Partial Correlation Analysis Reveals Abnormal Retinotopically Organized Functional Connectivity of Visual Areas in Amblyopia

Abstract

Amblyopia is a prevalent developmental visual disorder of childhood that typically persists in adults. Due to altered visual experience during critical periods of youth, the structure and function of adult visual cortex is abnormal. In addition to substantial deficits shown with task-based fMRI, previous studies have used resting state measures to demonstrate altered long-range connectivity in amblyopia. This is the first study in amblyopia to analyze connectivity between regions of interest that are smaller than a single cortical area and to apply partial correlation analysis to reduce network effects. We specifically assess short-range connectivity between retinotopically defined regions of interest within the occipital lobe of 8 subjects with amblyopia and 7 subjects with normal vision (aged 19-45). The representations of visual areas V1, V2, and V3 within each of the four quadrants of visual space were further subdivided into three regions based on maps of visual field eccentricity. Connectivity between pairs of all nine regions of interest in each quadrant was tested via correlation and partial correlation for both groups. Only the tests of partial correlation, i.e., correlation between time courses of two regions following the regression of time courses from all other regions, yielded significant differences between resting state functional connectivity in amblyopic and normal subjects. Subjects with amblyopia showed significantly higher partial correlation between para-foveal and more eccentric representations within V1, and this effect associated with poor acuity of the worse eye. In addition, we observed reduced correlation in amblyopic subjects between isoeccentricity regions in V1 and V2, and separately, between such regions in V2 and V3. We conclude that partial correlation-based connectivity is altered in an eccentricity-dependent pattern in visual field maps of amblyopic patients. Moreover, results are consistent with known clinical and psychophysical vision loss. More broadly, this provides evidence that abnormal cortical adaptations to disease may be better isolated with tests of partial correlation connectivity than with the regular correlation techniques that are currently widely used.