Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder (Warnecke et al., 2023). It is characterized by degeneration of the nigrostriatal dopaminergic pathway, which broadly impairs the function of the basal ganglia–thalamocortical neural network. This dysfunction notably involves altered physiology/activity in the primary motor cortex (M1) and supplementary motor area (SMA), leading to aberrant neural activity within motor circuits and resulting in classic motor symptoms including bradykinesia, resting tremor, rigidity, and postural instability (Burciu and Vaillancourt, 2018; Leodori et al., 2022).

PD patients often present with asymmetric motor impairments in the early stages, which typically begin unilaterally and gradually progress to bilateral involvement as the disease advances. This lateralized pattern of motor dysfunction originates from the asymmetric degenerative changes in the basal ganglia (BG) and corresponding unilateral dopamine depletion (Riederer et al., 2018; Riederer and Sian-Hülsmann, 2012). While neuroimaging techniques such as fMRI and PET provide valuable structural and functional insights, they are often resource-intensive and may not capture neural dynamics with high temporal resolution. Therefore, it is an urgent need to develop objective, accurate, and cost-effective biological markers for clinical use.

Electroencephalography (EEG) is a non-invasive auxiliary examination method that assesses brain activity with high temporal resolution, capable of capturing rapid dynamic changes in neural processes (Waninger et al., 2020). EEG is well-suited to measuring oscillatory activity due to its high temporal resolution. Abnormal beta band (15–30 Hz) synchronization has been consistently correlated with the severity of motor deficits in PD (Gatev et al., 2006; Witcher et al., 2014; Nwogo et al., 2022; Wang and Choi, 2020). The pdBSI is a set of quantitative parameters derived from EEG power spectra that objectively reflects functional asymmetry between the cerebral hemispheres by measuring power differences across frequency bands (Wang et al., 2023). This index has been validated in contexts such as post-stroke motor recovery, which reduced pdBSI in low-frequency bands over motor regions correlates with better functional outcomes (Mauro et al., 2024; Agius et al., 2017; Gao et al., 2025). However, existing EEG studies in PD have largely focused on spectral power or network connectivity, and the application of quantitative symmetry indices such as the Brain Symmetry Index (BSI) or its pdBSI in this population remains limited, and its application in evaluating PD-related motor dysfunction remains unverified.

This study innovatively introduces pdBSI to assess motor staging in PD, aiming to characterize its disease-stage-dependent variations and correlation with motor impairment severity. Given that this study aims to characterize interhemispheric asymmetry in PD patients during a stable, routinely medicated state, all clinical and EEG assessments were conducted during the unified “ON” medication period. This ensures maximal comparability across participants and focuses the analysis on pathophysiological associations during the medication efficacy phase. This approach thereby provides new electrophysiological evidence for constructing an objective, EEG-based system for dynamic monitoring and staging of PD.

Early motor symptoms in PD are frequently asymmetric, typically manifesting unilaterally before progressing to bilateral involvement. This clinical lateralization is thought to mirror underlying asymmetric pathological changes, particularly the predominant degeneration of dopaminergic neurons in the contralateral substantia nigra. In this study, we applied the pdBSI—a quantitative metric of interhemispheric spectral power asymmetry—to investigate its relationship with disease stage and motor severity in PD. Our core finding is a distinct gradient of pdBSI values: ePD > aPD > HC. This pattern requires interpretation not merely as a measure of “more” or “less” abnormality, but as a dynamic electrophysiological signature of the disease’s pathological evolution.

The core pathology of PD involves the loss of dopaminergic neurons in the substantia nigra, which is markedly unilateral in the early stage. The asymmetry of motor symptoms in PD patients is associated with contralateral neurodegenerative changes and lateralized dopamine depletion at the level of the basal ganglia (BG) (Goedert et al., 2013; Barrett et al., 2011; Liu et al., 2024; Borghammer, 2021; Kaasinen, 2016; Kumakura et al., 2006). Dopamine Transporter Single Photon Emission Computed Tomography (DAT-SPECT) neuroimaging has revealed asymmetric impairment in both function and density of striatal dopamine transporters (DAT) in early-stage PD patients, whereas late-stage patients exhibit severe bilateral striatal dysfunction and reduced DAT density (Liu, 2007). The asymmetric cerebral pathological alterations lead to abnormal functional connectivity within motor networks, ultimately resulting in impaired motor coordination (Liuzzi et al., 2011). In our study, the H-Y stage was primarily based on motor symptom severity and postural stability, which was used to classify disease progression. The observed gradient (ePD > aPD > HC) offers a physiological interpretation of the clinical evolution from asymmetric to bilateral symptoms. In early-stage PD (ePD), pathological changes are markedly lateralized, leading to a strong interhemispheric contrast in oscillatory activity—captured as high pdBSI. As the disease advances to aPD, neurodegeneration and compensatory mechanisms likely involve the initially less-affected hemisphere, reducing the interhemispheric contrast. Thus, the decrease in pdBSI from ePD to aPD may not indicate “improvement” but rather a bilateralization of pathology, resulting in a more symmetrically abnormal oscillatory state across hemispheres. This interpretation aligns with the clinical observation of increasing bilateral motor deficits despite a potential reduction in the gross asymmetry metric.

Motor dysfunction in PD originates from disrupted neural activity across multiple interacting brain regions. In this study, the cerebral cortex was segmented into three functional regions, the anterior region (F7, F3, F4, F8), the central region (T3, C3, C4, T4), and the posterior region (T5, P3, P4, T6). Based on this parcellation, regional characteristics of the pdBSI were investigated. The results revealed that electroencephalographic spectral power asymmetry in PD patients was predominantly localized to the central and posterior regions. The M1 serves as a core structure in volitional motor control in humans. Midbrain dopaminergic neurons modulate neuronal firing rates and synchrony within M1 through both direct projections and indirect pathways involving the basal ganglia-thalamic circuitry (Galvan et al., 2015). The parietal cortex contributes to object-directed motor control and is crucial for postural stability, while the posterior parietal cortex integrates somatosensory information and plays a key role in lower limb motor control (Freund, 2003). Cortical thickness in specific brain areas decreases with increasing motor disability across PD stages. Early-stage PD patients often exhibit higher rates of cortical atrophy in the left insula and olfactory sulcus, whereas late-stage patients show more pronounced atrophy in bilateral occipital cortices (Claassen et al., 2016). The findings of this study demonstrate that alterations in pdBSI of PD patients are most prominent in the central and posterior regions. The concentration of pdBSI alterations in these areas underscores that hemispheric asymmetry in PD is not global but is functionally anchored to networks subserving motor planning, execution, and stability.

We further focused on the investigation of multi-band EEG activity. Existing evidence has demonstrated that cortical EEG activity in PD patients is generally slowed compared to healthy individuals. As early as the initial stages of the disease, fundamental EEG rhythms undergo alterations, characterized by a decrease in relative power in high-frequency bands and an increase in relative power in low-frequency bands (Wang et al., 2020). Neural oscillatory activity within the beta frequency range (13–35 Hz) is critically important for motor control, playing a role in movement regulation during both motor preparation and execution (van Wijk et al., 2012). Elevated beta activity in the motor cortex is associated with dopaminergic depletion in the brain (Mallet et al., 2008). Excessive beta-band oscillations have been recorded in the PD patients (Cassidy et al., 2002), and beta oscillations in the basal ganglia–subthalamic nucleus (STN) circuit are regarded as an electrophysiological hallmark of PD. Increased beta-band power has been empirically linked to several core motor symptoms of PD, including gait initiation failure, bradykinesia, and rigidity (Gatev et al., 2006; Oswal et al., 2013; Quynh et al., 2016).

Given the central role of the beta frequency band in the pathophysiology of PD, we further subdivided it into two functionally distinct sub-bands: low-beta (β1, 13–20 Hz) and high-beta (β2, 20–30 Hz). Synchronization in the β1 band is primarily involved in the regulation of movement execution and inhibition (Cao et al., 2024), while the functional mechanisms of the β2 band remain less clearly defined. Studies have shown that the intensity of β2 activity correlates positively with the severity of motor impairment in PD patients (Neumann et al., 2016), whereas improvement in motor symptoms is mainly associated with a reduction in β1 power (Priori et al., 2004). Moreover, PD patients with freezing of gait (FOG) often exhibit elevated β2 power, and a decrease in this band following levodopa administration is frequently accompanied by amelioration of FOG episodes (Toledo et al., 2014). The results of this study demonstrated a widespread elevation in both β1-pdBSI and β2-pdBSI across the whole brain in PD patients, with relative concentration in motor-related cortical regions. This suggests a broad dysregulation of beta-band symmetry and further supports the critical involvement of abnormal beta oscillations in PD motor dysfunction. These findings also indicate the presence of widespread asymmetric impairment in motor-related brain areas, leading to interhemispheric asymmetry in beta-band power. Furthermore, our results revealed that increased β2-pdBSI in the central and posterior region of the aPD group correlated positively with the UPDRS-III gait subscore. This suggests that more severe gait disturbances in aPD may be reflected by changes in β2-pdBSI, and that disrupted beta oscillatory symmetry in posterior sensory integration areas may serve as a key electrophysiological substrate for gait impairment. Specifically, the elevation of β2-pdBSI in posterior regions and its correlation with gait impairment in aPD suggest that even in advanced stages, a residual or evolving asymmetry in sensorimotor integration circuits is clinically significant. This asymmetry in the high-beta band may represent a maladaptive signature that persists despite broader bilateral pathology and higher medication doses.

Furthermore, this study identified significant differences in pdBSI within the theta and alpha frequency bands in PD patients, with the most prominent abnormalities localized to the central region. Additional evidence indicates that aberrant theta rhythm affects motor execution in PD patients with freezing of gait (Zampogna et al., 2022). Abnormal activities of the theta and alpha bands have been established as predictive indicators of cognitive impairment and the severity of motor symptoms in PD (Wang et al., 2020; Cozac et al., 2016; Palmer et al., 2010). Our observation of altered pdBSI in theta and alpha bands, primarily in the central region, further confirms the widespread dysregulation of oscillatory symmetry in PD. While these findings did not correlate with UPDRS scores in our cohort—potentially due to sample size or the predominant focus on motor items—they enrich the picture of multi-frequency network imbalance. The convergence of asymmetry across multiple bands underscores that PD affects interhemispheric balance broadly, not within a single oscillatory system.

This study has several limitations. Firstly, all EEG and clinical assessments were conducted exclusively in the dopaminergic medication-ON state. While this design enhances clinical applicability and was statistically controlled for LEDD, it cannot separate disease-related neural asymmetry from medication-induced modulation of oscillatory activity. Future studies incorporating OFF-medication assessments or within-subject ON–OFF designs are essential to confirm whether pdBSI reflects trait (disease) or state (medication) characteristics. Secondly, due to the limited sample size, the statistical power was reduced, which may have prevented the identification of more significant indicators. Additionally, the lack of imaging data made it impossible to correlate differences in EEG signals with imaging characteristics. Future studies should expand the sample size and incorporate imaging data to conduct subgroup analyses of lesions in the left and right hemispheres. Furthermore, integrating complementary measures such as gait kinematics or inertial measurement unit (IMU) data with EEG could enable a more comprehensive, multimodal analysis of motor dysfunction in PD.

There was hemispheric asymmetry in the PD patients. The pdBSI was a potential electrophysiological biomarker for hemispheric asymmetry in the PD. β2-pdBSI in the central and posterior region was significantly associated with the severity of gait impairment in aPD patients. In addition, the stage-dependent gradient elucidates the dynamic shift from unilateral to bilateral network involvement. Our findings underscore that quantifying interhemispheric asymmetry, beyond examining power in isolated regions, provides unique insights into the pathophysiology and clinical progression of PD.