Meta-analysis of structural integrity of white matter and functional connectivity in developmental stuttering

Developmental stuttering is a speech disfluency disorder characterized by repetitions, prolongations, and blocks of speech. While a number of neuroimaging studies have identified alterations in localized brain activation during speaking in persons with stuttering (PWS), it is unclear whether neuroimaging evidence converges on alterations in structural integrity of white matter and functional connectivity (FC) among multiple regions involved in supporting fluent speech. In the present study, we conducted coordinate-based meta-analyses according to the PRISMA guidelines for available publications that studied fractional anisotropy (FA) using tractbased spatial statistics (TBSS) for structural integrity and the seed-based voxel-wise FC analyses. The search retrieved 11 publications for the TBSS FA studies, 29 seed-based FC datasets from 6 publications for the restingstate, and 29 datasets from 6 publications for the task-based studies. The meta-analysis of TBSS FA revealed that PWS exhibited FA reductions in the middle and posterior segments of the left superior longitudinal fasciculus. Furthermore, the analysis of resting-state FC demonstrated that PWS had reduced FC in the right supplementary motor area and inferior parietal cortex, whereas an increase in FC was observed in the left cerebellum crus I. Conversely, we observed increased FC for task-based FC in regions implicated in speech production or sequential movements, including the anterior cingulate cortex, posterior insula, and bilateral cerebellum crus I in PWS. Functional network characterization of the altered FCs revealed that the sets of reduced resting-state and increased task-based FCs were largely distinct, but the somatomotor and striatum/thalamus networks were foci of alterations in both conditions. These observations indicate that developmental stuttering is characterized by structural and functional alterations in multiple brain networks that support speech fluency or sequential motor processes, including cortico-cortical and subcortical connections.