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Objective To investigate pathway-specific connectivity disrupted in psychosis. Methods We carried out a case study of a middle-aged patient who presented with new-onset psychosis associated with a space-occupying lesion localized in the right superior colliculus/periaqueductal gray. The study sought to investigate potential connectivity deficits related to the lesion by the use of diffusion tensor imaging and resting-state functional magnetic resonance imaging. To this aim, we generated a functional connectivity map of the patient’s brain, centered on the lesion area, and compared this map with the corresponding map of 10 sex- and age-matched control individuals identified from the Max Planck Institute–Leipzig Mind–Brain–Body database. Results Our analysis revealed a discrete area in the right rostral tectum, in the immediate vicinity of the lesion, whose activity is inversely correlated with the activity of left amygdala, whereas left amygdala is functionally associated with select areas of the temporal, parietal, and occipital lobes. Based on a comparative analysis of the patient with 10 control individuals, the lesion has impacted on the connectivity of rostral tectum (superior colliculus/periaqueductal gray) with left amygdala as well as on the connectivity of left amygdala with subcortical and cortical areas. Conclusions The superior colliculus/periaqueductal gray might play important roles in the initiation and perpetuation of psychosis, at least partially through dysregulation of left amygdala activity.

New-Onset Psychosis Associated With a Lesion Localized in the Rostral Tectum: Insights Into Pathway-Specific Connectivity Disrupted in Psychosis