Nonlinear Effects of Dopamine D1 Receptor Activation on Visuomotor Coordination Task Performance

Abstract

Dopamine plays an important role in the modulation of neuroplasticity, which serves as the physiological basis of cognition. The physiological effects of dopamine depend on receptor subtypes, and the D1 receptor is critically involved in learning and memory formation. Evidence from both animal and human studies shows a dose-dependent impact of D1 activity on performance. However, the direct association between physiology and behavior in humans remains unclear. In this study, four groups of healthy participants were recruited, and each group received placebo or medication inducing a low, medium, or high amount of D1 activation via the combination of levodopa and a D2 antagonist. After medication, fMRI was conducted during a visuomotor learning task. The behavioral results revealed an inverted U-shaped effect of D1 activation on task performance, where medium-dose D1 activation led to superior learning effects, as compared to placebo as well as low- and high-dose groups. A respective dose-dependent D1 modulation was also observed for cortical activity revealed by fMRI. Further analysis demonstrated a positive correlation between task performance and cortical activation at the left primary motor cortex. Our results indicate a nonlinear curve of D1 modulation on motor learning in humans and the respective physiological correlates in corresponding brain areas.

Monkeys exhibit a paradoxical decrease in performance in high-stakes scenarios

“…For example, dopamine neuron activity is known to scale with the magnitude of an anticipated reward (49,50). The inverted-U relationship present in the animals' success rates resembles those seen in studies relating the activity of neuromodulators such as dopamine and norepinephrine to performance in working memory, visuomotor, and attention tasks (37,38,51,52). These studies demonstrate that a graded release of a neurotransmitter can lead to discontinuities in behavioral performance.…”

Influence of age and cognitive performance on resting-state functional connectivity of dopaminergic and noradrenergic centres

“…Populations of dopaminergic neurons in the midbrain are implicated in reward processing by encoding incentive salience of the stimuli (Berridge and Kringelbach, 2015) and reward prediction error (Schultz, 2016). The research in animal models and humans supports the involvement of the dopaminergic system in cognitive functions such as sustained attention (Bellgrove et al, 2005), working memory (Bäckman and Lyberg, 2013), executive control (Saloner et al, 2020), as well as visuomotor search (Chen et al, 2020). Several resting-state studies have found the functional connectivity of VTA and SNc to be related to aspects of reward processing (Adrián-Ventura et al, 2019; Schmaal et al, 2012), impulsivity (Grimm et al, 2020), interoception (Chong et al, 2017) and gait speed (Karim et al, 2020).…”

Association of visual motor processing and social cognition in schizophrenia

“…The visual motor processing task has been used in several animal and human studies [83][84][85] with related to premotor cortex activation of motor movement and co-activated with middle temporal and superior temporal regions by human tCDS 83 and fMRI 84 exam. The basic psychometric properties of the task in human were considered adequate.…”

“…The basic psychometric properties of the task in human were considered adequate. 84 The participant is instructed to use the joystick provided to track the round dots randomly showed on the screen and the task was divided into three blocks (12 min each) with 41 trials each, and the initial correct score and the learning curve were both evaluated. Before the formal tasks, we demonstrated the task at first and made all the participants to practice to follow the target dot with the joystick five times to ensure they understand the task instruction.…”