Graph Theory Modeling on the BrainMap Community Portal: Network topology reveals a central role for the medial frontal gyrus in mesial temporal lobe epilepsy

"Mesial temporal lobe epilepsy(MTLE) is a disorder of neural networks, often amenable to surgical treatment. Yet, resection of the seizure-onset zone can be non-curative. Seizure recurrence is attributable to distributed network-mediation of ictogenesis(seizure-onset). To address reasons for surgical failure, it is crucial to understand higher-level network properties in MTLE pathology. Graph theory models(GTM) interrogate network properties by quantifying features of network topology. Imaging studies have leveraged graph theory to detect compensatory network changes and predict seizure-onset laterality in MTLE, portending GTM utility in biomarker development. GTM was recently adapted for coordinate-based meta-analysis(CBMA) of voxel-based morphometry(VBM) and physiology(VBP) studies, instantiating a multi-variate extension of activation likelihood estimation(mass-univariate-CBMA). We applied meta-analytic-GTM(M-GTM) to VBM/VBP-studies of MTLE, to infer organizational properties of MTLE network pathology. To quantify topological organization of MTLE network pathology, BrainMap applications (M-GTM/Mango) were used to derive a co-alteration GTM from 74 experiments. M-GTM was used to model coordinates of MTLE pathology as spatial probability distributions, defining nodes at peaks in the joint distribution of pathology and computing edges as co-alterations in individual studies. Clusters of network pathology (modules) were detected via spectral-partition and interpreted in Mango via Regional Behavioral/Diseases Analyses of the BrainMap database(21,435-Task-Activation/4,398-VBM-experiments;n=107,167/115,627-subjects). MATLAB/Cytoscape were used to compute topology metrics and nodal influence on MTLE network topology. Two distributed network-modules were identified in the MTLE co-alteration network, connected only via three most-influential nodes: hippocampus/MDN-thalamus/medial frontal gyrus. Module-1 regions(M1:mesial-temporal/deep-nuclear/frontal/precentral/postcentral/cingulate/inf-parietal structures) were associated with emotion-cognition(Z=3.7) and weakly with social-cognition/explicit-memory(Z=2.5/2.3). Module-2(M2:cerebellar/occipital/temporoparietal/precentral/inf.frontal/med.frontal gyri) regional associations included language/speech/semantic-cognition(Z=4.1/3.0/2.3). M1 matched known VBM-patterns in Alzheimer’s(Z=4.1); both M1/M2 matched those of structural epilepsy pathology(Z=3.4/3.6). A 2-node module(M3:parahippocampus/amygdala) and disconnected pair(M4:mid.frontal/cingulate gyri) were noted. Discrete co-alteration networks exist in MTLE. The medial frontal gyrus likely mediates interactions and evolution of limbic-M1 and verbal-M2 symptoms in MTLE. Pathology modules and intermodular connections represent potential targets for disease monitoring/therapeutic modulation. This study was funded by R01MH074457, T32GM113896, T32TR004545, F31NS131025, and the American Epilepsy Society."