title: Common therapeutic mechanisms of pallidal deep brain stimulation for hypo- and hyperkinetic movement disorders.
abstract: Abnormalities in cortico-basal ganglia (CBG) networks can cause a variety of movement disorders ranging from hypokinetic disorders, such as Parkinson's disease (PD), to hyperkinetic conditions, such as Tourette syndrome (TS). Each condition is characterized by distinct patterns of abnormal neural discharge (dysrhythmia) at both the local single-neuron level and the global network level. Despite divergent etiologies, behavioral phenotypes, and neurophysiological profiles, high-frequency deep brain stimulation (HF-DBS) in the basal ganglia has been shown to be effective for both hypo- and hyperkinetic disorders. The aim of this review is to compare and contrast the electrophysiological hallmarks of PD and TS phenotypes in nonhuman primates and discuss why the same treatment (HF-DBS targeted to the globus pallidus internus, GPi-DBS) is capable of ameliorating both symptom profiles. Recent studies have shown that therapeutic GPi-DBS entrains the spiking of neurons located in the vicinity of the stimulating electrode, resulting in strong stimulus-locked modulations in firing probability with minimal changes in the population-scale firing rate. This stimulus effect normalizes/suppresses the pathological firing patterns and dysrhythmia that underlie specific phenotypes in both the PD and TS models. We propose that the elimination of pathological states via stimulus-driven entrainment and suppression, while maintaining thalamocortical network excitability within a normal physiological range, provides a common therapeutic mechanism through which HF-DBS permits information transfer for purposive motor behavior through the CBG while ameliorating conditions with widely different symptom profiles.
authors.affiliation: Systems Neuroscience and Movement Disorders Laboratory, Korea Brain Research Institute, Daegu, Republic of Korea; kevin.mccairn@yahoo.com.
authors.forename: Kevin W
authors.identifier: http://orcid.org/0000-0002-8546-4095
authors.initials: KW
authors.lastname: McCairn
authors.affiliation: Laboratory for Symbolic Cognitive Development, RIKEN Brain Science Institute, Wako, Saitama, Japan; and.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Iriki
authors.affiliation: Department of Physiology, Kansai Medical University School of Medicine, Hirakata, Osaka, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Isoda
mesh_terms: D000818:Animals; D046690:Deep Brain Stimulation / Q000379:methods*; D005917:Globus Pallidus / Q000503:physiopathology*; D006801:Humans; D006948:Hyperkinesis / Q000503:physiopathology* / Q000628:therapy*; D018476:Hypokinesia / Q000503:physiopathology* / Q000628:therapy*
keywords: Parkinson's disease; Tourette syndrome; deep brain stimulation; globus pallidus; nonhuman primate