Computerized Cognitive Remediation Affects White Matter Microstructure in Relation to Improved Cognitive Function in Adults with Chronic Traumatic Brain Injury

Hannah M Lindsey; Joseph F Rath; Tamara Bushnik; Steven Flanagan; Mariana Lazar; Gerald T Voelbel

doi:10.1177/08977151251414085

Computerized Cognitive Remediation Affects White Matter Microstructure in Relation to Improved Cognitive Function in Adults with Chronic Traumatic Brain Injury

J Neurotrauma. 2026 Feb 17:8977151251414085. doi: 10.1177/08977151251414085. Online ahead of print.

Authors

Hannah M Lindsey^{1

2}, Joseph F Rath³, Tamara Bushnik³, Steven Flanagan³, Mariana Lazar^{4

5}, Gerald T Voelbel^{3

6}

Affiliations

¹ Traumatic Brain Injury and Concussion Center, Department of Neurology, University of Utah, Salt Lake City, Utah, USA.
² Department of Psychology, New York University, New York, New York, USA.
³ Department of Rehabilitation Medicine, NYU Grossman School of Medicine, New York, New York, USA.
⁴ Department of Radiology, NYU Grossman School of Medicine, New York, New York, USA.
⁵ Center for Biomedical Imaging at NYU Langone Health, New York, New York, USA.
⁶ Department of Occupational Therapy and Center of Health and Rehabilitation Research, Steinhardt School of Culture, Education, and Human Development, New York University, New York, New York, USA.

PMID: 41700705
DOI: 10.1177/08977151251414085

Abstract

Traumatic brain injury (TBI) frequently results in long-term cognitive deficits due to traumatic axonal injury and disruption of structural brain connectivity. Computerized cognitive remediation (CCR) has shown promise for improving cognitive outcomes in chronic TBI; however, diffusion imaging studies evaluating its effectiveness have often relied on tensor-based metrics that are limited in their ability to detect subtle treatment-related changes. This study used correlational tractography, a diffusion magnetic resonance imaging (dMRI) connectometry method sensitive to localized, fiber-specific changes, to investigate the effects of CCR on white matter microstructure in adults with chronic TBI and to further examine the relationship between white matter changes and improvements in cognitive function. Seventeen adults with chronic mild to severe TBI were assigned to an experimental group (n = 10), who received 40 hours of CCR over 14 weeks, or a nonintervention control group (n = 7). All participants underwent dMRI scans and cognitive assessments at pre- and postintervention visits. Correlational tractography was used to assess differences in longitudinal change of normalized quantitative anisotropy (QA), a tensor-free metric associated with axonal density and plasticity, across whole-brain white matter between CCR and nonintervention control groups. Following the intervention period, increased QA was observed in the CCR group, relative to the nonintervention control group, and changes in QA in the CCR group were related to improvements on objective measures of processing speed, attention, and working memory. These results provide preliminary evidence that CCR may promote white matter plasticity in relation to improved cognitive function in individuals with chronic TBI. Furthermore, by leveraging QA and correlational tractography, we were able to detect regionally specific changes that may have been overlooked using traditional tensor-derived diffusion metrics or tract-averaged approaches. Overall, our findings support the potential of CCR as a scalable intervention to facilitate structural and functional plasticity in adults with chronic TBI.

Keywords: chronic traumatic brain injury; cognitive rehabilitation; connectometry; diffusion magnetic resonance imaging; neuroplasticity; quantitative anisotropy.