Modulation of Subthalamic Beta Oscillations by Movement, Dopamine, and Deep Brain Stimulation in Parkinson's Disease

Overview

Journal NPJ Parkinsons Dis

Date 2024 Apr 5

PMID 38580641

Authors

Varvara Mathiopoulou

Roxanne Lofredi

Lucia K Feldmann

Jeroen Habets

Natasha Darcy

Wolf-Julian Neumann

Katharina Faust

Gerd-Helge Schneider

Andrea A Kuhn

Affiliations

Soon will be listed here.

Abstract

Subthalamic beta band activity (13-35 Hz) is known as a real-time correlate of motor symptom severity in Parkinson's disease (PD) and is currently explored as a feedback signal for closed-loop deep brain stimulation (DBS). Here, we investigate the interaction of movement, dopaminergic medication, and deep brain stimulation on subthalamic beta activity in PD patients implanted with sensing-enabled, implantable pulse generators. We recorded subthalamic activity from seven PD patients at rest and during repetitive movements in four conditions: after withdrawal of dopaminergic medication and DBS, with medication only, with DBS only, and with simultaneous medication and DBS. Medication and DBS showed additive effects in improving motor performance. Distinct effects of each therapy were seen in subthalamic recordings, with medication primarily suppressing low beta activity (13-20 Hz) and DBS being associated with a broad decrease in beta band activity (13-35 Hz). Movement suppressed beta band activity compared to rest. This suppression was most prominent when combining medication with DBS and correlated with motor improvement within patients. We conclude that DBS and medication have distinct effects on subthalamic beta activity during both rest and movement, which might explain their additive clinical effects as well as their difference in side-effect profiles. Importantly, subthalamic beta activity significantly correlated with motor symptoms across all conditions, highlighting its validity as a feedback signal for closed-loop DBS.

Citing Articles

Could adaptive deep brain stimulation treat freezing of gait in Parkinson's disease?.

Klocke P, Loeffler M, Lewis S, Gharabaghi A, Weiss D J Neurol. 2025; 272(4):267.

PMID: 40072634 PMC: 11903562. DOI: 10.1007/s00415-025-13000-8.

Subthalamic Activity Is Associated With Proactive Inhibition in Parkinson's Disease Patients.

Damiani L, Albares M, Laviron P, Le Douget J, Boulinguez P, Karachi C Eur J Neurosci. 2025; 61(5):e70055.

PMID: 40059835 PMC: 11891829. DOI: 10.1111/ejn.70055.

Significance of gender, brain region and EEG band complexity analysis for Parkinson's disease classification using recurrence plots and machine learning algorithms.

Sasidharan D, Sowmya V, Gopalakrishnan E Phys Eng Sci Med. 2025; .

PMID: 39869266 DOI: 10.1007/s13246-025-01521-5.

Machine learning explains response variability of deep brain stimulation on Parkinson's disease quality of life.

Ferrea E, Negahbani F, Cebi I, Weiss D, Gharabaghi A NPJ Digit Med. 2024; 7(1):269.

PMID: 39354049 PMC: 11445542. DOI: 10.1038/s41746-024-01253-y.

Current and future applications of local field potential-guided programming for Parkinson's disease with the Percept™ rechargeable neurostimulator.

Saengphatrachai W, Jimenez-Shahed J Neurodegener Dis Manag. 2024; 14(5):131-147.

PMID: 39344591 PMC: 11524207. DOI: 10.1080/17582024.2024.2404386.

References

Doyle L, Kuhn A, Hariz M, Kupsch A, Schneider G, Brown P . Levodopa-induced modulation of subthalamic beta oscillations during self-paced movements in patients with Parkinson's disease. Eur J Neurosci. 2005; 21(5):1403-12. DOI: 10.1111/j.1460-9568.2005.03969.x. View

Kuhn A, Tsui A, Aziz T, Ray N, Brucke C, Kupsch A . Pathological synchronisation in the subthalamic nucleus of patients with Parkinson's disease relates to both bradykinesia and rigidity. Exp Neurol. 2008; 215(2):380-7. DOI: 10.1016/j.expneurol.2008.11.008. View

Androulidakis A, Brucke C, Kempf F, Kupsch A, Aziz T, Ashkan K . Amplitude modulation of oscillatory activity in the subthalamic nucleus during movement. Eur J Neurosci. 2008; 27(5):1277-84. DOI: 10.1111/j.1460-9568.2008.06085.x. View

Lofredi R, Okudzhava L, Irmen F, Brucke C, Huebl J, Krauss J . Subthalamic beta bursts correlate with dopamine-dependent motor symptoms in 106 Parkinson's patients. NPJ Parkinsons Dis. 2023; 9(1):2. PMC: 9825387. DOI: 10.1038/s41531-022-00443-3. View

Priori A, Foffani G, Pesenti A, Tamma F, Bianchi A, Pellegrini M . Rhythm-specific pharmacological modulation of subthalamic activity in Parkinson's disease. Exp Neurol. 2004; 189(2):369-79. DOI: 10.1016/j.expneurol.2004.06.001. View

Lofredi R, Auernig G, Irmen F, Nieweler J, Neumann W, Horn A . Subthalamic stimulation impairs stopping of ongoing movements. Brain. 2020; 144(1):44-52. DOI: 10.1093/brain/awaa341. View

Eusebio A, Cagnan H, Brown P . Does suppression of oscillatory synchronisation mediate some of the therapeutic effects of DBS in patients with Parkinson's disease?. Front Integr Neurosci. 2012; 6:47. PMC: 3392592. DOI: 10.3389/fnint.2012.00047. View

Stam M, van Wijk B, Sharma P, Beudel M, Pina-Fuentes D, de Bie R . A comparison of methods to suppress electrocardiographic artifacts in local field potential recordings. Clin Neurophysiol. 2022; 146:147-161. DOI: 10.1016/j.clinph.2022.11.011. View

Jenkinson N, Brown P . New insights into the relationship between dopamine, beta oscillations and motor function. Trends Neurosci. 2011; 34(12):611-8. DOI: 10.1016/j.tins.2011.09.003. View

10.

Tsiokos C, Malekmohammadi M, AuYong N, Pouratian N . Pallidal low β-low γ phase-amplitude coupling inversely correlates with Parkinson disease symptoms. Clin Neurophysiol. 2017; 128(11):2165-2178. PMC: 5675765. DOI: 10.1016/j.clinph.2017.08.001. View

11.

Litvak V, Mattout J, Kiebel S, Phillips C, Henson R, Kilner J . EEG and MEG data analysis in SPM8. Comput Intell Neurosci. 2011; 2011:852961. PMC: 3061292. DOI: 10.1155/2011/852961. View

12.

Neumann W, Degen K, Schneider G, Brucke C, Huebl J, Brown P . Subthalamic synchronized oscillatory activity correlates with motor impairment in patients with Parkinson's disease. Mov Disord. 2016; 31(11):1748-1751. PMC: 5120686. DOI: 10.1002/mds.26759. View

13.

Darcy N, Lofredi R, Al-Fatly B, Neumann W, Hubl J, Brucke C . Spectral and spatial distribution of subthalamic beta peak activity in Parkinson's disease patients. Exp Neurol. 2022; 356:114150. DOI: 10.1016/j.expneurol.2022.114150. View

14.

Florin E, Dafsari H, Reck C, Barbe M, Pauls K, Maarouf M . Modulation of local field potential power of the subthalamic nucleus during isometric force generation in patients with Parkinson's disease. Neuroscience. 2013; 240:106-16. DOI: 10.1016/j.neuroscience.2013.02.043. View

15.

Kuhn A, Williams D, Kupsch A, Limousin P, Hariz M, Schneider G . Event-related beta desynchronization in human subthalamic nucleus correlates with motor performance. Brain. 2004; 127(Pt 4):735-46. DOI: 10.1093/brain/awh106. View

16.

Bronte-Stewart H, Barberini C, Koop M, Hill B, Henderson J, Wingeier B . The STN beta-band profile in Parkinson's disease is stationary and shows prolonged attenuation after deep brain stimulation. Exp Neurol. 2008; 215(1):20-8. DOI: 10.1016/j.expneurol.2008.09.008. View

17.

Little S, Pogosyan A, Kuhn A, Brown P . β band stability over time correlates with Parkinsonian rigidity and bradykinesia. Exp Neurol. 2012; 236(2):383-8. PMC: 3400051. DOI: 10.1016/j.expneurol.2012.04.024. View

18.

Oswal A, Beudel M, Zrinzo L, Limousin P, Hariz M, Foltynie T . Deep brain stimulation modulates synchrony within spatially and spectrally distinct resting state networks in Parkinson's disease. Brain. 2016; 139(Pt 5):1482-96. PMC: 4845255. DOI: 10.1093/brain/aww048. View

19.

Timmermann L, Braun M, Groiss S, Wojtecki L, Ostrowski S, Krause H . Differential effects of levodopa and subthalamic nucleus deep brain stimulation on bradykinesia in Parkinson's disease. Mov Disord. 2007; 23(2):218-27. DOI: 10.1002/mds.21808. View

20.

Kuhn A, Kupsch A, Schneider G, Brown P . Reduction in subthalamic 8-35 Hz oscillatory activity correlates with clinical improvement in Parkinson's disease. Eur J Neurosci. 2006; 23(7):1956-60. DOI: 10.1111/j.1460-9568.2006.04717.x. View