Association between COMT genotype and the control of memory guided saccades: Individual differences in healthy adults reveal a detrimental role of dopamine

Abstract

The neural circuits involved in oculomotor control are well described; however, neuromodulation of eye movements is still hardly understood. Memory guided saccades have been extensively studied and in particular neurophysiological evidence from monkey studies points to a crucial functional role of prefrontal dopamine activity. We exploited individual differences in dopamine regulation due to the well established COMT (catechol-O-methyltransferase) Val158Met polymorphism to explore the link between prefrontal dopamine activity and memory guided saccades in healthy subjects. The COMT genotype is thought to modulate dopamine metabolism in prefrontal cortex producing differences in dopamine availability. We investigated memory guided saccades in 111 healthy subjects and determined individual genotypes. Accuracy and precision were reduced in subjects with putatively higher prefrontal dopamine levels. In contrast, we found no modulation of saccade parameters by genotype in a visually guided control task. Our results suggest that increased dopamine activity can have a detrimental effect on saccades that rely on spatial memory representations. Although these findings await replication in larger and more diverse sample sizes, they provide persuasive support that specific oculomotor parameters are sensitive to dopaminergic variation in healthy subjects and add to a better understanding of how dopamine modulates saccadic control.