Fiore, VG; Rigoli, F; Stenner, MP; Zaehle, T; Hirth, F; Heinze, HJ; Dolan, RJ; (2016) Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive. Scientific Reports , 6 , Article 23327. 10.1038/srep23327.

Text Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive.pdf - Published Version Download (1MB)

Abstract

Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson's disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model.

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