Hernán F J González1, Saramati Narasimhan2, Graham W Johnson2, Kristin E Wills2, Kevin F Haas2, Peter E Konrad2, Catie Chang2, Victoria L Morgan2, Mikail Rubinov2, Dario J Englot2. 1. 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. hfjgonzalez@gmail.com. 2. 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.
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.
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.
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