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January 18, 2022; 98 (3) Research Article

Functional Connectivity as a Potential Mechanism for Language Plasticity

View ORCID ProfileAlyssa S. Ailion, View ORCID ProfileXiaozhen You, View ORCID ProfileJuma S. Mbwana, Eleanor J. Fanto, Manu Krishnamurthy, View ORCID ProfileChandan J. Vaidya, Leigh N. Sepeta, William D. Gaillard, Madison M. Berl
First published November 18, 2021, DOI: https://doi.org/10.1212/WNL.0000000000013071
Alyssa S. Ailion
From the Departments of Psychiatry and Neurology (A.S.A.), Boston Children's Hospital, Harvard Medical School, MA; Departments of Neurology (X.Y., J.S.M., E.J.F., M.K., W.D.G.) and Neuropsychology (L.N.S., M.M.B.), Children's National Hospital; and Department of Psychology (C.J.V.), Georgetown University, Washington, DC.
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Xiaozhen You
From the Departments of Psychiatry and Neurology (A.S.A.), Boston Children's Hospital, Harvard Medical School, MA; Departments of Neurology (X.Y., J.S.M., E.J.F., M.K., W.D.G.) and Neuropsychology (L.N.S., M.M.B.), Children's National Hospital; and Department of Psychology (C.J.V.), Georgetown University, Washington, DC.
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Juma S. Mbwana
From the Departments of Psychiatry and Neurology (A.S.A.), Boston Children's Hospital, Harvard Medical School, MA; Departments of Neurology (X.Y., J.S.M., E.J.F., M.K., W.D.G.) and Neuropsychology (L.N.S., M.M.B.), Children's National Hospital; and Department of Psychology (C.J.V.), Georgetown University, Washington, DC.
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Eleanor J. Fanto
From the Departments of Psychiatry and Neurology (A.S.A.), Boston Children's Hospital, Harvard Medical School, MA; Departments of Neurology (X.Y., J.S.M., E.J.F., M.K., W.D.G.) and Neuropsychology (L.N.S., M.M.B.), Children's National Hospital; and Department of Psychology (C.J.V.), Georgetown University, Washington, DC.
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Manu Krishnamurthy
From the Departments of Psychiatry and Neurology (A.S.A.), Boston Children's Hospital, Harvard Medical School, MA; Departments of Neurology (X.Y., J.S.M., E.J.F., M.K., W.D.G.) and Neuropsychology (L.N.S., M.M.B.), Children's National Hospital; and Department of Psychology (C.J.V.), Georgetown University, Washington, DC.
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Chandan J. Vaidya
From the Departments of Psychiatry and Neurology (A.S.A.), Boston Children's Hospital, Harvard Medical School, MA; Departments of Neurology (X.Y., J.S.M., E.J.F., M.K., W.D.G.) and Neuropsychology (L.N.S., M.M.B.), Children's National Hospital; and Department of Psychology (C.J.V.), Georgetown University, Washington, DC.
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Leigh N. Sepeta
From the Departments of Psychiatry and Neurology (A.S.A.), Boston Children's Hospital, Harvard Medical School, MA; Departments of Neurology (X.Y., J.S.M., E.J.F., M.K., W.D.G.) and Neuropsychology (L.N.S., M.M.B.), Children's National Hospital; and Department of Psychology (C.J.V.), Georgetown University, Washington, DC.
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William D. Gaillard
From the Departments of Psychiatry and Neurology (A.S.A.), Boston Children's Hospital, Harvard Medical School, MA; Departments of Neurology (X.Y., J.S.M., E.J.F., M.K., W.D.G.) and Neuropsychology (L.N.S., M.M.B.), Children's National Hospital; and Department of Psychology (C.J.V.), Georgetown University, Washington, DC.
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Madison M. Berl
From the Departments of Psychiatry and Neurology (A.S.A.), Boston Children's Hospital, Harvard Medical School, MA; Departments of Neurology (X.Y., J.S.M., E.J.F., M.K., W.D.G.) and Neuropsychology (L.N.S., M.M.B.), Children's National Hospital; and Department of Psychology (C.J.V.), Georgetown University, Washington, DC.
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Functional Connectivity as a Potential Mechanism for Language Plasticity
Alyssa S. Ailion, Xiaozhen You, Juma S. Mbwana, Eleanor J. Fanto, Manu Krishnamurthy, Chandan J. Vaidya, Leigh N. Sepeta, William D. Gaillard, Madison M. Berl
Neurology Jan 2022, 98 (3) e249-e259; DOI: 10.1212/WNL.0000000000013071

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Abstract

Background and Objectives Task fMRI is a clinical tool for language lateralization, but has limitations, and cannot provide information about network-level plasticity. Additional methods are needed to improve the precision of presurgical language mapping. We investigate language resting-state functional connectivity (RS fMRI; FC) in typically developing children (TD) and children with epilepsy. Our objectives were to (1) understand how FC components differ between TD children and those with epilepsy; (2) elucidate how the location of disease (frontal/temporal epilepsy foci) affects FC; and (3) investigate the relationship between age and FC.

Methods Our sample included 55 TD children (mean age 12 years, range 7–18) and 31 patients with focal epilepsy (mean age 13 years, range 7–18). All participants underwent RS fMRI. Using a bilateral canonical language map as target, vertex-wise intrahemispheric FC map and interhemispheric FC map for each participant were computed and thresholded at top 10% to compute an FC laterality index (FCLI; [(L – R)/(L + R)]) of the frontal and temporal regions for both integration (intrahemispheric FC; FCLIi) and segregation (interhemispheric FC; FCLIs) maps.

Results We found FC differences in the developing language network based on disease, seizure foci location, and age. Frontal and temporal FCLIi was different between groups (t[84] = 2.82, p < 0.01; t[84] = 4.68, p < 0.01, respectively). Frontal epilepsy foci had the largest differences from TD (Cohen d frontal FCLIi = 0.84, FCLIs = 0.51; temporal FCLIi = 1.29). Development and disease have opposing influences on the laterality of FC based on groups. In the frontal foci group, FCLIi decreased with age (r = −0.42), whereas in the temporal foci group, FCLIi increased with age (r = 0.40). Within the epilepsy group, increases in right frontal integration FCLI relates to increased right frontal task activation in our mostly left language dominant group (r = 0.52, p < 0.01). Language network connectivity is associated with higher verbal intelligence in children with epilepsy (r = 0.45, p < 0.05).

Discussion These findings lend preliminary evidence that FC reflects network plasticity in the form of adaptation and compensation, or the ability to recruit support and reallocate resources within and outside of the traditional network to compensate for disease. FC expands on task-based fMRI and provides complementary and potentially useful information about the language network that is not captured using task-based fMRI alone.

Glossary

EPI=
patients with focal epilepsy;
FC=
functional connectivity;
FCi=
functional connectivity integration;
FCLI=
functional connectivity laterality index;
FCs=
functional connectivity segregation;
HC=
hemispheric contrast;
IFG=
inferior frontal gyrus;
MFG=
middle frontal gyrus;
MNI=
Montreal Neurological Institute;
RS=
resting-state;
TD=
typically developing;
VIQ=
verbal intelligence

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article. The Article Processing Charge was funded by the authors.

  • Received June 7, 2021.
  • Accepted in final form November 2, 2021.
  • © 2021 American Academy of Neurology
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