Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi-Cohort Mega-Analysis.

OBJECTIVE: The long-term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. Given evidence that a single significant brain injury event increases the risk of dementia, brain-age estimation could provide a novel and efficient indexing of the long-term consequences of TBI. Brain-age procedures use predictive modeling to calculate brain-age scores for an individual using structural magnetic resonance imaging (MRI) data. Complicated mild, moderate, and severe TBI (cmsTBI) is associated with a higher predicted age difference (PAD), but the progression of PAD over time remains unclear. We sought to examine whether PAD increases as a function of time since injury (TSI) and if injury severity and sex interacted to influence this progression. METHODS: Through the ENIGMA Adult Moderate and Severe (AMS)-TBI working group, we examine the largest TBI sample to date (n = 343), along with controls, for a total sample size of n = 540, to replicate and extend prior findings in the study of TBI brain age. Cross-sectional T1w-MRI data were aggregated across 7 cohorts, and brain age was established using a similar brain age algorithm to prior work in TBI. RESULTS: Findings show that PAD widens with longer TSI, and there was evidence for differences between sexes in PAD, with men showing more advanced brain age. We did not find strong evidence supporting a link between PAD and cognitive performance. INTERPRETATION: This work provides evidence that changes in brain structure after cmsTBI are dynamic, with an initial period of change, followed by relative stability in brain morphometry, eventually leading to further changes in the decades after a single cmsTBI. ANN NEUROL 2024;96:365-377.

Diffusion-Weighted Imaging in Mild Traumatic Brain Injury: A Systematic Review of the Literature.

There is evidence that diffusion-weighted imaging (DWI) is able to detect tissue alterations following mild traumatic brain injury (mTBI) that may not be observed on conventional neuroimaging; however, findings are often inconsistent between studies. This systematic review assesses patterns of differences in DWI metrics between those with and without a history of mTBI. A PubMed literature search was performed using relevant indexing terms for articles published prior to May 14, 2020. Findings were limited to human studies using DWI in mTBI. Articles were excluded if they were not full-length, did not contain original data, if they were case studies, pertained to military populations, had inadequate injury severity classification, or did not report post-injury interval. Findings were reported independently for four subgroups: acute/subacute pediatric mTBI, acute/subacute adult mTBI, chronic adult mTBI, and sport-related concussion, and all DWI acquisition and analysis methods used were included. Patterns of findings between studies were reported, along with strengths and weaknesses of the current state of the literature. Although heterogeneity of sample characteristics and study methods limited the consistency of findings, alterations in DWI metrics were most commonly reported in the corpus callosum, corona radiata, internal capsule, and long association pathways. Many acute/subacute pediatric studies reported higher FA and lower ADC or MD in various regions. In contrast, acute/subacute adult studies most commonly indicate lower FA within the context of higher MD and RD. In the chronic phase of recovery, FA may remain low, possibly indicating overall demyelination or Wallerian degeneration over time. Longitudinal studies, though limited, generally indicate at least a partial normalization of DWI metrics over time, which is often associated with functional improvement. We conclude that DWI is able to detect structural mTBI-related abnormalities that may persist over time, although future DWI research will benefit from larger samples, improved data analysis methods, standardized reporting, and increasing transparency.

Discriminating Mild Traumatic Brain Injury and Posttraumatic Stress Disorder Using Latent Neuroimaging and Neuropsychological Profiles in Active-Duty Military Service Members.

OBJECTIVE: Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) commonly occur among military Service Members and Veterans and have heterogenous, but also overlapping symptom presentations, which often complicate the diagnoses of underlying impairments and development of effective treatment plans. Thus, we sought to examine whether the combination of whole brain gray matter (GM) and white matter (WM) structural measures with neuropsychological performance can aid in the classification of military personnel with mTBI and PTSD. METHODS: Active-Duty US Service Members ( n = 156; 87.8% male) with a history of mTBI, PTSD, combined mTBI+PTSD, or orthopedic injury completed a neuropsychological battery and T1- and diffusion-weighted structural neuroimaging. Cortical, subcortical, ventricular, and WM volumes and whole brain fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD) were calculated. Latent profile analyses were performed to determine how the GM and WM indicators, together with neuropsychological indicators, classified individuals. RESULTS: For both GM and WM, respectively, a 4-profile model was the best fit. The GM model identified greater ventricular volumes in Service Members with cognitive symptoms, including those with a diagnosis of mTBI, either alone or with PTSD. The WM model identified reduced FA and elevated RD in those with psychological symptoms, including those with PTSD or mTBI and comorbid PTSD. However, contrary to expectation, a global neural signature unique to those with comorbid mTBI and PTSD was not identified. CONCLUSIONS: The findings demonstrate that neuropsychological performance alone is more robust in differentiating Active-Duty Service Members with mTBI and PTSD, whereas global neuroimaging measures do not reliably differentiate between these groups.

Assessment of Neurocognitive Functions, Olfaction, Taste, Mental, and Psychosocial Health in COVID-19 in Adults: Recommendations for Harmonization of Research and Implications for Clinical Practice.

OBJECTIVE: To propose a set of internationally harmonized procedures and methods for assessing neurocognitive functions, smell, taste, mental, and psychosocial health, and other factors in adults formally diagnosed with COVID-19 (confirmed as SARS-CoV-2 + WHO definition). METHODS: We formed an international and cross-disciplinary NeuroCOVID Neuropsychology Taskforce in April 2020. Seven criteria were used to guide the selection of the recommendations' methods and procedures: (i) Relevance to all COVID-19 illness stages and longitudinal study design; (ii) Standard, cross-culturally valid or widely available instruments; (iii) Coverage of both direct and indirect causes of COVID-19-associated neurological and psychiatric symptoms; (iv) Control of factors specifically pertinent to COVID-19 that may affect neuropsychological performance; (v) Flexibility of administration (telehealth, computerized, remote/online, face to face); (vi) Harmonization for facilitating international research; (vii) Ease of translation to clinical practice. RESULTS: The three proposed levels of harmonization include a screening strategy with telehealth option, a medium-size computerized assessment with an online/remote option, and a comprehensive evaluation with flexible administration. The context in which each harmonization level might be used is described. Issues of assessment timelines, guidance for home/remote assessment to support data fidelity and telehealth considerations, cross-cultural adequacy, norms, and impairment definitions are also described. CONCLUSIONS: The proposed recommendations provide rationale and methodological guidance for neuropsychological research studies and clinical assessment in adults with COVID-19. We expect that the use of the recommendations will facilitate data harmonization and global research. Research implementing the recommendations will be crucial to determine their acceptability, usability, and validity.

Latent Neuropsychological Profiles to Discriminate Mild Traumatic Brain Injury and Posttraumatic Stress Disorder in Active-Duty Service Members.

OBJECTIVE: To determine whether cognitive and psychological symptom profiles differentiate clinical diagnostic classifications (eg, history of mild traumatic brain injury [mTBI] and posttraumatic stress disorder [PTSD]) in military personnel. METHODS: US Active-Duty Service Members ( N = 209, 89% male) with a history of mTBI ( n = 56), current PTSD ( n = 23), combined mTBI + PTSD ( n = 70), or orthopedic injury controls ( n = 60) completed a neuropsychological battery assessing cognitive and psychological functioning. Latent profile analysis was performed to determine how neuropsychological outcomes of individuals clustered together. Diagnostic classifications (ie, mTBI, PTSD, mTBI + PTSD, and orthopedic injury controls) within each symptom profile were examined. RESULTS: A 5-profile model had the best fit. The profiles differentiated subgroups with high (34.0%) or normal (21.5%) cognitive and psychological functioning, cognitive symptoms (19.1%), psychological symptoms (15.3%), and combined cognitive and psychological symptoms (10.0%). The symptom profiles differentiated participants as would generally be expected. Participants with PTSD were mainly represented in the psychological symptom subgroup, while orthopedic injury controls were mainly represented in the high-functioning subgroup. Further, approximately 79% of participants with comorbid mTBI and PTSD were represented in a symptomatic group (∼24% = cognitive symptoms, ∼29% = psychological symptoms, and 26% = combined cognitive/psychological symptoms). Our results also showed that approximately 70% of military personnel with a history of mTBI were represented in the high- and normal-functioning groups. CONCLUSIONS: These results demonstrate both overlapping and heterogeneous symptom and performance profiles in military personnel with a history of mTBI, PTSD, and/or mTBI + PTSD. The overlapping profiles may underscore why these diagnoses are often difficult to diagnose and treat, but suggest that advanced statistical models may aid in identifying profiles representing symptom and cognitive performance impairments within patient groups and enable identification of more effective treatment targets.

Intimate Partner Violence-Related Brain Injury: Unmasking and Addressing the Gaps.

Intimate partner violence (IPV) is a significant, global public health concern. Women, individuals with historically underrepresented identities, and disabilities are at high risk for IPV and tend to experience severe injuries. There has been growing concern about the risk of exposure to IPV-related head trauma, resulting in IPV-related brain injury (IPV-BI), and its health consequences. Past work suggests that a significant proportion of women exposed to IPV experience IPV-BI, likely representing a distinct phenotype compared with BI of other etiologies. An IPV-BI often co-occurs with psychological trauma and mental health complaints, leading to unique issues related to identifying, prognosticating, and managing IPV-BI outcomes. The goal of this review is to identify important gaps in research and clinical practice in IPV-BI and suggest potential solutions to address them. We summarize IPV research in five key priority areas: (1) unique considerations for IPV-BI study design; (2) understanding non-fatal strangulation as a form of BI; (3) identifying objective biomarkers of IPV-BI; (4) consideration of the chronicity, cumulative and late effects of IPV-BI; and (5) BI as a risk factor for IPV engagement. Our review concludes with a call to action to help investigators develop ecologically valid research studies addressing the identified clinical-research knowledge gaps and strategies to improve care in individuals exposed to IPV-BI. By reducing the current gaps and answering these calls to action, we will approach IPV-BI in a trauma-informed manner, ultimately improving outcomes and quality of life for those impacted by IPV-BI.

Structural and functional changes of the cingulate gyrus following traumatic brain injury: relation to attention and executive skills.

Impairments of attention and executive functions are common sequelae of traumatic brain injury (TBI). The anterior cingulate is implicated in conflict-related task performance, such as the Stroop, and is susceptible to TBI-related injury due to its frontal location and proximity to the rough surface of the falx cerebri. We investigated the relationship between cingulate cortex volume and performance on tasks of selective attention and cognitive flexibility (single-trial Stroop and Auditory Consonant Trigrams [ACT]). Participants consisted of 12 adults with severe TBI and 18 controls. T1-weighted volumetric MRI data were analyzed using automated cortical reconstruction, segmentation, parcellation, and volume measurement. Cortical volume reductions were prominent bilaterally in frontal, temporal, and inferior parietal regions.Specific regional reduction of the cingulate cortex was observed only for cortical volume of right caudal anterior cingulate(cACC). The TBI group performed significantly worse than control participants on the Stroop and ACT tasks. Findings suggest that atrophy of the right cACC may contribute to reduced performance on executive function tasks, such as the Stroop and ACT, although this is likely but one node of an extensive brain network involved in these cognitive processes.

How functional connectivity between emotion regulation structures can be disrupted: preliminary evidence from adolescents with moderate to severe traumatic brain injury.

Outcome of moderate to severe traumatic brain injury (TBI) includes impaired emotion regulation. Emotion regulation has been associated with amygdala and rostral anterior cingulate (rACC). However, functional connectivity between the two structures after injury has not been reported. A preliminary examination of functional connectivity of rACC and right amygdala was conducted in adolescents 2 to 3 years after moderate to severe TBI and in typically developing (TD)control adolescents, with the hypothesis that the TBI adolescents would demonstrate altered functional connectivity in the two regions. Functional connectivity was determined by correlating fluctuations in the blood oxygen level dependent(BOLD) signal of the rACC and right amygdala with that of other brain regions. In the TBI adolescents, the rACC was found to be significantly less functionally connected to medial prefrontal cortices and to right temporal regions near the amygdala (height threshold T = 2.5, cluster level p < .05, FDR corrected), while the right amygdala showed a trend in reduced functional connectivity with the rACC (height threshold T = 2.5, cluster level p = .06, FDR corrected). Data suggest disrupted functional connectivity in emotion regulation regions. Limitations include small sample sizes. Studies with larger sample sizes are necessary to characterize the persistent neural damage resulting from moderate to severe TBI during development.

Challenges and opportunities for harmonization of cross-cultural neuropsychological data.

OBJECTIVE: In this position article, we highlight the importance of considering cultural and linguistic variables that influence neuropsychological test performance and the possible moderating impact on our understanding of brain/behavior relationships. Increasingly, neuropsychologists are realizing that cultural and language differences between countries, regions, and ethnic groups influence neuropsychological outcomes, as test scores may not have the same interpretative meaning across cultures. Furthermore, attempts to apply the same norms across diverse populations without accounting for culture and language variations will result in detrimental ethical dilemmas, such as misdiagnosis of clinical conditions and inaccurate interpretations of research outcomes. Given the lack of normative data for ethnically and linguistically diverse communities, it is often challenging to merge data across diverse populations to investigate research questions of global significance. Methodological Considerations: We highlight some of the inherent challenges, limitations, and opportunities for efforts to harmonize cross-cultural neuropsychological data. We also explore some of the cultural factors that should be considered when attempting to harmonize cross-cultural neuropsychological data, sources of variance that should be accounted for in data analyses, and the need to identify evaluative criteria for interpreting data outcomes of cross-cultural harmonization approaches. CONCLUSION: In the future, it will be important to further solidify principles for aggregating data across diverse cultural and linguistic cohorts, validate whether assumptions are being satisfied regarding the relationship between neuropsychological measures and the brain and/or behavior of individuals from diverse cultural and linguistic backgrounds, as well as methods for evaluating relative successful validation for data harmonization efforts. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Regional Cortical Thickness Correlates of Intellectual Abilities Differ in Children With Traumatic Brain Injury Versus Those With Orthopedic Injury in the Chronic Post-Injury Phase.

A decline in intellectual functioning (intelligence quotient [IQ]) is often observed following more severe forms of traumatic brain injury (TBI) and is a useful index for long-term outcome. Identifying brain correlates of IQ can serve to inform developmental trajectories of behavior in this population. Using magnetic resonance imaging (MRI), we examined the relationship between intellectual abilities and patterns of cortical thickness in children with a history of TBI or with orthopedic injury (OI) in the chronic phase of injury recovery. Participants were 47 children with OI and 58 children with TBI, with TBI severity ranging from complicated-mild to severe. Ages ranged from 8 to 14 years old, with an average age of 10.47 years, and an injury-to-test range of ∼1-5 years. The groups did not differ in age or sex. The intellectual ability estimate (full-scale [FS]IQ-2) was derived from a two-form (Vocabulary and Matrix Reasoning subtests) Wechsler Abbreviated Scale of Intelligence (WASI). MRI data were processed using the FreeSurfer toolkit and harmonized across data collection sites using neuroComBat procedures, while holding demographic features (i.e., sex, socioeconomic status [SES]), TBI status, and FSIQ-2 constant. Separate general linear models per group (TBI and OI) and a single interaction model with all participants were conducted with all significant results withstanding correction for multiple comparisons via permutation testing. Intellectual ability was higher (p < 0.001) in the OI group (FSIQ-2 = 110.81) than in the TBI group (FSIQ-2 = 99.81). In children with OI, bi-hemispheric regions, including the right pre-central gyrus and precuneus and bilateral inferior temporal and left occipital areas were related to IQ, such that higher IQ was associated with thicker cortex in these regions. In contrast, only cortical thickness in the right pre-central gyrus and bilateral cuneus positively related to IQ in children with TBI. Significant interaction effects were found in the bilateral temporal, parietal, and occipital lobes and left frontal regions, indicating that the relationship between IQ and cortical thickness differed between groups in these regions. Changes in cortical associations with IQ after TBI may reflect direct injury effects and/or adaptation in cortical structure and intellectual functioning, particularly in the bilateral posterior parietal and inferior temporal regions. This suggests that the substrates of intellectual ability are particularly susceptible to acquired injury in the integrative association cortex. Longitudinal work is needed to account for normal developmental changes and to investigate how cortical thickness and intellectual functioning and their association change over time following TBI. Improved understanding of how TBI-related cortical thickness alterations relate to cognitive outcome could lead to improved predictions of outcome following brain injury.

Diffusion tensor imaging and volumetric analysis of the ventral striatum in adults with traumatic brain injury.

OBJECTIVES: The aim was to determine if there are changes in the integrity and volume of the ventral striatum following severe traumatic brain injury (TBI) and if these changes relate to executive functioning. METHODS: This study recruited 14 participants with severe TBI (mean age: 22 years) and 15 demographically-matched controls. All participants underwent magnetic resonance imaging with diffusion tensor imaging (DTI) and volumetric analysis at 6 months post-injury. Participants with TBI underwent neuropsychological testing and the relation between imaging data and cognitive performance was examined. RESULTS: Differences in DTI parameters (fractional anisotropy (FA) and apparent diffusion coefficient (ADC)) were found between participants with TBI and controls. Correlations between right and left ventral striatum ADC and the executive functioning factor of the Neurobehavioural Rating Scale-Revised (NRS-R) were found. Correlations between right ventral striatum FA and the Controlled Oral Word Association Test, Trails Making Test Part B (TMT-B) time and NRS-R executive functioning factor were also found. Volumetric analysis showed a difference only in left nucleus accumbens between TBI and control groups. CONCLUSIONS: The integrity of the ventral striatum is affected following severe TBI. Decreases in executive functioning are related to damage to the ventral striatum and its associated structures.

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.

Challenges and opportunities for neuroimaging in young patients with traumatic brain injury: a coordinated effort towards advancing discovery from the ENIGMA pediatric moderate/severe TBI group.

Traumatic brain injury (TBI) is a major cause of death and disability in children in both developed and developing nations. Children and adolescents suffer from TBI at a higher rate than the general population, and specific developmental issues require a unique context since findings from adult research do not necessarily directly translate to children. Findings in pediatric cohorts tend to lag behind those in adult samples. This may be due, in part, both to the smaller number of investigators engaged in research with this population and may also be related to changes in safety laws and clinical practice that have altered length of hospital stays, treatment, and access to this population. The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Pediatric Moderate/Severe TBI (msTBI) group aims to advance research in this area through global collaborative meta-analysis of neuroimaging data. In this paper, we discuss important challenges in pediatric TBI research and opportunities that we believe the ENIGMA Pediatric msTBI group can provide to address them. With the paucity of research studies examining neuroimaging biomarkers in pediatric patients with TBI and the challenges of recruiting large numbers of participants, collaborating to improve statistical power and to address technical challenges like lesions will significantly advance the field. We conclude with recommendations for future research in this field of study.

A global collaboration to study intimate partner violence-related head trauma: The ENIGMA consortium IPV working group.

Intimate partner violence includes psychological aggression, physical violence, sexual violence, and stalking from a current or former intimate partner. Past research suggests that exposure to intimate partner violence can impact cognitive and psychological functioning, as well as neurological outcomes. These seem to be compounded in those who suffer a brain injury as a result of trauma to the head, neck or body due to physical and/or sexual violence. However, our understanding of the neurobehavioral and neurobiological effects of head trauma in this population is limited due to factors including difficulty in accessing/recruiting participants, heterogeneity of samples, and premorbid and comorbid factors that impact outcomes. Thus, the goal of the Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium Intimate Partner Violence Working Group is to develop a global collaboration that includes researchers, clinicians, and other key community stakeholders. Participation in the working group can include collecting harmonized data, providing data for meta- and mega-analysis across sites, or stakeholder insight on key clinical research questions, promoting safety, participant recruitment and referral to support services. Further, to facilitate the mega-analysis of data across sites within the working group, we provide suggestions for behavioral surveys, cognitive tests, neuroimaging parameters, and genetics that could be used by investigators in the early stages of study design. We anticipate that the harmonization of measures across sites within the working group prior to data collection could increase the statistical power in characterizing how intimate partner violence-related head trauma impacts long-term physical, cognitive, and psychological health.

The ENIGMA sports injury working group:- an international collaboration to further our understanding of sport-related brain injury.

Sport-related brain injury is very common, and the potential long-term effects include a wide range of neurological and psychiatric symptoms, and potentially neurodegeneration. Around the globe, researchers are conducting neuroimaging studies on primarily homogenous samples of athletes. However, neuroimaging studies are expensive and time consuming, and thus current findings from studies of sport-related brain injury are often limited by small sample sizes. Further, current studies apply a variety of neuroimaging techniques and analysis tools which limit comparability among studies. The ENIGMA Sports Injury working group aims to provide a platform for data sharing and collaborative data analysis thereby leveraging existing data and expertise. By harmonizing data from a large number of studies from around the globe, we will work towards reproducibility of previously published findings and towards addressing important research questions with regard to diagnosis, prognosis, and efficacy of treatment for sport-related brain injury. Moreover, the ENIGMA Sports Injury working group is committed to providing recommendations for future prospective data acquisition to enhance data quality and scientific rigor.

White Matter Disruption in Pediatric Traumatic Brain Injury: Results from ENIGMA Pediatric Moderate to Severe Traumatic Brain Injury.

OBJECTIVE: Our study addressed aims: (1) test the hypothesis that moderate-severe TBI in pediatric patients is associated with widespread white matter (WM) disruption; (2) test the hypothesis that age and sex impact WM organization after injury; and (3) examine associations between WM organization and neurobehavioral outcomes. METHODS: Data from ten previously enrolled, existing cohorts recruited from local hospitals and clinics were shared with the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Pediatric msTBI working group. We conducted a coordinated analysis of diffusion MRI (dMRI) data using the ENIGMA dMRI processing pipeline. RESULTS: Five hundred and seven children and adolescents (244 with complicated mild to severe TBI [msTBI] and 263 controls) were included. Patients were clustered into three post-injury intervals: acute/subacute - <2 months, post-acute - 2-6 months, chronic - 6+ months. Outcomes were dMRI metrics and post-injury behavioral problems as indexed by the Child Behavior Checklist (CBCL). Our analyses revealed altered WM diffusion metrics across multiple tracts and all post-injury intervals (effect sizes ranging between d=-0.5 to -1.3). Injury severity is a significant contributor to the extent of WM alterations but explained less variance in dMRI measures with increasing time post-injury. We observed a sex-by-group interaction: females with TBI had significantly lower fractional anisotropy in the uncinate fasciculus than controls (𝞫=0.043), which coincided with more parent-reported behavioral problems (𝞫=-0.0027). CONCLUSIONS: WM disruption after msTBI is widespread, persistent, and influenced by demographic and clinical variables. Future work will test techniques for harmonizing neurocognitive data, enabling more advanced analyses to identify symptom clusters and clinically-meaningful patient subtypes.

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.

Longitudinal changes in the corpus callosum following pediatric traumatic brain injury.

BACKGROUND: Atrophy of the corpus callosum (CC) is a documented consequence of moderate-to-severe traumatic brain injury (TBI), which has been expressed as volume loss using quantitative magnetic resonance imaging (MRI). Other advanced imaging modalities such as diffusion tensor imaging (DTI) have also detected white matter microstructural alteration following TBI in the CC. The manner and degree to which macrostructural changes such as volume and microstructural changes develop over time following pediatric TBI, and their relation to a measure of processing speed is the focus of this longitudinal investigation. As such, DTI and volumetric changes in the CC in participants with TBI and a comparison group at approximately 3 and 18 months after injury as well as their relation to processing speed were determined. METHODS: Forty-eight children and adolescents aged 7-17 years who sustained either complicated mild or moderate-to-severe TBI (n = 23) or orthopedic injury (OI; n = 25) were studied. The participants underwent brain MRI and were administered the Eriksen flanker task at both time points. RESULTS: At 3 months after injury, there were significant group differences in DTI metrics in the total CC and its subregions (genu/anterior, body/central and splenium/posterior), with the TBI group demonstrating significantly lower fractional anisotropy (FA) and a higher apparent diffusion coefficient (ADC) in comparison to the OI group. These group differences were also present at 18 months after injury in all CC subregions, with lower FA and a higher ADC in the TBI group. In terms of longitudinal changes in DTI, despite the group difference in mean FA, both groups generally demonstrated a modest increase in FA over time though this increase was only significant in the splenium/posterior subregion. Interestingly, the TBI group also generally demonstrated ADC increases from 3 to 18 months though the OI group demonstrated ADC decreases over time. Volumetrically, the group differences at 3 months were marginal for the midanterior and body/central subregions and total CC. However, by 18 months, the TBI group demonstrated a significantly decreased volume in all subregions except the splenium/posterior area relative to the OI group. Unlike the OI group, which showed a significant volume increase in subregions of the CC over time, the TBI group demonstrated a significant and consistent volume decrease. Performance on a measure of processing speed did not differentiate the groups at either visit, and only the OI group showed significantly improved performance over time. Processing speed was related to FA in the splenium/posterior and total CC only in the TBI group on both occasions, with a stronger relation at 18 months. CONCLUSION: In response to TBI, macrostructural volume loss in the CC occurred over time; yet, at the microstructural level, DTI demonstrated both indicators of continued maturation and development even in the damaged CC, as well as evidence of potential degenerative change. Unlike volumetrics, which likely reflects the degree of overall neuronal loss and axonal damage, DTI may reflect some aspects of postinjury maturation and adaptation in white matter following TBI. Multimodality imaging studies may be important to further understand the long-term consequences of pediatric TBI.

Age-related regional network of magnetic resonance imaging gray matter in the rhesus macaque.

Human structural neuroimaging studies have supported the preferential effects of healthy aging on frontal cortex, but reductions in other brain regions have also been observed. We investigated the regional network pattern of gray matter using magnetic resonance imaging (MRI) in young adult and old rhesus macaques (RMs) to evaluate age effects throughout the brain in a nonhuman primate model of healthy aging in which the full complement of Alzheimer's disease (AD) pathology does not occur. Volumetric T1 MRI scans were spatially normalized and segmented for gray matter using statistical parametric mapping (SPM2) voxel-based morphometry. Multivariate network analysis using the scaled subprofile model identified a linear combination of two gray matter patterns that distinguished the young from old RMs. The combined pattern included reductions in bilateral dorsolateral and ventrolateral prefrontal and orbitofrontal and superior temporal sulcal regions with areas of relative preservation in vicinities of the cerebellum, globus pallidus, visual cortex, and parietal cortex in old compared with young RMs. Higher expression of this age-related gray matter pattern was associated with poorer performance in working memory. In the RM model of healthy aging, the major regionally distributed effects of advanced age on the brain involve reductions in prefrontal regions and in the vicinity of the superior temporal sulcus. The age-related differences in gray matter reflect the effects of healthy aging that cannot be attributed to AD pathology, providing support for the targeted effects of aging on the integrity of frontal lobe regions and selective temporal lobe areas and their associated cognitive functions.