A review of basal ganglia circuits and physiology: Application to deep brain stimulation

Abstract

Introduction: Drawing on the seminal work of DeLong, Albin, and Young, we have now entered an era of basal ganglia neuromodulation. Understanding, re-evaluating, and leveraging the lessons learned from neuromodulation will be crucial to facilitate an increased and improved application of neuromodulation in human disease cohorts. Methods: We will focus on deep brain stimulation (DBS)-the most common form of basal ganglia neuromodulation-however, similar principles can apply to other neuromodulation modalities. We start with a brief review of DBS for Parkinson's disease, essential tremor, dystonia, and Tourette syndrome. We then review hallmark studies on basal ganglia circuits and electrophysiology resulting from decades of experience in neuromodulation. The organization and content of this paper follow Dr. Okun's Lecture from the 2018 Parkinsonism and Related Disorders World Congress. Results: Information gained from neuromodulation has led to an expansion of the basal ganglia rate model, an enhanced understanding of nuclei dynamics, an emerging focus on pathological oscillations, a revision of the tripartite division of the basal ganglia, and a redirected focus toward individualized symptom-specific stimulation. Though there have been many limitations of the basal ganglia "box model," the construct provided the necessary foundation to advance the field. We now understand that information in the basal ganglia is encoded through complex neural responses that can be reliably measured and used to infer disease states for clinical translation. Conclusions: Our deepened understanding of basal ganglia physiology will drive new neuromodulation strategies such as adaptive DBS or cell-specific neuromodulation through the use of optogenetics.

Neuroimaging Advances in Deep Brain Stimulation: Review of Indications, Anatomy, and Brain Connectomics

“…35 Although it is not part of the original rate model of the basal ganglia, the more recently described hyperdirect pathway consists of direct connections from the cortex to the STN ( Fig 3A). 38,39 In keeping with the tripartite division of the STN, hyperdirect connections extend to the motor cortex from the posterior STN, associative cortex from the mid-STN, and limbic regions from the anterior STN. The hyperdirect pathway has been implicated in symptomatology of PD and associated with motor improvement seen with STN DBS in PD using diffusion tractography.…”

The effect on deep brain stimulation of subthalamic nucleus and dopaminergic treatment in Parkinson disease

“…The failure to initiate a clear beginning or end of sensory events lead to the inability to distinguish relevant environmental stimuli and provide adaptive responses. [ 27 ]…”

Interference of functional dual-tasks on gait in untrained people with Parkinson’s disease and healthy controls: a cross-sectional study

“…Gait assessment with secondary functional tasks, such as talking with another person or carrying something with the hands, would allow observing the performance of people with PD in everyday contexts and guiding physical therapy with the aim of preparing patients for these probable challenges. This is of special interest in PD because the basal ganglia are involved in the control of different aspects besides motor control [8,9] and the onset of cognitive impairment can further impair the performance of the inevitable daily dual-tasks.…”