Abstract
The external part of the globus pallidus (GPe) is a core nucleus of the basal ganglia (BG) whose activity is disrupted under conditions of low dopamine release, as in Parkinson's disease. Current models assume decreased dopamine release in the dorsal striatum results in deactivation of dorsal GPe, which in turn affects motor expression via a regulatory effect on other nuclei of the BG. However, recent studies in healthy and pathological animal models have reported neural dynamics that do not match with this view of the GPe as a relay in the BG circuit. Thus, the computational role of the GPe in the BG is still to be determined. We previously proposed a neural model that revisits the functions of the nuclei of the BG, and this model predicts that GPe encodes values which are amplified under a condition of low striatal dopaminergic drive. To test this prediction, we used an fMRI paradigm involving a within-subject placebo-controlled design, using the dopamine antagonist risperidone, wherein healthy volunteers performed a motor selection and maintenance task under low and high reward conditions. ROI-based fMRI analysis revealed an interaction between reward and dopamine drive manipulations, with increased BOLD activity in GPe in a high compared to low reward condition, and under risperidone compared to placebo. These results confirm the core prediction of our computational model, and provide a new perspective on neural dynamics in the BG and their effects on motor selection and cognitive disorders.
Highlights
Pioneering studies (Albin et al, 1989, 1991; Alexander et al, 1986; DeLong, 1983, 1990; Smith et al, 1998) investigating the function of the basal ganglia (BG) proposed these interconnected nuclei play a fundamental role in action facilitation, and in the regulation of voluntary movement
We have recently proposed a different perspective on BG function and neural dynamics, with particular attention on the role played by the globus pallidus pars externa (GPe) and the indirect pathway
In keeping with the prediction of our model, we found the interaction between the two variables had a significant effect: 1) in the left dorsal GPe, as the representation of action-state values improves under reduced DA drive; 2) in the right substantia nigra pars reticulata (SNr), where we found the value representation is inverted when comparing placebo and risperidone conditions
Summary
Pioneering studies (Albin et al, 1989, 1991; Alexander et al, 1986; DeLong, 1983, 1990; Smith et al, 1998) investigating the function of the basal ganglia (BG) proposed these interconnected nuclei play a fundamental role in action facilitation, and in the regulation of voluntary movement. Subsequent local connectome analyses resulted in further model developments (Frank, 2005, 2006; Gurney et al, 2004; Humphries et al, 2006; Nambu, 2004), including the suggestion that biophysical dysfunctions in the BG circuit might explain specific behavioural disorders and diseases (Obeso et al, 2014). These models propose that the output of the BG exerts a tonic inhibition of all motor commands to mediate a gating function. The hyperdirect pathway bypasses the striatum as input structure, and conveys cortical information to the SNr and GPi via the STN, establishing a recurrent circuit with the GPe (Smith et al, 1998)
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