Human adult neurogenesis loss corresponds with cognitive decline during epilepsy progression

Mesial temporal lobe epilepsy (MTLE) is a syndromic disorder presenting with seizures and cognitive comorbidities. Although 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 dramatically declines in MTLE patients with increased disease duration. Here, we investigate when multiple cognitive domains become affected during epilepsy progression and how human neurogenesis levels contribute to it. We find that intelligence, verbal learning, and memory decline at a critical period of 20 years disease duration. In contrast to rodents, the number of human immature neurons positively associates with auditory verbal, rather than visuospatial, learning and memory. Moreover, this association does not apply to mature granule neurons. Our study provides cellular evidence of how adult neurogenesis corresponds with human cognition and signifies an opportunity to advance regenerative medicine for patients with MTLE and other cognitive disorders.