Goal-Oriented Attentional Self-Regulation Training in Chronic Mild Traumatic Brain Injury Leads to Microstructural Plasticity in Prefrontal White Matter

Impaired attention is one of the most common, debilitating, and persistent consequence of traumatic brain injury (TBI), which impacts overall cognitive and executive functions in these patients. Previous neuroimaging studies, trying to understand the neural mechanism underlying attention impairment post TBI, have highlighted the role of prefrontal white matter tracts in attentional functioning in mild TBI. Goal-Oriented Attentional Self-Regulation (GOALS) is a cognitive rehabilitation training program that targets executive control functions in participants by applying mindfulness-based attention regulation and goal management strategies. GOALS training has been demonstrated to improve attention and executive functioning in patients with chronic TBI. However, its impact on microstructural integrity of attention-associated prefrontal white matter tracts is still unclear. Here, using diffusion MRI in a pilot randomized controlled trial, we investigated the effect of GOALS training on prefrontal white matter microstructure in US military veterans with chronic mild TBI (mTBI), compared to a matched control group of veterans with chronic mTBI who received standard of care brain health education. We also tested for an association between microstructural white matter changes and sustained attention ability in these patients pre- and post-GOALS training. Our results show significantly better white matter microstructural integrity in left and right anterior corona radiata in the GOALS group compared to the control group post-training. Moreover, we found a significant correlation between sustained attention ability of GOALS training participants and white matter integrity of their right anterior corona radiata pre- and post-training. Finally, our findings indicated that the improved white matter integrity of the anterior corona radiata in GOALS training participants was the result of increased neurite density and decreased fiber orientation dispersion within this tract. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial NCT02920788 ### Funding Statement This research was supported by grant 1 I01 RX002300 awarded to PM by VA Rehabilitation Research & Development and the Office of Academic Affiliations Department of Veterans Affairs. The data analysis and writing of the manuscript was supported by Advanced Fellowship in Polytrauma by Office of Academic Affiliations of Veterans Affairs awarded to HK. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committee/IRB of University of California San Francisco gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the corresponding authors.