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

Author(s):  
Joanne L Doherty ◽  
Adam C Cunningham ◽  
Samuel JRA Chawner ◽  
Hayley M Moss ◽  
Diana C Dima ◽  
...  

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.

NeuroImage ◽  
2017 ◽  
Vol 149 ◽  
pp. 85-97 ◽  
Author(s):  
Daniela Zöller ◽  
Marie Schaer ◽  
Elisa Scariati ◽  
Maria Carmela Padula ◽  
Stephan Eliez ◽  
...  

2017 ◽  
Author(s):  
Charles Schleifer ◽  
Amy Lin ◽  
Leila Kushan ◽  
Jie Lisa Ji ◽  
Genevieve Yang ◽  
...  

ABSTRACT22q11.2 deletion syndrome (22q11DS) is a recurrent copy number variant (CNV) with high penetrance for developmental neuropsychiatric disorders. Study of individuals with 22q11DS therefore may offer key insights into neural mechanisms underlying such complex illnesses. Resting-state functional MRI (rs-fMRI) studies in idiopathic schizophrenia have consistently revealed disruption of thalamic and hippocampal circuitry. Here, we sought to test whether this circuitry is similarly disrupted in the context of this genetic high-risk condition. To this end, resting-state functional connectivity patterns were assessed in a sample of young men and women with 22q11DS (n=42) and demographically matched healthy controls (n=39). Neuroimaging data were acquired via single-band protocols, and analyzed in line with methods provided by the Human Connectome Project (HCP). We computed functional relationships between individual-specific anatomically-defined thalamic and hippocampal seeds and all gray matter voxels in the brain. Whole-brain type I error protection was achieved through nonparametric permutation-based methods. 22q11DS patients displayed reciprocal disruptions in thalamic and hippocampal functional connectivity relative to control subjects. Thalamo-cortical coupling was increased in sensorimotor cortex, and reduced across associative networks. The opposite effect was observed for the hippocampus in regards to sensory and associative network connectivity. The thalamic and hippocampal dysconnectivity observed in 22q11DS suggest that high genetic risk for psychiatric illness is linked with disruptions in large-scale cortico-subcortical networks underlying higher-order cognitive functions. These effects highlight the translational importance of large-effect CNVs for informing mechanisms underlying neural disruptions observed in idiopathic developmental neuropsychiatric disorders.SIGNIFICANCE STATEMENTInvestigation of neuroimaging biomarkers in highly penetrant genetic syndromes represents a more biologically tractable approach to identify neural circuit disruptions underlying developmental neuropsychiatric conditions. 22q11.2 deletion syndrome confers particularly high risk for psychotic disorders, and is thus an important translational model in which to investigate systems-level mechanisms implicated in idiopathic illness. Here, we show resting-state fMRI evidence of large-scale sensory and executive network disruptions in youth with 22q11DS. In particular, this study provides the first evidence that these networks are disrupted in a reciprocal fashion with regard to the functional connectivity of the thalamus and hippocampus, suggesting circuit-level dysfunction.


2018 ◽  
Vol 14 (1) ◽  
Author(s):  
Leah M. Mattiaccio ◽  
Ioana L. Coman ◽  
Carlie A. Thompson ◽  
Wanda P. Fremont ◽  
Kevin M. Antshel ◽  
...  

2014 ◽  
Vol 157 (1-3) ◽  
pp. 175-181 ◽  
Author(s):  
Miralena I. Tomescu ◽  
Tonia A. Rihs ◽  
Robert Becker ◽  
Juliane Britz ◽  
Anna Custo ◽  
...  

Author(s):  
Maria Carmela Padula ◽  
Marie Schaer ◽  
Elisa Scariati ◽  
Maude Schneider ◽  
Dimitri Van De Ville ◽  
...  

2012 ◽  
Vol 139 (1-3) ◽  
pp. 33-39 ◽  
Author(s):  
Martin Debbané ◽  
Marine Lazouret ◽  
AnnaLaura Lagioia ◽  
Maude Schneider ◽  
Dimitri Van De Ville ◽  
...  

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