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Abnormalities_in_fronto-striatal_connectivity_within_language_networks.pdf (1.13 MB)

Abnormalities in fronto-striatal connectivity within language networks relate to differences in grey-matter heterogeneity in Asperger syndrome

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posted on 2023-06-08, 17:15 authored by Eugenia Radulescu, Ludovico Minati, Balaji Ganeshan, Neil Harrison, Marcus A Gray, Felix D C C Beacher, Chris ChatwinChris Chatwin, Rupert YoungRupert Young, Hugo CritchleyHugo Critchley
Abstract Asperger syndrome (AS) is an Autism Spectrum Disorder (ASD) characterised by qualitative impairment in the development of emotional and social skills with relative preservation of general intellectual abilities, including verbal language. People with AS may nevertheless show atypical language, including rate and frequency of speech production. We previously observed that abnormalities in grey matter homogeneity (measured with texture analysis of structural MR images) in AS individuals when compared with controls are also correlated with the volume of caudate nucleus. Here, we tested a prediction that these distributed abnormalities in grey matter compromise the functional integrity of brain networks supporting verbal communication skills. We therefore measured the functional connectivity between caudate nucleus and cortex during a functional neuroimaging study of language generation (verbal fluency), applying psycho-physiological interaction (PPI) methods to test specifically for differences attributable to grey matter heterogeneity in AS participants. Furthermore, we used dynamic causal modelling (DCM) to characterise the causal directionality of these differences in interregional connectivity during word production. Our results revealed a diagnosis-dependent influence of grey matter heterogeneity on the functional connectivity of the caudate nuclei with right insula/inferior frontal gyrus and anterior cingulate, respectively with the left superior frontal gyrus and right precuneus. Moreover, causal modelling of interactions between inferior frontal gyri, caudate and precuneus, revealed a reliance on bottom-up (stimulus-driven) connections in AS participants that contrasted with a dominance of top-down (cognitive control) connections from prefrontal cortex observed in control participants. These results provide detailed support for previously hypothesised central disconnectivity in ASD and specify discrete brain network targets for diagnosis and therapy in ASD.


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NeuroImage: Clinical







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Highlights •We used MRI techniques to assess the connectivity in language networks in AS. •Grey-matter heterogeneity of MR images correlated with volume of caudate in AS. •Hence, caudate nuclei were used as seed ROIs in connectivity analyses: PPI, DCM. •Grey-matter heterogeneity differently tuned caudate connectivity in AS, controls. •DCM of language circuitry featured bottom-up models in AS and top-down in controls.

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