenia compared to healthy controls. Publicly shared fMRI data from the UCLA Consortium for Neuropsychiatric Phenomics LA5C study were analyzed. Forty-four patients with schizophrenia and 78 healthy controls performed a paired-associates encoding task. Constrained principal component analysis for fMRI (fMRI-CPCA) revealed three distinct functional networks recruited during encoding: a responding (RESP) network, a linguistic processing/attention network (LANG/ATTN), and the default mode network (DMN). Relative to healthy controls, patients showed aberrant activity in all three networks; namely, hypo-activation in the LANG/ATTN network during successful encoding, lower peak activation and weaker post-activation suppression of the RESP network, and weaker suppression in the DMN during successful encoding. Independent of group effects, a pattern of stronger anticorrelating LANG/ATTN-DMN activity during successful encoding significantly predicted subsequent retrieval of paired associates. Together with previous observations of language network hypoactivation during controlled semantic associative memory processes, these results suggest that reduced activity in linguistic processing areas is a reliable biological marker associated with impaired semantic memory in schizophrenia.