Altered Modulation of Silent Period in Tongue Motor Cortex of Persistent Developmental Stuttering in Relation to Stuttering Severity

Abstract

Motor balance in developmental stuttering (DS) was investigated with Transcranial Magnetic Stimulation (TMS), with the aim to define novel neural markers of persistent DS in adulthood. Eleven DS adult males were evaluated with TMS on tongue primary motor cortex, compared to 15 matched fluent speakers, in a “state” condition (i.e. stutterers vs. fluent speakers, no overt stuttering). Motor and silent period thresholds (SPT), recruitment curves, and silent period durations were acquired by recording tongue motor evoked potentials. Tongue silent period duration was increased in DS, especially in the left hemisphere (P<0.05; Hedge’s g or Cohen’s dunbiased = 1.054, i.e. large effect size), suggesting a “state” condition of higher intracortical inhibition in left motor cortex networks. Differences in motor thresholds (different excitatory/inhibitory ratios in DS) were evident, as well as significant differences in SPT. In fluent speakers, the left hemisphere may be marginally more excitable than the right one in motor thresholds at lower muscular activation, while active motor thresholds and SPT were higher in the left hemisphere of DS with respect to the right one, resulting also in a positive correlation with stuttering severity. Pre-TMS electromyography data gave overlapping evidence. Findings suggest the existence of a complex intracortical balance in DS tongue primary motor cortex, with a particular interplay between excitatory and inhibitory mechanisms, also in neural substrates related to silent periods. Findings are discussed with respect to functional and structural impairments in stuttering, and are also proposed as novel neural markers of a stuttering “state” in persistent DS, helping to define more focused treatments (e.g. neuro-modulation).

Stuttering as a matter of delay in neural activation: A combined TMS/EEG study

“…This has been explained as being related to compensation mechanisms (Neumann et al, 2003;Preibisch et al, 2003;Kell et al, 2009), although activity in the right frontal cortex (and its connections with the supplementary motor ''complex"basal ganglia system) may have also a role in the pathophysiology of DS (Neef et al, 2016) within the context of excessive motor inhibition (see also Duann et al, 2009). These ''neural markers" may be a consequence of abnormal modulations in intracortical motor networks as demonstrated by TMS experiments (Busan et al, 2017(Busan et al, , 2016(Busan et al, , 2013(Busan et al, , 2009Neef et al, 2015aNeef et al, , 2015bNeef et al, , 2011Whillier et al, 2018). They may also be due to defective white matter, especially in brain regions close to and around the left inferior frontal regions, comprising motor/premotor structures, but also in fibers in longrange neural pathways directed toward muscular effectors (Lu et al 2009;Sommer et al, 2002;Watkins et al, 2008).…”

Biomarkers Obtained by Transcranial Magnetic Stimulation in Neurodevelopmental Disorders

“…168 These results suggested a deficit in controlling speech motor plans in DS, likely in the left M1. Consistent with these results, Busan et al 169 found an abnormally prolonged cSP in the left M1 representation of tongue and significantly higher aMT in the left hemisphere of patients with DS relative to their right hemisphere, the extent of which correlated with stuttering severity. Abnormalities of TMS measures in DS, especially in the left hemisphere, including reduced corticospinal and corticobulbar excitability, and reduced ICF and prolonged cSP, can indicate a decreased tonic excitation of afferent inputs to M1, 170 possibly because of the white-matter abnormalities reported in DS involving the left superior longitudinal fasciculus and the white-matter fibers between the left frontal and premotor cortices.…”

Speech Fluency Improvement in Developmental Stuttering Using Non-invasive Brain Stimulation: Insights From Available Evidence

“…Interestingly, these abnormalities are not only strictly related to speech tasks but can also be evident during non-speech motor tasks (e.g., Sommer et al, 2003 ; Chang et al, 2009 ; Neef et al, 2011 ; Busan et al, 2013 , 2016 ) or even at rest (e.g., Wu et al, 1997 ; Sommer et al, 2003 ; Alm et al, 2013 ; Busan et al, 2013 ; Desai et al, 2017 ; Chang et al, 2018 ). The altered networks highlighted in DS are fundamental to the programming/execution of complex motor sequences, especially when they are voluntary or internally driven, as is the case for cortico-basal-thalamo-cortical networks (see Busan, 2020 ; Chang and Guenther, 2020 ).…”

“…However, current evidence more properly suggests that DS should be considered as a “dynamic” timing and motor control disorder, affecting broader neural networks in the brain and their communications (e.g., Ludlow and Loucks, 2003 ; Alm, 2004 ; Etchell et al, 2014 ). Dysfluencies may be the result of “poor” neural synchronization (or “delayed” neural activation) among different brain regions (see Salmelin et al, 2000 ; Etchell et al, 2014 ; Busan et al, 2019 ), altering the balance among excitatory and inhibitory (motor) signals (e.g., Busan et al, 2016 , 2017 , 2020 ).…”

“…The SMA is fundamental to the correct implementation of complex (internally driven) motor sequences (as well as in motor inhibition), thanks to the information shared with regions such as the basal ganglia, prefrontal regions, and the inferior frontal cortex (Ikeda et al, 1999;Seitz et al, 2006;Narayana et al, 2012;Rochas et al, 2013;Ruan et al, 2018). In this context, the altered functioning of the basal ganglia frequently highlighted in DS (e.g., Wu et al, 1995Wu et al, , 1997Alm, 2004;Watkins et al, 2008) and often associated with stuttering severity (e.g., Giraud et al, 2008;Toyomura et al, 2011) is likely to result in a "disequilibrium" among excitatory and inhibitory motor signals (compare with Busan et al, 2016Busan et al, , 2017. This may affect the correct functioning of connected cortical targets, thus resulting in the defective programming/implementation of complex motor sequences.…”