Neural substrates of psychosis revealed by altered dependencies between brain activity and white-matter architecture in individuals with 22q11 deletion syndrome

Article Article scientifique Article Neural substrates of psychosis revealed by altered dependencies between brain activity and white-matter architecture in individuals with 22q11 deletion syndrome eng 2022-06-08 2022-06-08 author Bortolin Karin 901271 author Delavari Farnaz 930325 author Preti Maria Giulia 808407 author Sandini Corrado 846736 author Mancini Valentina 0000-0003-4411-896X 898584 author Mullier Emeline 941074 author Van De Ville Dimitri 0000-0002-2879-3861 638484 author Eliez Stéphan 39336 103075 10.1016/j.nicl.2022.103075 35717884 2213-1582 PMC9218553 https://www.sciencedirect.com/science/article/pii/S2213158222001401 Background: Dysconnectivity has been consistently proposed as a major key mechanism in psychosis. Indeed, disruptions in large-scale structural and functional brain networks have been associated with psychotic symptoms. However, brain activity is largely constrained by underlying white matter pathways and the study of function-structure dependency, compared to conventional unimodal analysis, allows a biologically relevant assessment of neural mechanisms. The 22q11.2 deletion syndrome (22q11DS) constitutes a remarkable opportunity to study the pathophysiological processes of psychosis. Methods: 58 healthy controls and 57 deletion carriers, aged from 16 to 32 years old,underwent resting-state functional and diffusion-weighted magnetic resonance imaging. Deletion carriers were additionally fully assessed for psychotic symptoms. Firstly, we used a graph signal processing method to combine brain activity and structural connectivity measures to obtain regional structural decoupling indexes (SDIs). We use SDI to assess the differences of functional structural dependency (FSD) across the groups. Subsequently we investigated how alterations in FSDs are associated with the severity of positive psychotic symptoms in participants with 22q11DS. Results: In line with previous findings, participants in both groups showed a spatial gradient of FSD ranging from sensory-motor regions (stronger FSD) to regions involved in higher-order function (weaker FSD). Compared to controls, in participants with 22q11DS, and further in deletion carriers with more severe positive psychotic symptoms, the functional activity was more strongly dependent on the structure in parahippocampal gyrus and subcortical dopaminergic regions, while it was less dependent within the cingulate cortex. This analysis revealed group differences not otherwise detected when assessing the structural and functional nodal measures separately. Conclusions: Our findings point toward a disrupted modulation of functional activity on the underlying structure, which was further associated to psychopathology for candidate critical regions in 22q11DS. This study provides the first evidence for the clinical relevance of function-structure dependency and its contribution to the emergence of psychosis. 22q11 Deletion syndrome Function-structure dependency Graph signal processing Psychosis dMRI fMRI Dewey 616.89 Dewey 616.0757 Dewey 576.5 Swiss National Science Foundation The Swiss 22q11DS longitudinal cohort: understanding psychosis proneness through negative symptoms 179404 CH Projects Swiss National Science Foundation Swiss VCFS Cohort: a 10-year longitudinal investigation from genes to brain to cognition for understanding psychosis proneness in 22q11.2 deletion 144260 CH Projects Swiss National Science Foundation NCCR 'SYNAPSY - The synaptic bases of mental diseases' (phase III) 185897 CH Programmes 60 Département de psychiatrie 225 62 Département de radiologie et informatique médicale 227 135 Département de médecine génétique et développement 21D false 421 Laboratoire d'imagerie et de psychopathologie développementale 693 552 Traitement d'images médicales 893 NeuroImage. Clinical 35 77eedd5b-c93e-4347-9f0a-7ed011fde711 Article (Published version) Public Neural_substrate.pdf 3763954 application/pdf CC BY-NC-ND-4.0 32eb1269-e085-4bfa-8e12-715942914ea0 Supplemental data Public 1-s2.0-S2213158222001401-mmc1.docx 2850620 application/vnd.openxmlformats-officedocument.wordprocessingml.document openAccess Faculté de médecine / Section de médecine clinique / Département de psychiatrie Faculté de médecine / Section de médecine clinique / Département de radiologie et informatique médicale Faculté de médecine / Section de médecine fondamentale / Département de médecine génétique et développement

Title	Published in	Year	Views	Downloads

Neural substrates of psychosis revealed by altered dependencies between brain activity and white-matter architecture in individuals with 22q11 deletion syndrome	NeuroImage. Clinical	2022	158	90
Dynamic spatiotemporal patterns of brain connectivity reorganize across development	Network Neuroscience	2020	358	114

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