Cerebellar Continuous Theta Burst Stimulation Facilitates Auditory–Vocal Integration in Spinocerebellar Ataxia

Abstract

Clinical studies have shown the efficacy of transcranial magnetic stimulation in treating movement disorders in patients with spinocerebellar ataxia (SCA). However, whether similar effects occur for their speech motor disorders remains largely unknown. The present event-related potential study investigated whether and how abnormalities in auditory–vocal integration associated with SCA can be modulated by neuronavigated continuous theta burst stimulation (c-TBS) over the right cerebellum. After receiving active or sham cerebellar c-TBS, 19 patients with SCA were instructed to produce sustained vowels while hearing their voice unexpectedly pitch-shifted by ±200 cents. Behaviorally, active cerebellar c-TBS led to smaller magnitudes of vocal compensations for pitch perturbations than sham stimulation. Parallel modulatory effects were also observed at the cortical level, as reflected by increased P1 and P2 responses but decreased N1 responses elicited by active cerebellar c-TBS. Moreover, smaller magnitudes of vocal compensations were predicted by larger amplitudes of cortical P1 and P2 responses. These findings provide the first neurobehavioral evidence that c-TBS over the right cerebellum produces modulatory effects on abnormal auditory–motor integration for vocal pitch regulation in patients with SCA, offering a starting point for the treatment of speech motor disorders associated with SCA with cerebellar c-TBS.

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

“…Moreover, not all behavioral and neural responses were modulated in the same direction: following c-TBS over the left SMA, 78–84% of vocal, P1, and P2 responses were reduced and 72% of N1 responses were enhanced, while the others showed the opposite pattern (see Figure 3 ). Such inter-individual variability has also been reported in previous empirical and clinical studies that investigated the TMS effects on motor and cognitive behaviors ( Lopez-Alonso et al, 2014 ; Corp et al, 2020 ; Lin et al, 2022 ), depending on many factors such as stimulation protocol, brain structure, hormonal levels, and genetic polymorphisms ( Polania et al, 2018 ). Addressing inter-individual variability of TMS effects has crucial implications for improving the efficacy of this non-invasive brain stimulation approach for the treatment of motor speech disorders in PD.…”

Cerebellar Continuous Theta Burst Stimulation for Aphasia Rehabilitation: Study Protocol for a Randomized Controlled Trial

“…On the other hand, Sebastian et al (2020) found greater beneficial effects on naming functions (relative to sham) when chronic post-stroke patients received cathodal tDCS over the right cerebellum than when they received anodal cerebellar tDCS. And applying inhibitory cTBS over the right cerebellum led to facilitatory effects on impaired vocal motor control in patients with SCA ( Lin et al, 2022 ). As compared to rTMS, cTBS induces robust, long-lasting changes in activation in much shorter periods.…”

“…The reported average depth of the lateral cerebellar gray matter is approximately 14.6–14.7 mm from the scalp surface, which is within a range of ∼30 mm at 100% peak output of the figure-of-8 coil ( Hardwick et al, 2014 ). Several studies have successfully applied rTMS or TBS over the cerebellum with a figure-of-8 coil to change motor or speech performance ( Theoret et al, 2001 ; Koch et al, 2008 ; Popa et al, 2010 ; Demirtas-Tatlidede et al, 2011 ; Lin et al, 2022 ). On the other hand, the present study protocol performs acoustic signal analysis to extract speech parameters for the evaluation of language function with the WAB, BDAE, and BNT scores.…”

“…The AMT is defined as the lowest stimulus intensity that produces a motor evoked potential (MEP) of >200 μV in at least 5–10 consecutive trials with 10% maximal voluntary contraction of the first dorsal interosseous muscle of the non-paretic hand ( Koch et al, 2020 ). Each participant receives real or sham cTBS over the Crus I of the right lateral cerebellum (3 cm right and 1 cm inferior to the inion) at 80% of AMT ( Lin et al, 2022 ). A standard cTBS protocol consists of bursts of 3 pulses at 50 Hz that are repeatedly presented at 5 Hz, resulting in a total of 600 pulses in 40 s. The coil is oriented vertically to the target with the handle pointing superiorly during real stimulation; while the stimulation face of the coil is turned 90°, so that the side of the coil is placed on the target during sham stimulation ( Rastogi et al, 2017 ).…”

“…The previous studies have shown that the cerebellar cTBS modulates motor cortical excitability and improves motor symptoms (e.g., gait ataxia and dyskinesia) in a variety of neurodegenerative diseases, such as Parkinson’s disease (PD) and spinocerebellar ataxia (SCA) ( Koch et al, 2009 , 2014 ; Benussi et al, 2020 ; Maas et al, 2020 ). Moreover, one recent study on patients with SCA showed that single-session c-TBS over the right cerebellum produces facilitatory effects on their abnormalities in auditory-motor integration for vocal pitch regulation ( Lin et al, 2022 ). Therefore, it is plausible to assume that stimulating the right cerebellum with inhibitory cTBS coupled with SLT leads to beneficial effects on chronic post-stroke aphasia, which is yet to be answered.…”