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March 02, 2021; 96 (9) Article

Role of the Nucleus Basalis as a Key Network Node in Temporal Lobe Epilepsy

View ORCID ProfileHernán F.J. González, View ORCID ProfileSaramati Narasimhan, View ORCID ProfileGraham W. Johnson, View ORCID ProfileKristin E. Wills, Kevin F. Haas, Peter E. Konrad, View ORCID ProfileCatie Chang, View ORCID ProfileVictoria L. Morgan, Mikail Rubinov, View ORCID ProfileDario J. Englot
First published January 13, 2021, DOI: https://doi.org/10.1212/WNL.0000000000011523
Hernán F.J. González
From the Departments of Biomedical Engineering (H.F.J.G., G.W.J., P.E.K., C.C., V.L.M., M.R., D.J.E.) and Electrical Engineering and Computer Science (C.C., V.L.M., M.R., D.J.E.), Vanderbilt University; Departments of Neurological Surgery (S.N., K.E.W., P.E.K., D.J.E.), Radiology and Radiological Sciences (V.L.M., D.J.E.), and Neurology (K.F.H.) and Vanderbilt University Institute of Imaging Science (H.F.J.G., S.N., G.W.J., K.E.W., C.C., V.L.M., D.J.E.), Vanderbilt University Medical Center, Nashville, TN; and Department of Psychology (M.R.), Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA.
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Saramati Narasimhan
From the Departments of Biomedical Engineering (H.F.J.G., G.W.J., P.E.K., C.C., V.L.M., M.R., D.J.E.) and Electrical Engineering and Computer Science (C.C., V.L.M., M.R., D.J.E.), Vanderbilt University; Departments of Neurological Surgery (S.N., K.E.W., P.E.K., D.J.E.), Radiology and Radiological Sciences (V.L.M., D.J.E.), and Neurology (K.F.H.) and Vanderbilt University Institute of Imaging Science (H.F.J.G., S.N., G.W.J., K.E.W., C.C., V.L.M., D.J.E.), Vanderbilt University Medical Center, Nashville, TN; and Department of Psychology (M.R.), Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA.
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Graham W. Johnson
From the Departments of Biomedical Engineering (H.F.J.G., G.W.J., P.E.K., C.C., V.L.M., M.R., D.J.E.) and Electrical Engineering and Computer Science (C.C., V.L.M., M.R., D.J.E.), Vanderbilt University; Departments of Neurological Surgery (S.N., K.E.W., P.E.K., D.J.E.), Radiology and Radiological Sciences (V.L.M., D.J.E.), and Neurology (K.F.H.) and Vanderbilt University Institute of Imaging Science (H.F.J.G., S.N., G.W.J., K.E.W., C.C., V.L.M., D.J.E.), Vanderbilt University Medical Center, Nashville, TN; and Department of Psychology (M.R.), Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA.
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Kristin E. Wills
From the Departments of Biomedical Engineering (H.F.J.G., G.W.J., P.E.K., C.C., V.L.M., M.R., D.J.E.) and Electrical Engineering and Computer Science (C.C., V.L.M., M.R., D.J.E.), Vanderbilt University; Departments of Neurological Surgery (S.N., K.E.W., P.E.K., D.J.E.), Radiology and Radiological Sciences (V.L.M., D.J.E.), and Neurology (K.F.H.) and Vanderbilt University Institute of Imaging Science (H.F.J.G., S.N., G.W.J., K.E.W., C.C., V.L.M., D.J.E.), Vanderbilt University Medical Center, Nashville, TN; and Department of Psychology (M.R.), Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA.
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Kevin F. Haas
From the Departments of Biomedical Engineering (H.F.J.G., G.W.J., P.E.K., C.C., V.L.M., M.R., D.J.E.) and Electrical Engineering and Computer Science (C.C., V.L.M., M.R., D.J.E.), Vanderbilt University; Departments of Neurological Surgery (S.N., K.E.W., P.E.K., D.J.E.), Radiology and Radiological Sciences (V.L.M., D.J.E.), and Neurology (K.F.H.) and Vanderbilt University Institute of Imaging Science (H.F.J.G., S.N., G.W.J., K.E.W., C.C., V.L.M., D.J.E.), Vanderbilt University Medical Center, Nashville, TN; and Department of Psychology (M.R.), Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA.
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Peter E. Konrad
From the Departments of Biomedical Engineering (H.F.J.G., G.W.J., P.E.K., C.C., V.L.M., M.R., D.J.E.) and Electrical Engineering and Computer Science (C.C., V.L.M., M.R., D.J.E.), Vanderbilt University; Departments of Neurological Surgery (S.N., K.E.W., P.E.K., D.J.E.), Radiology and Radiological Sciences (V.L.M., D.J.E.), and Neurology (K.F.H.) and Vanderbilt University Institute of Imaging Science (H.F.J.G., S.N., G.W.J., K.E.W., C.C., V.L.M., D.J.E.), Vanderbilt University Medical Center, Nashville, TN; and Department of Psychology (M.R.), Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA.
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Catie Chang
From the Departments of Biomedical Engineering (H.F.J.G., G.W.J., P.E.K., C.C., V.L.M., M.R., D.J.E.) and Electrical Engineering and Computer Science (C.C., V.L.M., M.R., D.J.E.), Vanderbilt University; Departments of Neurological Surgery (S.N., K.E.W., P.E.K., D.J.E.), Radiology and Radiological Sciences (V.L.M., D.J.E.), and Neurology (K.F.H.) and Vanderbilt University Institute of Imaging Science (H.F.J.G., S.N., G.W.J., K.E.W., C.C., V.L.M., D.J.E.), Vanderbilt University Medical Center, Nashville, TN; and Department of Psychology (M.R.), Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA.
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Victoria L. Morgan
From the Departments of Biomedical Engineering (H.F.J.G., G.W.J., P.E.K., C.C., V.L.M., M.R., D.J.E.) and Electrical Engineering and Computer Science (C.C., V.L.M., M.R., D.J.E.), Vanderbilt University; Departments of Neurological Surgery (S.N., K.E.W., P.E.K., D.J.E.), Radiology and Radiological Sciences (V.L.M., D.J.E.), and Neurology (K.F.H.) and Vanderbilt University Institute of Imaging Science (H.F.J.G., S.N., G.W.J., K.E.W., C.C., V.L.M., D.J.E.), Vanderbilt University Medical Center, Nashville, TN; and Department of Psychology (M.R.), Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA.
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Mikail Rubinov
From the Departments of Biomedical Engineering (H.F.J.G., G.W.J., P.E.K., C.C., V.L.M., M.R., D.J.E.) and Electrical Engineering and Computer Science (C.C., V.L.M., M.R., D.J.E.), Vanderbilt University; Departments of Neurological Surgery (S.N., K.E.W., P.E.K., D.J.E.), Radiology and Radiological Sciences (V.L.M., D.J.E.), and Neurology (K.F.H.) and Vanderbilt University Institute of Imaging Science (H.F.J.G., S.N., G.W.J., K.E.W., C.C., V.L.M., D.J.E.), Vanderbilt University Medical Center, Nashville, TN; and Department of Psychology (M.R.), Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA.
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Dario J. Englot
From the Departments of Biomedical Engineering (H.F.J.G., G.W.J., P.E.K., C.C., V.L.M., M.R., D.J.E.) and Electrical Engineering and Computer Science (C.C., V.L.M., M.R., D.J.E.), Vanderbilt University; Departments of Neurological Surgery (S.N., K.E.W., P.E.K., D.J.E.), Radiology and Radiological Sciences (V.L.M., D.J.E.), and Neurology (K.F.H.) and Vanderbilt University Institute of Imaging Science (H.F.J.G., S.N., G.W.J., K.E.W., C.C., V.L.M., D.J.E.), Vanderbilt University Medical Center, Nashville, TN; and Department of Psychology (M.R.), Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA.
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Citation
Role of the Nucleus Basalis as a Key Network Node in Temporal Lobe Epilepsy
Hernán F.J. González, Saramati Narasimhan, Graham W. Johnson, Kristin E. Wills, Kevin F. Haas, Peter E. Konrad, Catie Chang, Victoria L. Morgan, Mikail Rubinov, Dario J. Englot
Neurology Mar 2021, 96 (9) e1334-e1346; DOI: 10.1212/WNL.0000000000011523

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Abstract

Objective To determine whether the nucleus basalis of Meynert (NBM) may be a key network structure of altered functional connectivity in temporal lobe epilepsy (TLE), we examined fMRI with network-based analyses.

Methods We acquired resting-state fMRI in 40 adults with TLE and 40 matched healthy control participants. We calculated functional connectivity of NBM and used multiple complementary network-based analyses to explore the importance of NBM in TLE networks without biasing our results by our approach. We compared patients to controls and examined associations of network properties with disease metrics and neurocognitive testing.

Results We observed marked decreases in connectivity between NBM and the rest of the brain in patients with TLE (0.91 ± 0.88, mean ± SD) vs controls (1.96 ± 1.13, p < 0.001, t test). Larger decreases in connectivity between NBM and fronto-parietal-insular regions were associated with higher frequency of consciousness-impairing seizures (r = −0.41, p = 0.008, Pearson). A core network of altered nodes in TLE included NBM ipsilateral to the epileptogenic side and bilateral limbic structures. Furthermore, normal community affiliation of ipsilateral NBM was lost in patients, and this structure displayed the most altered clustering coefficient of any node examined (3.46 ± 1.17 in controls vs 2.23 ± 0.93 in patients). Abnormal connectivity between NBM and subcortical arousal community was associated with modest neurocognitive deficits. Finally, a logistic regression model incorporating connectivity properties of ipsilateral NBM successfully distinguished patients from control datasets with moderately high accuracy (78%).

Conclusions These results suggest that while NBM is rarely studied in epilepsy, it may be one of the most perturbed network nodes in TLE, contributing to widespread neural effects in this disabling disorder.

Glossary

ARAS=
ascending reticular activating system;
AUC=
area under the curve;
BOLD=
blood oxygenation level–dependent;
NBM=
nucleus basalis of Meynert;
ROI=
region of interest;
TLE=
temporal lobe epilepsy

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.

  • Received May 12, 2020.
  • Accepted in final form November 18, 2020.
  • © 2021 American Academy of Neurology
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