White matter correlates of cognitive dysfunction after mild traumatic brain injury

Iain D Croall, Christopher J A Cowie, Jiabao He, Anna Peel, Joshua Wood, Benjamin S Aribisala, Patrick Mitchell, A David Mendelow, Fiona E Smith, David Millar, Tom Kelly, Andrew M Blamire

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)


OBJECTIVE: To relate neurophysiologic changes after mild/moderate traumatic brain injury to cognitive deficit in a longitudinal diffusion tensor imaging investigation.

METHODS: Fifty-three patients were scanned an average of 6 days postinjury (range = 1-14 days). Twenty-three patients were rescanned 1 year later. Thirty-three matched control subjects were recruited. At the time of scanning, participants completed cognitive testing. Tract-Based Spatial Statistics was used to conduct voxel-wise analysis on diffusion changes and to explore regressions between diffusion metrics and cognitive performance.

RESULTS: Acutely, increased axial diffusivity drove a fractional anisotropy (FA) increase, while decreased radial diffusivity drove a negative regression between FA and Verbal Letter Fluency across widespread white matter regions, but particularly in the ascending fibers of the corpus callosum. Raised FA is hypothesized to be caused by astrogliosis and compaction of axonal neurofilament, which would also affect cognitive functioning. Chronically, FA was decreased, suggesting myelin sheath disintegration, but still regressed negatively with Verbal Letter Fluency in the anterior forceps.

CONCLUSIONS: Acute mild/moderate traumatic brain injury is characterized by increased tissue FA, which represents a clear neurobiological link between cognitive dysfunction and white matter injury after mild/moderate injury.

Original languageEnglish
Pages (from-to)494-501
Number of pages8
Issue number6
Early online date16 Jul 2014
Publication statusPublished - 5 Aug 2014

Bibliographical note

© 2014 American Academy of Neurology.
The authors thank the radiographers who assisted in this work: Tim Hodgson, Louise Ward, Carol Smith, and Tamsin Gaudie.

Funding for the study and a studentship to I.D.C. has been provided by Sir Jules Thorn Charitable Trust Biomedical Research Award.

From the Institute of Cellular Medicine & Newcastle MR Centre (I.D.C., C.J.A.C., J.W., F.E.S., A.M.B.), Newcastle University; Departments of Neurosurgery (C.J.A.C., P.M., A.D.M.) and Neuropsychology (T.K.), Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne; Aberdeen Biomedical Imaging Centre (J.H.), School of Medicine and Dentistry, University of Aberdeen; Department of Psychology (A.P.), Durham University; Brain Research Imaging Centre (B.S.A.), Neuroimaging Sciences, University of Edinburgh; and NeuroCog (D.M.), John Buddle Village, Newcastle upon Tyne, UK.


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