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

Abstract

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. 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.

Chemotherapy-Induced Cognitive Impairment and Hippocampal Neurogenesis: A Review of Physiological Mechanisms and Interventions

“…Accordingly, when mice were subsequently trained on the spatial water maze task using a strong training protocol, which typically supports robust spatial memory in control mice [ 122 ], spatial memory deficits were observed in juvenile mice, but not in adult mice. These findings predict that chemotherapeutic treatments in younger patients will have more severe consequences on their neural development and hippocampal integrity, as has been observed in juvenile cancer survivors [ 20 , 127 , 128 ]. While TMZ-mediated suppression of hippocampal neurogenesis is detrimental to the establishment of new hippocampus-dependent memories in young mice, paradoxically, TMZ-induced suppression of hippocampal cell proliferation prevents forgetting of previously established context memories, possibly by preventing the dynamic remodeling of existing DG neural networks and synaptic connections supporting existing memory traces, leading to the persistence of previously acquired memories in the young brain [ 129 , 130 , 131 ].…”

Age-Related Increases in Posterior Hippocampal Granularity Are Associated with Remote Detailed Episodic Memory in Development

“…One strength of this study is the presence of both recent (immediate) and remote (;2 week) retention intervals, a feature not commonly seen in memory research in either youth or adult populations (but see Dandolo and Schwabe, 2018;Sekeres et al, 2018). Using this design, we found that postencoding granularity in posterior hippocampus was important for detailed remote (but not immediate) memory recall.…”

Neurological and endocrinological manifestations of 49 children with intracranial pure germinoma at initial diagnosis in Taiwan

“…Reductions in hippocampal volume and cortical volume in regions of the recollection network appeared to contribute to impaired ability to form new autobiographical memories but increased the acquisition of autobiographical memories. 27 Pre-and posttreatment evaluation may be required because the tumor and subsequent operations may induce hippocampal volume loss.…”