Personalized rTMS Protocol Based on Functional Reserve to Enhance Ambulatory Function in PD Patients

The objective of this study was to determine the effects of protocols of repetitive transcranial magnetic stimulation (rTMS) therapy based on the functional reserve of each patient with Parkinson's disease, compared to conventional high-frequency rTMS therapy on bilateral primary motor cortex (M1). Investigators hypothesized that the functional reserve of each patient with Parkinson's disease will be different, and therefore an appropriate simulating target for rTMS therapy is needed. In addition, this approach could be more effective compared to conventional protocols applied to patient with Parkinson's disease regardless of their severity, predicted mechanism of motor function recovery, or functional reserves.

rTMS treatment for patients with Parkinson's disease is traditionally based on stimulating the neural network of brain. The widely-used traditional rTMS treatment protocol involves high-frequency stimulation over the bilateral primary motor cortex (M1) to enhance motor and gait functions. However, concerns have arisen regarding the effect of rTMS on motor recovery in patients with Parkinson's disease. Although still subject to debate, a possible reason for the diverse results of rTMS applied is the uniform application protocol to individuals with varying pathologies and functional reserves, aimed at enhancing recovery.

Therefore, this study was aimed to determine the effects of protocols of rTMS therapy based on the functional reserve of each patient with Parkinson's disease.

Based on screening evaluations (Timed Up and Go Test (TUG), Timed Up and Go Dual Task-Cognitive (TUG-Cog)), investigators hypothesized that patients could be categorized into two groups: 1) priority in motor functional reserve, 2) priority in cognitive functional reserve. For each group, investigators plan to randomly assign patients to experimental and control groups to demonstrate the efficacy of different rTMS protocols based on functional reserves compared to conventional high-frequency rTMS applied to the bilateral M1.

Eligibility Criteria:
Inclusion Criteria:

1. patients with Parkinson's disease, diagnosed by the United Kingdom (UK) Parkinson's Disease Society Brain Bank Diagnostic Criteria,
2. Modified Hoehn and Yahr (H\&Y) scale, stage 2\~4,
3. patients who can walk on flat surfaces without the need for a gait aid,
4. aged ≥50 years old,
5. patients willing to sign the informed consent.

Exclusion Criteria:

1. those with contraindications to rTMS, such as epilepsy, implanted metal objects in the head, or a history of craniotomy,
2. those with cognitive impairment, confirmed through the Montreal Cognitive Assessment (MoCA) test as follows: \< 7 points: Illiterate \< 13 points: Education duration 0.5-3 years \< 16 points: Education duration 4-6 years \< 19 points: Education duration 7-9 years \< 20 points: Education duration 10 years or more
3. those with coexisting neurological conditions, such as spinal cord injury or Stroke,
4. those with major psychiatric disorders, such as major depression, schizophrenia, or dementia,
5. those with severe on-off phenomena or severe dyskinesia, deemed by the investigators to render participation in the study inappropriate.
6. those having contraindications to conduct an MRI study,
7. those who are pregnant or lactating,
8. patients who have refused to participate in this study.