Advanced brain age in deployment-related traumatic brain injury: A LIMBIC-CENC neuroimaging study.

OBJECTIVE: To determine if history of mild traumatic brain injury (mTBI) is associated with advanced or accelerated brain aging among the United States (US) military Service Members and Veterans. METHODS: Eight hundred and twenty-two participants (mean age = 40.4 years, 714 male/108 female) underwent MRI sessions at eight sites across the US. Two hundred and one participants completed a follow-up scan between five months and four years later. Predicted brain ages were calculated using T1-weighted MRIs and then compared with chronological ages to generate an Age Deviation Score for cross-sectional analyses and an Interval Deviation Score for longitudinal analyses. Participants also completed a neuropsychological battery, including measures of both cognitive functioning and psychological health. RESULT: In cross-sectional analyses, males with a history of deployment-related mTBI showed advanced brain age compared to those without (t(884) = 2.1, p = .038), while this association was not significant in females. In follow-up analyses of the male participants, severity of posttraumatic stress disorder (PTSD), depression symptoms, and alcohol misuse were also associated with advanced brain age. CONCLUSION: History of deployment-related mTBI, severity of PTSD and depression symptoms, and alcohol misuse are associated with advanced brain aging in male US military Service Members and Veterans.

Preliminary Validation of the Learning Ratio for the HVLT-R and BVMT-R in Older Adults.

BACKGROUND: The learning slope is typically represented as the raw difference between the final score and the score of the first learning trial. A new method for calculating the learning slope, the learning ratio (LR), was recently developed; it is typically represented as the number of items that are learned after the first trial divided by the number of items that are yet to be learned. OBJECTIVE: To evaluate the convergent and criterion validity of the LR in order to understand its sensitivity to Alzheimer disease (AD) pathology. METHOD: Fifty-six patients from a memory clinic underwent standard neuropsychological assessment and quantitative brain imaging. LR scores were calculated from the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised and were compared with both standard memory measures and total hippocampal volumes, as well as between individuals with AD and those with mild cognitive impairment. RESULTS: Lower LR scores were consistently associated with poorer performances on standard memory measures and smaller total hippocampal volumes, generally more so than traditional learning slope scores. The LR scores of the AD group were smaller than those of the group with mild cognitive impairment. Furthermore, the aggregation of LR scores into a single metric was partially supported. CONCLUSION: The LR is sensitive to AD pathology along the AD continuum. This result supports previous claims that the LR score can reflect learning capacity better than traditional learning calculations can by considering the amount of information that is learned at trial 1.

Age- and sex-related effects in children with mild traumatic brain injury on diffusion magnetic resonance imaging properties: A comparison of voxelwise and tractography methods.

Although there are several techniques to analyze diffusion-weighted imaging, any technique must be sufficiently sensitive to detect clinical abnormalities. This is especially critical in disorders like mild traumatic brain injury (mTBI), where pathology is likely to be subtle. mTBI represents a major public health concern, especially for youth under 15 years of age. However, the developmental period from birth to 18 years is also a time of tremendous brain changes. Therefore, it is important to establish the degree of age- and sex-related differences. Participants were children aged 8-15 years with mTBI or mild orthopedic injuries. Imaging was obtained within 10 days of injury. We performed tract-based spatial statistics (TBSS), deterministic tractography using Automated Fiber Quantification (AFQ), and probabilistic tractography using TRACULA (TRActs Constrained by UnderLying Anatomy) to evaluate whether any method provided improved sensitivity at identifying group, developmental, and/or sex-related differences. Although there were no group differences from any of the three analyses, many of the tracts, but not all, revealed increases of fractional anisotropy and decreases of axial, radial, and mean diffusivity with age. TBSS analyses resulted in age-related changes across all white matter tracts. AFQ and TRACULA revealed age-related changes within the corpus callosum, cingulum cingulate, corticospinal tract, inferior and superior longitudinal fasciculus, and uncinate fasciculus. The results are in many ways consistent across all three methods. However, results from the tractography methods provided improved sensitivity and better tract-specific results for identifying developmental and sex-related differences within the brain.

Assessment of quantitative magnetic resonance imaging metrics in the brain through the use of a novel phantom.

OBJECTIVE: Multisite and longitudinal neuroimaging studies are important in uncovering trajectories of recovery and neurodegeneration following traumatic brain injury (TBI) and concussion through the use of diffusion tensor imaging (DTI) and other imaging modalities. This study assessed differences in anisotropic diffusion measurement across four scanners using a human and a novel phantom developed in conjunction with the Chronic Effects of Neurotrauma Consortium. METHOD: Human scans provided measurement within biological tissue, and the novel physical phantom provided measures of anisotropic intra-tubular diffusion to serve as a model for intra-axonal water diffusion. Intra- and inter-scanner measurement variances were compared, and the impact on effect size was calculated. RESULTS: Intra-scanner test-retest reliability estimates for fractional anisotropy (FA) demonstrated relative stability over testing intervals. The human tissue and phantom showed similar FA ranges, high linearity and large within-device effect sizes. However, inter-scanner measures of FA indicated substantial differences, some of which exceeded typical DTI effect sizes in mild TBI. CONCLUSION: The diffusion phantom may be used to better elucidate inter-scanner variability in DTI-based measurement and provides an opportunity to better calibrate results obtained from scanners used in multisite and longitudinal studies. Novel solutions are being evaluated to understand and potentially overcome these differences.

Functional brain connectivity and cortical thickness in relation to chronic pain in post-911 veterans and service members with mTBI.

OBJECTIVES: Investigate the relation of chronic pain interference to functional connectivity (FC) of brain regions and to cortical thickness in post-911 Veterans and Service Members (SMs) who sustained a mild traumatic brain injury (mTBI). METHODS: This is an observational study with cross-sectional analyses. A sample of 65 enrollees completing initial evaluation at a single site of the Chronic Effects of Neurotrauma Consortium (CENC) reported pain interference ratings on the TBI QOL. Functional connectivity and cortical thickness were measured. RESULTS: Severity of pain interference was negatively related to FC of the default mode network (DMN), i.e., participants who reported more severe pain interference had less FC between mesial prefrontal cortex and posterior regions of the DMN including posterior cingulate cortex and precuneus. Cortical thickness of specific regions was positively related to severity of pain interference. CONCLUSION: The more that pain was perceived to interfere with daily life, the less the FC between regions in a network associated with self-referential thought and mind wandering. Although cortical thickness in specific brain regions was positively related to severity of pain interference, follow-up longitudinal data, control group data, and study of individual differences in this cohort will expand this initial report and replicate these findings.

Quantitative structural neuroimaging of mild traumatic brain injury in the Chronic Effects of Neurotrauma Consortium (CENC): Comparison of volumetric data within and across scanners.

BACKGROUND: An important component of the multicentre Chronic Effects of Neurotrauma Consortium (CENC) project is the development of improved quantitative magnetic resonance imaging (MRI) methods, including volumetric analysis. Although many studies routinely employ quality assurance (QA) procedures including MR and human phantoms to promote accuracy and monitor site differences, few studies perform rigorous direct comparisons of these data nor report findings that enable inference regarding site-to-site comparability. These gaps in evaluating cross-site differences are concerning, especially given the well-established differences that can occur between data acquired on scanners with different manufacturer, hardware or software. METHODS: This study reports findings on (1) a series of studies utilizing two MR phantoms to interrogate machine-based variability using data collected on the same magnet, (2) a human phantom repeatedly imaged on the same scanner to investigate within-subject, within-site variability and (3) a human phantom imaged on three different scanners to examine within subject, between-site variability. RESULTS: Although variability is relatively minimal for the phantom scanned on the same magnet, significantly more variability is introduced in a human subject, particularly when regions are relatively small or multiple sites used. CONCLUSION: Vigilance when combining data from different sites is suggested and that future efforts address these issues.

Supervised learning technique for the automated identification of white matter hyperintensities in traumatic brain injury.

BACKGROUND: White matter hyperintensities (WMHs) are foci of abnormal signal intensity in white matter regions seen with magnetic resonance imaging (MRI). WMHs are associated with normal ageing and have shown prognostic value in neurological conditions such as traumatic brain injury (TBI). The impracticality of manually quantifying these lesions limits their clinical utility and motivates the utilization of machine learning techniques for automated segmentation workflows. METHODS: This study develops a concatenated random forest framework with image features for segmenting WMHs in a TBI cohort. The framework is built upon the Advanced Normalization Tools (ANTs) and ANTsR toolkits. MR (3D FLAIR, T2- and T1-weighted) images from 24 service members and veterans scanned in the Chronic Effects of Neurotrauma Consortium's (CENC) observational study were acquired. Manual annotations were employed for both training and evaluation using a leave-one-out strategy. Performance measures include sensitivity, positive predictive value, [Formula: see text] score and relative volume difference. RESULTS: Final average results were: sensitivity = 0.68 ± 0.38, positive predictive value = 0.51 ± 0.40, [Formula: see text] = 0.52 ± 0.36, relative volume difference = 43 ± 26%. In addition, three lesion size ranges are selected to illustrate the variation in performance with lesion size. CONCLUSION: Paired with correlative outcome data, supervised learning methods may allow for identification of imaging features predictive of diagnosis and prognosis in individual TBI patients.

Longitudinal changes in cortical thickness in autism and typical development.

The natural history of brain growth in autism spectrum disorders remains unclear. Cross-sectional studies have identified regional abnormalities in brain volume and cortical thickness in autism, although substantial discrepancies have been reported. Preliminary longitudinal studies using two time points and small samples have identified specific regional differences in cortical thickness in the disorder. To clarify age-related trajectories of cortical development, we examined longitudinal changes in cortical thickness within a large mixed cross-sectional and longitudinal sample of autistic subjects and age- and gender-matched typically developing controls. Three hundred and forty-five magnetic resonance imaging scans were examined from 97 males with autism (mean age = 16.8 years; range 3-36 years) and 60 males with typical development (mean age = 18 years; range 4-39 years), with an average interscan interval of 2.6 years. FreeSurfer image analysis software was used to parcellate the cortex into 34 regions of interest per hemisphere and to calculate mean cortical thickness for each region. Longitudinal linear mixed effects models were used to further characterize these findings and identify regions with between-group differences in longitudinal age-related trajectories. Using mean age at time of first scan as a reference (15 years), differences were observed in bilateral inferior frontal gyrus, pars opercularis and pars triangularis, right caudal middle frontal and left rostral middle frontal regions, and left frontal pole. However, group differences in cortical thickness varied by developmental stage, and were influenced by IQ. Differences in age-related trajectories emerged in bilateral parietal and occipital regions (postcentral gyrus, cuneus, lingual gyrus, pericalcarine cortex), left frontal regions (pars opercularis, rostral middle frontal and frontal pole), left supramarginal gyrus, and right transverse temporal gyrus, superior parietal lobule, and paracentral, lateral orbitofrontal, and lateral occipital regions. We suggest that abnormal cortical development in autism spectrum disorders undergoes three distinct phases: accelerated expansion in early childhood, accelerated thinning in later childhood and adolescence, and decelerated thinning in early adulthood. Moreover, cortical thickness abnormalities in autism spectrum disorders are region-specific, vary with age, and may remain dynamic well into adulthood.

Day of injury CT and late MRI findings: Cognitive outcome in a paediatric sample with complicated mild traumatic brain injury.

OBJECTIVES: Complicated mild traumatic brain injury (mTBI) or cmTBI is based on the presence of visibly identifiable brain pathology on the day-of-injury computed tomography (CT) scan. In a paediatric sample the relation of DOI CT to late MRI findings and neuropsychological outcome was examined. METHODS: MRI (>12 months) was obtained in paediatric cmTBI patients and a sample of orthopaedically injured (OI) children. Those children with positive imaging findings (MRI+) were quantitatively compared to those without (MRI-) or with the OI sample. Groups were also compared in neurocognitive outcome from WASI sub-tests and the WISC-IV Processing Speed Index (PSI), along with the Test of Everyday Attention for Children (TEA-Ch) and a parent-rated behavioural functioning measure (ABAS-II). RESULTS: Despite the MRI+ group having significantly more DOI CT findings than the MRI- group, no quantitative differences were found. WASI Vocabulary and Matrix Reasoning scores were significantly lower, but not PSI, TEA-Ch or ABAS-II scores. MRI+ and MRI- groups did not differ on these measures. CONCLUSIONS: Heterogeneity in the occurrence of MRI-identified focal pathology was not associated with uniform changes in quantitative analyses of brain structure in cmTBI. Increased number of DOI CT abnormalities was associated with lowered neuropsychological performance.

Microstructural Organization of Distributed White Matter Associated With Fine Motor Control in US Service Members With Mild Traumatic Brain Injury.

Mild traumatic brain injury (mTBI) is the most common form of brain injury. While most individuals recover from mTBI, roughly 20% experience persistent symptoms, potentially including reduced fine motor control. We investigate relationships between regional white matter organization and subcortical volumes associated with performance on the Grooved Pegboard (GPB) test in a large cohort of military Service Members and Veterans (SM&Vs) with and without a history of mTBI(s). Participants were enrolled in the Long-term Impact of Military-relevant Brain Injury Consortium-Chronic Effects of Neurotrauma Consortium. SM&Vs with a history of mTBI(s) (n = 847) and without mTBI (n = 190) underwent magnetic resonance imaging and the GPB test. We first examined between-group differences in GPB completion time. We then investigated associations between GPB performance and regional structural imaging measures (tractwise diffusivity, subcortical volumes, and cortical thickness) in SM&Vs with a history of mTBI(s). Lastly, we explored whether mTBI history moderated associations between imaging measures and GPB performance. SM&Vs with mTBI(s) performed worse than those without mTBI(s) on the non-dominant hand GPB test at a trend level (p < 0.1). Higher fractional anisotropy (FA) of tracts including the posterior corona radiata, superior longitudinal fasciculus, and uncinate fasciculus were associated with better GPB performance in the dominant hand in SM&Vs with mTBI(s). These findings support that the organization of several white matter bundles are associated with fine motor performance in SM&Vs. We did not observe that mTBI history moderated associations between regional FA and GPB test completion time, suggesting that chronic mTBI may not significantly influence fine motor control.

Peer relationships of children with traumatic brain injury.

This study examined peer relationships in children with traumatic brain injury (TBI) relative to children with orthopedic injuries (OI), and explored whether differences in peer relationships correlated with white matter volumes. Classroom procedures were used to elicit peer perceptions of social behavior, acceptance, and friendships for eighty-seven 8- to 13-year-old children, 15 with severe TBI, 40 with complicated mild/moderate TBI, and 32 with OI. Magnetic resonance imaging (MRI) and voxel-based morphometry (VBM) were used to investigate volumetric correlates of peer relationship measures. Children with severe TBI were rated higher in rejection-victimization than children with OI, and were less likely than children with OI to have a mutual friendship in their classroom (47% vs. 88%). Children with TBI without a mutual friend were rated lower than those with a mutual friend on sociability-popularity and prosocial behavior and higher on rejection-victimization, and had lower peer acceptance ratings. Mutual friendship ratings were related to white matter volumes in several posterior brain regions, but not to overall brain atrophy. Severe TBI in children is associated with detrimental peer relationships that are related to focal volumetric reductions in white matter within regions of the brain involved in social information-processing.

Regional cortical volume and cognitive functioning following traumatic brain injury.

There has been limited examination of the effect of brain pathology on subsequent function. The current study examined the relationships between regional variation in grey matter volume, age and cognitive impairment using a semi-automated image analysis tool. This study included 69 individuals with mild-to-severe TBI, 41 of whom also completed neuropsychological tests of attention, working memory, processing speed, memory and executive functions. A widespread reduction in grey matter volume was associated with increasing age. Regional volumes that were affected also related to the severity of injury, whereby the most severe TBI participants displayed the most significant pathology. Poorer retention of newly learned material was associated with reduced cortical volume in frontal, parietal, and occipital brain regions. In addition, poorer working memory and executive control performance was found for individuals with lower cortical volume in temporal, parietal, and occipital regions. These findings are largely in line with previous literature, which suggests that frontal, temporal, and parietal regions are integral for the encoding of memories into long-term storage, memory retrieval, and working memory. The present study suggests that automated image analysis methods may be used to explore the relationships between regional variation in grey matter volume and cognitive function following TBI.

Consideration of different scoring approaches for a verbal incidental learning measure from the WAIS-IV using hippocampal volumes.

Objective: While Spencer's verbal incidental learning (IL) task-from Vocabulary and Similarities subtests of the WAIS-has been validated relative to traditional memory measures and Alzheimer's disease (AD) pathology, the effectiveness of the particular scoring method used has not been assessed relative to alternative scoring weightings. The purpose of this study was to compare original and alternative scoring methods of this IL task by using an AD biomarker-benchmark to arrive at an optimal approach. Methods: Fifty-five memory-clinic patients aged 59-87 received neuropsychological assessment, measures of IL, and quantitative brain imaging. Partial correlation coefficients with total hippocampal volume-controlling for age, sex, and intracranial volume-were assessed across several IL scoring methods, and partial correlations with measures of memory were examined to evaluate convergent validity.Results: IL scoring methods maximizing the contribution of paired-associate-recall-performance were significantly correlated with both hippocampal volumes and traditional memory measures, whereas discrimination-emphasized scoring methods were not.Conclusions: IL scoring methods emphasizing memory paired-associate recall appeared to be preferable to those emphasizing memory discrimination. Administration of the IL- Similarities subtest alone, without IL- Vocabulary, may strike a balance between strength of relationships with both hippocampal volumes and standard memory measures, while also limiting administration time.

Scheltens ratings, clinical white matter hyperintensities and executive functioning in the Cache County Memory Study.

OBJECTIVE: Examine the association between neuropsychologically assessed executive function and clinically identifiable white matter burden from magnetic resonance imaging, using a visual rating system (Scheltens Rating System) applied to the Cache County Memory Study (CCMS) archival database. METHOD: We used the Scheltens Ratings Scale to quantify white matter lesion burden in the CCMS sample and used this metric as a predictor of executive function. The sample included 60 individuals with dementia and 13 healthy controls. RESULTS: Higher Scheltens ratings were associated with poorer task performance on an Executive Function composite score of common neuropsychological tests. This association held true for both controls and dementing cases. CONCLUSIONS: The current findings support extensive prior literature demonstrating the association between brain vascular health determined by white matter burden and clinical outcomes based on neuropsychological assessment of cognitive performance.

Cognitive Sparing in Proton versus Photon Radiotherapy for Pediatric Brain Tumor Is Associated with White Matter Integrity: An Exploratory Study.

Radiotherapy for pediatric brain tumors is associated with reduced white matter structural integrity and neurocognitive decline. Superior cognitive outcomes have been reported following proton radiotherapy (PRT) compared to photon radiotherapy (XRT), presumably due to improved sparing of normal brain tissue. This exploratory study examined the relationship between white matter change and late cognitive effects in pediatric brain tumor survivors treated with XRT versus PRT. Pediatric brain tumor survivors treated with XRT (n = 10) or PRT (n = 12) underwent neuropsychological testing and diffusion weighted imaging >7 years post-radiotherapy. A healthy comparison group (n = 23) was also recruited. Participants completed age-appropriate measures of intellectual functioning, visual-motor integration, and motor coordination. Tractography was conducted using automated fiber quantification (AFQ). Fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) were extracted from 12 tracts of interest. Overall, both white matter integrity (FA) and neuropsychological performance were lower in XRT patients while PRT patients were similar to healthy control participants with respect to both FA and cognitive functioning. These findings support improved long-term outcomes in PRT versus XRT. This exploratory study is the first to directly support for white matter integrity as a mechanism of cognitive sparing in PRT.

Decreased interhemispheric functional connectivity in autism.

The cortical underconnectivity theory asserts that reduced long-range functional connectivity might contribute to a neural mechanism for autism. We examined resting-state blood oxygen level-dependent interhemispheric correlation in 53 males with high-functioning autism and 39 typically developing males from late childhood through early adulthood. By constructing spatial maps of correlation between homologous voxels in each hemisphere, we found significantly reduced interhemispheric correlation specific to regions with functional relevance to autism: sensorimotor cortex, anterior insula, fusiform gyrus, superior temporal gyrus, and superior parietal lobule. Observed interhemispheric connectivity differences were better explained by diagnosis of autism than by potentially confounding neuropsychological metrics of language, IQ, or handedness. Although both corpus callosal volume and gray matter interhemispheric connectivity were significantly reduced in autism, no direct relationship was observed between them, suggesting that structural and functional metrics measure different aspects of interhemispheric connectivity. In the control but not the autism sample, there was decreasing interhemispheric correlation with subject age. Greater differences in interhemispheric correlation were seen for more lateral regions in the brain. These findings suggest that long-range connectivity abnormalities in autism are spatially heterogeneous and that transcallosal connectivity is decreased most in regions with functions associated with behavioral abnormalities in autism. Autism subjects continue to show developmental differences in interhemispheric connectivity into early adulthood.

Developmental Alterations in Cortical Organization and Socialization in Adolescents Who Sustained a Traumatic Brain Injury in Early Childhood.

This study investigated patterns of cortical organization in adolescents who had sustained a traumatic brain injury (TBI) during early childhood to determine ways in which early head injury may alter typical brain development. Increased gyrification in other patient populations is associated with polymicrogyria and aberrant development, but this has not been investigated in TBI. Seventeen adolescents (mean age = 14.1 ± 2.4) who sustained a TBI between 1-8 years of age, and 17 demographically-matched typically developing children (TDC) underwent a high-resolution, T1-weighted 3-Tesla magnetic resonance imaging (MRI) at 6-15 years post-injury. Cortical white matter volume and organization was measured using FreeSurfer's Local Gyrification Index (LGI). Despite a lack of significant difference in white matter volume, participants with TBI demonstrated significantly increased LGI in several cortical regions that are among those latest to mature in normal development, including left parietal association areas, bilateral dorsolateral and medial frontal areas, and the right posterior temporal gyrus, relative to the TDC group. Additionally, there was no evidence of increased surface area in the regions that demonstrated increased LGI. Higher Vineland-II Socialization scores were associated with decreased LGI in right frontal and temporal regions. The present results suggest an altered pattern of expected development in cortical gyrification in the TBI group, with changes in late-developing frontal and parietal association areas. Such changes in brain structure may underlie cognitive and behavioral deficits associated with pediatric TBI. Alternatively, increased gyrification following TBI may represent a compensatory mechanism that allows for typical development of cortical surface area, despite reduced brain volume.

Diffuse damage in pediatric traumatic brain injury: a comparison of automated versus operator-controlled quantification methods.

This investigation had two main objectives: 1) to assess the comparability of volumes determined by operator-controlled image quantification with automated image analysis in evaluating atrophic brain changes related to traumatic brain injury (TBI) in children, and 2) to assess the extent of diffuse structural changes throughout the brain as determined by reduced volume of a brain structure or region of interest (ROI). Operator-controlled methods used ANALYZE software for segmentation and tracing routines of pre-defined brain structures and ROIs. For automated image analyses, the open-access FreeSurfer program was used. Sixteen children with moderate-to-severe TBI were compared to individually matched, typically developing control children and the volumes of 18 brain structures and/or ROIs were compared between the two methods. Both methods detected atrophic changes but differed in the magnitude of the atrophic effect with the best agreement in subcortical structures. The volumes of all brain structures/ROIs were smaller in the TBI group regardless of method used; overall effect size differences were minimal for caudate and putamen but moderate to large for all other measures. This is reflective of the diffuse nature of TBI and its widespread impact on structural brain integrity, indicating that both FreeSurfer and operator-controlled methods can reliably assess cross-sectional volumetric changes in pediatric TBI.

Examining the Relationship between a Verbal Incidental Learning Measure from the WAIS-IV and Neuroimaging Biomarkers for Alzheimer's Pathology.

Convergent validation of a verbal incidental learning (IL) task from the WAIS-IV using neuroimaging biomarkers is warranted to understand its sensitivity to Alzheimer's disease (AD) pathology. Fifty-five memory clinic patients aged 59 to 87 years received neuropsychological assessment, and measures of IL and quantitative brain imaging. Worse IL-Total Score and IL-Similarities performances were significantly associated with smaller hemispheric hippocampal volumes. IL measures were not significantly correlated with cerebral ß-amyloid burden, though a trend was present and effect sizes were mild. These hippocampal volume results suggest that this IL task may be sensitive to AD pathology along the AD continuum.

A preliminary investigation of corpus callosum subregion white matter vulnerability and relation to chronic outcome in boxers.

Microstructural neuropathology occurs in the corpus callosum (CC) after repetitive sports concussion in boxers and can be dose-dependent. However, the specificity and relation of CC changes to boxing exposure extent and post-career psychiatric and neuropsychological outcomes are largely unknown. Using deterministic diffusion tensor imaging (DTI) techniques, boxers and demographically-matched, noncontact sport athletes were compared to address literature gaps. Ten boxers and 9 comparison athletes between 26 and 59 years old (M = 44.63, SD = 9.24) completed neuropsychological testing and MRI. Quantitative DTI metrics were estimated for CC subregions. Group×Region interaction effects were observed on fractional anisotropy (FA; η2p ≥ .21). Follow-up indicated large effects of group (η2p ≥ .26) on splenium FA (boxerscomparisons), but not radial diffusivity (RD). The group of boxers had moderately elevated number of psychiatric symptoms and reduced neuropsychological scores relative to the comparison group. In boxers, years sparring, professional bouts, and knockout history correlated strongly (r > |.40|) with DTI metrics and fine motor dexterity. In the comparison group, splenium FA correlated positively with psychiatric symptoms. In the boxer group, neuropsychological scores correlated with DTI metrics in all CC subregions. Results suggested relative vulnerability of the splenium and, to a lesser extent, the genu to chronic, repetitive head injury from boxing. Dose-dependent associations of professional boxing history extent with DTI white matter structure indices as well as fine motor dexterity were supported. Results indicated that symptoms of depression and executive dysfunction may provide the strongest indicators of global CC disruption from boxing.