Background: In Parkinson's disease, invasive brain recordings show that dopaminergic medication can induce narrowband gamma rhythms in the motor cortex and subthalamic nucleus, which co-fluctuate with dyskinesia scores. Deep brain stimulation can entrain these gamma oscillations to a subharmonic stimulation frequency. However, the incidence of entrainment during chronic therapeutic stimulation, its relationship to the basal ganglia stimulation site, and its effect on dyskinesia remain unknown.

Objective: Determine whether the behavioral effects and statistical properties of levodopa-induced gamma oscillations are altered when entrained with deep brain stimulation.

Methods: We used a sensing-enabled deep brain stimulator system, attached to both motor cortex and subthalamic (n = 15) or pallidal (n = 5) leads, to record 993 h of multisite field potentials, with 656 h recorded prior to initiating stimulation. 13 subjects (20 hemispheres) with Parkinson's disease (1/13 female, mean age 59 ± 9 years) streamed data while at home on their usual antiparkinsonian medication. Recordings during stimulation occurred at least five months after initiating stimulation.

Results: Cortical entrained gamma oscillations were detected in 4/5 hemispheres undergoing pallidal stimulation and 12/15 hemispheres undergoing subthalamic stimulation. Entraining levodopa-induced gamma oscillations at either site reduced their prodyskinetic effects. Cortical entrained gamma oscillations had reduced variance in peak frequency, increased spectral power, and higher variance in spectral power than levodopa-induced gamma oscillations.

Conclusion: Stimulation-entrained gamma oscillations are functionally and physiologically distinct from levodopa-induced gamma oscillations that occur in the absence of deep brain stimulation. Understanding the discrepancies between types of gamma oscillations may improve programming protocols.

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http://dx.doi.org/10.1016/j.brs.2025.01.011DOI Listing

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