Decreased Cerebellar-Orbitofrontal Connectivity Correlates with Stuttering Severity: Whole-Brain Functional and Structural Connectivity Associations with Persistent Developmental Stuttering

Abstract

Persistent developmental stuttering is characterized by speech production disfluency and affects 1% of adults. The degree of impairment varies widely across individuals and the neural mechanisms underlying the disorder and this variability remain poorly understood. Here we elucidate compensatory mechanisms related to this variability in impairment using whole-brain functional and white matter connectivity analyses in persistent developmental stuttering. We found that people who stutter had stronger functional connectivity between cerebellum and thalamus than people with fluent speech, while stutterers with the least severe symptoms had greater functional connectivity between left cerebellum and left orbitofrontal cortex (OFC). Additionally, people who stutter had decreased functional and white matter connectivity among the perisylvian auditory, motor, and speech planning regions compared to typical speakers, but greater functional connectivity between the right basal ganglia and bilateral temporal auditory regions. Structurally, disfluency ratings were negatively correlated with white matter connections to left perisylvian regions and to the brain stem. Overall, we found increased connectivity among subcortical and reward network structures in people who stutter compared to controls. These connections were negatively correlated with stuttering severity, suggesting the involvement of cerebellum and OFC may underlie successful compensatory mechanisms by more fluent stutterers.

Speaking-related changes in cortical functional connectivity associated with assisted and spontaneous recovery from developmental stuttering

“…Interestingly, the functional disconnection from the speech production network included not only the left orbitofrontal cortex but also caudal parts of the superior cerebellum. A functional connection between these two regions has recently been related to compensation attempts in PS (Sitek et al, 2016), and efficient stuttering therapy was shown to disconnect the superior cerebellum from the speech production system during rest (Lu et al, 2012). We show here that the cortical normalization of auditory-motor mapping can lead to long-lasting recovery in case it is accompanied by plasticity involving the superior cerebellum and left orbitofrontal cortex.…”

“…Yet, during resting state, subjects do not necessarily enter a consistent 'default mode', because participants may differ largely in covert behavior or vigilance (Tagliazucchi & Laufs, 2014). Altogether, functional connectivity studies in adults who stutter revealed abnormal connectivity between Broca's region and the premotor cortex (Chang et al, 2011) or the rest of the resting state language network in the bilateral fronto-temporo-parietal cortex (Lu et al, 2012), reduced auditory-motor coupling (Watkins, 2011), a hyper-connectivity in right homologue areas (Chang et al, 2011), and enhanced, compensatory cerebello-orbitofrontal connectivity (Sitek et al, 2016). Auditory-motor hypo-connectivity was confirmed in boys who stutter together with connectivity changes of the putamen (Chang & Zhu, 2013).…”

“…Comprehensive interpretation of recovery-associated changes indeed requires taking into account changes at the level of inter-regional functional connectivity. Several functional connectivity studies have already been performed in PS, either during speaking (Chang, Horwitz, Ostuni, Reynolds, & Ludlow, 2011;Lu et al, 2010;Watkins, 2011) or while resting silently inside the scanner (Lu et al, 2012;Sitek et al, 2016,Yang, Jia, Siok, & Tan, 2016. Both approaches have their advantages and drawbacks.…”

“…The whole brain group comparison did not reveal significant positive connectivity when a voxel-wise correction for multiple comparisons was applied. Yet, when the original threshold of p<0.001, uncorrected, as in (Kell et al, 2009), was applied for the PPI*group interaction, there was increased connectivity between the left BA 47/12 and the superior cerebellum, a region that has previously been associated with compensation attempts and therapy effects in PS (Etchell, Johnson, & Sowman, 2014; Lu et al, 2012;Sitek et al, 2016; Yang et al, 2016). We thus decided to report this effect although it is not corrected for multiple comparisons.…”

Abnormal neural response to phonological working memory demands in persistent developmental stuttering

“…Furthermore, we found a significantly negative correlation between the activation of the right inferior frontal gyrus and its connectivity with the left cerebellum, suggesting that hyperactivity in this region may compensate for its reduced functional connectivity with other regions. In addition, the structural connectivity of the left cerebellum has been found to be negatively correlated with the severity of stuttering (Sitek et al, 2016). Previous studies have reported alternated resting-state functional connectivity of the left cerebellum in PWS Yang et al, 2016).…”