Objective: ​​​​​ ​​To assess the feasibility of continuously amplifying or suppressing subthalamic beta oscillations in real-time in Parkinson’s disease (PD) patients using a bidirectional, closed-loop brain machine interface.

Background: Studies aimed to clarify whether 13-30 Hz (“beta” band) oscillations in the subthalamic nucleus (STN) are causally linked to the manifestation of bradykinesia and rigidity in PD are needed to better understand PD pathophysiology and advance personalized neuromodulation devices. A recent study in the human showed that amplification or suppression of beta-band oscillations in the internal segment of the globus pallidus (GPi) could be achieved using beta-band neural responses evoked by electrical stimulation in the GPi[1]. This approach, known as closed-loop evoked interference deep brain stimulation (eiDBS), operates on the principle that synaptic-mediated, stimulation-evoked responses can modulate spontaneous oscillations through synaptic summation. To achieve this modulation, electrical pulses are delivered with precise amplitude and timing relative to the targeted oscillation’s phase[1,2].

Method: The Cleveland Clinic IRB approved all patient procedures. Local field potentials (LFPs) in the off-stimulation state and during 2.93 Hz stimulation were recorded from the STN of two PD patients 2-7 days after DBS surgery. We characterized the spectral dynamics of spontaneous and stimulation-evoked STN activity and, based on this characterization, deployed real-time control algorithms to implement eiDBS. The frequency band targeted for modulation was centered at each participant’s peak beta frequency of the LFP power spectrum. A computer interface was used to identify the stimulation amplitude and phase that maximized suppression or amplification of the targeted oscillations. We evaluated the differences in LFP power across the off-stimulation, suppression, and amplification conditions and associated effect sizes using the rank-sum and Cohen’s U3 tests.

Results: eiDBS could suppress or amplify frequency-specific neural activity in real-time in the studied subjects (p<0.01, effect size> 0.79).

Conclusion: Our findings provide support for conducting clinical studies to investigate the causal relationship between controlled suppression or amplification of STN beta oscillations and specific PD motor signs using eiDBS.

References: [1] Escobar Sanabria D, Aman JE, Amaya VZ, Johnson LA, Farooqi H, Wang J, Hill M, Patriat R, Sovell-Brown K, Molnar GF, Darrow D, McGovern R, Cooper SE, Harel N, MacKinnon CD, Park MC, Vitek JL. (2022). Controlling pallidal oscillations in real-time in Parkinson’s disease using evoked interference deep brain stimulation (eiDBS): Proof of concept in the human. Brain Stimulation. 15(5):1111–1119.

[2] Escobar Sanabria D, Johnson LA, Yu Y, Busby Z, Nebeck S, Zhang J, Harel N, Johnson MD, Molnar GF, Vitek JL. (2022). Real-time suppression and amplification of frequency-specific neural activity using stimulation evoked oscillations. Brain Stimulation. 13(6):1732–1742.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/amplifying-or-suppressing-subthalamic-beta-oscillations-in-real-time-in-parkinsons-disease-using-evoked-interference-deep-brain-stimulation-eidbs-feasibility-in-the-human/