title: Effective deep brain stimulation suppresses low-frequency network oscillations in the basal ganglia by regularizing neural firing patterns.
abstract: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for the motor symptoms of Parkinson's disease (PD). The effects of DBS depend strongly on stimulation frequency: high frequencies (>90 Hz) improve motor symptoms, while low frequencies (<50 Hz) are either ineffective or exacerbate symptoms. The neuronal basis for these frequency-dependent effects of DBS is unclear. The effects of different frequencies of STN-DBS on behavior and single-unit neuronal activity in the basal ganglia were studied in the unilateral 6-hydroxydopamine lesioned rat model of PD. Only high-frequency DBS reversed motor symptoms, and the effectiveness of DBS depended strongly on stimulation frequency in a manner reminiscent of its clinical effects in persons with PD. Quantification of single-unit activity in the globus pallidus externa (GPe) and substantia nigra reticulata (SNr) revealed that high-frequency DBS, but not low-frequency DBS, reduced pathological low-frequency oscillations (∼9 Hz) and entrained neurons to fire at the stimulation frequency. Similarly, the coherence between simultaneously recorded pairs of neurons within and across GPe and SNr shifted from the pathological low-frequency band to the stimulation frequency during high-frequency DBS, but not during low-frequency DBS. The changes in firing patterns in basal ganglia neurons were not correlated with changes in firing rate. These results indicate that high-frequency DBS is more effective than low-frequency DBS, not as a result of changes in firing rate, but rather due to its ability to replace pathological low-frequency network oscillations with a regularized pattern of neuronal firing.
authors.affiliation: Department of Biomedical Engineering, Duke University, Durham, North Carolina 27708, USA.
authors.forename: George C
authors.initials: GC
authors.lastname: McConnell
authors.forename: Rosa Q
authors.initials: RQ
authors.lastname: So
authors.forename: Justin D
authors.initials: JD
authors.lastname: Hilliard
authors.forename: Paola
authors.initials: P
authors.lastname: Lopomo
authors.forename: Warren M
authors.initials: WM
authors.lastname: Grill
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001479:Basal Ganglia / Q000503:physiopathology*; D001522:Behavior, Animal / Q000502:physiology; D046690:Deep Brain Stimulation; D005260:Female; D009043:Motor Activity / Q000502:physiology; D009415:Nerve Net / Q000503:physiopathology*; D009474:Neurons / Q000502:physiology*; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000503:physiopathology*; D051381:Rats; D020318:Rats, Long-Evans
chemical_list: D016627:Oxidopamine