Faculty Collaboration Database

Regional and global resting-state functional MR connectivity in temporal lobe epilepsy: Results from the Epilepsy Connectome Project. Epilepsy Behav 2021 Apr;117:107841

Date

02/22/2021

Pubmed ID

33611101

Pubmed Central ID

PMC8035304

DOI

10.1016/j.yebeh.2021.107841

Scopus ID

2-s2.0-85100881402 (requires institutional sign-in at Scopus site)   19 Citations

Abstract

Temporal lobe epilepsy (TLE) has been conceptualized as focal disease with a discrete neurobiological focus and can respond well to targeted resection or ablation. In contrast, the neuro-cognitive deficits resulting from TLE can be widespread involving regions beyond the primary epileptic network. We hypothesize that this seemingly paradoxical findings can be explained by differences in connectivity between the primary epileptic region which is hyper-connected and its secondary influence on global connectome organization. This hypothesis is tested using regional and global graph theory metrics where we anticipate that regional mesial-temporal hyperconnectivity will be found and correlate with seizure frequency while global networks will be disorganized and be more closely associated with neuro-cognitive deficits. Resting-state fMRI was used to examine temporal lobe regional connectivity and global functional connectivity from 102 patients with TLE and 55 controls. Connectivity matrices were calculated for subcortical volumes and cortical parcellations. Graph theory metrics (global clustering coefficient (GCC), degree, closeness) were compared between groups and in relation to neuropsychological profiles and disease covariates using permutation testing and causal analysis. In TLE there was a decrease in GCC (p = 0.0345) associated with a worse neuropsychological profile (p = 0.0134). There was increased connectivity in the left hippocampus/amygdala (degree p = 0.0103, closeness p = 0.0104) and a decrease in connectivity in the right lateral temporal lobe (degree p = 0.0186, closeness p = 0.0122). A ratio between the hippocampus/amygdala and lateral temporal lobe-temporal lobe connectivity ratio (TLCR) revealed differences between TLE and controls for closeness (left p = 0.00149, right p = 0.0494) and for degree on left p = 0.00169; with trend on right p = 0.0567. Causal analysis suggested that "Epilepsy Activity" (seizure frequency, anti-seizure medications) was associated with increase in TLCR but not in GCC, while cognitive decline was associated with decreased GCC. These findings support the hypothesis that in TLE there is hyperconnectivity in the hippocampus/amygdala and hypoconnectivity in the lateral temporal lobe associated with "Epilepsy Activity." While, global connectome disorganization was associated with worse neuropsychological phenotype.

Author List

Struck AF, Boly M, Hwang G, Nair V, Mathis J, Nencka A, Conant LL, DeYoe EA, Raghavan M, Prabhakaran V, Binder JR, Meyerand ME, Hermann BP

Authors

Jeffrey R. Binder MD Professor in the Neurology department at Medical College of Wisconsin
Andrew S. Nencka PhD Director, Associate Professor in the Radiology department at Medical College of Wisconsin
Manoj Raghavan MD, PhD Professor in the Neurology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Connectome
Epilepsy, Temporal Lobe
Functional Laterality
Hippocampus
Humans
Magnetic Resonance Imaging
Nerve Net
Temporal Lobe