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. 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. 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. 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.