Repairing the brain with physical exercise: Cortical thickness and brain volume increases in long-term pediatric brain tumor survivors in response to a structured exercise intervention

Abstract

There is growing evidence that exercise induced experience dependent plasticity may foster structural and functional recovery following brain injury. We examined the efficacy of exercise training for neural and cognitive recovery in long-term pediatric brain tumor survivors treated with radiation.We conducted a controlled clinical trial with crossover of exercise training (vs. no training) in a volunteer sample of 28 children treated with cranial radiation for brain tumors (mean age = 11.5 yrs.; mean time since diagnosis = 5.7 yrs). The endpoints were anatomical T1 MRI data and multiple behavioral outcomes presenting a broader analysis of structural MRI data across the entire brain. This included an analysis of changes in cortical thickness and brain volume using automated, user unbiased approaches. A series of general linear mixed effects models evaluating the effects of exercise training on cortical thickness were performed in a voxel and vertex-wise manner, as well as for specific regions of interest. In exploratory analyses, we evaluated the relationship between changes in cortical thickness after exercise with multiple behavioral outcomes, as well as the relation of these measures at baseline.Exercise was associated with increases in cortical thickness within the right pre and postcentral gyri. Other notable areas of increased thickness related to training were present in the left pre and postcentral gyri, left temporal pole, left superior temporal gyrus, and left parahippocampal gyrus. Further, we observed that compared to a separate cohort of healthy children, participants displayed multiple areas with a significantly thinner cortex prior to training and fewer differences following training, indicating amelioration of anatomical deficits. Partial least squares analysis (PLS) revealed specific patterns of relations between cortical thickness and various behavioral outcomes both after training and at baseline.Overall, our results indicate that exercise training in pediatric brain tumor patients treated with radiation has a beneficial impact on brain structure. We argue that exercise training should be incorporated into the development of neuro-rehabilitative treatments for long-term pediatric brain tumor survivors and other populations with acquired brain injury. (ClinicalTrials.gov, NCT01944761)

Post-operative cerebellar mutism syndrome: rehabilitation issues

“…Interventions, particularly those focused on the cognitive consequences of pCMS, should consider the use of telemedicine or alternative intervention delivery (e.g., home-based computer intervention programs) to maximize access and feasibility to these interventions. In addition, the emerging literature on the positive impact of physical exercise programs in pediatric brain tumor survivors also supports this as a target for future research and clinical implementation [5,50,60].…”

“…Two studies have been published to date and others are in progress evaluating the effect of exercise programs in pediatric brain tumor survivors [5,50,60]. In a controlled crossover exercise program study in long-term survivors of pediatric brain tumors treated with radiation, there is some evidence of structural brain changes including increased white matter and hippocampal volume and increased cortical thickness in multiple brain regions [50,60]. Additionally, improvements in reaction time were demonstrated [50].…”

“…Aside from emerging evidence for its benefit on cognitive outcomes [5,60], there is a particular lack of literature on physical rehabilitation for children with pCMS to improve motor outcomes. However, there is evidence of functional improvement in children with brain tumors in general following acute inpatient multidisciplinary rehabilitation [44].…”

Neurocognitive Outcomes in Children with Brain Tumors

“…The mechanism by which physical activity improves cognitive performance may be related to increased cortical thickness and overall brain volume and mitigation of neuronal injury in the hippocampus. 66,67 Another approach by which survivors of pediatric brain tumors, particularly those exposed to CRT, can avoid progression of neurocognitive injury includes lifestyle modifications to decrease the elevated stroke risk. To help decrease risk of stroke and cardiovascular disease in pediatric cancer survivors who have been exposed to CRT, the Children's Oncology Group has put together comprehensive, disease-stratified screening guidelines for providers.…”

Physical activity after mild traumatic brain injury: What are the relationships with fatigue and sleep quality? Is physical activity a key to prevention of post-concussive symptoms?

“…9e11 In a controlled crossover exercise program study in long-term survivors of pediatric brain tumors treated with radiation, there appears to be some evidence of structural brain changes including increased white matter and hippocampal volume and increased cortical thickness in multiple brain regions. 10,11 Additionally, improvements in reaction time were demonstrated. 11 Each of these primary areas of neurorehabilitation research have yet to be studied in more detail in victims of TBI.…”