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

Abstract

We previously reported speaking-related activity changes associated with assisted recovery induced by a fluency shaping therapy program and unassisted recovery from developmental stuttering (Kell et al., Brain 2009). While assisted recovery re-lateralized activity to the left hemisphere, unassisted recovery was specifically associated with the activation of the left BA 47/12 in the lateral orbitofrontal cortex. These findings suggested plastic changes in speakingrelated functional connectivity between left hemispheric speech network nodes. We reanalyzed these data involving 13 stuttering men before and after fluency shaping, 13 men who recovered spontaneously from their stuttering, and 13 male control participants, and examined functional connectivity during overt vs. covert reading by means of psychophysiological interactions computed across left cortical regions involved in articulation control. Persistent stuttering was associated with reduced auditory-motor coupling and enhanced integration of somatosensory feedback between the supramarginal gyrus and the prefrontal cortex. Assisted recovery reduced this hyper-connectivity and increased functional connectivity between the articulatory motor cortex and the auditory feedback processing anterior superior temporal gyrus. In spontaneous recovery, both auditory-motor coupling and integration of somatosensory feedback were normalized. In addition, activity in the left orbitofrontal cortex and superior cerebellum appeared uncoupled from the rest of the speech production network. These data suggest that therapy and spontaneous recovery normalizes the left hemispheric speaking-related activity via an improvement of auditory-motor mapping. By contrast, long-lasting unassisted recovery from stuttering is additionally supported by a functional isolation of the superior cerebellum from the rest of the speech production network, through the pivotal left BA 47/12. KeywordsPsychophysiological interactions; speech production; overt reading; auditorymotor interactions, left inferior frontal gyrus Corresponding AuthorChristian Kell To view all the submission files, including those not included in the PDF, click on the manuscript title on your EVISE Homepage, then click 'Download zip file'. We dealt with all their remarks, hopefully convincingly, and we hope that this version is now acceptable for publication. Order of Authors GOETHE UNIVERSITY FRANKFURT MEDICAL FACULTYYours faithfully, Christian Kell Response to ReviewersWe thank both reviewers for their careful evaluation of the manuscript. We have reanalyzed the data, updated all results, and re-written parts of the Introduction and Discussion based on their suggestions. Please find our answers below. Reviewer #1 INTRODUCTIONComment: The authors claim that "relapses are frequent" and "rarely adults who stutter recover spontaneously", "fluency induction due to scanner noise", and statements about subjects not entering a consistent "default mode". Can they provide citations for each of these statements? I have heard t...

Differential contributions of the two human cerebral hemispheres to action timing

“…These observations suggest left-lateralized auditory-motor loops could improve rhythm integration by cross-frequency coupling both during speech perception and production. Indeed, reduced auditory-motor coupling in the left hemisphere of people who stutter is associated with overt deficits in controlling speech rhythm (Neef et al, 2015; Chang and Zhu, 2013; Kell et al, 2018). The deficit in rhythm integration in people who stutter is associated with an over-recruitment of the right hemisphere during speech production that is reduced upon recovery (Kell et al, 2009; Kell et al, 2018).…”

“…Indeed, reduced auditory-motor coupling in the left hemisphere of people who stutter is associated with overt deficits in controlling speech rhythm (Neef et al, 2015; Chang and Zhu, 2013; Kell et al, 2018). The deficit in rhythm integration in people who stutter is associated with an over-recruitment of the right hemisphere during speech production that is reduced upon recovery (Kell et al, 2009; Kell et al, 2018). The right over-activation during speaking may be regarded as a strategy to separate competing attractors that arise from insufficient auditory-motor mapping in the left hemisphere (Hickok et al, 2011).…”

Assisted and unassisted recession of functional anomalies associated with dysprosody in adults who stutter

“…Assisted recovery instead relied on a cerebellar recruitment for emotional prosody control. Note that cerebellar activation does not automatically imply automatization of articulatory processes, because unassisted recovery disconnects the activated cerebellum from the articulatory neocortical network (Kell et al, 2017). Therapy-induced speech fluency was associated with additional recruitment of limbic regions for the generation of linguistic prosody.…”

“…It is important to understand that the fMRI measurements did not focus on the use of the trained speech pattern but on the plastic cerebral changes associated with their acquisition, independently of the actual speech behavior. Before therapy, AWS had already read fluently inside the scanner, owing to a quasi-constant scanner noise and the isolation inside the bore (see also Kell, Neumann, Behrens, von Gudenberg, & Giraud, 2017). After therapy, AWS were asked not to use the newly acquired speaking technique inside the scanner deliberately, but to read freely as they did pre-treatment.…”

Fluency shaping increases integration of the command-to-execution and the auditory-to-motor pathways in persistent developmental stuttering

“…Other studies that tested stuttering intervention induced neuroplasticity used speech tasks such as overt single word reading36, overt sentence reading 28,37–41 , and picture naming 42 . Fluency shaping, the stuttering intervention also tested in the current study, induced a re-lateralization of speech-induced brain activity towards the left hemisphere 38,40 possibly due to an improvement of auditory-motor mapping 41 and a restructuring of prosody production 43 . Across stuttering intervention studies, induced plasticity mainly involved the left inferior frontal gyrus 36,40,41,43 .…”