Abstract

Increased task-related blood oxygen level dependent (BOLD) activation is commonly observed in functional magnetic resonance imaging (fMRI) studies of moderate/severe traumatic brain injury (msTBI), but the functional relevance of these hyperactivations and how they are linked to more direct measures of neuronal function remain largely unknown. Here, we investigated how working memory load (WML)-dependent BOLD activation was related to an electrophysiological measure of interhemispheric transfer time (IHTT) in a sample of 18 msTBI patients and 26 demographically matched controls from the UCLA RAPBI (Recovery after Pediatric Brain Injury) study. In the context of highly similar fMRI task performance, a subgroup 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 treated as a continuous variable was also associated with BOLD hyperactivation 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 previous work has shown that a subgroup of children with slow IHTT after pediatric msTBI has increased risk for poor white matter organization, long-term neurodegeneration, and poor cognitive outcome. BOLD hyperactivations 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 hyperactivations and slow IHTT adds to the multi-modal validation of this electrophysiological measure as a promising biomarker.

Highlights

  • Increased task-related blood oxygen level dependent (BOLD) activation is the most common observation in functional magnetic resonance imaging studies of moderate-to-severe traumatic brain injury

  • Interpretation of functional magnetic resonance imaging (fMRI) findings in pediatric moderate-to-severe traumatic brain injury (msTBI) is complicated by the heterogeneous nature of msTBI pathology, small sample sizes, and the fact that few studies have linked BOLD alterations to clinical variables (e.g., Glasgow Coma Scale [GCS] score, time post-injury, and neuropsychological test measures), and none have investigated the relationship to more direct measures of neuronal functioning

  • This study demonstrated that BOLD hyperactivation in children with msTBI is associated with an electrophysiological ERP measure of interhemispheric transfer time (IHTT)

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Summary

Introduction

Increased task-related blood oxygen level dependent (BOLD) activation is the most common observation in functional magnetic resonance imaging (fMRI) studies of moderate-to-severe traumatic brain injury (msTBI). Interpretation of fMRI findings in pediatric msTBI is complicated by the heterogeneous nature of msTBI pathology, small sample sizes, and the fact that few studies have linked BOLD alterations to clinical variables (e.g., Glasgow Coma Scale [GCS] score, time post-injury, and neuropsychological test measures), and none have investigated the relationship to more direct measures of neuronal functioning. Extant studies do not provide a clear understanding of the functional and clinical significance of BOLD alterations after msTBI in children and adolescents. To further increase our understanding of BOLD alterations after msTBI, the role of these alterations should be further validated by traditional neurocognitive and clinical measures, and more direct measures of neuronal functioning

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