Supplementary Motor Area is a Potential Target for Speech Disturbance in Parkinson Disease

Study Overview
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Brief Summary
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Speech disturbance is common in patients with Parkinson disease. Pharmacotherapy improves motor symptoms but has inconsistent effects on speech disturbance in PD patients. Transcranial magnetic stimulation (TMS) is a safe and non-invasive tool used for brain stimulation. Repetitive transcranial magnetic stimulation (rTMS) has positive effects on motor function of PD. Yet, its effect on speech disturbance seems to be inconclusive. Previous rTMS studies mainly focused on the primary motor cortex for PD speech disturbance. Nevertheless, we think supplementary motor area (SMA) may be a better target. Speech disturbance in PD may be associated with basal ganglia-thalamocortical motor circuits and SMA involves in the cortex part. In addition, neuroimaging studies showed that SMA were under-activation in PD patients. Therefore, we conduct this 3-year study including two experiments. The aim of the study is to determine if rTMS over SMA can improve the speech function of PD patients and change the functional connectivity of speech pathway in the brain. This will be the first study to investigate the effect of rTMS over SMA on speech.

Official Title
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Supplementary Motor Area is a Potential Target for Speech Disturbance in Parkinson Disease

Conditions
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Parkinson Disease

Intervention / Treatment
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* Device: MAGSTIM Repetitive transcranial magnetic stimulator (rTMS) system


Participation Criteria
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Eligibility Criteria
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Experiment 1 Inclusion Criteria: right-handed healthy adult volunteers who understand and agree on the informed consent of the study Exclusion Criteria: pregnancy or possibility of pregnancy history of seizure family history of epilepsy metals in any part of the body. Experiment 2 Inclusion Criteria: PD patients with speech disturbance who understand and agree on the informed consent of the study. The speech item scored 2 or 3 in the unified Parkinson's disease rating scale (UPDRS) part III. Exclusion Criteria: dementia the history of stroke, brain lesion, other central nervous system diseases the contraindication of TMS which described above any contraindication of MRI

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PD patients with speech disturbance treated with 10 Hz rTMS<br> | Device: MAGSTIM Repetitive transcranial magnetic stimulator (rTMS) system<br>* we plan to recruit 60 patients with Parkinson disease, comprising 30 patients with speech disturbance and 30 age- and sex-match patients without speech disturbance. Each group of patients will be randomly divided into sham stimulation or rTMS. A total of 10 rTMS sessions will be applied in 2 weeks. The effect of rTMS will be evaluated via the changes of speech performance and functional connectivity which was analyzed from resting-state functional magnetic resonance imaging.<br>|
| Sham Comparator: PD patients with speech disturbance treated with sham rTMS<br> | Device: MAGSTIM Repetitive transcranial magnetic stimulator (rTMS) system<br>* we plan to recruit 60 patients with Parkinson disease, comprising 30 patients with speech disturbance and 30 age- and sex-match patients without speech disturbance. Each group of patients will be randomly divided into sham stimulation or rTMS. A total of 10 rTMS sessions will be applied in 2 weeks. The effect of rTMS will be evaluated via the changes of speech performance and functional connectivity which was analyzed from resting-state functional magnetic resonance imaging.<br>|
| Experimental: PD patients without speech disturbance treated with 10 Hz rTMS<br> | Device: MAGSTIM Repetitive transcranial magnetic stimulator (rTMS) system<br>* we plan to recruit 60 patients with Parkinson disease, comprising 30 patients with speech disturbance and 30 age- and sex-match patients without speech disturbance. Each group of patients will be randomly divided into sham stimulation or rTMS. A total of 10 rTMS sessions will be applied in 2 weeks. The effect of rTMS will be evaluated via the changes of speech performance and functional connectivity which was analyzed from resting-state functional magnetic resonance imaging.<br>|
| Sham Comparator: PD patients without speech disturbance with sham rTMS<br> | Device: MAGSTIM Repetitive transcranial magnetic stimulator (rTMS) system<br>* we plan to recruit 60 patients with Parkinson disease, comprising 30 patients with speech disturbance and 30 age- and sex-match patients without speech disturbance. Each group of patients will be randomly divided into sham stimulation or rTMS. A total of 10 rTMS sessions will be applied in 2 weeks. The effect of rTMS will be evaluated via the changes of speech performance and functional connectivity which was analyzed from resting-state functional magnetic resonance imaging.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of speech performance from baseline in experiment 1 | sustained phonation of /a/ for as long and steady as possible in one breath fast pa-/ta-/ka- repetition at least nine times in one breath reading a standardized paragraph composed of 80 words as clear and fast as possible | Baseline ((1) before rTMS), (2) immediately after rTMS | 
| Change of speech performance from baseline in experiment 2 | sustained phonation of /a/ for as long and steady as possible in one breath fast pa-/ta-/ka- repetition at least nine times in one breath reading a standardized paragraph composed of 80 words as clear and fast as possible | Baseline ((1) before rTMS), (2) within 24 hours after 10 times of rTMS (3) 8 weeks later after 10 times of rTMS | 
| Change of functional connectivity from baseline in experiment 2 | use rs-fMRI to compare the functional connectivity between PD patients with and without speech disturbance and the changes of connectivity after rTMS over SMA | Baseline ((1) before rTMS), (2) within 24 hours after 10 times of rTMS | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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speech disturbance, transcranial magnetic stimulation