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

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22q11.2 deletion syndrome (22q11DS) is linked to executive function (EF) deficits. Altered prefrontal cortex structure may underlie these EF impairments in individuals with 22q11DS.

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Cognitive functionCopy number variationDopamineMagnetic resonance imagingNeurodevelopmentNeurogeneticsPrefrontal cortex

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Area of Science:

  • Neurogenetics
  • Neurodevelopmental Disorders
  • Cognitive Neuroscience

Background:

  • 22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder.
  • Individuals with 22q11DS often exhibit executive function (EF) deficits and increased rates of neuropsychiatric disorders.
  • Altered brain structure-function relationships are hypothesized to contribute to EF impairments in 22q11DS.

Purpose of the Study:

  • To investigate brain structure-executive function relationships in 22q11DS.
  • To compare real-world EF and cognitive measures between patients with 22q11DS and controls.
  • To identify specific prefrontal cortical regions associated with EF deficits in 22q11DS.

Main Methods:

  • The Behavior Rating Inventory of Executive Function (BRIEF) and cognitive tests were administered to 86 patients with 22q11DS and matched controls (ages 6-17).
  • Whole-brain vertex cortical thickness was analyzed using FreeSurfer.
  • Brain structure-EF relationships were examined in both groups.

Main Results:

  • Patients with 22q11DS demonstrated significant impairments across multiple EF measures.
  • Right orbitofrontal cortical thickness showed a distinct relationship with real-world EF in 22q11DS patients compared to controls.
  • Differences were observed in the association between behavioral regulation/metacognition and prefrontal cortical thickness (ventral/dorsolateral, respectively).

Conclusions:

  • Executive dysfunction in 22q11DS is associated with altered prefrontal cortical structure.
  • Specific prefrontal regions, including orbitofrontal and dorsolateral areas, are implicated in the EF deficits seen in 22q11DS.
  • These findings highlight the neurobiological underpinnings of executive dysfunction in this population.