Effects of methylphenidate on basic and higher-order oculomotor functions

Abstract

Eye movements are sensitive indicators of pharmacological effects on sensorimotor and cognitive processing. Methylphenidate (MPH) is one of the most prescribed medications in psychiatry. It is increasingly used as a cognitive enhancer by healthy individuals. However, little is known of its effect on healthy cognition. Here we used oculomotor tests to evaluate the effects of MPH on basic oculomotor and executive functions. Twenty-nine males were given 20mg of MPH orally in a double-blind placebo-controlled crossover design. Participants performed visually-guided saccades, sinusoidal smooth pursuit, predictive saccades and antisaccades one hour post-capsule administration. Heart rate and blood pressure were assessed prior to capsule administration, and again before and after task performance. Visually-guided saccade latency decreased with MPH (p<0.004). Smooth pursuit gain increased on MPH (p<0.001) and number of saccades during pursuit decreased (p<0.001). Proportion of predictive saccades increased on MPH (p<0.004), specifically in conditions with predictable timing. Peak velocity of predictive saccades increased with MPH (p<0.01). Antisaccade errors and latency were unaffected. Physiological variables were also unaffected. The effects on visually-guided saccade latency and peak velocity are consistent with MPH effects on dopamine in basal ganglia. The improvements in predictive saccade conditions and smooth pursuit suggest effects on timing functions.

Neural effects of methylphenidate and nicotine during smooth pursuit eye movements

“…We also did not find an effect of methylphenidate on smooth pursuit performance with the current dosage (corresponding to a range from 0.43 to 0.62mg/kg), whilst in a previous study with lower dosage (corresponding to an average of 0.26mg/kg) we observed a significant increase in maintenance gain and a significant reduction in saccadic frequency (Allman et al, 2012). The current dosage has been shown to improve performance in more challenging visual tasks (Finke et al, 2010), but has the lowest proportion of effects on cognition in healthy samples compared to medium and low dose (≤20mg) (Linssen et al, 2014).…”

“…One of the aims of such investigations is to increase knowledge on the specific and shared neuronal underpinnings of enhancing compounds. Both nicotine and methylphenidate have been shown to enhance overlapping measures of attentional performance (Bizarro et al, 2004;Levin et al, 2001) and smooth pursuit (Allman et al, 2012;Sherr et al, 2002). Here, for the first time we directly compared the effects of these two compounds on smooth pursuit performance and brain function.…”

“…Yet, methylphenidate which amplifies dopaminergic and noradrenergic signalling in fronto-striatal regions has been shown to improve pursuit performance in children with ADHD and healthy adults (Allman et al, 2012;Bylsma and Pivik, 1989). There are no imaging studies of methylphenidate effects on smooth pursuit; however, previous literature suggests that the localization of methylphenidate effects may be task-dependent (Costa et al, 2013;Dodds et al, 2008;Pauls et al, 2012) and modulated by the effects of the compound on dorsal attention and default mode networks (Liddle et al, 2011;Linssen et al, 2014;Marquand et al, 2011;Mueller et al, 2014;Tomasi et al, 2011).…”

“…Both nicotine and methylphenidate have been found to improve pursuit maintenance gain (Allman et al, 2012;Dépatie et al, 2002), although they primarily act on different neurotransmitter systems. So far, however, there are no direct comparisons of nicotine and methylphenidate that explore shared and distinct characteristics of their enhancing effects in healthy subjects.…”

“…There is evidence that significant drug effects may be limited to certain subgroups, such as groups with low baseline performance (Petrovsky et al, 2012) or specific genetic variation (Bellgrove et al, 2005). However, Allman et al (Allman et al, 2012) did not find baseline dependent effects in the modulation of methylphenidate for smooth pursuit.…”