Functional connectivity alterations in traumatic brain injury patients with late seizures

PTE is a neurological disorder characterized by recurrent and spontaneous epileptic seizures. PTE is a major public health problem occurring in 2-50% of TBI patients. Identifying PTE biomarkers is crucial for the development of effective treatments. Functional neuroimaging studies in patients with epilepsy and in epileptic rodents have observed that abnormal functional brain activity plays a role in the development of epilepsy. Network representations of complex systems ease quantitative analysis of heterogeneous interactions within a unified mathematical framework. In this work, graph theory was used to study resting state functional magnetic resonance imaging (rs-fMRI) and reveal functional connectivity abnormalities that are associated with seizure development in traumatic brain injury (TBI) patients. We examined rs-fMRI of 75 TBI patients from Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) which aims to identify validated Post-traumatic epilepsy (PTE) biomarkers and antiepileptogenic therapies using multimodal and longitudinal data acquired from 14 international sites. The dataset includes 28 subjects who had at least one late seizure after TBI and 47 subjects who had no seizures within 2 years post-injury. Each subject's neural functional network was investigated by computing the correlation between the low frequency time series of 116 regions of interest (ROIs). Each subject's functional organization was represented as a network consisting of nodes, brain regions, and edges that show the relationship between the nodes. Then, several graph measures concerning the integration and the segregation of the functional brain networks were extracted in order to highlight changes in functional connectivity between the two TBI groups. Results showed that the late seizure-affected group had a compromised balance between integration and segregation and presents functional networks that are hyperconnected, hyperintegrated but at the same time hyposegregated compared with seizure-free patients. Moreover, TBI subjects who developed late seizures had more low betweenness hubs.