Noradrenergic modulation of saccades in Parkinson's disease

Noradrenaline is a powerful modulator of cognitive processes, including action decisions underlying saccadic control. Changes in saccadic eye movements are common across neurodegenerative diseases of ageing, including Parkinson's disease. With growing interest in noradrenergic treatment potential for non-motor symptoms in Parkinson's disease, the temporal precision of oculomotor function is advantageous to assess the effects of this modulation. Here, we studied the effect of 40 mg atomoxetine, a noradrenaline reuptake inhibitor, in 19 people with idiopathic Parkinson's disease using a single dose, randomized double-blind, crossover, placebo-controlled design. Twenty-five healthy adult participants completed the assessments to provide normative data. Participants performed prosaccade and antisaccade tasks. The latency, velocity and accuracy of saccades, and resting pupil diameter, were measured. Increased pupil diameter on the drug confirmed its expected effect on the locus coeruleus ascending arousal system. Atomoxetine altered key aspects of saccade performance: prosaccade latencies were faster and the saccadic main sequence was normalized. These changes were accompanied by increased antisaccade error rates on the drug. Together, these findings suggest a shift in the speed-accuracy trade-off for visuomotor decisions in response to noradrenergic treatment. Our results provide new evidence to substantiate a role for noradrenergic modulation of saccades, and based on known circuitry, we advance the hypothesis that this reflects modulation at the level of the locus coeruleus-superior colliculus pathway. Given the potential for noradrenergic treatment of non-motor symptoms of Parkinson's disease and related conditions, the oculomotor system can support the assessment of cognitive effects without limb-motor confounds on task performance.