Non-invasive brain stimulation for speech in Parkinson’s disease: A randomized controlled trial

Abstract

Background: Hypokinetic dysarthria is a common but difficult-to-treat symptom of Parkinson's disease (PD). Objectives: We evaluated the long-term effects of multiple-session repetitive transcranial magnetic stimulation on hypokinetic dysarthria in PD. Neural mechanisms of stimulation were assessed by functional MRI. Methods: A randomized parallel-group sham stimulation-controlled design was used. Patients were randomly assigned to ten sessions (2 weeks) of real (1 Hz) or sham stimulation over the right superior temporal gyrus. Stimulation effects were evaluated at weeks 2, 6, and 10 after the baseline assessment. Articulation, prosody, and speech intelligibility were quantified by speech therapist using a validated tool (Phonetics score of the Dysarthric Profile). Activations of the speech network regions and intrinsic connectivity were assessed using 3T MRI. Linear mixed models and post-hoc tests were utilized for data analyses. Results: Altogether 33 PD patients completed the study (20 in the real stimulation group and 13 in the sham stimulation group). Linear mixed models revealed significant effects of time (F(3, 88.1) ¼ 22.7, p < 0.001) and time-by-group interactions: F(3, 88.0) ¼ 2.8, p ¼ 0.040) for the Phonetics score. Real as compared to sham stimulation led to activation increases in the orofacial sensorimotor cortex and caudate nucleus and to increased intrinsic connectivity of these regions with the stimulated area. Conclusions: This is the first study to show the long-term treatment effects of non-invasive brain stimulation for hypokinetic dysarthria in PD. Neural mechanisms of the changes are discussed.

Continuous theta burst stimulation over left supplementary motor area facilitates auditory-vocal integration in individuals with Parkinson’s disease

“…First of all, the present study reported the immediate effects of SMA c-TBS on auditory-motor integration for vocal pitch regulation in a single-session manner, limiting the assessment of treatment outcome with the measures of speech characteristics, such as vocal acoustics (e.g., f o , intensity), articulatory function, and speech intelligibility, and clinical assessment, such as voice handicap index (VHI) and visual analog scale (VAS). Also, the sample size is relatively small, although it is consistent with other studies that investigated PD-related speech disorders ( Huang et al, 2016 ; Mollaei et al, 2016 ; Brabenec et al, 2019 , 2021 ). In order to fully address the clinical efficacy and long-term effects of c-TBS for the treatment of PD dysarthria, future randomized, double-blind, sham-controlled studies are warranted in a multiple-session manner, and a comprehensive assessment of speech motor skills with larger sample sizes should be conducted in future.…”

“…Moreover, these behavioral effects were paralleled by systematic changes in cortical brain activity in individuals with PD, as reflected by reduced P1 and P2 responses and enhanced N1 responses to pitch perturbations following c-TBS over the left SMA. Similarly, other PD studies showed that multiple sessions of low-frequency rTMS over the right STG led to enhanced resting-state functional connectivity between the right STG and parahippocampal gyrus ( Brabenec et al, 2019 ) and increased activation of the SM1 and caudate nucleus ( Brabenec et al, 2021 ). These two studies also reported significant correlations between improved speech articulation and enhanced right STG activation during sentence reading ( Brabenec et al, 2019 ) and resting-state STG-SM1 functional connectivity ( Brabenec et al, 2021 ), which is in line with our results showing that reduced vocal compensations were predicted by enhanced N1 responses and reduced P2 responses.…”

“…The enhancement of N1 may be indicative of downstream effects of c-TBS over the left SMA. For example, a recent study of 10 sessions of low-frequency rTMS over the right STG in individuals with PD showed increased activation of the SM1 and caudate nucleus during sentence reading ( Brabenec et al, 2021 ). There is evidence for dysfunctional self-monitoring of auditory feedback in PD ( Arnold et al, 2014 ; Railo et al, 2020 ).…”

“…However, beneficial effects were not found when they received high-frequency rTMS over the right STG or SM1. Brabenec et al (2021) subsequently found that following 10 sessions of low-frequency rTMS over the right STG, individuals with PD exhibited long-term improvement (2-10 weeks) in their phonetics score of Dysarthric Profile that was correlated with resting-state STG-SM1 functional connectivity. Therefore, there is mixed evidence for the benefits of TMS intervention for PD dysarthria.…”

“…This hypothesis is in line with the findings of improved articulatory functions in individuals with PD following low-frequency but not high-frequency rTMS over the right STG ( Brabenec et al, 2019 ). On the other hand, acoustic (e.g., fundamental frequency or f o , intensity, and formant frequency) and/or perceptual (e.g., phonetics score and speech intelligibility) analyses of PD speech were generally used to evaluate the outcome of TMS intervention ( Dias et al, 2006 ; Eliasova et al, 2013 ; Brabenec et al, 2019 , 2021 ). These speech characteristics, however, reflect a broad range of mental processes, including voluntary attempts to compensate for the symptoms of PD.…”