Characterizing the frequency-specific and spatiotemporal dynamics of β-γ Phase-Amplitude Coupling in Parkinson's disease

Loehrer, P. A.; Yassine, S.; Weber, I.; Sanner, V.; He, S. A.; Pogosyan, A.; Chen, L.; Witt, L.; Fink, G. R.; Pedrosa, D. J.; Timmermann, L.; Tan, H.

doi:10.1101/2025.05.14.653744

bioRxiv · 10.1101/2025.05.14.653744

Characterizing the frequency-specific and spatiotemporal dynamics of β-γ Phase-Amplitude Coupling in Parkinson's disease

Loehrer, P. A.·Yassine, S.·Weber, I.·Sanner, V.·He, S. A.·Pogosyan, A.·Chen, L.·Witt, L.·Fink, G. R.·Pedrosa, D. J.·Timmermann, L.·Tan, H.

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Abstract

Cross-frequency coupling (CFC) has been proposed to facilitate neural information transfer across spatial and temporal scales. Phase-amplitude coupling (PAC), a type of CFC in which the amplitude of a faster brain oscillation is coupled to the phase of a slower brain oscillation, is implicated in various higher-order cognitive functions and was shown to be pathologically altered in neurological and psychiatric disease. In Parkinsons disease (PD), the coupling between gamma amplitude (50-150 Hz) to beta phase (13-35 Hz) is exaggerated. Enhanced {beta}-{gamma} PAC was found in the subthalamic nucleus and various cortical sources and shown to be responsive to dopaminergic therapy and deep brain stimulation (DBS). Therefore, exaggerated {beta}-{gamma} PAC has been proposed to be a disease marker and a potential target for brain circuit interventions. Despite these promising findings, a significant knowledge gap remains, as the spatial and frequency-specific dynamics of {beta}-{gamma} PAC and its association with motor symptoms and therapy remain elusive. To address this knowledge gap, we employed high-density electroencephalography (EEG) with advanced source localisation techniques for PD patients at rest. We highlight three key findings: (1) a frequency-specific increase in high {beta} (23-35 Hz)-{gamma} PAC within and between sources of the cortical motor network, (2) a link between elevated high {beta}-{gamma} PAC and bradykinesia and rigidity when OFF medication, but not tremor, and (3) a medication-induced reduction in high {beta}-{gamma} PAC in the supplementary motor area correlating with clinical improvement. Altogether, this study provides novel insights into the pathophysiology of PD as an oscillopathy and identifies high {beta}-{gamma} PAC as a potential marker of Parkinsonian symptoms and treatment effects. This has important implications for invasive as well as non-invasive therapeutic strategies as high {beta}-{gamma} PAC targeting might hold greater promise than targeting {beta}-{gamma} PAC per se.

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Loehrer, P. A., Yassine, S., Weber, I., Sanner, V., He, S. A., Pogosyan, A., Chen, L., Witt, L., Fink, G. R., Pedrosa, D. J., Timmermann, L., Tan, H.. 2025-05-18. Characterizing the frequency-specific and spatiotemporal dynamics of β-γ Phase-Amplitude Coupling in Parkinson's disease. https://doi.org/10.1101/2025.05.14.653744

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