Network topology of the cognitive phenotypes of temporal lobe epilepsy

Abstract Purpose The neuropsychological complications of temporal lobe epilepsy are characterized by a spectrum of reproducible cognitive phenotypes that vary in the presence, type and degree of impairment. The nature of the disruptions to the neuropsychological networks that underlie these phenotypes remain to be characterized and represent the subject of this investigation. Methods Participants included 30 healthy controls and 104 patients with temporal lobe epilepsy who fell into three cognitive phenotypes (intact, focal impairment, generalized impairment). Eighteen neuropsychological measures representing multiple cognitive domains (language, memory, executive function, visuoperception, motor speed) were examined by graph theory techniques within the control and each epilepsy cognitive phenotype group to characterize their global and local network properties. Results Across the control and epilepsy cognitive phenotype groups (intact to focal to generalized impairment), there was: 1) an orderly breakdown in the positive manifold reflected by a stepwise reduction of positive associations among the neuropsychological tests, 2) stepwise abnormal increases in global measures including the normalized clustering coefficient and modularity index, 3) stepwise abnormal decreases in normalized global efficiency, 4) a community structure demonstrating well organized modules within the control group while each epilepsy group showed deviations from controls, and 5) lower strength, compared to controls, across 8 nodes in the focal and generalized impairment groups compared to only 3 nodes in the no-impairment epilepsy group, pointing to the superior integration of local connections in controls. Discussion The cognitive phenotypes of temporal lobe epilepsy are characterized by orderly abnormalities in their underlying neuropsychological networks. These findings inform the network perturbations that underlie the taxonomy of cognitive abnormality in temporal lobe epilepsy and provide a model for examination of similar issues in other focal and generalized epilepsies.