Learning without contingencies: A loss of synergy between memory and reward circuits in schizophrenia.

Motivational deficits in schizophrenia may interact with foundational cognitive processes including learning and memory to induce impaired cognitive proficiency. If such a loss of synergy exists, it is likely to be underpinned by a loss of synchrony between the brains learning and reward sub-networks. Moreover, this loss should be observed even during tasks devoid of explicit reward contingencies given that such tasks are better models of real world performance than those with artificial contingencies. Here we applied undirected functional connectivity (uFC) analyses to fMRI data acquired while participants engaged in an associative learning task without contingencies or feedback. uFC was estimated and inter-group differences (between schizophrenia patients and controls, n = 54 total, n = 28 patients) were assessed within and between reward (VTA and NAcc) and learning/memory (Basal Ganglia, DPFC, Hippocampus, Parahippocampus, Occipital Lobe) sub-networks. The task paradigm itself alternated between Encoding, Consolidation, and Retrieval conditions, and uFC differences were quantified for each of the conditions. Significantly reduced uFC dominated the connectivity profiles of patients across all conditions. More pertinent to our motivations, these reductions were observed within and across classes of sub-networks (reward-related and learning/memory related). We suggest that disrupted functional connectivity between reward and learning sub-networks may drive many of the performance deficits that characterize schizophrenia. Thus, cognitive deficits in schizophrenia may in fact be underpinned by a loss of synergy between reward-sensitivity and cognitive processes.

Neural activity is modulated by trial history: a functional magnetic resonance imaging study of the effects of a previous antisaccade.

Saccadic latencies are influenced by what occurred during the previous trial. When the previous trial is an antisaccade, the latencies of both prosaccades and antisaccades are prolonged. The aim of this study was to identify neural correlates of this intertrial effect of antisaccades. Specifically, based on both monkey electrophysiology and human neuroimaging findings, we expected trials preceded by antisaccades to be associated with reduced frontal eye field (FEF) activity relative to those preceded by prosaccades. Twenty-one healthy participants performed pseudorandom sequences of prosaccade and antisaccade trials during functional magnetic resonance imaging (fMRI) with concurrent monitoring of eye position. We compared activity in trials preceded by an antisaccade with activity in trials preceded by a prosaccade. The primary result was that a previous antisaccade prolonged saccadic latency and reduced fMRI activity in the FEF and other regions. No regions showed increased activity. We interpret the reduced FEF activity and slower saccadic responses to reflect inhibitory influences on the response system as a consequence of performing an antisaccade in the previous trial. This demonstrates that neural activity is modulated by trial history, consistent with a rapid, dynamic form of learning. More generally, these results highlight the importance of trial history as a source of variability in both behavioral and neuroimaging studies.