Objective: To investigate EEG-based functional connectivity (FC) differences between patients with early-onset Parkinson’s disease (EOPD) and late-onset Parkinson’s disease (LOPD) at an early disease stage, and their association with motor features.

Background: EOPD, defined by symptom onset before age 50, may differ clinically from LOPD, including a greater early predisposition to motor fluctuations [1]. However, specific neurophysiological profiles of whole-brain FC underlying these subtypes have not yet been characterized.

Method: The study involved twenty patients with EOPD and forty with LOPD, all within 36 months from diagnosis. Resting-state EEG was recorded with a 64 channel system. Source reconstruction based on individual brain MRI identified regional cortical activity. Cortico-cortical FC was estimated using the weighted phase lag index across θ, α, β, and γ bands [2]. Network-based statistics assessed between-group differences. Motor severity was assessed with the Movement Disorder Society Unified Parkinson’s Disease Rating Scale part III (MDS-UPDRS III).

Results: Compared with LOPD, EOPD showed a hypoconnected network in high-γ band, mainly involving sensorimotor regions (t=2.3, p=0.01). Conversely, EOPD exhibited an α-band hyperconnected network relative to LOPD (t=2.2, p=0.03) centered on prefrontal and temporo-parietal cortices. No differences emerged in θ or β bands. MDS-UPDRS-III scores did not differ significantly between groups.

Conclusion: Despite similar motor burden, early-stage EOPD patients showed FC patterns distinct from those of LOPD, suggesting that network organization in PD may segregate by age at onset. The finding of high γ-band FC hypoconnectivity is noteworthy: despite the possibility that younger age might favor greater prokinetic high frequency recruitment, the opposite pattern emerged in EOPD, possibly reflecting early sensorimotor integration disruption and increasing vulnerability to motor fluctuations. Moreover, the α-band enhanced FC may indicate relatively preserved cholinergic circuitry in EOPD, whereas in LOPD circuit derangement may be compounded by aging-related network vulnerability [3]. These findings support age at onset as a relevant biological dimension in Parkinson’s disease and suggest that early FC signatures may improve disease subtyping and guide future targeted neuromodulation strategies.

References: [1] R. Bovenzi et al., “Shaping the course of early-onset Parkinson’s disease: insights from a longitudinal cohort,” Neurological Sciences, 2023, doi: 10.1007/s10072-023-06826-5.
[2] M. Conti et al., “Band-Specific Altered Cortical Connectivity in Early Parkinson’s Disease and its Clinical Correlates,” Movement Disorders, vol. 38, no. 12, 2023, doi: 10.1002/mds.29615.
[3] M. Conti et al., “Clinical, Biological, and Functional Connectivity Profile of Patients With De Novo Parkinson Disease Who Are APOE ε4 Carriers,” Neurology, vol. 106, no. 1, p. e214449, Jan. 2026, doi: 10.1212/WNL.0000000000214449.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/distinct-hd-eeg-functional-connectivity-patterns-in-early-onset-parkinsons-disease/