This study included 27 PD patients (PD group) who were diagnosed at the Department of Neurology, The Second Affiliated Hospital of Dalian Medical University, between February 2023 and February 2024, as well as 29 age- and gender-matched healthy individuals as the control group. The diagnosis of PD was based on the clinical diagnostic criteria for PD established by the Movement Disorder Society (MDS) in 2015 (Leng et al., 2022), and the disease stages were classified according to the Hoehn-Yahr staging scale, ranging from stage I to stage III. Inclusion criteria for the PD group were as follows: (1) PD patients aged between 40 and 80 years; (2) No severe visual impairments (e.g., inability to clearly distinguish visual cues or inability to reach normal vision levels even with corrective lenses); (3) No history of other severe neurological or psychiatric disorders (e.g., vestibular system disorders, epilepsy, encephalitis, dementia, schizophrenia, or severe depression); (4) No use of medications within the past 3 months that could potentially interfere with the study results, such as antipsychotics or anticonvulsants. Inclusion criteria for the control group were as follows: participants should have no history of neurological or psychiatric disorders and normal vision, or corrected vision reaching normal levels. Exclusion criteria for both groups included: (1) Presence of severe cardiovascular diseases, respiratory diseases, or other serious systemic conditions that could affect participation in the experiment; (2) Pregnant or breastfeeding women; (3) Known allergic reactions or intolerance to the equipment or procedures used in the experiment; (4) Patients who had previously participated in similar studies, potentially causing data bias; (5) Patients unable to comply with the experimental requirements.

There were no marked differences between the two groups in basic demographic characteristics such as gender and age (p > 0.05; Table 1). All participants provided written informed consent prior to the experiment, and the study was approved by the Ethics Committee of The Second Affiliated Hospital of Dalian Medical University, ensuring that the experimental procedures adhered to the ethical standards outlined in the Declaration of Helsinki.

The eye movement task in this experiment was conducted using VR equipment, with the task designed as a visual tracking task. Participants were required to fixate on and maintain visual tracking of a moving target within the virtual environment. The target moved randomly at varying speeds and directions to increase the complexity of the task. Specifically, the task was based on a “Whack-a-Mole” game on the VR platform. When a mole appeared on the screen, participants were instructed to fixate on it, and the mole would automatically disappear once the participant’s gaze was directed at it. Prior to the formal test, all participants underwent a 3-min familiarization practice to ensure they were comfortable with the task process and operations. The practice results were not included in the formal data analysis. The formal test consisted of 15 “Whack-a-Mole” game modules, each lasting 10.5 s, with a 10-s rest between modules. In each game module, the frequency of mole appearances was dynamically adjusted based on the participant’s performance. If a participant responded quickly and accurately in the initial modules, the mole appearance frequency was increased to make the task more challenging. Conversely, if the participant had slower response times or lower accuracy, the frequency of mole appearances was decreased accordingly. In each module, the mole appearance frequency ranged from 1 to 2 times per second, with the appearance interval fluctuating between 0.5 and 1 s. Additionally, as the game progressed, the speed and randomness of the moles’ movements gradually increased to further enhance task difficulty and maintain challenge. During the test, participants were required to quickly identify and fixate on the moles to make them disappear. The VR system integrated a high-precision eye tracker that recorded the participants’ eye movement trajectories, fixation point changes, and reaction times in real-time. This system offered high spatial and temporal resolution, ensuring the accuracy and reliability of the eye movement data. All experimental data were used to analyze the eye movement characteristics of PD patients and the differences compared to the healthy control group.

This study utilized the NirScan fNIRS brain function imaging device, manufactured by Danyang Huichuang Medical Equipment Co., Ltd., to collect near-infrared spectroscopy signals from the frontal, parietal, and occipital regions of the brain. The device consists of 26 optical fibers, with 14 serving as the light emission fibers and 12 as the light reception fibers. The linear distance between the emission and reception fibers is maintained at 3 cm, forming a total of 28 channels. The experiment used dual-wavelength (760 nm and 850 nm) near-infrared light for signal acquisition, with a sampling frequency of 10 Hz. Brain activity was recorded based on the estimation of near-infrared light absorption at both wavelengths for each channel and was converted into changes in the concentrations of oxygenated hemoglobin (HbO₂) and deoxygenated hemoglobin (HbR) using the modified Beer–Lambert law. During the placement of the optical probe, the experiment continuously monitored and displayed the signal strength of each channel in real-time through the acquisition software to ensure data quality. The placement of the probes was based on the international “10–20” system. The most anterior probe was positioned around the FP1 and FP2 regions, the most lateral probes were placed in the PO7 and PO8 areas, the far left probe was near T3, and the far right probe was near T4. The primary measurement regions included the fronto-polar areas (Frontopolar Area, FPA) in both hemispheres, the dorsolateral prefrontal cortex (Dorsolateral Prefrontal Cortex, DLPFC), the ventrolateral prefrontal cortex (Ventrolateral Prefrontal Cortex, VLPFC), the frontal eye fields (Frontal Eye Fields, FEF), the pre-motor and supplementary motor cortex (Pre-Motor and Supplementary Motor Cortex, PM&SMA), the primary somatosensory cortex (Somatosensory Cortex, S1), and the primary visual cortex (Primary Visual Cortex, V1). With this setup, this study was able to accurately measure changes in brain activity in specific regions during the execution of the VR eye movement task by PD patients (Figure 1).

Eye movement behavioral data analysis was conducted. In this study, the “Whack-a-Mole” error rate and the average fixation time were selected as the primary indicators to assess participants’ eye movement abilities. The “Whack-a-Mole” error rate is defined as the percentage of moles that did not disappear after the participant fixated on them, relative to the total number of moles. This metric reflects the participant’s visual recognition and eye movement control abilities. The average fixation time is defined as the average time the participant fixates on the mole from its appearance to its disappearance, reflecting the participant’s eye movement speed and fixation stability. All behavioral data were statistically analyzed using SPSS version 26.0. First, the normality of the data was tested using the Shapiro–Wilk test. For data conforming to a normal distribution, two-sample t-tests were conducted to compare the differences in eye movement metrics between the PD group and the healthy control group. A significance level of p < 0.05 was set.

Brain function data analysis was conducted. The average blood oxygen changes in the task and resting states from the 15 task blocks were calculated by subtracting the baseline values. The baseline was defined as the average blood oxygen concentration during a 5-s period before the formal test, which served as the baseline level. The average blood oxygen changes during the task state, resting state, and the difference between the task and resting states were calculated. A two-sample t-test was performed on the blood oxygen changes in the task state, resting state, and task-resting state to compare the differences between the two groups. A significance level of p < 0.05 was set.

The task error rate was significantly higher in the PD group (35.62 ± 28.74%) than in the control group (19.45 ± 21.44%; p = 0.02). The average fixation time was also significantly longer in the PD group (880.62 ± 12.86 ms) than in the control group (742.98 ± 158.86 ms; p = 0.001; Table 2).

The specific brain region activation differences are shown in Figure 2, which highlights significant activations in these regions (yellow and red areas in the figure). In the eye movement “Whack-a-Mole” task, changes in blood oxygen concentration between the task and resting states were calculated, and a two-sample t-test was used to analyze the differences in oxygenated hemoglobin concentration in brain regions between the PD group and the healthy control group. The results showed that the PD group had significantly higher concentrations of oxygenated hemoglobin in the bilateral primary visual cortex (V1), visual association cortex, primary somatosensory cortex (S1), and auditory cortex compared to the control group (p < 0.05).

(The statistical map (t-values) overlaid on a brain template shows brain regions with significantly higher oxygenated hemoglobin concentration in the PD group compared to the controls (p < 0.05). Yellow-to-red colors indicate higher activation in the PD group. Views from the top, front, left, right, and rear are displayed).