Altered Relationship between Working Memory and Brain Microstructure after Mild Traumatic Brain Injury

S. Chung; X. Wang; E. Fieremans; J.F. Rath; P. Amorapanth; F.-Y.A. Foo; C.J. Morton; D.S. Novikov; S.R. Flanagan; Y.W. Lui

doi:10.3174/ajnr.A6146

Abstract

BACKGROUND AND PURPOSE: Working memory impairment is one of the most troubling and persistent symptoms after mild traumatic brain injury (MTBI). Here we investigate how working memory deficits relate to detectable WM microstructural injuries to discover robust biomarkers that allow early identification of patients with MTBI at the highest risk of working memory impairment.

MATERIALS AND METHODS: Multi-shell diffusion MR imaging was performed on a 3T scanner with 5 b-values. Diffusion metrics of fractional anisotropy, diffusivity and kurtosis (mean, radial, axial), and WM tract integrity were calculated. Auditory-verbal working memory was assessed using the Wechsler Adult Intelligence Scale, 4th ed, subtests: 1) Digit Span including Forward, Backward, and Sequencing; and 2) Letter-Number Sequencing. We studied 19 patients with MTBI within 4 weeks of injury and 20 healthy controls. Tract-Based Spatial Statistics and ROI analyses were performed to reveal possible correlations between diffusion metrics and working memory performance, with age and sex as covariates.

RESULTS: ROI analysis found a significant positive correlation between axial kurtosis and Digit Span Backward in MTBI (Pearson r = 0.69, corrected P = .04), mainly present in the right superior longitudinal fasciculus, which was not observed in healthy controls. Patients with MTBI also appeared to lose the normal associations typically seen in fractional anisotropy and axonal water fraction with Letter-Number Sequencing. Tract-Based Spatial Statistics results also support our findings.

CONCLUSIONS: Differences between patients with MTBI and healthy controls with regard to the relationship between microstructure measures and working memory performance may relate to known axonal perturbations occurring after injury.

ABBREVIATIONS:

AK: axial kurtosis
AWF: axonal water fraction
bCC: body of the corpus callosum
DKI: diffusional kurtosis imaging
DSF: Digit Span Forward
DSB: Digit Span Backward
DSS: Digit Span Sequencing
FA: fractional anisotropy
gCC: genu of the corpus callosum
HC: healthy control
LNS: Letter-Number Sequencing
MTBI: mild traumatic brain injury
pCR: posterior corona radiata
sCC: splenium of the corpus callosum
sCR: superior corona radiata
SLF: superior longitudinal fasciculus
WMTI: white matter tract integrity
WAIS: Wechsler Adult Intelligence Scale
WRAT: Wide Range Achievement Test

Footnotes

Disclosures: Sohae Chung—RELATED: Grant: National Institutes of Health, Comments: R01 NS039135-11, R21 NS090349, P41 EB017183.* Els Fieremans—UNRELATED: Board Membership: MicSi, Comments: No money has been paid to me or my institution, but for full disclosure, I am an advisory board member of MicSi, a company that provides advanced image-processing and denoising tools; Royalties: GE Healthcare, Comments: I received $2125 in royalties for patent licensing. My institution, NYU School of Medicine, also received royalties; Stock/Stock Options: MicSi, Comments: No money has been paid to me or my institution for stock, but for full disclosure, I own stock (3%), as well as NYU School of Medicine, in MicSi, a company that provides advanced image-processing and denoising tools. Joseph F. Rath—RELATED: Grant: National Institutes of Health/National Institute for Neurological Disorders and Stroke, Comments: This article reports on grant-funded research, R01 NS039135.* Charles J. Morton—UNRELATED: Employment: Massachusetts General Hospital, Comments: I worked here from September 2013 to August 2016 as a research coordinator. Dmitry S. Novikov—UNRELATED: Board Membership: Microstructure Imaging, Comments: no money paid; Stock/Stock Options: Microstructure Imaging, Comments: no money paid. Steven R. Flanagan—UNRELATED: Consultancy: McGovern School of Medicine, Icahn School of Medicine at Mount Sinai, Comments: Consultant to McGovern School of Medicine for an external review of their Department of Physical Medicine and Rehabilitation. Education sessions were provided to Icahn School of Medicine at Mount Sinai; Grants/Grants Pending: Brain Injury Association of America, Comments: grant support for the development of guidelines for traumatic brain injury*; Royalties: Springer, Comments: royalties from a textbook; Travel/Accommodations/Meeting Expenses Unrelated to Activities Listed: American Academy of Physical Medicine and Rehabilitation, Comments: Travel and accommodations were provided for face-to-face meetings, which I attend as part of my responsibilities as a member of the Board of Governors of the American Academy of Physical Medicine and Rehabilitation. Yvonne Lui—RELATED: Grant: National Institutes of Health, Comments: R01 NS039135-11, R21 NS090349, P41 EB017183.* *Money paid to the institution.
This work was supported, in part, by grant funding from the National Institutes of Health/National Institute for Neurological Disorders and Stroke: R01 NS039135–11 and R21 NS090349. This work was also performed under the rubric of the Center for Advanced Imaging Innovation and Research (www.cai2r.net), a National Institute of Biomedical Imaging and Bioengineering, Biomedical Technology Resource Center (NIH P41 EB017183).