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Individuals with 22q11.2 deletion syndrome show intact prediction but reduced adaptation in responses to repeated sounds: evidence from Bayesian mapping

By Kit Melissa Larsen, Morten Mørup, Michelle Rosgaard Birknow, Elvira Fischer, Line Olsen, Michael Didriksen, William Frans Christiaan Baaré, Thomas Mears Werge, Marta Isabel Garrido, Hartwig R Siebner

Posted 15 Oct 2018
bioRxiv DOI: 10.1101/441634 (published DOI: 10.1016/j.nicl.2019.101721)

Background: One of the most common copy number variants, the 22q11.2 microdeletion, confers a increased risk for schizophrenia. Since schizophrenia has been associated with an aberrant neural response to repeated stimuli through both reduced adaptation and prediction, we here hypothesized that this may also be the case in nonpsychotic individuals with a 22q11.2 deletion. Methods: We recorded high-density EEG from 19 individuals with 22q11.2 deletion syndrome (12-25 years), as well as 27 healthy volunteers with comparable age and sex distribution, while they listened to a sequence of sounds arranged in a roving oddball paradigm. Using posterior probability maps and dynamic causal modelling we tested three different models accounting for repetition dependent changes in cortical responses as well as in effective connectivity; namely an adaptation model, a prediction model, and a model including both adaptation and prediction. Results: Repetition-dependent changes were parametrically modulated by a combination of adaptation and prediction and were apparent in both cortical responses and in the underlying effective connectivity. This effect was reduced in individuals with a 22q11.2 deletion and was negatively correlated with negative symptom severity. Follow-up analysis showed that the reduced effect of the combined adaptation and prediction model seen in individuals with 22q11.2 deletion was driven by reduced adaptation rather than prediction failure. Conclusions: Our findings suggest that adaptation is reduced in individuals with a 22q11.2 deletion, which can be interpreted in light of the framework of predictive coding as a failure to suppress prediction errors.

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