Objective: To investigate how onset mode in Parkinson’s disease relates to cortical phase-amplitude coupling, a putative electrophysiological marker of pathological hypersynchronization.

Background: Cortical circuitry in Parkinson’s disease is not well understood. Invasive electrophysiological recordings have reported strong phase-amplitude coupling between the phase of beta oscillations and the amplitude of high frequency oscillations (PAC_ß-HFO) in the sensorimotor cortex in Parkinson’s disease. However, it remains unclear how these focal and sparsely sampled measurements integrate into the broader cortical context and how elevated PAC_ß-HFO relates to the range of clinical motor phenotypes of Parkinson’ disease.

Methods: In this study, we non-invasively measured cortical PAC_ß-HFO with magnetoencephalography (MEG) in eight subjects whose initial disease burden was dominated by tremor (tremor onset, TO group), ten subjects whose initial disease burden was dominated by bradykinesia (non-tremor onset, NTO group), and ten age-matched healthy control subjects (control group). Cortical PAC_ß-HFO was measured in the resting state in all subjects, and both off and on dopaminergic replacement therapy in the Parkinson’s disease subjects. Phase-amplitude coupling was computed from source-localized cortical signals, with regions of ‘high’ phase-amplitude coupling values clustered by cortical regions.

Results: The MEG data showed that the intensity and spatial distribution of PAC_ß-HFO was stronger and more variable across the Parkinson’s disease subjects compared to control subjects. The MEG data also showed that a higher proportion of subjects in the NTO group had strong PAC_ß-HFO clustered in the frontal cortex, compared to subjects in the TO and control groups. However, these PAC_ß-HFO clusters exhibited no consistent change with dopamine replacement therapy.

Conclusions: These results suggest that the spatial distribution of cortical PAC_ß-HFO has relevance to the initial disease burden of parkinsonian motor signs. In addition, the results indicate that the motor signs used to identify clinical phenotypes may not be the only factors determining abnormal cortical neurophysiology in Parkinson’s disease.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cortical-phase-amplitude-coupling-across-parkinsons-disease-phenotypes-measured-with-magnetoencephalograph/