Anomalous neural circuit function in schizophrenia during a virtual Morris water task

Abstract

Previous studies have reported learning and navigation impairments in schizophrenia patients during virtual reality allocentric learning tasks. The neural bases of these deficits have not been explored using functional MRI despite well-explored anatomic characterization of these paradigms in non-human animals. Our objective was to characterize the differential distributed neural circuits involved in virtual Morris water task performance using independent component analysis (ICA) in schizophrenia patients and controls. Additionally, we present behavioral data in order to derive relationships between brain function and performance, and we have included a general linear model-based analysis in order to exemplify the incremental and differential results afforded by ICA. Thirty-four individuals with schizophrenia and twenty-eight healthy controls underwent fMRI scanning during a block design virtual Morris water task using hidden and visible platform conditions. Independent components analysis was used to deconstruct neural contributions to hidden and visible platform conditions for patients and controls. We also examined performance variables, voxel-based morphometry and hippocampal subparcellation, and regional BOLD signal variation. Independent component analysis identified five neural circuits. Mesial temporal lobe regions, including the hippocampus, were consistently task-related across conditions and groups. Frontal, striatal, and parietal circuits were recruited preferentially during the visible condition for patients, while frontal and temporal lobe regions were more saliently recruited by controls during the hidden platform condition. Gray matter concentrations and BOLD signal in hippocampal subregions were associated with task performance in controls but not patients. Patients exhibited impaired performance on the hidden and visible conditions of the task, related to negative symptom severity. While controls showed coupling between neural circuits, regional neuroanatomy, and behavior, patients activated different task-related neural circuits, not associated with appropriate regional neuroanatomy. GLM analysis elucidated several comparable regions, with the exception of the hippocampus. Inefficient allocentric learning and memory in patients may be related to an inability to recruit appropriate task-dependent neural circuits.