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

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Transcranial magnetic stimulation (TMS) device (The Magstim Company Ltd, Whitland, UK) will be used to determine the neurophysiology of corticomotor excitability.

Transcranial magnetic stimulation (TMS) device (The Magstim Company Ltd, Whitland, UK) will be used to determine the neurophysiology of corticocortical connectivity.