Abstract

Neural habituation, the decrease in brain response to repeated stimuli, is a fundamental, highly conserved mechanism that acts as an essential filter for our complex sensory environment. Convergent evidence indicates neural habituation is disrupted in both early and chronic stages of schizophrenia, with deficits co-occurring in brain regions that show inhibitory dysfunction. As inhibitory deficits have been proposed to contribute to the onset and progression of illness, habituation may be an important treatment target. However, a crucial first step is clarifying whether habituation deficits progress with illness. In the present study, we measured neural habituation in 138 participants (70 early psychosis patients (<2 years of illness), 68 healthy controls), with 108 participants assessed longitudinally at both baseline and 2-year follow-up. At follow-up, all early psychosis patients met criteria for a schizophrenia spectrum disorder (i.e., schizophreniform disorder, schizophrenia, schizoaffective disorder). Habituation slopes (i.e., rate of fMRI signal change) to repeated images were computed for the anterior hippocampus, occipital cortex, and the fusiform face area. Habituation slopes were entered into a linear mixed model to test for effects of group and time by region. We found that early psychosis patients showed habituation deficits relative to healthy control participants across brain regions, and that these deficits were maintained, but did not worsen, over two years. These results suggest a stable period of habituation deficits in the early stage of schizophrenia.

Highlights

  • Habituation, defined as the decrease in response to repeated stimulus exposures, is an elementary and ubiquitous form of behavioral plasticity[1]

  • We found a main effect of group in each region, with early psychosis patients habituating ~11–16% slower than healthy control participants across regions

  • We examined whether habituation deficits identified in a cohort of early psychosis patients at baseline within a visual processing network—the hippocampus, fusiform face area (FFA), and occipital pole—progressed over two years of illness

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Summary

Introduction

Habituation, defined as the decrease in response to repeated stimulus exposures, is an elementary and ubiquitous form of behavioral plasticity[1]. Rapid habituation may conserve limited processing resources and act as a building block for normal cognitive function[3,4]. Failure to rapidly habituate has been proposed to lead to diminished attentional focus[5], cognitive fragmentation[6], and inappropriate behavioral responses[7]. Habituation deficits have been consistently identified at all levels of measurement, including at the behavioral, electrophysiological, and neural level. Habituation deficits in schizophrenia were identified using wellvalidated measurements such as habituation of eye-blink startle[9,10] and autonomic nervous system response[11,12]

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