Alterations of PAC-based resting state networks in Parkinson’s disease are partially alleviated by levodopa medication

Abstract

IntroductionParkinson’s disease (PD) is a neurodegenerative disorder affecting the whole brain, leading to several motor and non-motor symptoms. In the past, it has been shown that PD alters resting state networks (RSN) in the brain. These networks are usually derived from fMRI BOLD signals. This study investigated RSN changes in PD patients based on maximum phase-amplitude coupling (PAC) throughout the cortex. We also tested the hypothesis that levodopa medication shifts network activity back toward a healthy state.MethodsWe recorded 23 PD patients and 24 healthy age-matched participants for 30 min at rest with magnetoencephalography (MEG). PD patients were measured once in the dopaminergic medication ON and once in the medication OFF state. A T1-MRI brain scan was acquired from each participant for source reconstruction. After correcting the data for artifacts and performing source reconstruction using a linearly constrained minimum variance beamformer, we extracted visual, sensorimotor (SMN), and frontal RSNs based on PAC.ResultsWe found significant changes in all networks between healthy participants and PD patients in the medication OFF state. Levodopa had a significant effect on the SMN but not on the other networks. There was no significant change in the optimal PAC coupling frequencies between healthy participants and PD patients.DiscussionOur results suggest that RSNs, based on PAC in different parts of the cortex, are altered in PD patients. Furthermore, levodopa significantly affects the SMN, reflecting the clinical alleviation of motor symptoms and leading to a network normalization compared to healthy controls.

Resting State Network alterations during Deep Brain Stimulation in Parkinson’s Disease

“…Taking the previous findings into consideration, we hypothesized that DBS and dopaminergic medication distinctly alter functional connectivity in RSNs, which would help to explain their differential effectiveness. Both medication and DBS together would lead to RSNs similar to healthy controls along the same line as the improvement already demonstrated with medication alone (Mertiens et al, 2023; Schneider et al, 2020)…”

“…Taking the previous findings into consideration, we hypothesized that DBS and dopaminergic medication distinctly alter functional connectivity in RSNs, which would help to explain their differential effectiveness. Both medication and DBS together would lead to RSNs similar to healthy controls along the same line as the improvement already demonstrated with medication alone (Mertiens et al, 2023;Schneider et al, 2020) To test our hypothesis, we recorded resting state activity with eyes open in the magnetoencephalogram (MEG) of PD patients implanted with DBS. The patients were recorded in 4 different conditions: baseline (no medication, DBS turned off), only medication, only DBS turned on, and medication + DBS turned on.…”

“…To compare the conditions statistically, we also created surrogate RSNs using the jackknife resampling method (Mertiens et al, 2023; Sure et al, 2023). To this end, we followed the same megPAC routine with the exception of leaving one subject out each time and concatenating the time series of remaining subjects to derive the RSNs.…”

Predicting Motor Vigor from EEG Phase Amplitude Coupling (PAC) in Parkinson’s Disease: Effects of Dopaminergic Medication and Non-invasive Modulation

“…In an animal model, deltahigh-gamma PAC in the motor cortex and striatum has been observed by dopamine D2 receptor blockade (Reakkamnuan et al, 2023). Altered PAC in PD has been observed at rest in both the MEG (Mertiens et al, 2023) and EEG (Miller et al, 2019;Zhang et al, 2021). This has led to speculation that PAC might be a valuable biomarker to target neuromodulation strategies (Hwang et al, 2020;Salimpour et al, 2022;Yeh et al, 2023).…”

“…In an animal model, delta-high-gamma PAC in the motor cortex and striatum has been observed by dopamine D2 receptor blockade [11]. Altered PAC in PD has been observed at rest in both the MEG [12] and EEG [13, 14]. This has led to speculation that PAC might be a valuable biomarker to target neuromodulation strategies [15, 16, 17].…”