There is a long history of eye movement research in patients with psychiatric diseases for which dysfunctions of neurotransmission are considered to be the major pathologic mechanism. However, neuromodulation of oculomotor control is still hardly understood. We aimed to investigate in particular the impact of dopamine on smooth pursuit eye movements. Systematic variability in dopaminergic transmission due to genetic polymorphisms in healthy subjects offers a non-invasive opportunity to determine functional associations. We measured smooth pursuit in 110 healthy subjects genotyped for two well-documented polymorphisms, the COMT Val158Met polymorphism and the SLC6A3 3′-UTR-VNTR polymorphism. Pursuit paradigms were chosen to particularly assess the ability of the pursuit system to initiate tracking when target motion onset is blanked, reflecting the impact of extra-retinal signals. In contrast, when following a fully visible target sensory, retinal signals are available. Our results highlight the crucial functional role of dopamine for anticipatory, but not for sensory driven pursuit processes. We found the COMT Val158Met polymorphism specifically associated with anticipatory pursuit parameters emphasizing the dominant impact of prefrontal dopamine activity on complex oculomotor control. In contrast, modulation of striatal dopamine activity by the SLC6A3 3′-UTR-VNTR polymorphism had no significant functional effect. Though often neglected so far, individual differences in healthy subjects provide a promising approach to uncovering functional mechanisms and can be used as a bridge to understanding deficits in patients.
Significance StatementAlthough the neuronal bases of oculomotor control are well documented, the modulating role of neurotransmitters has remained elusive. Oculomotor deficits have been reported in diseases characterized by disturbed neurotransmission; however, clinical findings lack specificity and are ambiguous due to confounding issues. We used genetic polymorphisms in healthy subjects as an elegant way to investigate the effect of individual differences in dopaminergic circuitry on smooth pursuit eye movements. We found a specific impact of prefrontal dopamine on high-level, but not on low-level processes involved in pursuit. Our results provide an immediate link between dopamine and oculomotor control in humans. They highlight the value of individual differences for uncovering functional processes and provide insights into the mechanisms underlying oculomotor phenotypes of diseases.
The authors declare no competing financial interests.