Abstract
BACKGROUND: Learning and memory are impaired in schizophrenia. However, little is known about a highly conserved form of memory—habituation, the reduced response to repeated exposures to a stimulus—in schizophrenia. Preliminary evidence indicates failed hippocampal habituation is associated with memory impairments in chronic schizophrenia patients. Here, we use a targeted analysis to investigate the regional specificity of hippocampal habituation failure and associations with relational memory in the early stage of psychosis. METHODS: We measured hippocampal activity in 62 patients in the early stage (< 2 years following index episode) of non-affective psychosis and 70 demographically-similar healthy control participants using fMRI. Participants viewed two repeated neutral face blocks followed by two repeated neutral objects block. Habituation slopes in the anterior and posterior hippocampus were calculated following initial novelty response, during the first block of each stimulus category. We tested for main effects of habituation and between-group differences. Outside the scanner, participants completed a relational memory task where eye movements were recorded to assess memory for face-scene pairs. We used Spearman correlations to test for relationships between relational memory performance and hippocampal habituation. Familywise error adjusted p-values were calculated using permutation testing. RESULTS: Habituation of the anterior hippocampus during viewing of repeated objects was significantly decreased in early psychosis patients (F1, 131 = 7.51, p = 0.01). In contrast, habituation in the posterior hippocampus was similar between groups, resulting in a group by region interaction (F1, 131 = 7.11, p = 0.008). Relational memory was better in healthy control subjects than early psychosis patients (F1, 113 = 22.31, p < 0.001) and was associated with faster anterior hippocampal habituation to faces (r = -0.28, p = 0.03). In contrast, early psychosis patients with low memory performance showed the opposite pattern; better memory was associated with a more sustained response in the anterior hippocampus (r = 0.46, p = 0.02). DISCUSSION: We find that hippocampal habituation is disrupted in the early stage of psychosis and is associated with relational memory impairments. Habituation deficits and brain/behavior relationships were specific to the anterior hippocampus, with habituation differences in the posterior hippocampus. These results suggest neural habituation may provide a novel target for early cognitive interventions in psychosis.