Introduction: Pathophysiological beta oscillations across cortico-subcortical structures are thought to be a central causative feature in Parkinson disease (PD) [1]. Furthermore, recent evidence suggests that features of beta oscillations, such as bursting [2], waveform shape [3] and phase-amplitude coupling [4], are abnormal in the dopamine depleted state. Here we show that cortical beta bursting is prolonged in PD and associated with increased interregional synchrony. Waveform shape of beta oscillations is distinct during beta bursts, contrasting with non-burst episodes, and bursts are accompanied by increases in local cortical phase-amplitude coupling.
Methods: We studied 32 patients undergoing deep brain stimulation (DBS) surgery for PD (22 patients) and essential tremor (10 patients). A subdural strip of 8 electrodes was advanced intracranially to lie rostro-caudally over sensorimotor cortices. Patients made cued opening and closing hand movements in blocks of 30s interpolated with 30s rest periods. MRI/CT fusion combined with SSEPs allowed for accurate identification of sensorimotor cortices.
Results: All cortices studied (S1, M1 and premotor) showed significantly increased higher amplitude beta oscillations (20-35Hz) in PD compared to ET patients. Both ET and PD patients showed similarly increased synchrony during beta bursting compared to non-bursting. Waveform analysis shows that burst episodes are associated with a more 'sawtooth' oscillation shape. Beta bursting was associated with increased beta to broadband gamma phase-amplitude coupling in motor cortex and prolongation of beta bursting shows a correlation with clinical bradykinesia and rigidity scores on the UPDRS.
Conclusions: Here we link together several strands of research to show that not only are beta bursts longer in duration in PD motor cortex but that they can be characterized as episodes of high interregional synchrony, phase-locking premotor and motor cortices. Furthermore, waveform shape of beta bursts is altered, potentially explaining why burst episodes show increased phase amplitude coupling between the beta band and broadband gamma.
Patient Care: A greater understanding of the role of beta oscillations may prove fundamental in developing new treatments for this common and debilitating neurodegenerative disorder. As a biomarker of PD severity beta prolongation may also serve as a useful feedback signal for closed-loop DBS systems.
Learning Objectives: Participants should be able to understand how various aspects of PD neurophysiology relate to one another and how this leads to expression of the symptoms of the disorder at the behavioral level.
References: 1. Jenkinson, N. & Brown, P. New insights into the relationship between dopamine, beta oscillations and motor function. Trends Neurosci. 34, 611–618 (2011).
2. Tinkhauser, G. et al. Beta burst dynamics in Parkinson’s disease OFF and ON dopaminergic medication. Brain 140, 2968–2981 (2017).
3. Cole, S. R. et al. Nonsinusoidal Beta Oscillations Reflect Cortical Pathophysiology in Parkinson’s Disease. J. Neurosci. 37, 4830–4840 (2017).
4. de Hemptinne, C. et al. Therapeutic deep brain stimulation reduces cortical phase-amplitude coupling in Parkinson’s disease. Nat. Neurosci. advance online publication, (2015).
5. de Hemptinne, C. et al. Exaggerated phase–amplitude coupling in the primary motor cortex in Parkinson disease. Proc. Natl. Acad. Sci. U. S. A. 110, 4780–4785 (2013).