パーキンソン病の運動症状に対する遠隔監視下在宅経頭蓋時間干渉刺激

Participants in this arm will receive active transcranial temporal interference stimulation targeting the internal globus pallidus over a four-week intervention period.

Transcranial temporal interference stimulation (TIS) is a noninvasive brain stimulation technique that delivers two high-frequency alternating currents through scalp electrodes to generate a low-frequency interference field in deep brain regions. In this study, TIS targets the internal globus pallidus (GPi) to modulate neural activity in people with Parkinson's disease. Participants will receive one stimulation session per day, seven days per week, for four weeks in a home-based setting under real-time remote supervision.

The electrode placement is based on a standard 10-10 electroencephalography (EEG) system. For stimulation targeting the right GPi, electrode pairs will be positioned at CP3-CP6 and F3-F6; for stimulation targeting the left GPi, electrode pairs will be positioned at CP4-CP5 and F4-F5.

The sham TIS condition uses the same setup and procedures but does not deliver effective stimulation, thereby maintaining blinding.

Participants in this arm will receive sham transcranial temporal interference stimulation using the same electrode placement and experimental setup as the active intervention. The sham procedure consists of 28 sessions delivered over a four-week period, without therapeutic stimulation.

Transcranial temporal interference stimulation (TIS) is a noninvasive brain stimulation technique that delivers two high-frequency alternating currents through scalp electrodes to generate a low-frequency interference field in deep brain regions. In this study, TIS targets the internal globus pallidus (GPi) to modulate neural activity in people with Parkinson's disease. Participants will receive one stimulation session per day, seven days per week, for four weeks in a home-based setting under real-time remote supervision.

The electrode placement is based on a standard 10-10 electroencephalography (EEG) system. For stimulation targeting the right GPi, electrode pairs will be positioned at CP3-CP6 and F3-F6; for stimulation targeting the left GPi, electrode pairs will be positioned at CP4-CP5 and F4-F5.

The sham TIS condition uses the same setup and procedures but does not deliver effective stimulation, thereby maintaining blinding.

Change in motor symptoms assessed using the Movement Disorder Society-Unified Parkinson's Disease Rating Scale-III (MDS-UPDRS III). The total score ranges from 0 to 132, with higher scores indicating more severe motor impairment (worse outcome).

Participants will wear six wearable sensors of Mobility Lab system (Clario, Philadelphia, PA) to measure the kinematic data when performing iTUG test. In each trial, participants will be asked to stand up from a chair, walk straightforward for 3 meters, make a 180-degree turn, walk back straightly to the chair and sit down.

Time (in seconds) required to stand up from a seated position and return to sitting during the 3m-iTUG test, in which participants stand up from a chair, walk 3 meters, perform a 180-degree turn, walk back, and sit down. Lower values indicate better performance.

Time (in seconds) required to complete the 180-degree turn during the 3m-iTUG test, which includes standing up from a seated position, walking 3 meters, turning, walking back, and sitting down. Lower values indicate better performance.

The number of participants who had a clinically meaningful improvement after the stimulation within each group. Clinically meaningful improvement will be defined as a reduction of ≥ 5 points in the MDS-UPDRS-III total score. For gait outcomes, an increase in gait speed of ≥ 0.10 m/s or ≥ 10% improvement from baseline will be considered meaningful

Absolute change from baseline in four prespecified MDS-UPDRS-III sub scores in medication- "ON" and- "OFF" states, including rigidity, bradykinesia, tremor, and axial symptoms, with higher scores indicating more severe motor impairment (worse outcome).

A 20-item self-report scale (range: 0-20), with higher scores indicating greater anxiety severity; scores ≥8-10 suggest clinically relevant anxiety.

A 15-item self-report scale (range: 0-15), with higher scores indicating greater depressive symptom severity; categorized as normal (0-4), mild (5-8), moderate (9-11), and severe (12-15).

a 25-item self-report scale assessing autonomic dysfunction in Parkinson's disease (range: 0-69), with higher scores indicating more severe autonomic symptoms.

a 30-point screening tool (range: 0-30), with lower scores indicating worse global cognitive function.

The Trail Making Test assesses processing speed (Part A) and executive function (Part B), with longer completion times indicating poorer cognitive performance.

The Digit Span Test evaluates (DST) attention and working memory, with higher scores indicating better cognitive performance.

a 15-item scale (range: 0-60), with higher scores indicating more severe sleep disturbances.

an 8-item scale (range: 0-24), with higher scores indicating greater daytime sleepiness; scores ≥10 suggest excessive daytime sleepiness.

a 39-item questionnaire (range: 0-100, scaled), with higher scores indicating poorer quality of life.

Participants will record daily information including perceived medication- "ON" and- "OFF" periods [ref], time to medication onset, daily physical activity, sleep duration, and the occurrence of any adverse events.

1. Adverse events: The incidence and severity of adverse events recorded throughout the intervention and follow-up period, with higher frequency and severity indicating lower safety.
2. Attrition rate: The proportion of participants who withdraw before completing the intervention, with higher attrition indicating lower tolerability and acceptability.
3. Adherence rate: The proportion of completed stimulation sessions relative to the total prescribed sessions, with higher adherence indicating better feasibility and tolerability.