Methylphenidate Effects on Neural Activity During Response Inhibition in Healthy Humans

Abstract

Methylphenidate (MPH) is a catecholamine transporter blocker, with dopamine agonistic effects in the basal ganglia. Response inhibition, error detection, and its mediating frontostriatal brain activation are improved by MPH in patients with attention-deficit/hyperactivity disorder. However, little is known about the effects of MPH on response inhibition and error processing or its underlying brain function in healthy individuals. Therefore, this study employed functional magnetic resonance imaging (fMRI) and 2 response inhibition tasks in 52 healthy males. Subjects underwent fMRI during a go/no-go task and a tracking stop-signal task after administration of 40 mg MPH and placebo in a double-blind, placebo-controlled, repeated-measures design. Results revealed task- and condition-specific neural effects of MPH: it increased activation in the putamen only during inhibition errors but not during successful inhibition and only in the go/no-go task. We speculate that task specificity of the effect might be due to differences in the degree of error saliency in the 2 task designs, whereas errors were few in the go/no-go task and thus had high saliency and the stop-signal task was designed to elicit 50% of errors in all subjects, diminishing the error saliency effect. The findings suggest that neural MPH effects interact with the saliency of the behavior under investigation.

Methylphenidate Effects on Brain Activity as a Function of SLC6A3 Genotype and Striatal Dopamine Transporter Availability

“…We expected that MPH would lead to alterations in frontostriatal networks (Costa et al, 2013b;Rubia et al, 2011). Concerning SLC6A3 genotype, in line with previous meta-analyses, we expected higher striatal DAT binding for 9R carriers in comparison with 10/10 homozygotes (Costa et al, 2011;Faraone et al, 2014).…”

“…We have previously shown MPH effects on striatal BOLD during a Go/No-Go task (Costa et al, 2013b). Here, we extend these findings by combining genetic and molecular information to explore the MPH-induced changes in dependency of DAT genotype and availability.…”

Neural effects of methylphenidate and nicotine during smooth pursuit eye movements

“…An additional interpretation of the significant difference between the nicotine and methylphenidate groups concerns the effects of methylphenidate on enhancing task-related activations, as observed in response inhibition (Costa et al, 2013;Nandam et al, 2014) and working memory (Tomasi et al, 2011). Activation of the FEFs, as observed more strongly in our methylphenidate group compared to the nicotine group, has been associated with spatial attention (Corbetta et al, 1998) and the voluntary control of eye movements (Pierrot-Deseilligny et al, 2004).…”

“…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).…”

“…The administered dosage of 40mg oral methylphenidate has previously been shown to affect BOLD during different cognitive tasks (Costa et al, 2013;Farr et al, 2014;Pauls et al, 2012;Ramaekers et al, 2013;Sripada et al, 2013). The dose is comparable to a therapeutic daily dosage for an adult with ADHD and is expected to block approximately 72% of dopamine transporters (Volkow et al, 1998).…”