Abnormalities in gray matter microstructure in young adults with 22q11.2 deletion syndrome

Zora Kikinis, Nikos Makris, Valerie J. Sydnor, Sylvain Bouix, Ofer Pasternak, Ioana L. Coman, Kevin Martin Antshel, Wanda Fremont, Marek R. Kubicki, Martha E. Shenton, Wendy R. Kates, Yogesh Rathi

Research output: Contribution to journalArticle

Abstract

Background: 22q11.2 Deletion Syndrome (22q11DS) is a genetic, neurodevelopmental disorder characterized by a chromosomal deletion and a distinct cognitive profile. Although abnormalities in the macrostructure of the cortex have been identified in individuals with 22q11DS, it is not known if there are additional microstructural changes in gray matter regions in this syndrome, and/or if such microstructural changes are associated with cognitive functioning. Methods: This study employed a novel diffusion MRI measure, the Heterogeneity of Fractional Anisotropy (HFA), to examine variability in the microstructural organization of the cortex in healthy young adults (N = 30) and those with 22q11DS (N = 56). Diffusion MRI, structural MRI, clinical and cognitive data were acquired. Results: Compared to controls, individuals with 22q11DS evinced increased HFA in cortical association (p =.003, d = 0.86) and paralimbic (p <.0001, d = 1.2) brain areas, whereas no significant differences were found between the two groups in primary cortical brain areas. Additionally, increased HFA of the right paralimbic area was associated with poorer performance on tests of response inhibition, i.e., the Stroop Test (rho = −0.37 p =.005) and the Gordon Diagnostic System Vigilance Commission (rho = −0.41 p =.002) in the 22q11DS group. No significant correlations were found between HFA and cognitive abilities in the healthy control group. Conclusions: These findings suggest that cortical microstructural disorganization may be a neural correlate of response inhibition in individuals with 22q11DS. Given that the migration pattern of neural crest cells is disrupted at the time of early brain development in 22q11DS, we hypothesize that these neural alterations may be neurodevelopmental in origin, and reflect cortical dysfunction associated with cognitive deficits.

Original languageEnglish (US)
Number of pages1
JournalNeuroImage: Clinical
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

DiGeorge Syndrome
Young Adult
Anisotropy
Diffusion Magnetic Resonance Imaging
Brain
Stroop Test
Inborn Genetic Diseases
Aptitude
Neural Crest
Gray Matter
Control Groups

Keywords

  • 22q11.2 deletion syndrome
  • Cognition
  • Diffusion magnetic resonance imaging
  • Fractional anisotropy
  • Gray matter
  • Response inhibition

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology
  • Cognitive Neuroscience

Cite this

Kikinis, Z., Makris, N., Sydnor, V. J., Bouix, S., Pasternak, O., Coman, I. L., ... Rathi, Y. (Accepted/In press). Abnormalities in gray matter microstructure in young adults with 22q11.2 deletion syndrome. NeuroImage: Clinical. https://doi.org/10.1016/j.nicl.2018.101611

Abnormalities in gray matter microstructure in young adults with 22q11.2 deletion syndrome. / Kikinis, Zora; Makris, Nikos; Sydnor, Valerie J.; Bouix, Sylvain; Pasternak, Ofer; Coman, Ioana L.; Antshel, Kevin Martin; Fremont, Wanda; Kubicki, Marek R.; Shenton, Martha E.; Kates, Wendy R.; Rathi, Yogesh.

In: NeuroImage: Clinical, 01.01.2018.

Research output: Contribution to journalArticle

Kikinis, Z, Makris, N, Sydnor, VJ, Bouix, S, Pasternak, O, Coman, IL, Antshel, KM, Fremont, W, Kubicki, MR, Shenton, ME, Kates, WR & Rathi, Y 2018, 'Abnormalities in gray matter microstructure in young adults with 22q11.2 deletion syndrome', NeuroImage: Clinical. https://doi.org/10.1016/j.nicl.2018.101611
Kikinis, Zora ; Makris, Nikos ; Sydnor, Valerie J. ; Bouix, Sylvain ; Pasternak, Ofer ; Coman, Ioana L. ; Antshel, Kevin Martin ; Fremont, Wanda ; Kubicki, Marek R. ; Shenton, Martha E. ; Kates, Wendy R. ; Rathi, Yogesh. / Abnormalities in gray matter microstructure in young adults with 22q11.2 deletion syndrome. In: NeuroImage: Clinical. 2018.
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abstract = "Background: 22q11.2 Deletion Syndrome (22q11DS) is a genetic, neurodevelopmental disorder characterized by a chromosomal deletion and a distinct cognitive profile. Although abnormalities in the macrostructure of the cortex have been identified in individuals with 22q11DS, it is not known if there are additional microstructural changes in gray matter regions in this syndrome, and/or if such microstructural changes are associated with cognitive functioning. Methods: This study employed a novel diffusion MRI measure, the Heterogeneity of Fractional Anisotropy (HFA), to examine variability in the microstructural organization of the cortex in healthy young adults (N = 30) and those with 22q11DS (N = 56). Diffusion MRI, structural MRI, clinical and cognitive data were acquired. Results: Compared to controls, individuals with 22q11DS evinced increased HFA in cortical association (p =.003, d = 0.86) and paralimbic (p <.0001, d = 1.2) brain areas, whereas no significant differences were found between the two groups in primary cortical brain areas. Additionally, increased HFA of the right paralimbic area was associated with poorer performance on tests of response inhibition, i.e., the Stroop Test (rho = −0.37 p =.005) and the Gordon Diagnostic System Vigilance Commission (rho = −0.41 p =.002) in the 22q11DS group. No significant correlations were found between HFA and cognitive abilities in the healthy control group. Conclusions: These findings suggest that cortical microstructural disorganization may be a neural correlate of response inhibition in individuals with 22q11DS. Given that the migration pattern of neural crest cells is disrupted at the time of early brain development in 22q11DS, we hypothesize that these neural alterations may be neurodevelopmental in origin, and reflect cortical dysfunction associated with cognitive deficits.",
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AU - Pasternak, Ofer

AU - Coman, Ioana L.

AU - Antshel, Kevin Martin

AU - Fremont, Wanda

AU - Kubicki, Marek R.

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