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Functional Connectivity Decreases with Metabolic Stress in Sickle Cell Disease

Melanie E Fields1, Amy E Mirro1, Kristin P Guilliams1,2

  • 1Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, USA.

Annals of Neurology
|September 2, 2020
PubMed

Insights

Children with sickle cell disease (SCD) show reduced brain connectivity, even without cognitive deficits. Increased metabolic stress in white matter further lowers connectivity, suggesting potential early markers for cognitive decline.

Area of Science:

  • Neuroscience
  • Pediatric Neurology
  • Medical Imaging

Background:

  • Sickle cell disease (SCD) is associated with cognitive deficits in children, potentially linked to underlying neurobiological changes.
  • Functional connectivity magnetic resonance imaging (fMRI) offers a potential biomarker for assessing brain function in pediatric SCD.
  • Metabolic stress, indicated by oxygen extraction fraction (OEF), may impact brain connectivity in children with SCD.

Purpose of the Study:

  • To investigate functional brain connectivity in children with SCD using fMRI.
  • To determine if decreased functional connectivity is present in children with SCD, irrespective of overt cognitive deficits.
  • To explore the relationship between metabolic stress (white matter OEF) and functional connectivity in pediatric SCD.

Main Methods:

  • Prospective acquisition of brain MRIs and cognitive testing in children with SCD and healthy controls.
  • Analysis of fMRI data to assess functional connectivity across various brain networks.
  • Correlation analysis between white matter oxygen extraction fraction and functional connectivity measures.

Main Results:

  • No significant differences in global cognition or cognitive subdomains were observed between children with SCD and controls.
  • Children with SCD exhibited decreased functional connectivity in sensory-motor, auditory, salience, and subcortical networks compared to controls.
  • Increased white matter oxygen extraction fraction was significantly associated with reduced connectivity in visual, default mode, and cingulo-opercular networks.

Conclusions:

  • Diminished functional connectivity exists within specific brain networks in children with SCD, even in the absence of detectable cognitive impairments.
  • Elevated white matter oxygen extraction fraction is linked to decreased functional connectivity in select neural networks.
  • Disrupted functional connectivity and elevated oxygen extraction fraction may serve as presymptomatic neuroimaging biomarkers for cognitive decline in pediatric SCD.
Abstract

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