Delayed, transient, lateralized deficits in pattern separation and pattern completion after focal hippocampal irradiation in humans

Adult hippocampal neurogenesis is essential for discriminating between similar contexts (pattern separation) in animals. In humans, the link between neurogenesis and pattern separation remains tenuous due to the inherent constraints on manipulating neurogenesis. Here, we report a longitudinal study of patients with benign cavernous sinus meningiomas localized immediately adjacent to the hippocampus. Patients underwent focal stereotactic radiotherapy, which, while targeted at the tumor, inevitably affected the ipsilateral hippocampus. At different timepoints post-therapy (up to 2 years), patients were presented with mnemonic similarity task (MST) to assess pattern separation, pattern completion, and recognition memory. While hippocampal irradiation did not affect the overall recall or recognition memory, we found delayed, transient, laterally-restricted effects on pattern separation and completion. In patients with right-sided (but not left-sided) hippocampal irradiation deficits in pattern separation and completion accumulated by 12 months post-treatment, but returned to the initial levels by 24 months. The observed changes are consistent with the vulnerability of dividing neural progenitors in the dentate gyrus, the protracted maturation of new neurons in the adult human brain, and the involvement of adult-born neurons in pattern separation and pattern completion. Our findings support the notion that ongoing hippocampal neurogenesis contributes to defined cognitive functions in humans.