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Garnett, E. O.

Publications and source records attributed to Garnett, E. O..

2 recordsLinked to original sources

Neural subtypes in developmental stuttering

Developmental stuttering is a complex neurodevelopmental disorder characterized by disfluent speech. At the individual level, the behavioral manifestations of stuttering vary considerably, likely reflecting heterogeneity in underlying neural mechanisms. In this study, we examined individual-specific differences in the brains of children who stutter (CWS), by implementing normative modeling, a framework that quantifies how an individual deviates from an age- and sex-matched reference population. We applied this approach to identify individual-specific structural brain atypicalities using gray and white matter volumes. These volumes were derived from MRI scans from a large mixed-longitudinal dataset of 235 and 240 scans from CWS and fluent controls respectively, aged between 3 and 12 years. Individual deviation maps capturing these atypicalities were then used to cluster CWS into subtypes based on similarities in their neuroanatomical profiles. This analysis identified four neural subtypes with distinct neuroanatomical atypicalities relative to fluent controls. The key findings were a basal ganglia-thalamo-cerebellar subtype associated with higher stuttering severity and lower rates of recovery, and a white matter subtype characterized by mild severity and a higher likelihood of recovery. The remaining two subtypes showed cerebellar differences alongside alterations in brain regions involved in sensorimotor integration. Moreover, cerebellar volume atypicalities were present in all four subtypes, indicating that cerebellar alterations were present across otherwise distinct neural profiles and may represent a shared neuroanatomical feature of stuttering. These findings indicate that examining individual-specific neural differences and subtyping based on patterns of neural atypicalities provides valuable insight into the heterogeneity of developmental stuttering and represents a promising direction for improving our understanding of the disorder.

neuroscience↗

Linking lysosomal enzyme targeting genes and energy metabolism with altered gray matter volume in children with persistent stuttering

Developmental stuttering is a childhood onset neurodevelopmental disorder with an unclear etiology. Subtle changes in brain structure and function are present in both children and adults who stutter. It is a highly heritable disorder, and up to 12-20% of stuttering cases may carry a mutation in one of four genes involved in mannose-6-phosphate mediated protein intracellular trafficking. To better understand the relationship between genetic factors and brain structural changes, we used gene expression data from the Allen Institute for Brain Science (AIBS) and voxel-based morphometry (VBM) to investigate the spatial correspondence between gene expression patterns and differences in gray matter volume (GMV) between children with persistent stuttering (n=26, 87 scans) and their fluent peers (n=44, 139 scans). We found that expression patterns of two stuttering-related genes (GNPTG and NAGPA) in the brain exhibit a strong positive spatial correlation with the magnitude of GMV differences between groups. Further gene set enrichment analyses revealed that genes whose expression was highly correlated with the GMV differences were enriched for glycolysis and oxidative metabolism in mitochondria. Although the results are correlational and cannot inform us about underlying casual mechanisms, our results suggest a possibility that regions with high expression level of genes associated with stuttering may be particularly vulnerable to the effect of alterations in these genes. This effect may be further exacerbated by the relatively high energy utilization in those brain during the period of a sharp increase in brain energy utilization, which coincides with a period of rapid language development and the onset of stuttering during childhood.

neuroscience↗