GABAergic Modulation of Brain Function During Prosaccade and Antisaccade Eye Movements: Evidence From...

Benzodiazepines act as positive allosteric modulators of the GABA_A receptor and affect several motor and cognitive functions. By engaging perceptual-motor as well as inhibitory control processes, the antisaccade task was used in previous studies to investigate effects of benzodiazepines on behavioral performance. Using a randomized, double-blind, placebo-controlled within-subjects design, this study combined eye-tracking with BOLD fMRI in order to examine the neural correlates of these effects for the first time. N = 39 healthy participants completed an antisaccade task after administration of either 1 mg lorazepam or placebo. On a behavioral level, lorazepam led to reduced (anti-)saccadic peak velocity as well as increased (anti-)saccadic latency. On a neural level, drug-induced reduction of BOLD was found in a fronto-parietal-occipital network, including key oculomotor regions. This result was further supported by our finding of increased GABA_A receptor density in the affected network. On an individual level, decline in peak velocity under lorazepam was associated with decreased neural activation in several cortical regions, including medial frontal eye fields. No interactions between drug and saccade condition (prosaccade, antisaccade) were found. Our results therefore suggest GABAergic modulation of a more general saccade-related network rather than of specific components for inhibitory control processes. Future studies may rely on BOLD signal as a sensitive marker for benzodiazepine activity during saccadic eye movements.