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Title: Atypical development of Broca's area in a large family with inherited stuttering.
Austin Authors: Thompson-Lake, Daisy G Y;Scerri, Thomas S;Block, Susan;Turner, Samantha J;Reilly, Sheena;Kefalianos, Elaina;Bonthrone, Alexandra F;Helbig, Ingo;Bahlo, Melanie;Scheffer, Ingrid E ;Hildebrand, Michael S ;Liégeois, Frédérique J;Morgan, Angela T
Affiliation: Medicine (University of Melbourne)
Department of Medical Biology, University of Melbourne, 1G Royal Parade, Parkville 305, Australia..
Department of Biomedical and Health Informatics, Children's Hospital of Philadelphia, Philadelphia, PA 19104 USA..
The Epilepsy NeuroGenetics Initiative, Children's Hospital of Philadelphia, Philadelphia, PA 19104 USA..
Division of Neurology, Children's Hospital of Philadelphia, Philadelphia, PA 19104 USA..
The Florey Institute of Neuroscience and Mental Health
Murdoch Children's Research Institute, Parkville 3052, Australia..
UCL Great Ormond Street Institute of Child Health, London, UK..
Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Parkville 3052, Australia..
Department of Audiology and Speech Pathology, University of Melbourne, Parkville 3052, Australia..
Menzies Health Institute Queensland, Griffith University, Southport 4215, Australia..
Speech and Language, Murdoch Children's Research Institute, Parkville 3052, Australia..
Discipline of Speech Pathology, School of Allied Health, Human Services & Sport, La Trobe University, Bundoora 3086, Australia..
Department of Neurology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104 USA..
Population Health and Immunity Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville 3052, Australia..
Issue Date: 29-Apr-2022
Date: 2021
Publication information: Brain : a journal of neurology 2022; 145(3): 1177-1188
Abstract: Developmental stuttering is a condition of speech dysfluency, characterized by pauses, blocks, prolongations and sound or syllable repetitions. It affects around 1% of the population, with potential detrimental effects on mental health and long-term employment. Accumulating evidence points to a genetic aetiology, yet gene-brain associations remain poorly understood due to a lack of MRI studies in affected families. Here we report the first neuroimaging study of developmental stuttering in a family with autosomal dominant inheritance of persistent stuttering. We studied a four-generation family, 16 family members were included in genotyping analysis. T1-weighted and diffusion-weighted MRI scans were conducted on seven family members (six male; aged 9-63 years) with two age and sex matched controls without stuttering (n = 14). Using Freesurfer, we analysed cortical morphology (cortical thickness, surface area and local gyrification index) and basal ganglia volumes. White matter integrity in key speech and language tracts (i.e. frontal aslant tract and arcuate fasciculus) was also analysed using MRtrix and probabilistic tractography. We identified a significant age by group interaction effect for cortical thickness in the left hemisphere pars opercularis (Broca's area). In affected family members this region failed to follow the typical trajectory of age-related thinning observed in controls. Surface area analysis revealed the middle frontal gyrus region was reduced bilaterally in the family (all cortical morphometry significance levels set at a vertex-wise threshold of P < 0.01, corrected for multiple comparisons). Both the left and right globus pallidus were larger in the family than in the control group (left P = 0.017; right P = 0.037), and a larger right globus pallidus was associated with more severe stuttering (rho = 0.86, P = 0.01). No white matter differences were identified. Genotyping identified novel loci on chromosomes 1 and 4 that map with the stuttering phenotype. Our findings denote disruption within the cortico-basal ganglia-thalamo-cortical network. The lack of typical development of these structures reflects the anatomical basis of the abnormal inhibitory control network between Broca's area and the striatum underpinning stuttering in these individuals. This is the first evidence of a neural phenotype in a family with an autosomal dominantly inherited stuttering.
DOI: 10.1093/brain/awab364
ORCID: 0000-0003-3096-0910
Journal: Brain : a journal of neurology
PubMed URL: 35296891
PubMed URL:
Type: Journal Article
Subjects: Broca’s area
basal ganglia
cortical thickness
inherited stuttering
Appears in Collections:Journal articles

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