Effects and Mechanisms of RAS Training on Upper-limb Movements in PD Patients

Official title

Effects and Neural Mechanisms of Training Involving Rhythmic Auditory Stimulation on Upper-limb Movements in Patients With Parkinson's Disease

Overview

Introduction Bradykinesia (i.e., slow movements) is one of the most prominent symptoms of Parkinson's disease (PD) and has a negative impact on quality of life. Rhythmic auditory stimulation (RAS), a widely used and promising treatment technique, has been shown to effectively improve gait speed in PD patients. However, only few studies have explored effects and neural mechanisms of RAS on upper-limb movements. We will conduct two studies to investigate effects and mechanisms of RAS on upper-limb movements in PD patients. The purpose of this study is to examine effects and neural mechanisms of upper-limb movement training involving RAS in PD patients. Methods This study will recruit patients with PD and healthy controls. This study will randomly assign PD patients into two groups: the PD-RAS group and the PD-noRAS group, and healthy controls into the HC-RAS group and the HC-noRAS group. A 7-day upper-limb training involving RAS (for the PD-RAS group and the HC-RAS group) or without RAS (for the PD-noRAS group and the HC-noRAS group) will be provided. EEG and behavioral assessments will be conducted before and after the first day of training, and after the seven-day training program. Two-way repeated measures analysis of variance will be performed to investigate the group and time effects on upper-limb function and neural activity. Study significance The training program will serve as a reference for clinical practitioners who are interested in using RAS in clinical training for PD patients.

Interventions

• Behavioral Upper-limb training involving RAS
  Three target bowls, labeled as the left, middle, and right target bowl, will be placed on the table at an equal distance from the main bowl. The distance between a target bowl and the main bowl is set at 30 cm. Wooden beads with a diameter of 2 cm will be put in target bowls. The main bowl will be placed in front of the patient. Patients will be asked to listen to the RAS sound, use the right hand to take one bead at a time from the left target bowl to the main bowl, repeat this movement for th
• Behavioral Upper-limb training without the aid of RAS
  Three target bowls, labeled as the left, middle, and right target bowl, will be placed on the table at an equal distance from the main bowl. The distance between a target bowl and the main bowl is set at 30 cm. Wooden beads with a diameter of 2 cm will be put in target bowls. The main bowl will be placed in front of the patient. Patients will be asked to use the right hand to take one bead at a time from the left target bowl to the main bowl, repeat this movement for the middle and right target

Primary outcome measures

• Electroencephalography (EEG) [Time frame: Assessments will be performed before the first day of training.]
• Electroencephalography (EEG) [Time frame: Assessments will be performed after the seven-day training program.]
• Electroencephalography (EEG) [Time frame: Assessments will be performed before the first day of training.]
• Electroencephalography (EEG) [Time frame: Assessments will be performed after the seven-day training program.]
• The box and block test (BBT) [Time frame: Assessments will be performed before the first day of training.]
• The box and block test (BBT) [Time frame: Assessments will be performed after the seven-day training program.]
• The nine hole peg test (NHPT) [Time frame: Assessments will be performed before the first day of training.]
• The nine hole peg test (NHPT) [Time frame: Assessments will be performed after the seven-day training program.]

Secondary outcome measures (4)

• The Jebsen Hand Function Test (JHFT) [Time frame: Assessments will be performed before the first day of training.]
• The Jebsen Hand Function Test (JHFT) [Time frame: Assessments will be performed after the 7-day training.]
• Ruler Drop Test (RDT) [Time frame: Assessments will be performed before the first day of training.]
• Ruler Drop Test (RDT) [Time frame: Assessments will be performed after the 7-day training.]

Eligibility criteria

Inclusion criteria

• (a) idiopathic PD diagnosed by a neurologist based on the Movement Disorders Society clinical diagnostic criteria;
• (b) the Hoehn and Yahr stage is 2 or 3, meaning that bilateral movement problems or combination with mild postural instability;
• (c) a score of Montreal Cognitive Assessment (MoCA) is equal to or higher than 21 to ensure that they understand experimental instructions;
• (d) a score of Edinburgh Handedness Inventory is above 60 to ensure that they are right-handed;
• (e) types and doses of medications remain unchanged in the past month right before participation.
• Age- and sex-matched healthy controls who filled the criteria (c) and (d) will be recruited from communities.

Exclusion criteria

• the presence of medical conditions or diseases that may affect hand movements, vision, or hearing based on self-report.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Bengtsson SL, Ullen F, Ehrsson HH, Hashimoto T, Kito T, Naito E, Forssberg H, Sadato N. Listening to rhythms activates motor and premotor cortices. Cortex. 2009 Jan;45(1):62-71. doi: 10.1016/j.cortex.2008.07.002. Epub 2008 Oct 30. PMID 19041965
• Braunlich K, Seger CA, Jentink KG, Buard I, Kluger BM, Thaut MH. Rhythmic auditory cues shape neural network recruitment in Parkinson's disease during repetitive motor behavior. Eur J Neurosci. 2019 Mar;49(6):849-858. doi: 10.1111/ejn.14227. Epub 2018 Dec 3. PMID 30375083
• Buard I, Dewispelaere WB, Thaut M, Kluger BM. Preliminary Neurophysiological Evidence of Altered Cortical Activity and Connectivity With Neurologic Music Therapy in Parkinson's Disease. Front Neurosci. 2019 Feb 19;13:105. doi: 10.3389/fnins.2019.00105. eCollection 2019. PMID 30837830
• Cahn DA, Sullivan EV, Shear PK, Pfefferbaum A, Heit G, Silverberg G. Differential contributions of cognitive and motor component processes to physical and instrumental activities of daily living in Parkinson's disease. Arch Clin Neuropsychol. 1998 Oct;13(7):575-83. PMID 14590618
• Chen JL, Penhune VB, Zatorre RJ. Listening to musical rhythms recruits motor regions of the brain. Cereb Cortex. 2008 Dec;18(12):2844-54. doi: 10.1093/cercor/bhn042. Epub 2008 Apr 3. PMID 18388350
• Dalrymple-Alford JC, MacAskill MR, Nakas CT, Livingston L, Graham C, Crucian GP, Melzer TR, Kirwan J, Keenan R, Wells S, Porter RJ, Watts R, Anderson TJ. The MoCA: well-suited screen for cognitive impairment in Parkinson disease. Neurology. 2010 Nov 9;75(19):1717-25. doi: 10.1212/WNL.0b013e3181fc29c9. PMID 21060094
• Desrosiers J, Bravo G, Hebert R, Dutil E, Mercier L. Validation of the Box and Block Test as a measure of dexterity of elderly people: reliability, validity, and norms studies. Arch Phys Med Rehabil. 1994 Jul;75(7):751-5. PMID 8024419
• Dong VA, Fong KN, Chen YF, Tseng SS, Wong LM. 'Remind-to-move' treatment versus constraint-induced movement therapy for children with hemiplegic cerebral palsy: a randomized controlled trial. Dev Med Child Neurol. 2017 Feb;59(2):160-167. doi: 10.1111/dmcn.13216. Epub 2016 Aug 9. PMID 27503605

Identifiers

NCT: NCT05782322 · HongKongPU21037721r_20230221

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗