Content area
Abstract
Inhibition is a fundamentally important ability for the successful navigation of social relationships and adaptive functioning in an ever-changing environment. Alterations in this function are believed to be central to a variety of clinical problems. Saccade paradigms are a widely used neurophysiological method for investigating inhibitory functions, yet previous studies of the neural mechanisms supporting the inhibitory control of behavior leave important questions unanswered.
The current event-related fMRI study with 28 healthy subjects made use of uniquely designed tasks and a novel image analysis approach based on animal models to characterize and compare regional brain activity during the preparatory periods of prosaccade and antisaccade tasks. Prosaccades examine basic visual attention and sensorimotor abilities and requires subjects to look at unpredictably appearing peripheral visual stimuli. Antisaccades examine the ability to voluntarily suppress context-inappropriate but prepotent response tendencies and require subjects to inhibit saccades toward peripheral visual stimuli and instead look to the mirror location in the opposite hemifield.
Within-task analyses showed greater preparatory activity in supplementary eye fields, frontal eye fields, and visual cortex, but not in dorsolateral prefrontal cortex compared to other oculomotor regions in both tasks. Increased preparatory activity was observed during antisaccade trials relative to prosaccade trials in pre-supplementary eye fields, frontal eye fields, anterior cingulate, cingulate motor area, posterior cingulate, and lateral cerebellum, but not in parietal and visual cortices or striatum. These findings suggest that inhibitory processes are primarily mediated by top-down suppression of the motor system rather than the sensory system. While the inhibition of prepotent, but context-inappropriate responses has traditionally been thought of as a prefrontally mediated aspect of behavioral control, results of the current study suggest that the preparation to inhibit responses relies more on the input of premotor and other midline structures that the input of prefrontal regions.
The present findings expand and validate translational models established in the non-human primate literature on neural substrates involved in adaptive cognitive control of behavior. Results may have broad implications in understanding important aspects of choice behavior in healthy and clinical populations.
