Exercise training for neural recovery in a restricted sample of pediatric brain tumor survivors: a controlled clinical trial with crossover of training versus no training

Abstract

Background. Exercise promotes repair processes in the mouse brain and improves cognition in both mice and humans. It is not known whether these benefits translate to human brain injury, particularly the significant injury observed in children treated for brain tumors. Methods. We conducted a clinical trial with crossover of exercise training versus no training in a restricted sample of children treated with radiation for brain tumors. The primary outcome was change in brain structure using MRI measures of white matter (ie, fractional anisotropy [FA]) and hippocampal volume [mm 3 ]). The secondary outcome was change in reaction time (RT)/accuracy across tests of attention, processing speed, and short-term memory. Linear mixed modeling was used to test the effects of time, training, training setting, and carryover. Results. Twenty-eight participants completed training in either a group (n=16) or a combined group/home (n=12) setting. Training resulted in increased white matter FA (Δ=0.05, P<.001). A carryover effect was observed for participants ~12 weeks after training (Δ=0.05, P<.001). Training effects were observed for hippocampal volume (Δ=130.98mm 3 ; P=.001) and mean RT (Δ=-457.04ms, P=0.36) but only in the group setting. Related carryover effects for hippocampal volume (Δ=222.81mm 3 , P=.001), and RT (Δ=-814.90ms, P=.005) were also observed. Decreased RT was predicted by increased FA (R=-0.62, P=.01). There were no changes in accuracy. Conclusions. Exercise training is an effective means for promoting white matter and hippocampal recovery and improving reaction time in children treated with cranial radiation for brain tumors. Key wordsbrain recovery | cranial radiation | exercise | neuroplasticity | pediatric brain tumor

Smaller hippocampal subfield volumes predict verbal associative memory in pediatric brain tumor survivors

“…Indeed, evidence suggests that physical exercise may restore neurogenesis in the irradiated rodent DG (Naylor et al, ). Moreover, a recent study found that physical activity increases hippocampal volume in PBTS treated with radiation and chemotherapy (Riggs et al, ). Future research should aim to characterize whether different types of interventions, such as exercise and cognitive training, promote widespread repair across the hippocampus or local repair in distinct subfields…”

Randomized web‐based physical activity intervention in adolescent survivors of childhood cancer

“…Riggs et al. found that aerobic exercise training increased white matter, hippocampal volume, and cognitive reaction times in children who were survivors of brain tumors, after a 12‐week training period, with increases still observed at 24 weeks . Additionally, in a noncancer population, Hillman et al .…”

White matter plasticity and maturation in human cognition

“…Controlled clinical trials provide compelling evidence of the role white matter plasticity plays in improved cognition in children and adolescents, as changes in white matter are observed following a direct intervention design that controls for maturation and learning. We recently demonstrated activity‐dependent white matter repair in children with a brain injury from their curative treatment for a brain tumor who participated in a physical exercise program (Riggs et al, ). Specifically, using a controlled crossover design, we showed that increased FA within the corpus callosum following a 12‐week exercise program predicted increased speed of processing in these children (Riggs et al, ).…”

“…We recently demonstrated activity‐dependent white matter repair in children with a brain injury from their curative treatment for a brain tumor who participated in a physical exercise program (Riggs et al, ). Specifically, using a controlled crossover design, we showed that increased FA within the corpus callosum following a 12‐week exercise program predicted increased speed of processing in these children (Riggs et al, ).…”