Catecholaminergic effects on inhibitory control depend on the interplay of prior task experience and working memory demands

Abstract

Background: Catecholamines affect response inhibition, but the effects of methylphenidate on inhibitory control in healthy subjects are heterogenous. Theoretical considerations suggest that working memory demands and learning/familiarization processes are important factors to consider regarding catecholaminergic effects on response inhibition. Aims: The purpose of this study was to examine the role of working memory demands and familiarization for methylphenidate effects on response inhibition. Methods: Twenty-eight healthy adults received a single dose of methylphenidate (0.5 mg/kg) or placebo in a randomised, double-blind, crossover study design. The subjects were tested using a working memory-modulated response inhibition paradigm that combined a Go/Nogo task with a mental rotation task. Results: Methylphenidate effects were largest in the most challenging mental rotation condition. The direction of effects depended on the extent of the participants’ task experience. When performing the task for the first time, methylphenidate impaired response inhibition performance in the most challenging mental rotation condition, as reflected by an increased false alarm rate. In sharp contrast to this, methylphenidate seemed to improve response execution performance in the most challenging condition when performing the task for the second time as reflected by reaction times on Go trials. Conclusion: Effects of catecholamines on inhibitory control processes depend on the interplay of two factors: (a) working memory demands, and (b) learning or familiarization with a task. It seems that the net effect of increases in gain control and decreases in working memory processes determines the methylphenidate effect on response inhibition. Hence, crossover study designs likely underestimate methylphenidate effects on cognitive functions.

Short-term Focused Attention Meditation Restricts the Retrieval of Stimulus-Response Bindings to Relevant Information

“…Regarding the level of familiarity of the task performed, besides the possibility that this effect may arise from better ability to extract salient information (Krueger 1975), several lines of evidence using pharmacological modulations targeting the noradrenergic and dopaminergic system have shown that the effects of the pharmacological modulation depend on learning performance or prior task experience (Adelhöfer et al 2019;Bensmann et al 2019;Mückschel et al 2020a, b). It has been argued that learning/prior task experience and actions of the noradrenergic/dopaminergic system tap into similar mechanisms or principles.…”

“…It has been argued that learning/prior task experience and actions of the noradrenergic/dopaminergic system tap into similar mechanisms or principles. This common neural principle likely refers to 'gain control' mechanisms (Bensmann et al 2019). Gain control is a general working principle in neural networks found at sensory, cognitive (Adelhöfer et al 2018;Salinas and Thier 2000;Servan-Schreiber et al 1990;Beste et al 2016), and motor levels (Greenhouse et al 2015;Thura and Cisek 2016).…”

Passive perceptual learning modulates motor inhibitory control in superior frontal regions

“…Without the use of a perceptual learning protocol, a decline in inhibition performance occurs when the task is executed for the second time likely because the repetition is amplifying the automation of the response tendency triggered by more frequent GO stimuli compared to NOGO stimuli (Dippel et al, ). The tendency to respond to GO stimuli is assumed to automate with an increase in task experience (Bensmann, Zink, Roessner, Stock, & Beste, ; Dippel et al, ; Dippel, Chmielewski, Mückschel, & Beste, ; Helton, ). The perceptual learning protocol, however, seems to have a “protective effect” since repeated task administration that likely induces a prepotent tendency to respond did not modulate response inhibition performance.…”

Perception-Action Integration Is Modulated by the Catecholaminergic System Depending on Learning Experience

“…However, there is mounting evidence that the effects of MPH depend on the level of prior experience or familiarity with a given task ( Bensmann et al, 2019 ; Mückschel et al, 2020a , 2020b ). These insights have been gained through the use of cross-over study designs.…”