Premotor cortical beta synchronization and the network neuromodulation of externally paced finger tapping in Parkinson's disease.

Parkinson's disease (PD) is characterized by the disruption of repetitive, concurrent and sequential motor actions due to compromised timing-functions principally located in cortex-basal ganglia (BG) circuits. Increasing evidence suggests that motor impairments in untreated PD patients are linked to an excessive synchronization of cortex-BG activity at beta frequencies (13-30 Hz). Levodopa and subthalamic nucleus deep brain stimulation (STN-DBS) suppress pathological beta-band reverberation and improve the motor symptoms in PD. Yet a dynamic tuning of beta oscillations in BG-cortical loops is fundamental for movement-timing and synchronization, and the impact of PD therapies on sensorimotor functions relying on neural transmission in the beta frequency-range remains controversial. Here, we set out to determine the differential effects of network neuromodulation through dopaminergic medication (ON and OFF levodopa) and STN-DBS (ON-DBS, OFF-DBS) on tapping synchronization and accompanying cortical activities. To this end, we conducted a rhythmic finger-tapping study with high-density EEG-recordings in 12 PD patients before and after surgery for STN-DBS and in 12 healthy controls. STN-DBS significantly ameliorated tapping parameters as frequency, amplitude and synchrony to the given auditory rhythms. Aberrant neurophysiologic signatures of sensorimotor feedback in the beta-range were found in PD patients: their neural modulation was weaker, temporally sluggish and less distributed over the right cortex in comparison to controls. Levodopa and STN-DBS boosted the dynamics of beta-band modulation over the right hemisphere, hinting to an improved timing of movements relying on tactile feedback. The strength of the post-event beta rebound over the supplementary motor area correlated significantly with the tapping asynchrony in patients, thus indexing the sensorimotor match between the external auditory pacing signals and the performed taps. PD patients showed an excessive interhemispheric coherence in the beta-frequency range during the finger-tapping task, while under DBS-ON the cortico-cortical connectivity in the beta-band was normalized. Ultimately, therapeutic DBS significantly ameliorated the auditory-motor coupling of PD patients, enhancing the electrophysiological processing of sensorimotor feedback-information related to beta-band activity, and thus allowing a more precise cued-tapping performance.
Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Authors T.R. Schneider, A. Pino, S. Zittel, C. Gerloff, M. Westphal, and A.K. Engel declare no relevant conflicts of interest. Some of the authors (A. Gulberti, C.K.E. Moll, W. Hamel, C. Buhmann, M. Heise). have occasionally been reimbursed for travel expenses from Medtronic Inc. C. Buhmann served on the scientific advisory boards for Bial, Desitin, Kyowa Kirin, Merz, Stadapharm and Zambon and received honoraria for lectures from Abbott, Abbvie, Bial, Desitin, Hormosan, Merz, l, TAD Pharma, UCB and Zambon. S. Zittel served on the scientific advisory board for Biomarin and received honoraria for lectures from Merz Pharmaceuticals. C. Gerloff reports personal fees and other from Bayer Healthcare and Boehringer Ingelheim, personal fees from Abbott, Amgen, BMS, Sanofi Aventis, and Prediction Biosciences. C.K.E. Moll received lecture, teaching and proctoring fees from Abbott. W. Hamel received lecture fees and honoraria for serving on advisory boards and travel grants from Boston Scientific, Medtronic, and Abbott. M. Pötter-Nerger received lecture fees from Abbott and Licher, and served as consultant for Medtronic, Boston Scientific and Abbvie.
(Copyright © 2023. Published by Elsevier Inc.)