Altered Brain Structure-Function Relationships Underlie Executive Dysfunction in 22q11.2 Deletion Syndrome

Abstract

22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder associated with elevated rates of developmental neuropsychiatric disorders and impaired executive function (EF). Disrupted brain structure-function relationships may underlie EF deficits in 22q11DS. We administered the Behavior Rating Inventory of Executive Function (BRIEF) to assess real-world EF in patients with 22q11DS and matched controls (n = 86; age 6-17 years), along with cognitive measures that tap behavioral regulation and metacognition aspects of EF. Using FreeSurfer's whole-brain vertex cortical thickness pipeline, we investigated brain structure-EF relationships in patients with 22q11DS and controls. Behaviorally, patients with 22q11DS were impaired on multiple EF measures. Right orbitofrontal cortical thickness showed a differential relationship between real-world EF in patients with 22q11DS and controls. We also observed a group difference in the relationship between behavioral regulation and metacognition measures with thickness of ventral and dorsolateral prefrontal regions, respectively. Our findings suggest that executive dysfunction characteristic of 22q11DS is underscored by altered prefrontal cortical structure.

Atypical response inhibition and error processing in 22q11.2 Deletion Syndrome and schizophrenia: Towards neuromarkers of disease progression and risk

“…While lower d-prime scores suggest diminished ability to discriminate between signal and noise, or in this context, to monitor performance in order to adaptively balance demands to detect and rapidly respond or inhibit responses, longer reaction times may be a consequence of the motor slowing described in this population ( Morrens et al, 2007 ). Poorer behavioral performance has likewise been reported in 22q11.2DS ( Jonas et al, 2015 ), but not consistently so. For example, in an fMRI study investigating response inhibition, adolescents with 22q11.2DS did not differ from their age-matched peers in hit and false alarm rates and reaction times, despite the presence of between-groups differences in activation in a region of the left parietal lobe.…”

Study protocol for The Emory 3q29 Project: evaluation of neurodevelopmental, psychiatric, and medical symptoms in 3q29 deletion syndrome

“…Finally, standardized assessment and systematic data capture of manifestations in 3q29 deletion syndrome, operationalized according to the protocol described here, allows for cross-comparison with other rare genetic syndromes, such as 16p11.2 duplication [ 5 ] and 22q11.2 deletion [ 37 ], where nearly identical instruments are deployed. As new syndromes with high risk for neuropsychiatric phenotypes are identified, it will become even more important to have harmonized systems for phenotypic evaluation.…”

Neuroanatomical Correlates of Cognitive Dysfunction in 22q11.2 Deletion Syndrome

“…However, the literature on this topic is currently sparse. A relatively rare study of executive functioning in 43 adolescents with 22q11.2DS found worse performance in real-world executive functioning was associated with increased CT in the right orbitofrontal cortex, working memory and sustained attention was associated with increased CT in both the right pars orbitalis of the inferior frontal gyrus (IFG) and the STG, and working memory and attentional control was associated with increased CT in the right precentral gyrus [104]. However, in the typically developing control group, the opposite trends between CT and behavioral measures were found.…”