Dataset Information

Neuroanatomical anomalies associated with rare AP4E1 mutations in people who stutter.

ABSTRACT: Developmental stuttering is a common speech disorder with strong genetic underpinnings. Recently, stuttering has been associated with mutations in genes involved in lysosomal enzyme trafficking. However, how these mutations affect the brains of people who stutter remains largely unknown. In this study, we compared grey matter volume and white matter fractional anisotropy between a unique group of seven subjects who stutter and carry the same rare heterozygous AP4E1 coding mutations and seven unrelated controls without such variants. The carriers of the AP4E1 mutations are members of a large Cameroonian family in which the association between AP4E1 and persistent stuttering was previously identified. Compared to controls, mutation carriers showed reduced grey matter volume in the thalamus, visual areas and the posterior cingulate cortex. Moreover, reduced fractional anisotropy was observed in the corpus callosum, consistent with the results of previous neuroimaging studies of people who stutter with unknown genetic backgrounds. Analysis of gene expression data showed that these structural differences appeared at the locations in which expression of AP4E1 is relatively high. Moreover, the pattern of grey matter volume differences was significantly associated with AP4E1 expression across the left supratentorial regions. This spatial congruency further supports the connection between AP4E1 mutations and the observed structural differences.

SUBMITTER: Chow HM

PROVIDER: S-EPMC8633735 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Neuroanatomical anomalies associated with rare <i>AP4E1</i> mutations in people who stutter.

Chow Ho Ming HM Li Hua H Liu Siyuan S Frigerio-Domingues Carlos C Drayna Dennis D

Brain communications 20211113 4

Developmental stuttering is a common speech disorder with strong genetic underpinnings. Recently, stuttering has been associated with mutations in genes involved in lysosomal enzyme trafficking. However, how these mutations affect the brains of people who stutter remains largely unknown. In this study, we compared grey matter volume and white matter fractional anisotropy between a unique group of seven subjects who stutter and carry the same rare heterozygous <i>AP4E1</i> coding mutations and se ...[more]

PMID: 34859215

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Project description:An increasing body of studies has revealed neuroanatomical impairments in developmental dyslexia. However, whether these structural anomalies are driven by dyslexia (disorder-specific effects), absolute reading performance (performance-dependent effects), and/or further influenced by age (maturation-sensitive effects) remains elusive. To help disentangle these sources, the current study used a novel disorder (dyslexia vs. control) by maturation (younger vs. older) factorial design in 48 Chinese children who were carefully matched. This design not only allows for direct comparison between dyslexics versus controls matched for chronological age and reading ability, but also enables examination of the influence of maturation and its interaction with dyslexia. Voxel-based morphometry (VBM) showed that dyslexic children had reduced regional gray matter volume in the left temporo-parietal cortex (spanning over Heschl's gyrus, planum temporale and supramarginal gyrus), middle frontal gyrus, superior occipital gyrus, and reduced regional white matter in bilateral parieto-occipital regions (left cuneus and right precuneus) compared with both age-matched and reading-level matched controls. Therefore, maturational stage-invariant neurobiological signatures of dyslexia were found in brain regions that have been associated with impairments in the auditory/phonological and attentional systems. On the other hand, maturational stage-dependent effects on dyslexia were observed in three regions (left ventral occipito-temporal cortex, left dorsal pars opercularis and genu of the corpus callosum), all of which were previously reported to be involved in fluent reading and its development. These striking dissociations collectively suggest potential atypical developmental trajectories of dyslexia, where underlying mechanisms are currently unknown but may be driven by interactions between genetic and/or environmental factors. In summary, this is the first study to disambiguate maturational stage on neuroanatomical anomalies of dyslexia in addition to the effects of disorder, reading performance and maturational stage on neuroanatomical anomalies of dyslexia, despite the limitation of a relatively small sample-size. These results will hopefully encourage future research to place greater emphasis on taking a developmental perspective to dyslexia, which may, in turn, further our understanding of the etiological basis of this neurodevelopmental disorder, and ultimately optimize early identification and remediation.

Project description:IntroductionGrowing anecdotal evidence suggests the feasibility of robotic intervention for people who suffer from disorders related to state anxiety. Few studies have been conducted on utilizing robots for persons who stutter (PWS). The present study examines the feasibility of using a robot for speech therapy for PWS.MethodsWe prepared four settings (i.e., interviews with unfamiliar persons, interviews with unfamiliar communication robots, reading sentences aloud with a tandem robot that can utter the same words as a user by repeating the user's voice after a short delay, and reading sentences aloud while being alone). We assessed the potential of the robots as both interlocutors and practice partners in training with delayed auditory feedback (DAF) for PWS. Moreover, we assessed the relationship between the trait of stuttering and the participants' affinity to the robots.ResultsEleven PWS participated in the study. Eight (72.7%) participants had fewer stuttering-related psychological symptoms when they communicated with robots than when they communicated with humans. Spearman's rank correlation analysis revealed that there was a significant negative correlation between the Modified Erickson Communication Attitude scale (S-24) and the difference between the scores for stuttering-related psychological symptoms pertaining to the communication robot and humans (p < 0.01). Six participants (54.5%) had fewer stuttering-related psychological symptoms when they read aloud with the tandem robot than when they read aloud alone. There were significant positive correlations between S-24 and the differences between the scores for stuttering-related psychological symptoms when reading aloud with the tandem robot and those when reading aloud alone (p < 0.01).DiscussionThe communication robot and tandem utterance robot can sometimes be burdensome, although both robots were always easier to talk to for PWS in this preliminary study. The participants with positive speech-related attitudes were more inclined to decrease stuttering-related psychological symptoms when communicating with CommU than when communicating with humans. The participants whose speech-related attitudes were negative were more inclined to show a decrease in stuttering-related psychological symptoms when reading aloud with the tandem robot. Further studies are needed to provide more detailed information.

Dataset Information

Neuroanatomical anomalies associated with rare AP4E1 mutations in people who stutter.

Publications

Neuroanatomical anomalies associated with rare <i>AP4E1</i> mutations in people who stutter.

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