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.

Conflict of interest statement

Financial Disclosures:

Dr. Folley reported no biomedical financial interests or potential conflicts of interest. Dr. Astur reported no biomedical financial interests or potential conflicts of interest. Ms. Jagannathan reported no biomedical financial interests or potential conflicts of interest. Dr. Calhoun reported no biomedical financial interests or potential conflicts of interest. Dr. Pearlson reported no biomedical financial interests or potential conflicts of interest.

Copyright 2009 Elsevier Inc. All rights reserved.

Figures

Figure 1

The Virtual Reality Pool Task. All participants completed 2 runs each of the task. Each run contained 6 visible and 5 hidden conditions. Participants navigated the virtual environment with a joystick. Successfully locating the platform prompted a “Congratulations!” message at the bottom of the screen, and additional navigation trials were successively presented until the end of each block.

Figure 2

Proportion of Platforms Found per Condition. Behavioral data for the number of times participants of each group found the platform correctly are shown as a proportion of the number of times they found the platform per total trials administered per condition. Although both groups found the visible platform at a similar proportion, patients were significantly deficient compared to healthy controls in the hidden condition.

Figure 3

Spatial maps of the resulting ICA components. The distributed functional neuroanatomy identified by each component from the ICA analysis is shown here. Each component represents a network of spatially independent brain regions sharing similar patterns of hemodynamic signal change over time.

Figure 4

Component 5 in the coronal plane. In this figure, Component 5, which predominantly included regions from the mesial temporal lobe, including the hippocampus, is shown with the corresponding Talairach coordinates.

Figure 5

Spatial maps from the GLM analysis. In order to compare the spatiotemporal maps resulting from the ICA analysis to a more traditional approach for data analysis, we have included a GLM-based approach from the identical raw data. These data represent the group and condition contrasts (Healthy Controls – Patients) (Hidden – Visible). Corresponding coordinates can be observed in Table 4.