# Use of Novel Neuroimaging, Neuropsychological Methods, and Retrograde Memory Test to Detect Cognitive and Cerebral Disruption in Veterans with Mild Traumatic Brain Injury

> **NIH VA I01** · VA SAN DIEGO HEALTHCARE SYSTEM · 2023 · —

## Abstract

Identification of neuroimaging-based markers sensitive to mild neurotrauma and neuropsychological markers
of cognitive disruption is vital toward addressing the complex treatment needs of the large number of Veterans
with histories of mild traumatic brain injury (mTBI). Although neuroimaging methods, particularly in the area of
diffusion imaging (dMRI) continue to show promise, there are significant limitations in the traditional, diffusion
tensor imaging (DTI) based approach in white matter (WM). Specifically, a high degree of heterogeneity of WM
axon orientations and sampling from disparate tissue types within a voxel contribute to inaccurate estimates of
tissue properties. These limitations, inherent in standard and widely used DTI methods, likely attenuate DTI
sensitivity in the detection of mild forms of neurotrauma, particularly in key, complex WM regions shown to be
most susceptible to mTBI. Likewise, cognitive research findings in mTBI have been mixed, with conflicting reports
and unclear cognitive outcomes that likely cloud and confuse clinical decision-making. The heterogeneity of TBI,
differences in injury characteristics, and a non-uniform cognitive profile among affected Veterans likely contribute
to the decreased sensitivity and inconsistency shown across studies that have leveraged traditional means-
based comparisons of traditional neuropsychological test scores. Indeed, indicators of mTBI often fail to align
with imaging findings, cognitive reports, and functional outcomes reported by Veterans with histories of mTBI.
 In the proposed study, we will apply new tools and methods in order to more sensitively examine WM
disruption and neuropsychological performance in 60 Veterans with mTBI and 60 Veterans without a history of
TBI. Participants will complete a broad neurocognitive assessment, including a novel test of retrograde memory
for news facts, and will undergo a dMRI scan. We propose that leveraging a novel neuroimaging approach—one
that is robust to the limitations inherent in standard DTI protocols—will enable investigation of WM proximal to
the sulcal depths where all-cause mTBI is thought to inflict the greatest damage given shearing effects at the
gray matter-white matter border. We will use dMRI acquisition and analysis methods which combine single and
double pulsed field gradient dMRI acquisitions via a novel technique called Joint Estimation Diffusion Imaging
(JEDI) to integrate diffusion information at the voxel and subvoxel level. Equilibrium probability (EP), an
anisotropy measure that is more robust to the complexities of crossing fibers and partial voluming effects, will be
calculated using JEDI. In particular, we will interrogate EP of voxels residing in the sulci at the gray matter-white
matter border in the frontal lobe. Simulation and histopathological studies show these regions to be most
susceptible to acute and distal effects of mild neurotrauma given the shearing effects that are particularly
damaging becau...

## Key facts

- **NIH application ID:** 10696693
- **Project number:** 1I01CX002626-01
- **Recipient organization:** VA SAN DIEGO HEALTHCARE SYSTEM
- **Principal Investigator:** Lisa Delano-Wood
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2023
- **Award amount:** —
- **Award type:** 1
- **Project period:** 2023-04-01 → 2027-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10696693

## Citation

> US National Institutes of Health, RePORTER application 10696693, Use of Novel Neuroimaging, Neuropsychological Methods, and Retrograde Memory Test to Detect Cognitive and Cerebral Disruption in Veterans with Mild Traumatic Brain Injury (1I01CX002626-01). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10696693. Licensed CC0.

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