The neuromodulatory role of dopamine in improved reaction time by acute cardiovascular exercise

Abstract

Acute cardiovascular physical exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Here, using positron emission tomography (PET) with [11C]raclopride, in a multi‐experiment study we investigated whether acute exercise releases endogenous dopamine (DA) in the brain. We hypothesized that acute exercise augments the brain DA system, and that RT improvement is correlated with this endogenous DA release. The PET study (Experiment 1: n = 16) demonstrated that acute physical exercise released endogenous DA, and that endogenous DA release was correlated with improvements in RT of the Go/No‐Go task. Thereafter, using two electrical muscle stimulation (EMS) studies (Experiments 2 and 3: n = 18 and 22 respectively), we investigated what triggers RT improvement. The EMS studies indicated that EMS with moderate arm cranking improved RT, but RT was not improved following EMS alone or EMS combined with no load arm cranking. The novel mechanistic findings from these experiments are: (1) endogenous DA appears to be an important neuromodulator for RT improvement and (2) RT is only altered when exercise is associated with central signals from higher brain centres. Our findings explain how humans rapidly alter their behaviour using neuromodulatory systems and have significant implications for promotion of cognitive health. imageKey points Acute cardiovascular exercise improves cognitive performance, as evidenced by a reduction in reaction time (RT). However, the mechanistic understanding of how this occurs is elusive and has not been rigorously investigated in humans. Using the neurochemical specificity of [11C]raclopride positron emission tomography, we demonstrated that acute supine cycling released endogenous dopamine (DA), and that this release was correlated with improved RT. Additional electrical muscle stimulation studies demonstrated that peripherally driven muscle contractions (i.e. exercise) were insufficient to improve RT. The current study suggests that endogenous DA is an important neuromodulator for RT improvement, and that RT is only altered when exercise is associated with central signals from higher brain centres.

Fractional amplitude of low-frequency fluctuations associated with μ-opioid and dopamine receptor distributions in the central nervous system after high-intensity exercise bouts

“…An early PET study already demonstrated that a gait challenge significantly increased endogenous dopaminergic release in Parkinson patients, but did not examine possible relationships with motivational behavior (Ouchi et al, 2001 ), which is also a limitation of the present study. While a recent study in healthy individuals reported striatal dopamine release during acute exercise that also correlated with speeded reaction times in a cognitive task (Ando et al, 2024 ), this does not necessarily reflect motivational changes. Another PET ligand displacement study in Parkinson patients reported that ventral striatal dopamine release after steady-state cycling was more pronounced in habitual exercisers than in sedentary subjects with Parkinson's disease (Sacheli et al, 2018 ), suggesting an influence of training status.…”

“…PET ligand displacement studies allow in vivo monitoring of endogenous transmitter trafficking at the human whole-brain level after acute exercise bouts and, thereby, to identify the link between exercise-induced behavioral measures and endogenous neurotransmission (Boecker et al, 2008 ). Previous human PET studies reported endogenous dopaminergic (Ouchi et al, 2001 ; Sacheli et al, 2018 ; Ando et al, 2024 ) and opioidergic (Boecker et al, 2008 ; Hiura et al, 2017 ; Saanijoki et al, 2018a ) transmitter release following exercise challenges, with [11C]Carfentanil PET data indicating that aerobic exercise modulates anticipatory reward processing via the μ-opioid receptor system (Saanijoki et al, 2018b ), and 6-O-(2-[(18)F]fluoroethyl)-6-O-desmethyldiprenorphine ([18F]DPN) PET data showing correlations between running-induced opioid release in prefrontal and limbic/paralimbic brain structures and subjective euphoria ratings (Boecker et al, 2008 ). While exercise increases circulating endocannabinoid levels in humans in an intensity-dependent manner (Raichlen et al, 2013 ; Desai et al, 2022 ), to the best of our knowledge, no PET tracer studies on endocannabinoid neurotransmission changes due to acute or long-term exercise challenges were published so far.…”

Combined effects of electrical muscle stimulation and cycling exercise on cognitive performance

“…Hence, the findings concerning the effects of acute EMS on cognitive performance are conflicting, but physiological changes induced by EMS alone may be insufficient to improve performance in all cognitive domains. Intriguingly, a follow-up experiment revealed that a combination of EMS and arm cranking exercise improves cognitive performance (Ando et al, 2024). These results may emphasize that brain activity associated with voluntary exercise is necessary for cognitive improvements induced by acute exercise.…”

“…Emerging evidence has examined the benefits of EMS on cognitive performance. For example, two studies indicated that EMS does not improve cognitive performance (Miyamoto et al, 2018;Ando et al, 2024), while another recent study indicated that EMS improved cognitive performance in the Stroop congruent task and short-term memory performance, but not in the Stroop incongruent task or the trail making test (Descollonges et al, 2024). Hence, the findings concerning the effects of acute EMS on cognitive performance are conflicting, but physiological changes induced by EMS alone may be insufficient to improve performance in all cognitive domains.…”

Postural Influence on Cognitive Dynamics during Esports Play: A Randomized Crossover Study (Preprint)

“…Video games are not just cognitive tasks; they also involve a significant play element known to activate the dopamine system as a reward mechanism 56 . Furthermore, although not directly tested in the context of standing posture, recent studies have suggested that muscle activity under central command activates the human dopaminergic system, thereby enhancing cognitive function 57 . Since maintaining a standing posture naturally involves central command, playing esports while standing could additively or synergistically stimulate the dopaminergic system, improving cognitive function and resulting esports performance.…”