Emily L Dennis1,2, Karen Caeyenberghs3, Kristen R Hoskinson4,5, Tricia L Merkley6,7,8, Stacy J Suskauer9,10, Robert F Asarnow, Talin Babikian11,12, Brenda Bartnik-Olson13, Kevin Bickart12,14, Erin D Bigler6,7,8, Linda Ewing-Cobbs15, Anthony Figaji16,17, Christopher C Giza12,18,19, Naomi J Goodrich-Hunsaker6,2,7, Cooper B Hodges7,20, Elizabeth S Hovenden Aa6, Andrei Irimia21,22, Marsh Königs23, Harvey S Levin24,25, Hannah M Lindsey6,2,7, Jeffrey E Max26,27, Mary R Newsome24,25, Alexander Olsen28,29, Nicholas P Ryan3,30,31, Adam T Schmidt32, Matthew S Spruiell24, Benjamin Sc Wade6,33, Ashley L Ware34, Christopher G Watson15, Anne L Wheeler35,36, Keith Owen Yeates34,37,38, Brandon A Zielinski6,39, Peter Kochunov40, Neda Jahanshad41, Paul M Thompson41,42, David F Tate6,2, Elisabeth A Wilde6,2,24. 1. Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT. emily.dennis@hsc.utah.edu. 2. George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT. 3. Cognitive Neuroscience Unit, School of Psychology, Deakin University, Geelong, Australia. 4. Center for Biobehavioral Health, The Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH. 5. Department of Pediatrics, The Ohio State University College of Medicine. 6. Department of Neurology, University of Utah School of Medicine, Salt Lake City, UT. 7. Department of Psychology, Brigham Young University, Provo, UT. 8. Neuroscience Center, Brigham Young University, Provo, UT. 9. Kennedy Krieger Institute, Baltimore, MD. 10. Johns Hopkins University School of Medicine, Departments of Physical Medicine & Rehabilitation and Pediatrics, Baltimore, MD. 11. Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, CA. 12. UCLA Steve Tisch BrainSPORT Program, Los Angeles, CA. 13. Department of Radiology, Loma Linda University Medical Center, Loma Linda, CA. 14. Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA. 15. Department of Pediatrics, Children's Learning Institute, University of Texas Health Science Center at Houston, Houston, TX. 16. Division of Neurosurgery, University of Cape Town, Cape Town, South Africa. 17. Neuroscience Institute, University of Cape Town, Cape Town, South Africa. 18. Department of Pediatrics, Division of Neurology, UCLA Mattel Children's Hospital, Los Angeles, CA. 19. Department of Neurosurgery, David Geffen School of Medicine at UCLA, Los Angeles, CA. 20. Department of Physical Medicine and Rehabilitation, Virginia Commonwealth University, Richmond, VA. 21. Ethel Percy Andrus Gerontology Center, Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA. 22. Department of Biomedical Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, CA. 23. Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, Emma Neuroscience Group, Amsterdam, The Netherlands. 24. H. Ben Taub Department of Physical Medicine and Rehabilitation, Baylor College of Medicine, Houston, TX. 25. Michael E. DeBakey Veterans Affairs Medical Center, Houston, TX. 26. Department of Psychiatry, University of California, San Diego, La Jolla, CA. 27. Department of Psychiatry, Rady Children's Hospital, San Diego, CA. 28. Department of Psychology, Norwegian University of Science and Technology, Trondheim, Norway. 29. Department of Physical Medicine and Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway. 30. Department of Clinical Sciences, Murdoch Children's Research Institute, Melbourne, Australia. 31. Department of Paediatrics, The University of Melbourne, Melbourne, Australia. 32. Department of Psychological Sciences, Texas Tech University, Lubbock, TX. 33. Ahmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California, Los Angeles, Los Angeles, CA. 34. Department of Psychology, University of Calgary, Alberta, Canada. 35. Hospital for Sick Children, Neuroscience and Mental Health Program, Toronto, Canada. 36. University of Toronto, Physiology Department, Toronto, Canada. 37. Alberta Children's Hospital Research Institute and Hotchkiss Brain Institute, University of Calgary, Alberta, Canada. 38. Departments of Pediatrics and Clinical Neurosciences, University of Calgary, Alberta, Canada. 39. Departments of Pediatrics, University of Utah School of Medicine, Salt Lake City, UT. 40. Maryland Psychiatric Research Center, University of Maryland School of Medicine, Baltimore, MD. 41. Imaging Genetics Center, Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of USC, Marina del Rey, CA. 42. Departments of Neurology, Pediatrics, Psychiatry, Radiology, Engineering, and Ophthalmology, USC, Los Angeles, CA.
Abstract
OBJECTIVE: Our study addressed aims: (1) test the hypothesis that moderate-severe TBI in pediatric patients is associated with widespread white matter (WM) disruption; (2) test the hypothesis that age and sex impact WM organization after injury; and (3) examine associations between WM organization and neurobehavioral outcomes. METHODS: Data from ten previously enrolled, existing cohorts recruited from local hospitals and clinics were shared with the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Pediatric msTBI working group. We conducted a coordinated analysis of diffusion MRI (dMRI) data using the ENIGMA dMRI processing pipeline. RESULTS: Five hundred and seven children and adolescents (244 with complicated mild to severe TBI [msTBI] and 263 controls) were included. Patients were clustered into three post-injury intervals: acute/subacute - <2 months, post-acute - 2-6 months, chronic - 6+ months. Outcomes were dMRI metrics and post-injury behavioral problems as indexed by the Child Behavior Checklist (CBCL). Our analyses revealed altered WM diffusion metrics across multiple tracts and all post-injury intervals (effect sizes ranging between d=-0.5 to -1.3). Injury severity is a significant contributor to the extent of WM alterations but explained less variance in dMRI measures with increasing time post-injury. We observed a sex-by-group interaction: females with TBI had significantly lower fractional anisotropy in the uncinate fasciculus than controls (𝞫=0.043), which coincided with more parent-reported behavioral problems (𝞫=-0.0027). CONCLUSIONS: WM disruption after msTBI is widespread, persistent, and influenced by demographic and clinical variables. Future work will test techniques for harmonizing neurocognitive data, enabling more advanced analyses to identify symptom clusters and clinically-meaningful patient subtypes.
OBJECTIVE: Our study addressed aims: (1) test the hypothesis that moderate-severe TBI in pediatric patients is associated with widespread white matter (WM) disruption; (2) test the hypothesis that age and sex impact WM organization after injury; and (3) examine associations between WM organization and neurobehavioral outcomes. METHODS: Data from ten previously enrolled, existing cohorts recruited from local hospitals and clinics were shared with the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Pediatric msTBI working group. We conducted a coordinated analysis of diffusion MRI (dMRI) data using the ENIGMA dMRI processing pipeline. RESULTS: Five hundred and seven children and adolescents (244 with complicated mild to severe TBI [msTBI] and 263 controls) were included. Patients were clustered into three post-injury intervals: acute/subacute - <2 months, post-acute - 2-6 months, chronic - 6+ months. Outcomes were dMRI metrics and post-injury behavioral problems as indexed by the Child Behavior Checklist (CBCL). Our analyses revealed altered WM diffusion metrics across multiple tracts and all post-injury intervals (effect sizes ranging between d=-0.5 to -1.3). Injury severity is a significant contributor to the extent of WM alterations but explained less variance in dMRI measures with increasing time post-injury. We observed a sex-by-group interaction: females with TBI had significantly lower fractional anisotropy in the uncinate fasciculus than controls (𝞫=0.043), which coincided with more parent-reported behavioral problems (𝞫=-0.0027). CONCLUSIONS: WM disruption after msTBI is widespread, persistent, and influenced by demographic and clinical variables. Future work will test techniques for harmonizing neurocognitive data, enabling more advanced analyses to identify symptom clusters and clinically-meaningful patient subtypes.
Authors: Elisabeth A Wilde; Ashley L Ware; Xiaoqi Li; Trevor C Wu; Stephen R McCauley; Amanda Barnes; Mary R Newsome; Brian D Biekman; Jill V Hunter; Zili D Chu; Harvey S Levin Journal: J Neurotrauma Date: 2018-10-10 Impact factor: 5.269
Authors: Emily L Dennis; David Baron; Brenda Bartnik-Olson; Karen Caeyenberghs; Carrie Esopenko; Frank G Hillary; Kimbra Kenney; Inga K Koerte; Alexander P Lin; Andrew R Mayer; Stefania Mondello; Alexander Olsen; Paul M Thompson; David F Tate; Elisabeth A Wilde Journal: Hum Brain Mapp Date: 2020-06-01 Impact factor: 5.038
Authors: Peter Kochunov; L Elliot Hong; Emily L Dennis; Rajendra A Morey; David F Tate; Elisabeth A Wilde; Mark Logue; Sinead Kelly; Gary Donohoe; Pauline Favre; Josselin Houenou; Christopher R K Ching; Laurena Holleran; Ole A Andreassen; Laura S van Velzen; Lianne Schmaal; Julio E Villalón-Reina; Carrie E Bearden; Fabrizio Piras; Gianfranco Spalletta; Odile A van den Heuvel; Dick J Veltman; Dan J Stein; Meghann C Ryan; Yunlong Tan; Theo G M van Erp; Jessica A Turner; Liz Haddad; Talia M Nir; David C Glahn; Paul M Thompson; Neda Jahanshad Journal: Hum Brain Mapp Date: 2020-04-16 Impact factor: 5.038
Authors: Cece C Kooper; Jaap Oosterlaan; Hilgo Bruining; Marc Engelen; Petra J W Pouwels; Arne Popma; Job B M van Woensel; Dennis R Buis; Marjan E Steenweg; Maayke Hunfeld; Marsh Königs Journal: BMJ Open Date: 2022-06-29 Impact factor: 3.006
Authors: Elisabeth A Wilde; Ilirjana Hyseni; Hannah M Lindsey; Jessica Faber; James M McHenry; Erin D Bigler; Brian D Biekman; Laura L Hollowell; Stephen R McCauley; Jill V Hunter; Linda Ewing-Cobbs; Mary E Aitken; Marianne MacLeod; Zili D Chu; Linda J Noble-Haeusslein; Harvey S Levin Journal: Front Neurol Date: 2021-12-23 Impact factor: 4.003