Anomalous network architecture of the resting brain in children who stutter

Chang, Soo-Eun; Angstadt, Mike; Chow, Ho Ming; Etchell, Andrew C.; Garnett, Emily O.; Choo, Ai Leen; Kessler, Daniel; Welsh, Robert C.; Sripada, Chandra

doi:10.1016/j.jfludis.2017.01.002

Cited by 70 publications

(58 citation statements)

References 174 publications

(201 reference statements)

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“…These were chosen to interrogate major brain cell types and brain areas previously suggested to be sites of the primary neurological deficit in stuttering. Our first hypothesis was chosen based on imaging studies of the brains of humans who stutter, which have detected associations between stuttering and white matter deficits, including altered connectivity (10,28,29). White matter contains no neuronal cell bodies or synapses but does contain tightly packed glial cells, including oligodendrocytes (which produce myelin), astrocytes, and microglia.…”

Section: Neuropathology Studies and Reduced Astrocyte Staining Densitmentioning

confidence: 99%

“…A primary goal for stuttering research has been to understand the neuropathology underlying this disorder. Imaging studies have identified differences in the brains of individuals who stutter (7)(8)(9)(10). However, such studies have been limited by the difficulty of determining whether these differences are the cause of stuttering or the result of stuttering, and by the fact that they do not provide resolution at the cellular and molecular level.…”

mentioning

confidence: 99%

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HumanGNPTABstuttering mutations engineered into mice cause vocalization deficits and astrocyte pathology in the corpus callosum

Han

Root

Reyes

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Stuttering is a common neurodevelopmental disorder that has been associated with mutations in genes involved in intracellular trafficking. However, the cellular mechanisms leading to stuttering remain unknown. Engineering a mutation in N-acetylglucosamine-1-phosphate transferase subunits α and β (GNPTAB) found in humans who stutter into the mouse Gnptab gene resulted in deficits in the flow of ultrasonic vocalizations similar to speech deficits of humans who stutter. Here we show that other human stuttering mutations introduced into this mouse gene, Gnptab Ser321Gly and Ala455Ser, produce the same vocalization deficit in 8-day-old pup isolation calls and do not affect other nonvocal behaviors. Immunohistochemistry showed a marked decrease in staining of astrocytes, particularly in the corpus callosum of the Gnptab Ser321Gly homozygote mice compared to wild-type littermates, while the staining of cerebellar Purkinje cells, oligodendrocytes, microglial cells, and dopaminergic neurons was not significantly different. Diffusion tensor imaging also detected deficits in the corpus callosum of the Gnptab Ser321Gly mice. Using a range of cell type-specific Cre-drivers and a Gnptab conditional knockout line, we found that only astrocyte-specific Gnptab-deficient mice displayed a similar vocalization deficit. These data suggest that vocalization defects in mice carrying human stuttering mutations in Gnptab derive from abnormalities in astrocytes, particularly in the corpus callosum, and provide support for hypotheses that focus on deficits in interhemispheric communication in stuttering.

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Section: Neuropathology Studies and Reduced Astrocyte Staining Densitmentioning

confidence: 99%

mentioning

confidence: 99%

HumanGNPTABstuttering mutations engineered into mice cause vocalization deficits and astrocyte pathology in the corpus callosum

Han

Root

Reyes

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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“…The pathophysiology of stuttering is still unclear. There is, however, increasing evidence of subtle structural and functional differences in the brains of adults and children who stutter relative to their fluent peers [Beal et al, 2013;Chang et al, 2015Chang et al, , 2017Chang and Zhu, 2013;Connally et al, 2014;Cykowski et al, 2010;Desai et al, 2017;O'Neill et al, 2017;Watkins et al, 2008]. One line of research investigated the property of white matter microstructure by measuring fractional anisotropy (FA), which reflects white matter coherence or integrity, through diffusion tensor imaging (DTI).…”

Section: Introductionmentioning

confidence: 99%

White matter developmental trajectories associated with persistence and recovery of childhood stuttering

Chow

Chang

2017

Human Brain Mapping

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Stuttering affects the fundamental human ability of fluent speech production, and can have a significant negative impact on an individual’s psychosocial development. While the disorder affects about 5% of all preschool children, approximately 80% of them recover naturally within a few years of stuttering onset. The pathophysiology and neuroanatomical development trajectories associated with persistence and recovery of stuttering are still largely unknown. Here, we report the first mixed longitudinal diffusion tensor imaging (DTI) study of childhood stuttering. A total of 195 high quality DTI scans from 35 children who stutter (CWS) and 43 controls between 3-12 years of age were acquired, with an average of three scans per child, each collected approximately a year apart. Fractional anisotropy (FA), a measure reflecting white matter structural coherence, was analyzed voxel-wise to examine group and age-related differences using a linear mixed-effects (LME) model. Results showed that CWS exhibited decreased FA relative to controls in the left arcuate fasciculus, underlying the inferior parietal and posterior temporal areas, and the mid body of corpus callosum. Further, white matter developmental trajectories reflecting growth rate of these tract regions differentiated children with persistent stuttering from those who recovered from stuttering. Specifically, we found a reduction in FA growth rate (i.e., slower FA growth with age) in persistent children relative to fluent controls in the left arcuate fasciculus and corpus callosum, which was not evident in recovered children. These findings provide first glimpses into the possible neural mechanisms of onset, persistence, and recovery of childhood stuttering.

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“…Niet onbelangrijk om te benoemen in dit verband is een zeer recente en omvangrijke hersenstudie naar 84 jonge kinderen die de gedachtegang van bredere en mogelijk niet-spraak gerelateerde oorzaken van stotteren bevestigt (Chang et al, 2017). In deze studie werd met behulp van fMRI de connectiviteit tussen neurale netwerken van het brein geanalyseerd tijdens rusttoestand.…”

Section: Experimenteel Bewijs Voor Afwijkende Monitoring In Stotterenunclassified

Is stotteren een spraak-motorische timingstoornis? Een alternatieve geïntegreerde benadering volgens het SAMI-model

Vorst

Gracco²

2018

SSTP

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SamenvattingStotteren kent vele theorieën die iets trachten te zeggen over de oorzaak en andere verschijnselen verbonden aan de stoornis. Opvallend is dat in Nederland de logopedische praktijk stotteren doorgaans als een "neuromusculaire timingstoornis" duidt en stelt dat de aanleg voor stotteren gerelateerd is aan een mistiming van spraakbewegingen. Naast stotteren als timingstoornis zijn er echter in de loop van de jaren ook andere theorieën geformuleerd. Aangezien de kern van stotteren meestal wordt gezien als een stoornis of verzwakking van spraak-motorische processen zijn in dit artikel specifiek een aantal spraak-motorische modellen besproken. Spraak-motorische theorieën verklaren echter niet altijd de contextuele variabiliteit die vaak gepaard gaat met stotteren; de Speech And Monitoring Interaction (SAMI; Arenas, 2017) hypothese beschouwt naast spraakproductie ook (een verstoorde) monitoring als een belangrijke, mogelijk causale, component van het stotteren. Tot slot is kort belicht welke implicaties de ontwikkeling in theorievorming over stotteren kan hebben voor de klinische praktijk. SummaryMultiple theories aim to explain the cause of stuttering as well as other characteristics related to stuttering. In the Netherlands, speech and language practice usually defines stuttering as a "neuromuscular timing disorder" and states the predisposition to stuttering is confined to mistiming of speech movements. Besides this definition of stuttering as a timing disorder, other theories have been proposed over the years. Since the core of stuttering is usually considered a deficit or limitation of speech-motor processes, several speech-motor models of stuttering are discussed in this paper. These Correspondentieadres: Robert van de Vorst, Centre for Research on Brain, Language and Music, 1 Tenzij expliciet anders aangegeven wordt met de term 'stotteren' verwezen naar ontwikkelingsstotteren. 2 Bron: http://www.nedverstottertherapie.nl/wp-content/uploads/2016/07/Toel.werkmodel.volw_.pubers.ouders-1.pdf; http://stotterinterventiecentrum.nl/volwassenen.html 3 Bron: https://www.nhnieuws.nl/nieuws/213872/Stotteren-op-de-basisschool-Vroeger-gingen-kinderen-mij-weleens-napraten

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Anomalous network architecture of the resting brain in children who stutter

Cited by 70 publications

References 174 publications

HumanGNPTABstuttering mutations engineered into mice cause vocalization deficits and astrocyte pathology in the corpus callosum

HumanGNPTABstuttering mutations engineered into mice cause vocalization deficits and astrocyte pathology in the corpus callosum

White matter developmental trajectories associated with persistence and recovery of childhood stuttering

Is stotteren een spraak-motorische timingstoornis? Een alternatieve geïntegreerde benadering volgens het SAMI-model

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