Serendipitous Stimulation of Nucleus Basalis of Meynert—The Effect of Unintentional, Long-Term High-Frequency Stimulation on Cognition in Parkinson’s Disease

There is a growing interest in deep brain stimulation (DBS) of the nucleus basalis of Meynert (NBM) as a potential therapeutic modality for Parkinson’s disease dementia (PDD). Low-frequency stimulation has yielded encouraging results in individual patients; however, these are not yet sustained in larger studies. With the aim to expand the understanding of NBM-DBS, we share our experience with serendipitous NBM-DBS in patients treated with DBS of the internal Globus pallidus (GPi) for Parkinson’s disease. Since NBM is anatomically located ventral to GPi, several GPi-treated patients appeared to have the distal contact of DBS-electrode(s) positioned in the NBM. We hypothesized that unintentional high-frequency NBM-DBS over a period of one year would result in the opposite effect of low-frequency NBM-stimulation and cause cognitive decline. We studied a cohort of 33 patients with bilateral high-frequency DBS in the GPi for Parkinson’s disease, of which twelve were unintentionally co-stimulated in NBM. The subgroups of unintentional unilateral (N = 7) and bilateral NBM-DBS (N = 5) were compared to the control group of bilateral GPi-DBS (N = 11). Here, we show that unintentional high-frequency NBM-DBS did not cause a significantly faster decline in cognitive function. Further research is warranted for characterizing the therapeutic role of NBM-DBS.

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Bilateral high-frequency stimulation of the internal globus pallidus in advanced Parkinson's disease

Annals of Neurology ◽

10.1002/ana.410440615 ◽

1998 ◽

Vol 44 (6) ◽

pp. 953-961 ◽

Cited By ~ 152

Author(s):

J. Volkmann ◽

V. Sturm ◽

P. Weiss ◽

J. Kappler ◽

J. Voges ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Globus Pallidus ◽

High Frequency ◽

High Frequency Stimulation ◽

Internal Globus Pallidus ◽

Advanced Parkinson’S Disease ◽

Frequency Stimulation ◽

Stimulation Of

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Electroceutically induced subthalamic high-frequency oscillations and evoked compound activity may explain the mechanism of therapeutic stimulation in Parkinson’s disease

Communications Biology ◽

10.1038/s42003-021-01915-7 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Musa Ozturk ◽

Ashwin Viswanathan ◽

Sameer A. Sheth ◽

Nuri F. Ince

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Pharmacological Treatment ◽

High Frequency ◽

High Frequency Stimulation ◽

High Frequency Oscillations ◽

Stimulation Pulse ◽

Main Challenge ◽

Frequency Stimulation ◽

Underlying Mechanisms

AbstractDespite having remarkable utility in treating movement disorders, the lack of understanding of the underlying mechanisms of high-frequency deep brain stimulation (DBS) is a main challenge in choosing personalized stimulation parameters. Here we investigate the modulations in local field potentials induced by electrical stimulation of the subthalamic nucleus (STN) at therapeutic and non-therapeutic frequencies in Parkinson’s disease patients undergoing DBS surgery. We find that therapeutic high-frequency stimulation (130–180 Hz) induces high-frequency oscillations (~300 Hz, HFO) similar to those observed with pharmacological treatment. Along with HFOs, we also observed evoked compound activity (ECA) after each stimulation pulse. While ECA was observed in both therapeutic and non-therapeutic (20 Hz) stimulation, the HFOs were induced only with therapeutic frequencies, and the associated ECA were significantly more resonant. The relative degree of enhancement in the HFO power was related to the interaction of stimulation pulse with the phase of ECA. We propose that high-frequency STN-DBS tunes the neural oscillations to their healthy/treated state, similar to pharmacological treatment, and the stimulation frequency to maximize these oscillations can be inferred from the phase of ECA waveforms of individual subjects. The induced HFOs can, therefore, be utilized as a marker of successful re-calibration of the dysfunctional circuit generating PD symptoms.

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Electroceutically induced subthalamic high frequency oscillations and evoked compound activity may explain the mechanism of therapeutic stimulation in Parkinson's Disease

10.21203/rs.3.rs-63781/v1 ◽

2020 ◽

Author(s):

Musa Ozturk ◽

Ashwin Viswanathan ◽

Sameer Sheth ◽

Nuri Ince

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Pharmacological Treatment ◽

High Frequency ◽

High Frequency Stimulation ◽

High Frequency Oscillations ◽

Stimulation Pulse ◽

Main Challenge ◽

Frequency Stimulation ◽

Underlying Mechanisms

Abstract Despite having remarkable utility in treating movement disorders, the lack of understanding of the underlying mechanisms of high-frequency deep brain stimulation (DBS) is a main challenge in choosing personalized stimulation parameters. Here we investigate the modulations in local field potentials induced by therapeutic and non-therapeutic electrical stimulation of the subthalamic nucleus (STN) in Parkinson’s disease patients undergoing DBS surgery. We find that therapeutic high-frequency stimulation (130-180 Hz) induces high-frequency oscillations (~300 Hz, HFO) similar to those observed with pharmacological treatment. Along with HFOs, we also observed evoked compound activity (ECA) after each stimulation pulse. While ECA was observed in both therapeutic and non-therapeutic (20Hz) stimulation, the HFOs were induced only with therapeutic frequencies and the associated ECA were significantly more resonant. The relative degree of enhancement in the HFO power was related to the interaction of stimulation pulse with the phase of ECA.We propose that high-frequency STN-DBS tunes the neural oscillations to their healthy/treated state, similar to pharmacological treatment, and the stimulation frequency to maximize these oscillations can be inferred from the phase of ECA waveforms of individual subjects. The induced HFOs can, therefore, be utilized as a marker of successful re-calibration of the dysfunctional circuit generating PD symptoms.

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