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Impaired recent, but preserved remote, autobiographical memory in pediatric brain tumor patients.

Medulloblastomas, the most common malignant brain tumor in children, are typically treated with radiotherapy. Refinement of this treatment has greatly improved survival rates in this patient population. However, radiotherapy also profoundly impacts the developing brain, and is, for example, associated with reduced hippocampal volume and blunted hippocampal neurogenesis. Such hippocampal (as well as extra-hippocampal) abnormalities likely contribute to cognitive impairments in this population. While several aspects of memory have been examined in this population, the impact of radiotherapy on autobiographical memory has not previously been evaluated. Here we evaluated autobiographical memory in male and female patients that received radiotherapy for posterior fossa tumors (PFT), including medullobastoma, during childhood. Using the Children's Autobiographical Interview, we retrospectively assessed episodic and non-episodic details for events that either preceded (i.e., remote) or followed (i.e., recent) treatment. For post-treatment events, PFT patients reported fewer episodic details compared to control subjects. For pre-treatment events, PFT patients reported equivalent episodic details compared to control subjects. In a range of conditions associated with reduced hippocampal volume (including medial temporal lobe amnesia, mild cognitive impairment, Alzheimer's disease, temporal lobe epilepsy, transient epileptic amnesia, frontal temporal dementia, traumatic brain injury, encephalitis and aging), loss of episodic details (even in remote memories) accompanies hippocampal volume loss. Spared, pre-treatment episodic memories in PFT patients with reduced hippocampal volume is therefore surprising. We discuss these findings in light of the anterograde and retrograde impact on memory of experimentally suppressing hippocampal neurogenesis in rodents. Significance Statement: Pediatric medulloblastoma survivors develop cognitive dysfunction following cranial radiotherapy treatment. Sekeres et al. report that radiotherapy treatment impairs the ability to form new autobiographical memories, but spares pre-operatively acquired autobiographical memories. Reductions in hippocampal volume and cortical volume in regions of the recollection network appear to contribute to this pattern of preserved pre-operative, but impaired post-operative memory. These findings have significant implications for understanding disrupted mnemonic processing in the medial temporal lobe memory system, and broader recollection network, which are inadvertently impacted by standard treatment methods for medulloblastoma tumors in children.

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