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

Kit Melissa Larsen*, Morten Mørup, Michelle Rosgaard Birknow, Elvira Fischer, Oliver Hulme, Anders Vangkilde, Henriette Schmock, William Frans Christiaan Baaré, Michael Didriksen, Line Olsen, Thomas Werge, Hartwig R. Siebner, Marta I. Garrido

*Corresponding author for this work

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Abstract

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 genetic liability model which enables studies to delineate 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 top-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 22q11.2 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 fronto-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-down, connection from the right inferior frontal gyrus 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.

Original languageEnglish
JournalSchizophrenia Research
Number of pages9
ISSN0920-9964
DOIs
Publication statusPublished - 2018

Keywords

  • 22q11 deletion syndrome
  • Dynamic causal modelling
  • EEG
  • Mismatch negativity
  • N1 component

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