Effects of Repetitive Transcranial Magnetic Stimulation (rTMS)-Primed Self-controlled Practice in People With Parkinson's Disease

Effects of Repetitive Transcranial Magnetic Stimulation (rTMS)-Primed Self-controlled Practice on Motor Behavior, Psychosocial Functioning, and Neurophysiological Mechanisms in People With Parkinson's Disease

Parkinson's disease (PD) is commonly associated with impaired motor learning and reduced motivation, both of which can negatively influence rehabilitation outcomes. Prior cross-sectional evidence suggests that providing individuals with PD self-controlled access to training parameters enhances motor learning, increases motivation, and facilitates cognitive processing. However, the effects of self-controlled practice implemented across repeated training sessions remain underexplored. Moreover, given that dysfunction of fronto-striatal circuits in PD may limit the neuroplastic response to motor training alone, adjunctive neuromodulatory priming approaches such as repetitive transcranial magnetic stimulation (rTMS) may be required to optimize therapeutic efficacy. To date, it remains unclear whether rTMS priming combined with self-controlled motor training yields superior clinical benefits, and whether stimulation of different cortical targets produces differential effects. In particular, the dorsolateral prefrontal cortex (DLPFC), a key region involved in cognitive control and motivation, may offer distinct therapeutic effects compared with stimulation of the primary motor cortex (M1). This study aims to investigate the effects of rTMS priming over the DLPFC or M1, followed by self-controlled motor training, in individuals with PD, and to compare these effects with a sham stimulation condition.

This single-blinded, randomized control trial will recruit 90 individuals with PD, who will be matched into 45 pairs and randomly assigned to one of three stimulation conditions: DLPFC, M1, or sham. Within each pair, one participant will be allocated to a self-controlled practice condition, and the other to a yoked (paired-control) condition that receives identical training content determined by their matched counterpart. Each participant will undergo 12 intervention sessions. In each session, rTMS will be applied first as a priming intervention, followed immediately by 45 minutes of standardized physical therapy-based motor training. For the DLPFC group, stimulation will target the left DLPFC; for the M1 group, stimulation will be applied over the M1 contralateral to the more affected limb; and for the sham condition, the coil will be rotated 90 degrees to mimic stimulation without effective cortical activation. During the training phase, participants in the self-controlled condition will be allowed to select aspects of their practice content, whereas yoked participants will follow the corresponding selections made by their matched partner.

The primary outcome measure is the Unified Parkinson's Disease Rating Scale (UPDRS). Secondary outcomes include assessments of cognitive function, apathy, non-motor symptoms, gait performance, balance, functional mobility, falls efficacy, and quality of life. Neurophysiological outcomes will be assessed using single- and paired-pulse TMS to evaluate corticospinal excitability and cortico-cortical connectivity, particularly between DLPFC and M1 networks. All assessments will be conducted in the medication-on state by blinded evaluators at baseline, immediately post-intervention, and at one-month follow-up. Data will be analyzed using mixed-effects repeated-measures ANOVA to examine group-by-time interactions and intervention effects. This study seeks to determine whether rTMS priming over cognitive-control versus motor networks differentially enhances the efficacy of self-controlled motor training, and whether such combined interventions can induce sustained improvements in motor and non-motor outcomes in PD.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease (PD)
• Intervention / Treatment: Device: Repetitive Transcranial Magnetic Stimulation (rTMS); Behavioral: Physical therapy

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ya-Yun Lee, PhD; Phone Number: +886-2-33668155; Email: yayunlee@ntu.edu.tw
• Study Contact Backup: Name: Pei-Ling Wu; Phone Number: +886-9-72197870; Email: r14428005@ntu.edu.tw

Study Locations

• Taiwan
  • Zhongzheng Dist.
    • Taipei, Zhongzheng Dist., Taiwan, 100
      • Recruiting
      • School and Graduate Institute of Physical Therapy
      • Contact: Jiu-Jenq Lin, PhD; Phone Number: +886-2-33668126; Email: jiujlin@ntu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosed of PD by neurologists and age above 18 years old
• able to follow the researcher's instruction (the Montreal Cognitive Assessment ≥ 24)
• able to stand and walk independently for 10 minutes with or without assistive devices

Exclusion Criteria:

• have neurological disorders other than PD (e.g., Parkinson plus syndrome, cognitive impairment, dementia, stroke)
• have contraindications to receive TMS, such as a pacemaker or deep brain stimulator implanted in the body
• a self-history of seizure or a family history of epilepsy
• pregnancy
• unstable medical conditions that is not under control

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: DLPFC-self	Device: Repetitive Transcranial Magnetic Stimulation (rTMS); The iTBS paradigm will be used to prime the neuronal excitability of the DLPFC or M1 based on the group allocation. The patterns of iTBS are triplets of stimuli at 50Hz frequency repeated in 5Hz bursts with a 2 second train repeated every 10 seconds for a total of 190 seconds, which will result in 600 stimulation pulses. The intensity will be set at 80%-120% of motor threshold of the tibialis anterior (TA) or first dorsal interosseous (FDI) muscle of the more affected limb. As for the sham rTMS groups, the coil will be placed over the M1 hotspot but turned 90 degrees away so that the surface of the coil will be 90 degrees perpendicular to the scalp.; Behavioral: Physical therapy; After the iTBS priming procedure, the participants will receive 45 minutes of one-on-one physical therapy training targeting whole body and lower extremity function. Each training session will involve flexibility exercise, gait training, balance training, resistance exercise, or cognitive-motor dual task training.
Experimental: DLPFC-yoked	Device: Repetitive Transcranial Magnetic Stimulation (rTMS); The iTBS paradigm will be used to prime the neuronal excitability of the DLPFC or M1 based on the group allocation. The patterns of iTBS are triplets of stimuli at 50Hz frequency repeated in 5Hz bursts with a 2 second train repeated every 10 seconds for a total of 190 seconds, which will result in 600 stimulation pulses. The intensity will be set at 80%-120% of motor threshold of the tibialis anterior (TA) or first dorsal interosseous (FDI) muscle of the more affected limb. As for the sham rTMS groups, the coil will be placed over the M1 hotspot but turned 90 degrees away so that the surface of the coil will be 90 degrees perpendicular to the scalp.; Behavioral: Physical therapy; After the iTBS priming procedure, the participants will receive 45 minutes of one-on-one physical therapy training targeting whole body and lower extremity function. Each training session will involve flexibility exercise, gait training, balance training, resistance exercise, or cognitive-motor dual task training.
Experimental: M1-self	Device: Repetitive Transcranial Magnetic Stimulation (rTMS); The iTBS paradigm will be used to prime the neuronal excitability of the DLPFC or M1 based on the group allocation. The patterns of iTBS are triplets of stimuli at 50Hz frequency repeated in 5Hz bursts with a 2 second train repeated every 10 seconds for a total of 190 seconds, which will result in 600 stimulation pulses. The intensity will be set at 80%-120% of motor threshold of the tibialis anterior (TA) or first dorsal interosseous (FDI) muscle of the more affected limb. As for the sham rTMS groups, the coil will be placed over the M1 hotspot but turned 90 degrees away so that the surface of the coil will be 90 degrees perpendicular to the scalp.; Behavioral: Physical therapy; After the iTBS priming procedure, the participants will receive 45 minutes of one-on-one physical therapy training targeting whole body and lower extremity function. Each training session will involve flexibility exercise, gait training, balance training, resistance exercise, or cognitive-motor dual task training.
Experimental: M1-yoked	Device: Repetitive Transcranial Magnetic Stimulation (rTMS); The iTBS paradigm will be used to prime the neuronal excitability of the DLPFC or M1 based on the group allocation. The patterns of iTBS are triplets of stimuli at 50Hz frequency repeated in 5Hz bursts with a 2 second train repeated every 10 seconds for a total of 190 seconds, which will result in 600 stimulation pulses. The intensity will be set at 80%-120% of motor threshold of the tibialis anterior (TA) or first dorsal interosseous (FDI) muscle of the more affected limb. As for the sham rTMS groups, the coil will be placed over the M1 hotspot but turned 90 degrees away so that the surface of the coil will be 90 degrees perpendicular to the scalp.; Behavioral: Physical therapy; After the iTBS priming procedure, the participants will receive 45 minutes of one-on-one physical therapy training targeting whole body and lower extremity function. Each training session will involve flexibility exercise, gait training, balance training, resistance exercise, or cognitive-motor dual task training.
Sham Comparator: Sham-self	Device: Repetitive Transcranial Magnetic Stimulation (rTMS); The iTBS paradigm will be used to prime the neuronal excitability of the DLPFC or M1 based on the group allocation. The patterns of iTBS are triplets of stimuli at 50Hz frequency repeated in 5Hz bursts with a 2 second train repeated every 10 seconds for a total of 190 seconds, which will result in 600 stimulation pulses. The intensity will be set at 80%-120% of motor threshold of the tibialis anterior (TA) or first dorsal interosseous (FDI) muscle of the more affected limb. As for the sham rTMS groups, the coil will be placed over the M1 hotspot but turned 90 degrees away so that the surface of the coil will be 90 degrees perpendicular to the scalp.; Behavioral: Physical therapy; After the iTBS priming procedure, the participants will receive 45 minutes of one-on-one physical therapy training targeting whole body and lower extremity function. Each training session will involve flexibility exercise, gait training, balance training, resistance exercise, or cognitive-motor dual task training.
Sham Comparator: Sham-yoked	Device: Repetitive Transcranial Magnetic Stimulation (rTMS); The iTBS paradigm will be used to prime the neuronal excitability of the DLPFC or M1 based on the group allocation. The patterns of iTBS are triplets of stimuli at 50Hz frequency repeated in 5Hz bursts with a 2 second train repeated every 10 seconds for a total of 190 seconds, which will result in 600 stimulation pulses. The intensity will be set at 80%-120% of motor threshold of the tibialis anterior (TA) or first dorsal interosseous (FDI) muscle of the more affected limb. As for the sham rTMS groups, the coil will be placed over the M1 hotspot but turned 90 degrees away so that the surface of the coil will be 90 degrees perpendicular to the scalp.; Behavioral: Physical therapy; After the iTBS priming procedure, the participants will receive 45 minutes of one-on-one physical therapy training targeting whole body and lower extremity function. Each training session will involve flexibility exercise, gait training, balance training, resistance exercise, or cognitive-motor dual task training.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	The MDS-UPDRS is currently the gold-standard scale used in the clinics as well as research to determine the disease severity of PD. The MDS-UPDRS contains four parts: (1) non-motor aspects of experiences of daily living, (2) motor aspects of experiences of daily living, (3) motor examination, and (4) motor complications. Each item is scored from 0 (no symptom) to 4 (most severe symptom), and the total score range for the MDS-UPDRS is from 0 to 260 with a higher score indicates greater disease severity.	Three time points: pre-test (before intervention, 0 week), post-test (after all intervention sessions, up to 4 weeks), follow-up test (one month after intervention, up to 8 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montreal cognitive assessment (MoCA)	The MoCA will be used to assess general cognitive function of the participants. It examines various cognitive functions, including set-shifting, visuospatial processing, abstract thinking, short-term memory, attention, verbal fluency, calculation, orientation, and digit span abilities. The total score of MoCA is 30 with a higher score suggests better cognitive function, and a score below 26 would suggest an increased risk of cognitive decline.	Three time points: pre-test (before intervention, 0 week), post-test (after all intervention sessions, up to 4 weeks), follow-up test (one month after intervention, up to 8 weeks)
Short-form Lille apathy rating scale (LARS)	The LARS scale has 12 items categorized into 7 domains: everyday productivity, interests, take the initiative, novelty seeking, motivation-voluntary actions, emotional responses, and social life. Each item is scored on a 5-point Likert scale or a binary yes/no scale. The score ranges from -15 to 15 with a higher score suggests more apathetic symptoms. It has been established that a short-form LARS score ≥ -7 points is the cut-off score for identifying apathy in PD.	Three time points: pre-test (before intervention, 0 week), post-test (after all intervention sessions, up to 4 weeks), follow-up test (one month after intervention, up to 8 weeks)
Non-motor symptoms scale for Parkinson's disease (NMSS)	The NMSS is a specifically designed 30-item scale to assess various non-motor symptoms of PD. It evaluates severity (score 0-3) and frequency (score 1-4) across nine non-motor domains: cardiovascular including falls, sleep/fatigue, mood /cognition, perceptual problems/hallucinations, attention/ memory, gastrointestinal tract, urinary, sexual function, and miscellaneous.	Three time points: pre-test (before intervention, 0 week), post-test (after all intervention sessions, up to 4 weeks), follow-up test (one month after intervention, up to 8 weeks)
Gait performances	To measure walking ability, the participants will be asked to walk along a 10-meter hallway with their comfortable walking speed and fastest walking speed in single- and dual-task conditions. The Physilog®5 system (Gait Up, Renens, Switzerland) including two inertial sensors with built-in 3D accelerometers and gyroscopes will be fixated to the shoelaces area of both feet to record the walking data. The data will be sampled at a rate of 128Hz and will then be analysed by the Gait Up© gait analysis package (Gait Up SA, Switzerland). Gait parameters of interest include velocity, step length, cadence, foot-strike angle, and foot clearance.	Three time points: pre-test (before intervention, 0 week), post-test (after all intervention sessions, up to 4 weeks), follow-up test (one month after intervention, up to 8 weeks)
New freezing of gait questionnaire (NFOG-Q)	The NFOG-Q is a self-reported questionnaire to determine the presence and severity of freezing of gait in people with PD. It contains 9 questions with the first question asking the participants whether they have experienced freezing episodes in the past 1 month. If an individual answers 'no' to this question, he/she will be classified as non-freezer and will not need to answer the following questions. One the other hand, if a person answers 'yes' to the first question, he/she will be asked to further complete the rest of the questions regarding the severity and duration of the freezing episodes.	Three time points: pre-test (before intervention, 0 week), post-test (after all intervention sessions, up to 4 weeks), follow-up test (one month after intervention, up to 8 weeks)
5-time sit to stand test (5TSTS)	The 5TSTS will be used to evaluate the lower extremity muscle strength and endurance. Using a standardized chair, the participants will be requested to stand up and then sit down as quickly as possible for 5 times, and the time to complete the test will be recorded.	Three time points: pre-test (before intervention, 0 week), post-test (after all intervention sessions, up to 4 weeks), follow-up test (one month after intervention, up to 8 weeks)
Timed up and go (TUG) test	The TUG is a gold standard to measure dynamic balance and gait ability. The participant will first sit on a standardized chair with back supported. After a GO signal, he/she will stand up, walk 3 meters, turn 180°, walk back and then sit down. The participants will be instructed to walk with their preferred and fastest walking speeds.	Three time points: pre-test (before intervention, 0 week), post-test (after all intervention sessions, up to 4 weeks), follow-up test (one month after intervention, up to 8 weeks)
Mini balance evaluation systems test (Mini-BESTest)	The Mini-BESTest assesses 4 aspects of balance ability, including anticipatory postural adjustments, reactive postural control, sensory orientation, and dynamic gait. It contains 14 items, and each item is scored on a 0-2 ordinal scale, with a total score of 28 points. A higher score indicates better balance control.	Three time points: pre-test (before intervention, 0 week), post-test (after all intervention sessions, up to 4 weeks), follow-up test (one month after intervention, up to 8 weeks)
Activities-Specific Balance Confidence (ABC) scale	The ABC scale will be utilized to assess an individual's confidence level of not falling when performing daily activities at home and in the community. Sixteen indoor and outdoor activities are involved in the scale, and the participants will rate their confidence level of not falling from 0 (no confidence at all) to 100 (very confident) when performing the activities. An average score of these questions will then be calculated with a higher score suggests greater confidence of not falling.	Three time points: pre-test (before intervention, 0 week), post-test (after all intervention sessions, up to 4 weeks), follow-up test (one month after intervention, up to 8 weeks)
Parkinson's Disease Questionnaire-39 (PDQ-39)	The PDQ-39 is a specifically designed self-report questionnaire to determine quality of life in individuals with PD. The questionnaire contains 39 health-related items, and the participants will answer these questions based on their own experience in the past one month. Each item is score on a 5-point Likert scale with a lower score suggests less difficulty performing the task. As a result, a lower total score will indicate better quality of life.	Three time points: pre-test (before intervention, 0 week), post-test (after all intervention sessions, up to 4 weeks), follow-up test (one month after intervention, up to 8 weeks)
Motivation questionnaire	The motivational questionnaire will be used to determine their motivation level after each training session. It consists of perceived competence, task interest/enjoyment, and autonomy. The questions for perceived competence and task interest/enjoyment are directly taken from Intrinsic Motivation Inventory (IMI), which originally consists of 22 items with 4 subscales including interest/enjoyment, perceived competence, perceived choice, and pressure/tension (McAuley et al., 1989). As for autonomy, the questions are referenced from the autonomy subscale used in a study by Carter and Ste-Marie (Carter & Ste-Marie, 2017b). The motivational questionnaire used in this study consists of 21 items scored with a 7-point Likert scale with a higher score indicates better in perceived competence, task interest/enjoyment, and autonomy.	Three time points: pre-test (before intervention, 0 week), post-test (after all intervention sessions, up to 4 weeks), follow-up test (one month after intervention, up to 8 weeks)
Corticomotor excitability	Transcranial magnetic stimulation (TMS) device (The Magstim Company Ltd, Whitland, UK) will be used to determine the neurophysiology of corticomotor excitability.	Three time points: pre-test (before intervention, 0 week), post-test (after all intervention sessions, up to 4 weeks), follow-up test (one month after intervention, up to 8 weeks)
Cortico-cortical connectivity	Transcranial magnetic stimulation (TMS) device (The Magstim Company Ltd, Whitland, UK) will be used to determine the neurophysiology of corticocortical connectivity.	Three time points: pre-test (before intervention, 0 week), post-test (after all intervention sessions, up to 4 weeks), follow-up test (one month after intervention, up to 8 weeks)

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Investigators: Principal Investigator: Graduate Institute of Physical Therapy, National Taiwan University

Publications and helpful links

General Publications

• De-Jun Lim. Effects of Autonomy on Motor Learning in People with Parkinson's Disease. 2024. doi:10.6342/NTU202401486. uri:http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/94704
• Chung CL, Mak MK, Hallett M. Transcranial Magnetic Stimulation Promotes Gait Training in Parkinson Disease. Ann Neurol. 2020 Nov;88(5):933-945. doi: 10.1002/ana.25881. Epub 2020 Sep 8.
• Yang YR, Tseng CY, Chiou SY, Liao KK, Cheng SJ, Lai KL, Wang RY. Combination of rTMS and treadmill training modulates corticomotor inhibition and improves walking in Parkinson disease: a randomized trial. Neurorehabil Neural Repair. 2013 Jan;27(1):79-86. doi: 10.1177/1545968312451915. Epub 2012 Jul 10.

Study record dates

Study Major Dates

• Study Start (Estimated): September 23, 2026
• Primary Completion (Estimated): December 31, 2031
• Study Completion (Estimated): December 31, 2032

Study Registration Dates

• First Submitted: September 15, 2026
• First Submitted That Met QC Criteria: September 15, 2026
• First Posted (Actual): September 22, 2026

Study Record Updates

• Last Update Posted (Actual): September 22, 2026
• Last Update Submitted That Met QC Criteria: September 15, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Motor learning; Priming; Repetitive Transcranial Magnetic Stimulation (rTMS); Self-controlled practice
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Therapeutics; Rehabilitation; Magnetic Field Therapy; Transcranial Magnetic Stimulation; Physical Therapy Modalities
• Other Study ID Numbers: 202601081DINC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No