Functional connectivity during smooth pursuit eye movements in major depressive disorder

Smooth pursuit eye movements (SPEM) allow the visual tracking of slowly moving objects. SPEM accuracy is adversely influenced by environmental complexity, such as background stimuli, and is impaired in psychiatric conditions including schizophrenia and major depressive disorder (MDD). In the presence of backgrounds, SPEM offer valuable tools to investigate cognitive control processes such as attentional allocation and interference control, thereby enabling the study of these cognitive functions in clinical populations. This preregistered study investigated behavioral and neural correlates of SPEM in individuals with MDD and healthy controls (N = 100). Participants performed a SPEM task during fMRI at 3T comprising blocks with and without a structured background pattern. Behaviorally, the presence of the structured background was associated with decreased pursuit gain, increased root mean square error (RMSE) and higher catch-up saccade rate (CUS), indicating reduced pursuit accuracy irrespective of group. At the neural level, the background condition elicited comparable BOLD response increases in both groups in smooth pursuit-related regions, particularly in occipital, and superior frontal areas. Exploratory functional connectivity analyses revealed increased connectivity in the background condition between key oculomotor and visual regions, including frontal eye fields, lateral geniculate nucleus, posterior parietal cortex, V1, and V5, with occipital fusiform gyri. Group comparisons indicated reduced connectivity within fronto-oculomotor and left fronto-striatal networks, but increased connectivity between visual and right prefrontal regions in MDD. These findings suggest altered and potentially compensatory neural mechanisms underlying SPEM pathways in MDD, despite preserved behavioral performance.