Sample Size N= 10 Parkinson's disease patients with self-reported freezing of gait and 10 without self-reported freezing of gait (in total, 20 Parkinson's disease patients)

Accrual Period Single visit for 2 hours

Study Design This is a cross-sectional study with an intervention to provoke freezing of gait using split-belt treadmill in Parkinson's disease patients with a randomized cross-over design.

After baseline evaluation (a), interventions to induce freezing of gait will be performed in a randomized order to avoid a practice/fatigue effect in the following conditions using combination of 4 interventions: walking speed (fast walking vs. natural walking), visual loading (passing through narrow pathway), cognitive loading (dual task), and asymmetry (best side reduction).

1. Natural and fast walking with self-paced mode to access gait parameters and decide the speed for evaluation (3 mins X2) remaining assessment will be randomized and performed on the treadmill:

2. Natural and fast walking passing through narrow pathway (2 mins X2)

3. Natural and fast walking with dual task (2 mins X2)

4. Natural and fast walking passing through narrow pathway and during cognitive dual task (2 mins X2)

5. Natural and fast walking reducing the best side (2 mins X2)

6. Natural and fast walking reducing the best side passing through narrow pathway (2 mins X2)

7. Natural and fast walking reducing the best side with cognitive dual task (2 mins X2)

8. Natural and fast walking reducing the best side passing through narrow pathway and during cognitive dual task (2 mins X2)

   • Conditions b-h will be carried out on a split-belt treadmill (Grail systems®, by Motek, Netherlands).
   • (b-i) freezing of gait episodes will be identified with synchronized videorecordings (screening done by two independent observers). Episodes identified by both observers will be confirmed and measured by comparing the relative height of metatarsal and heel markers of each foot, in keeping with a previous study evaluating freezing of gait episode on a treadmill.

Study Duration

1. (Baselines evaluation) Enrolment and assessment (Montreal cognitive assessment, Movement Disorders Society-unified Parkinson's disease rating scale part 2, 3 and 4, Activities-Specific Balance Confidence Scale, Parkinson's disease questionnaire-39, and New freezing of gait questionnaire)
2. (a) Formal gait analysis using split-belt treadmill (Grail systems®, by Motek, Netherlands) will be done for baseline assessment (normal walking) and to test patient's ability for fast walking (25% of the normal speed).
3. (b-h) Provocation of freezing of gait at split-belt treadmill (Grail systems®, by Motek, Netherlands) with natural and fast walking with/without additional loading or interventions on the asymmetry

Total time= 2 hours

Study Intervention Freezing of gait will be provoked based on the situations combined among 4 conditions; (1) interventions on asymmetry, (2) cognitive dual task, (3) visual loading - passing through narrow pathway, and (4) walking speed at a split-belt treadmill.

• Fast walking will be defined as walking 25% faster than the normal comfortable walking. Subjects who cannot reach this speed, will be asked to walk at their safest maximum speed.
• Passing narrow pathway will be done by walking in a "rope bridge" scene in virtual reality (VR).
• Dual cognitive task will be carried out with serial subtraction prompted on the screen in VR.
• Best side reduction will be defined as 25% slower speed on the best side based on the speed during the initial natural walking with tied configuration setting based on a previous study.3
• Condition b-h will be randomized.

Inclusion Criteria:

• Idiopathic Parkinson's disease
• Hoehn & Yahr Stage 1-3
• Ten with self-reported freezing of gait (score of 1 in part 1 of new freezing of gait questionnaire), and 10 without FOG..
• Sequence effect on feet (as score of at least 2 in the leg agility (item#3.8) of Movement Disorders Society-Unified Parkinson's disease rating scale part 3)
• Stable clinical response to medications or stimulation parameters for at least 1 months
• Able to walk on a motor-driven treadmill
• Ability to provide informed consent

Exclusion Criteria:

• Severe imbalance that limits ambulation (Hoehn &Yahr score above 4)
• Orthostatic hypotension
• Orthopedic conditions and other systemic disease affecting locomotion
• Shortness of breath and cardiac disease
• Psychiatric disorders needing medication
• Dementia
• Presence of other neurological disorder