Human Adult Neurogenesis Loss Underlies Cognitive Decline During Epilepsy Progression

Mesial temporal lobe epilepsy (MTLE) is a syndromic disorder presenting with seizures and cognitive comorbidities. While seizure etiology is increasingly understood, the pathophysiological mechanisms contributing to cognitive decline and epilepsy progression remain less recognized. We have previously shown that adult hippocampal neurogenesis, a process contributing to visual spatial learning and memory in rodents, dramatically declines in MTLE patients with increased disease duration. Here, we investigate when multiple cognitive domains become effected by epilepsy disease duration and how human neurogenesis levels contribute to it. We find that intelligence, and verbal learning and memory decline at a critical period of 20 years disease duration. Surprisingly, the number of human immature neurons positively associate with auditory verbal, rather than visuospatial, learning and memory. Moreover, we uncover cognitive functions enriched to either immature or mature granule neurons and functions shared between them. Our study provides cellular evidence of how adult neurogenesis contributes to human cognition, and signifies an opportunity to advance regenerative medicine for patients with MTLE and other cognitive disorders.