Objective: To characterize the effect of levodopa medication cycle on subthalamic nucleus (STN) local field potential (LFP) beta-band power in Parkinson’s disease (PD) in the setting of therapeutic deep brain stimulation (DBS).

Background: STN LFP beta power (13-30 Hz) has been previously demonstrated to reflect Parkinsonian symptoms such as bradykinesia and rigidity [1], and fluctuates in response to both a patient’s medication cycle and therapeutic DBS. [2] STN beta power has been proposed as a possible feedback signal for adaptive DBS (aDBS) systems, which are designed to modulate stimulation in response to the patient’s symptoms [3-4]. However, the relationship between stimulation and medication cycle effects on beta power modulation during STN stimulation has not been previously described.

Method: Four patients with PD participated who had investigational sensing DBS stimulators (Summit® RC+S, Medtronic) implanted with STN and motor cortical quadripolar leads (seven instrumented hemispheres). Each subject had standard-of-care DBS programming and subsequent adjustment in PD medications. LOW- and HIGH-stimulation states were then titrated to provide adequate symptom control during the OFF- and ON- states produced by the clinical medication cycle. At least 10 min of STN LFPs were recorded for all combinations of the two medication states (ON and OFF) and three stimulation states (OFF, LOW, and HIGH), during a standardized set of activities.

Results: Six of the seven hemispheres had prominent beta peaks in the OFF-medication + OFF-stimulation state. Active stimulation resulted in decreased beta peak amplitude and/or shifted peak beta frequency in all cases. In three of seven hemispheres, medication-induced beta power modulation was minimal when assessed with stimulation-ON. In other hemispheres, changes in medication state produced appreciable effects on beta amplitude when stimulation was ON.

Conclusion: In PD patients, medications dosed for concurrent use with active STN stimulation resulted in variable beta-power modulation across subjects. For some subjects, the effect of stimulation on beta power was more profound than the effect of medication. These results have implications for programming aDBS systems using STN beta power as a feedback signal reflecting a patient’s medication state.

References: [1] Kühn A.A., Kupsch A., Schneider G.-H., Brown P. Reduction in subthalamic 8–35 Hz oscillatory activity correlates with clinical improvement in Parkinson’s disease. Eur. J. Neurosci. 2006;23:1956–1960.
[2] Kühn, A. A., Kempf, F., Brücke, C., Doyle, L. G., Martinez-Torres, I., Pogosyan, A., … & Brown, P. High-frequency stimulation of the subthalamic nucleus suppresses oscillatory β activity in patients with Parkinson’s disease in parallel with improvement in motor performance. J. Neurosci. 2008;28(24):6165-6173.
[3] Little S, Pogosyan A, Neal S, Zavala B, Zrinzo L, Hariz M, Foltynie T, Limousin P, Ashkan K, FitzGerald J, Green AL, Aziz TZ, Brown P. Adaptive deep brain stimulation in advanced Parkinson disease. Ann Neurol. 2013;74(3):449–457.
[4] Velisar A, Syrkin-Nikolau J, Blumenfeld Z, Trager MH, Afzal MF, Prabhakar V, Bronte-Stewart H. Dual threshold neural closed loop deep brain stimulation in Parkinson disease patients. Brain Stimul. Elsevier Ltd; 2019;12(4):868–876.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/effect-of-clinical-levodopa-medication-cycle-on-subthalamic-beta-band-power-during-therapeutic-deep-brain-stimulation-in-parkinsons-disease/