Altered auditory processing and effective connectivity in 22q11.2 deletion syndrome

SCHIZOPHRENIA RESEARCH

卷:197

Article

Larsen, Kit Melissa^1,2,3,4  Morup, Morten²  Birknow, Michelle Rosgaard^3,4,5  Fischer, Elvira¹  Hulme, Oliver¹  Vangkilde, Anders³  Schmock, Henriette³  Baare, William Frans Christiaan¹  Olsen, Line^3,4  Werge, Thomas^3,4,6  Siebner, Hartwig R.^1,6,7  Garrido, Marta I.^8,9,10,11 

[1] Univ Copenhagen, Hosp Hvidovre, Ctr Funct & Diagnost Imaging & Res, Danish Res Ctr Magnet Resonance, Hvidovre, Denmark

[2] Tech Univ Denmark, Cognit Syst, DTU Compute, Lyngby, Denmark

[3] Copenhagen Univ Hosp, Mental Hlth Ctr Sct Hans, Inst Biol Psychait, Roskilde, Denmark

[4] Lundbeck Fdn Initiat Integrat Psychiat Res, IPSYCH, Aarhus, Denmark

[5] H Lundbeck & Co AS, Synapt Transmiss, Valby, Denmark

[6] Univ Copenhagen, Fac Hlth & Med Sci, Dept Clin Med, Copenhagen, Denmark

[7] Univ Copenhagen, Hosp Bispebjerg, Dept Neurol, Copenhagen, Denmark

[8] Univ Queensland, Queensland Brain Inst, Brisbane, Qld, Australia

[9] Univ Queensland, Ctr Adv Imaging, Brisbane, Qld, Australia

[10] Univ Queensland, Ctr Excellence Integrat Brain, Australian Res Council, Brisbane, Qld, Australia

[11] Univ Queensland, Sch Math & Phys, Brisbane, Qld, Australia

关键词: 22q11 deletion syndrome;    Dynamic causal modelling;    EEG;    Mismatch negativity;    N1 component;   

DOI  :  10.1016/J.schres.2018.01.026

来源: Elsevier

【 摘 要 】

22q11.2 deletion syndrome (22q11.2DS) is one of the most common copy number variants and confers a markedly increased risk for schizophrenia. As such, 22q11.2DS is a homogeneous genelic liability model which enables studies to delineale functional abnormalities that may precede disease onset.. Mismatch negativity (MMN), a brain marker of change detection, is reduced in people with schizophrenia compared to healthy controls. Using dynamic causal modelling (DCM), previous studies showed that Lop-down effective connectivity linking the frontal and temporal cortex is reduced in schizophrenia relative to healthy controls in MMN tasks. In the search for early risk-markers for schizophrenia we investigated the neural basis of change detection in a group with 22q11.2DS. We recorded high-density EEG from 19 young non psychotic 22811.2 deletion carriers, as well as from 27 healthy non-carriers with comparable age distribution and sex ratio, while they listened to a sequence of sounds arranged in a roving oddball paradigm. Despite finding no significant reduction in the MMN responses, whole-scalp spatiotemporal analysis of responses to the tones revealed a greater Pronto-temporal N1 component in the 22q11.2 deletion carriers. DCM showed reduced intrinsic connection within right primary auditory cortex as well as in the top clown, connection from the right inferior frontal gyms to right superior temporal gyrus for 22q11.2 deletion carriers although not surviving correction for multiple comparison. We discuss these findings in terms of reduced adaptation and a general increased sensitivity to tones in 22q11.2DS. (C) 2013 Elsevier B.V. All rights reserved

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