Alterations in resting-state activity and functional connectivity in children with 22q11.2 deletion syndrome

Background While genetic risk factors for psychiatric and neurodevelopmental disorders have been identified, the neurobiological route from genetic risk to neuropsychiatric outcome remains unclear. 22q11.2 deletion syndrome (22q11.2DS) is a copy number variant (CNV) syndrome associated with high rates of neurodevelopmental and psychiatric disorders including autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and schizophrenia. Alterations in neural integration and cortical connectivity have been linked to the spectrum of neuropsychiatric disorders seen in 22q11.2DS and may be a mechanism by which the CNV acts to increase risk. Despite this, few studies have investigated electrophysiological connectivity in this high-risk group. Studying children with 22q11.2DS provides a unique paradigm to identify brain markers of neurodevelopmental impairment and to relate these to underlying biology. Methods Magnetoencephalography (MEG) was used to investigate resting-state cortical oscillatory patterns in 34 children with 22q11.2DS and 25 controls aged 10-17 years old. Oscillatory activity and functional connectivity across six frequency bands were compared between groups. Regression analyses were used to explore the relationships between these measures, IQ and neurodevelopmental symptoms. Results Children with 22q11.2DS had atypical oscillatory activity and functional connectivity across multiple frequency bands (delta, beta and gamma bands). In the 22q11.2DS group, low frequency (alpha band) activity was negatively associated with cognitive ability and positively associated with ASD and ADHD symptoms. Frontal high frequency (gamma band) activity and connectivity were positively associated with ASD and ADHD symptoms, while posterior gamma activity was negatively associated with ASD symptoms. Conclusions These findings highlight that haploinsufficiency at the 22q11.2 locus alters both local and long-range cortical circuitry, which could be a mechanism underlying neurodevelopmental vulnerability in this high risk group.