Takayama, Y. | Search bioRxiv

bioRxiv2025

Visualization of functional and effective connectivity underlying auditory descriptive naming

ObjectiveWe visualized functional and effective connectivity within specific white matter networks in response to auditory descriptive questions. MethodsWe investigated 40 Japanese-speaking patients with focal epilepsy and estimated connectivity measures using cortical high-gamma dynamics and MRI tractography. ResultsHearing a wh-interrogative at question onset enhanced inter-hemispheric functional connectivity, with left-to-right callosal facilitatory flows between the superior-temporal gyri, contrasted by functional connectivity diminution with right-to-left callosal suppressive flows between dorsolateral prefrontal regions. Processing verbs associated with concrete objects or adverbs increased left intra-hemispheric connectivity, with bidirectional facilitatory flows through extensive white matter pathways. Questions beginning with what, compared to where, induced greater neural engagement in the left posterior inferior-frontal gyrus at question offset, linked to enhanced functional connectivity and bidirectional facilitatory flows to the temporal lobe neocortex via the arcuate fasciculus. During overt responses, inter-hemispheric functional connectivity was enhanced, with bidirectional callosal flows between Rolandic areas, and individuals with higher IQ scores exhibited less prolonged neural engagement in the left posterior middle frontal gyrus. ConclusionsVisualization of directional neural interactions within white matter networks during overt naming is feasible. SignificancePhrase order may influence network dynamics in listeners, even when presented with auditory descriptive questions conveying similar meanings.

neuroscience↗

bioRxiv2023

DNA methylation signature in NSD2 loss-of-function variants appeared similar to that in Wolf-Hirschhorn syndrome

PurposeWolf-Hirschhorn syndrome (WHS), a contiguous gene syndrome caused by the hemizygous deletion of the distal short arm of chromosome 4 where NSD2 is, reportedly exhibits specific DNA methylation signatures in peripheral blood cells. However, responsible genomic loci for signatures are unreported. The objective of the study is to define the loci of WHS-related DNA methylation signatures and to explore the role of NSD2 for the signatures. MethodsWe conducted genome-wide methylation analysis of individuals with WHS or NSD2 variants using array. We studied genome-edited knock in mice or induced pluripotent stem cells to explore the function of NSD2 variants which are observed in congenital anomaly cases. ResultsThree undiagnosed cases with NSD2 variants showed WHS-related DNA methylation signatures. These variants were validated to be NSD2 loss-of-function in induced pluripotent stem cells or genome-edited knock-in mice. p.Pro905Leu variant decreased Nsd2 protein levels, and changed Histone H3-Lysine 36 demethylation levels in similar way in the same genomic regions as Nsd2 knock out mice regulated. Nsd2 knock out mice exhibited common DNA methylation changes. ConclusionThese results revealed that WHS-related DNA methylation signatures are dependent on NSD2 dysfunction and are useful in diagnosing NSD2 variants of unknown significance.

genetics↗