Spontaneous Neural Responses Relate to Behavioural and Psychiatric Traits in 16p11.2 Deletion Carriers: A Joint Analysis of EEG Spectral Power and Multi-Scale Entropy.

Background: Copy number variations (CNV) at the 16p11.2 chromosomal region (~600 kb breakpoints 4–5 (BP4-BP5)) are rare high-risk CNVs associated with myriad clinical features and neurodevelopmental disorders including intellectual disability, developmental delays, and autism spectrum disorder. Previous studies reported atypical event-related neural activity in 16p11.2 deletion carriers in response to auditory (Jenkins et al., 2016), visual (LeBlanc and Nelson, 2016), and social stimuli (Hudac et al., 2015). However, to date, it is not clear if neural responses are related to behavioural and psychiatric traits in 16p11.2 deletion carriers. Here, we investigated resting-state spectral power and entropy in 16p11.2 del carriers and its link to core del symptoms.

Objectives: The aim of this study is to examine the impact of 16p11.2 deletions (del) on neural activity and its relationship to social and communication impairment, autism symptom severity, and other behavioural and psychiatric problems.

Methods: EEG data were previously collected as part of the Simons Variation in Individuals Project (Simons VIP Consortium, 2012). Using spectral power, complexity index (CI), and multi-scale-entropy (MSE) analysis techniques, we analysed whole-brain resting-state EEG data collected from 22 16p11.2 del carriers and 12 typical controls. Given the small sample size, permutation tests were used for investigating group differences in neural responses (i.e., power and entropy levels). Additionally, permutation correlation tests were performed to examine whether del neural responses correlate with scores in the Social Responsiveness Scale (SRS), Autism Diagnostic Observation Schedule Calibrated Severity Score (ADOS-CSS), and Child Behaviour Checklist for ages 1.15-5 (CBCL).

Results: In terms of neural responses, no significant group differences were observed in absolute and relative power within each frequency band (delta, theta, alpha, beta, and gamma) at each of the four examined regions (frontal, occipital, parietal, and temporal). Significant group differences were found, however, in CI and MSE at all brain regions. Specifically, del showed higher levels of CI and MSE than controls at all time-scales (1-20) and regions. In addition, these neural power and entropy responses strongly correlated with most of the CBCL symptoms in deletion carriers. However, no links were found between neural responses and SRS and ADOS-CSS scores.

Conclusions: Atypical neural entropy levels are implicated in 16p11.2 del carriers over all timescales and brain regions. This indicates that local and longer-range information processing were atypical in 16p11.2 del carriers and possibly driving cognitive inflexibility and impairment in CBCL symptoms.