Impaired Recent, but Preserved Remote, Autobiographical Memory in Pediatric Brain Tumor Patients

• Published in: The Journal of neuroscience Vol. 38; no. 38; pp. 8251 - 8261
• Main Authors: Sekeres, Melanie J., Riggs, Lily, Decker, Alexandra, de Medeiros, Cynthia B., Bacopulos, Agnes, Skocic, Jovanka, Szulc-Lerch, Kamila, Bouffet, Eric, Levine, Brian, Grady, Cheryl L., Mabbott, Donald J., Josselyn, Sheena A., Frankland, Paul W.
• Format: Journal Article
• Language: English
• Published: United States Society for Neuroscience 19.09.2018
• Subjects: Abnormalities; Adolescent; Aging; Alzheimer's disease; Amnesia; Anterograde transport; Brain; Brain cancer; Brain tumors; Cerebellar Neoplasms - diagnostic imaging; Cerebellar Neoplasms - psychology; Cerebellar Neoplasms - radiotherapy; Child; Children; Cognitive ability; Cranial Irradiation - adverse effects; Dementia disorders; Encephalitis; Epilepsy; Female; Head injuries; Hippocampus; Hippocampus - diagnostic imaging; Hippocampus - radiation effects; Humans; Magnetic Resonance Imaging; Male; Medulloblastoma; Medulloblastoma - diagnostic imaging; Medulloblastoma - psychology; Medulloblastoma - radiotherapy; Memory; Memory, Episodic; Mental Recall - radiation effects; Neurodegenerative diseases; Neurogenesis; Neuropsychological Tests; Organ Size; Patients; Radiation therapy; Retrograde transport; Retrospective Studies; Rodents; Temporal lobe; Traumatic brain injury; Tumors; episodic memory; neurogenesis; radiotherapy; autobiographical memory; hippocampus; medulloblastoma
• ISSN: 0270-6474; 1529-2401; 1529-2401
• DOI: 10.1523/JNEUROSCI.1056-18.2018

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 affects the developing brain and is associated with reduced hippocampal volume and blunted hippocampal neurogenesis. Such hippocampal (as well as extrahippocampal) 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 who received radiotherapy for posterior fossa tumors (PFTs), including medulloblastoma, during childhood. Using the Children's Autobiographical Interview, we retrospectively assessed episodic and nonepisodic 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 with control subjects. For pretreatment events, PFT patients reported equivalent episodic details compared with 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. It is therefore surprising that pretreatment episodic memories in PFT patients with reduced hippocampal volume are retained. 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. We report that radiotherapy treatment impairs the ability to form new autobiographical memories, but spares preoperatively acquired autobiographical memories. Reductions in hippocampal volume and cortical volume in regions of the recollection network appear to contribute to this pattern of preserved preoperative, but impaired postoperative, memory. These findings have significant implications for understanding disrupted mnemonic processing in the medial temporal lobe memory system and in the broader recollection network, which are inadvertently affected by standard treatment methods for medulloblastoma tumors in children.