Functional brain hyper-activations are linked to an electrophysiological measure of slow inter-hemispheric transfer time after pediatric moderate/severe traumatic brain injury.

Increased task-related blood oxygen level dependent (BOLD) activation is commonly observed in fMRI studies of moderate/severe traumatic brain injury (msTBI) but the functional relevance of these hyper-activations and how they are linked to more direct measures of neuronal function remains largely unknown. Here we investigated how working memory load (WML)-dependent BOLD activation was related to an electrophysiological measure of inter-hemispheric transfer time (IHTT) in a sample of 18 msTBI patients and 26 demographically matched controls from the UCLA Recovery after Pediatric Brain Injury (RAPBI) study. In the context of highly similar fMRI task performance, a sub-group of TBI patients with slow IHTT had greater BOLD activation with higher WML than both healthy control children and a subgroup of msTBI patients with normal IHTT. Slower IHTT included as a continuous variable was also associated with BOLD hyper-activation in the full TBI sample and in controls. Higher WML dependent BOLD activation was related to better performance on a clinical cognitive performance index, an association that was more pronounced within the patient group with slow IHTT. Our prior work has shown that a sub-group of children with slow IHTT after pediatric msTBI has increased risk for poor white matter organization, long-term neurodegeneration, and poor cognitive outcome. BOLD hyper-activations after msTBI may reflect neuronal compensatory processes supporting higher order capacity demanding cognitive functions in the context of inefficient neuronal transfer of information. The link between BOLD hyper-activations and slow IHTT adds to the multimodal validation of this electrophysiological measure as a promising biomarker.