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

Chang Gung Memorial Hospital60 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Parkinson Disease

Interventions

"MAGSTIM" Repetitive transcranial magnetic stimulator (rTMS) systemDEVICE

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.

Eligibility

Sex: ALLMin age: 20 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Change of speech performance from baseline in experiment 1

1. sustained phonation of /a/ for as long and steady as possible in one breath 2. fast pa-/ta-/ka- repetition at least nine times in one breath 3. reading a standardized paragraph composed of 80 words as clear and fast as possible

Time frame: Baseline ((1) before rTMS), (2) immediately after rTMS

Change of speech performance from baseline in experiment 2

Time frame: 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

Time frame: Baseline ((1) before rTMS), (2) within 24 hours after 10 times of rTMS