Voxelwise Lesion Symptom Mapping in Pediatric TBI: An ENIGMA Mega-Analysis
Year: 2026
Type: preprint
Abstract: Focal lesions are common after complicated mild-to-severe traumatic brain injury (cmsTBI) in children, yet it is unclear whether the location of focal damage relates to cognitive outcome beyond overall lesion burden. Combining 13 international cohorts through the ENIGMA Pediatric cmsTBI working group, we conducted voxelwise lesion-symptom mapping (VLSM) to test whether focal lesion location relates to cognitive outcome, and how this compares with overall lesion volume. From 357 patients with imaging that passed guality assurance, 67 had a focal lesion visible on T1-weighted MRI along with at least one performance-based cognitive outcome (D-KEFS Trail Making conditions and WISC/WAIS Coding). We tested whether lesion location related to cognitive outcome using VLSM, adjusting for age, sex, and time since injury, and separately tested total lesion volume as a predictor of each outcome. Lesions in the right middle frontal gyrus were associated with poorer performance on number sequencing (D-KEFS Trail Making condition 2), a timed visuomotor sequencing task (false discovery rate corrected). In separate regression analyses, greater lesion volume was associated with poorer number-letter switching and motor speed. The switching association remained significant after adjusting for injury severity, whereas the motor-speed association did not. In the largest lesion sample assembled in pediatric cmsTBI to date, focal lesion location and injury burden index separable contributions to cognitive outcome, with number sequencing linked to focal prefrontal damage and switching and motor speed to overall lesion volume, underscoring the value of precise lesion characterization for large-scale multi-site neuroimaging.
Source: medRxiv
Authors: Emily L Dennis, Lauren Blake, Evelyn M Deutscher, Morgan Hafen, Ella M Hartsell, Elizabeth S Hovenden, Jamie Johnson, Finian Keleher, Courtney McCabe, Jake Mitchell, Emma N Read, Madi Reading, Dayna B Thayn, Robert F Asarnow, Talin Babikian, Brenda Bartnik-Olson, Erin D Bigler, Karen Caeyenberghs, Dana DeMaster, Linda Ewing-Cobbs, Christopher C Giza, Kristen R Hoskinson, Marsh Königs, Jeffrey E Max, Tricia Merkley, Mary R Newsome, Alexander Olsen, Nicholas P Ryan, Gershon Spitz, Stacy J Suskauer, Anne L Wheeler, Brandon A Zielinski, Hannah M Lindsey, Elisabeth A Wilde
Institutions: University of Utah, George E. Wahlen Department of VA Medical Center, Murdoch Children's Research Institute, Brigham Young University, Monash University, University of California, Los Angeles, Loma Linda University Medical Center, Deakin University, The University of Texas Health Science Center at Houston, Mattel Children's Hospital, Nationwide Children's Hospital, Abigail Wexner Research Institute, The Ohio State University, Emma Kinderziekenhuis, Amsterdam University Medical Centers, University of Amsterdam, UC San Diego Health System, University of California San Diego, Baylor College of Medicine, Norwegian University of Science and Technology, St Olav's University Hospital, The University of Melbourne, Kennedy Krieger Institute, Johns Hopkins University, Johns Hopkins Medicine, University of Toronto, Hospital for Sick Children, University of Florida
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7221062444