Left posterior-dorsal area 44 couples with parietal areas to promote speech fluency, while right area 44 activity promotes the stopping of motor responses

Abstract

Area 44 is a cytoarchitectonically distinct portion of Broca's region. Parallel and overlapping large-scale networks couple with this region thereby orchestrating heterogeneous language, cognitive, and motor functions. In the context of stuttering, area 44 frequently comes into focus because structural and physiological irregularities affect developmental trajectories, stuttering severity, persistency, and etiology. A remarkable phenomenon accompanying stuttering is the preserved ability to sing. Speaking and singing are connatural behaviours recruiting largely overlapping brain networks including left and right area 44. Analysing which potential subregions of area 44 are malfunctioning in adults who stutter, and what effectively suppresses stuttering during singing, may provide a better understanding of the coordination and reorganization of large-scale brain networks dedicated to speaking and singing in general. We used fMRI to investigate functionally distinct subregions of area 44 during imagery of speaking and imaginary of humming a melody in 15 dextral males who stutter and 17 matched control participants. Our results are fourfold. First, stuttering was specifically linked to a reduced activation of left posterior-dorsal area 44, a subregion that is involved in speech production, including phonological word processing, pitch processing, working memory processes, sequencing, motor planning, pseudoword learning, and action inhibition. Second, functional coupling between left posterior area 44 and left inferior parietal lobule was deficient in stuttering. Third, despite the preserved ability to sing, males who stutter showed bilaterally a reduced activation of area 44 when imagine humming a melody, suggesting that this fluency-enhancing condition seems to bypass posterior-dorsal area 44 to achieve fluency. Fourth, time courses of the posterior subregions in area 44 showed delayed peak activations in the right hemisphere in both groups, possibly signaling the offset response. Because these offset response-related activations in the right hemisphere were comparably large in males who stutter, our data suggest a hyperactive mechanism to stop speech motor responses and thus possibly reflect a pathomechanism, which, until now, has been neglected. Overall, the current results confirmed a recently described co-activation based parcellation supporting the idea of functionally distinct subregions of left area 44.

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

“…This study, to the best of our knowledge, is the first to reveal the neural mechanisms underlying the phonological WM deficit in PWS, supporting the ill-developed cognitive-linguistic hypothesis of stuttering (Postma & Kolk, 1993). Specifically, in a phonological WM task that required simultaneous storage and manipulation of syllables, PWS exhibited greater activation in the right inferior frontal gyrus extending to the middle frontal gyrus than fluent controls, consistent with previous findings of increased brain activation in the right hemisphere in PWS (Chang et al, 2009;Fox et al, 1996;Fox et al, 2000;Neef et al, 2016;Preibisch et al, 2003). Post hoc analysis revealed significant negative correlation between the brain activity in the right inferior frontal gyrus and the backward digit span.…”

“…Abnormal activity in the right inferior frontal gyrus in PWS has been repeatedly reported in previous functional studies using other paradigms(Chang et al, 2009;Kell et al, 2009;Neef et al, 2016;Neef et al, 2017 ;Preibisch et al, 2003), and it has been thought to represent a compensatory mechanism in response to the left-side impairment(Neef et al, 2017; Abnormal activity in the right inferior frontal gyrus in PWS has been repeatedly reported in previous functional studies using other paradigms(Chang et al, 2009;Kell et al, 2009;Neef et al, 2016;Neef et al, 2017 ;Preibisch et al, 2003), and it has been thought to represent a compensatory mechanism in response to the left-side impairment(Neef et al, 2017; …”

The frontal aslant tract (FAT) and its role in speech, language and executive function

“…Furthermore, in cases where the FAT was spared from resection, patients experienced no post-operative stuttering. Finally, Neef and colleagues (Neef et al, 2018;Neef et al, 2016) investigated 31 adults with stuttering and 34 controls. They found that more severe stuttering was linked to stronger connectivity of the right FAT, which they interpreted as reflecting an overly active global motor inhibition commonly associated with the right inferior frontal gyrus.…”

Online cathodal transcranial direct current stimulation to the right homologue of Broca's area improves speech fluency in people who stutter

“…It has been proposed that the hyperdirect pathway connecting the subthalamic nucleus and RB (inferior frontal gyrus) mediates global response suppression . Therefore, overactivation of this pathway results in increased global inhibition of motor systems, which in turn disrupts control of ongoing and succeeding motor programs for fluent speech . It must also be noted that a recent study revealed altered structural abnormalities in the white matter pathway connecting the right frontal regions with the pre‐SMA, as well as with subcortical structures .…”