Connectome reorganization associated with temporal lobe pathology and its surgical resection

Abstract

Network neuroscience offers a unique framework to understand the organizational principles of the human brain. Despite recent progress, our understanding of how the brain is modulated by focal lesions remains incomplete. Resection of the temporal lobe is the most effective treatment to control seizures in pharmaco-resistant temporal lobe epilepsy (TLE), making this syndrome a powerful model to study lesional effects on network organization in young and middle-aged adults. Here, we assessed the downstream consequences of a focal lesion and its surgical resection on the brain’s structural connectome, and explored how this reorganization relates to clinical variables at the individual patient level. We included adults with pharmaco-resistant TLE (n= 37) who underwent anterior temporal lobectomy between two imaging time points, as well as age-and sex-matched healthy controls who underwent comparable imaging (n= 31). Core to our analysis was the projection of high-dimensional structural connectome data—derived from diffusion MRI tractography from each subject—into lower-dimensional gradients. We then compared connectome gradients in patients relative to controls before surgery, tracked surgically-induced connectome reconfiguration from pre-to postoperative time points, and examined associations to patient-specific clinical and imaging phenotypes. Before surgery, TLE presented with marked connectome changes in bilateral temporo-parietal regions, reflecting an increased segregation of the ipsilateral anterior temporal lobe from the rest of the brain. Surgery-induced connectome reorganization was localized to this temporo-parietal subnetwork, but primarily involved postoperative integration of contralateral regions with the rest of the brain. Using a partial least-squares analysis, we uncovered a latent clinical-imaging signature underlying this pre-to postoperative connectome reorganization, showing that patients who displayed postoperative integration in bilateral fronto-occipital cortices also had greater preoperative ipsilateral hippocampal atrophy, lower seizure frequency, and secondarily generalized seizures. Our results bridge the effects of focal brain lesions and their surgical resections with large-scale network reorganization and inter-individual clinical variability, thus offering new avenues to examine the fundamental malleability of the human brain.

HippoMaps: Multiscale cartography of the human hippocampal formation

“…Similar to neocortical surface extraction and registration procedures (Boucher et al, 2009;Dale et al, 1999;Fischl, Sereno, Tootell, et al, 1999;Kim et al, 2005;Lyttelton et al, 2007;MacDonald et al, 2000), this allows for topology-informed inter-subject registration to a standardized unfolded space (Jordan DeKraker et al, 2023). This has begun a new wave of high-sensitivity hippocampally-focused studies in topics including the mapping of histology features , blood perfusion (Haast et al, 2023;Ngo et al, 2023), biophysically-constrained diffusion (Karat et al, 2023), hippocampal sclerosis (Ripart et al, 2023), neurodevelopmental trajectories (Hanson et al, 2023), functional connectivity (Cabalo et al, 2023;Lariviere et al, 2023;Xie et al, 2023), visual receptive field mapping (Leferink et al, 2023), and crossspecies comparison (Eichert et al, 2023). With the increasing aggregation of hippocampal features in a common reference space, it is now possible to devise repositories that allow for a broad contextualization of hippocampal findings.…”