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. [Display omitted] •MTLE patients present progressive cognitive decline•Intelligence, verbal learning, and memory decline around 20 years’ disease duration•This critical period coincides with an exponential loss of immature granule neurons•Immature granule neuron numbers positively correlate with verbal learning performance Ammothumkandy et al. provide a functional role for adult neurogenesis in human cognition. They show that immature neuron levels benefit verbal learning in mesial temporal lobe epilepsy (MTLE) patients. The decline and eventual loss of immature neurons in MTLE hippocampus occurs during a critical period of disease progression.