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Functional Connectivity Decreases with Metabolic Stress in Sickle Cell Disease
Author(s) -
Fields Melanie E.,
Mirro Amy E.,
Guilliams Kristin P.,
Binkley Michael M.,
Gil Diaz Luisa,
Tan Jessica,
Fellah Slim,
Eldeniz Cihat,
Chen Yasheng,
Ford Andria L.,
Shimony Joshua S.,
King Allison A.,
An Hongyu,
Smyser Christopher D.,
Lee JinMoo
Publication year - 2020
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.25891
Subject(s) - cognition , white matter , neuroimaging , default mode network , functional magnetic resonance imaging , biomarker , blood oxygen level dependent , disease , alzheimer's disease neuroimaging initiative , magnetic resonance imaging , neuroscience , medicine , psychology , cognitive impairment , biology , biochemistry , radiology
Objective Children with sickle cell disease (SCD) experience cognitive deficits even when unaffected by stroke. Using functional connectivity magnetic resonance imaging (MRI) as a potential biomarker of cognitive function, we tested our hypothesis that children with SCD would have decreased functional connectivity, and that children experiencing the greatest metabolic stress, indicated by elevated oxygen extraction fraction, would have the lowest connectivity. Methods We prospectively obtained brain MRIs and cognitive testing in healthy controls and children with SCD. Results We analyzed data from 60 participants (20 controls and 40 with sickle cell disease). There was no difference in global cognition or cognitive subdomains between cohorts. However, we found decreased functional connectivity within the sensory‐motor, lateral sensory‐motor, auditory, salience, and subcortical networks in participants with SCD compared with controls. Further, as white matter oxygen extraction fraction increased, connectivity within the visual ( p = 0.008, parameter estimate = −0.760 [95% CI = −1.297, −0.224]), default mode ( p = 0.012, parameter estimate = −0.417 [95% CI = −0.731, −0.104]), and cingulo‐opercular ( p = 0.009, parameter estimate = −0.883 [95% CI = −1.517, −0.250]) networks decreased. Interpretation We conclude that there is diminished functional connectivity within these anatomically contiguous networks in children with SCD compared with controls, even when differences are not seen with cognitive testing. Increased white matter oxygen extraction fraction was associated with decreased connectivity in select networks. These data suggest that elevated oxygen extraction fraction and disrupted functional connectivity are potentially presymptomatic neuroimaging biomarkers for cognitive decline in SCD. ANN NEUROL 2020;88:995–1008