The Prefrontal Substrate of Reflexive Saccade Inhibition in Humans

Background Prefrontal dysfunction in neuropsychiatric disorders such as schizophrenia has been shown to impair inhibition of reflexive saccadic eye movements; however, it is unclear whether reflexive saccade inhibition can be attributed to a distinct subregion of the human prefrontal cortex. Methods We tested 15 patients with acute unilateral ischemic lesions of the prefrontal cortex and 20 control subjects with an antisaccade task. Lesions were reconstructed using Talairach coordinates, and possible candidate regions for reflexive saccade inhibition were identified. Results Significantly increased antisaccade error rates were observed in patients with lesions affecting a region in mid-dorsolateral prefrontal cortex or the white matter between this region and the anterior portions of the internal capsule. Antisaccade error rates of patients with lesions outside this region were normal. These findings were largely independent of lesion volume, postlesion delay, and subject age. Conclusions Our findings suggest that inhibition of reflexive saccades depends on a circumscribed subregion of the human dorsolateral prefrontal cortex. This region closely corresponds to Brodmann area 46 as defined by recent cytoarchitectonic studies. Increased antisaccade error rates in patients with prefrontal pathology may be explained by dysfunction of this region.