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.

Structural neuroimaging in mild traumatic brain injury: A chronic effects of neurotrauma consortium study.

OBJECTIVES: The chronic effects of neurotrauma consortium (CENC) observational study is a multisite investigation designed to examine the long-term longitudinal effects of mild traumatic brain injury (mTBI). All participants in this initial CENC cohort had a history of deployment in Operation Enduring Freedom (Afghanistan), Operation Iraqi Freedom (Iraq), and/or their follow-on conflicts (Operation Freedom's Sentinel). All participants undergo extensive medical, neuropsychological, and neuroimaging assessments and either meet criteria for any lifetime mTBI or not. These assessments are integrated into six CENC core studies-Biorepository, Biostatistics, Data and Study Management, Neuroimaging, and Neuropathology. METHODS: The current study outlines the quantitative neuroimaging methods managed by the Neuroimaging Core using FreeSurfer automated software for image quantification. RESULTS: At this writing, 319 participants from the CENC observational study have completed all baseline assessments including the imaging protocol and tertiary data quality assurance procedures. CONCLUSIONS/DISCUSSION: The preliminary findings of this initial cohort are reported to describe how the Neuroimaging Core manages neuroimaging quantification for CENC studies.

Cortical thickness in pediatric mild traumatic brain injury including sports-related concussion.

This investigation explored whether differences in cortical thickness could be detected in children who sustained a mild traumatic brain injury (mTBI) compared to those with orthopedic injury (OI) and whether cortical thickness related parental reporting of symptoms. To achieve this objective, FreeSurfer®-based cortical thickness measures were obtained in 330 children, 8 to 15 years of age, with either a history of mTBI or OI. Imaging was performed in all participants with the same 3 Tesla MRI scanner at six-months post-injury, where a parent-rated Post-Concussion Symptom Inventory (PCSI) was also obtained. Robust age-mediated reductions in cortical thickness were observed, but no consistent group-based differences between the mTBI and OI groups were observed. Also, the relation between mechanism of injury (i.e., sports-related, recreational, fall, motor vehicle accident or other) and cortical thickness was examined. Injuries associated with any type of abuse were excluded and children with OI could not have experienced a MVA. Mechanism of injury did not differentially relate to cortical thickness, although in the fall group, parental rating using the PCSI showed increased symptom reporting to be associated with reduced cortical thickness in the left interior frontal, temporal pole and lateral temporal lobe as well as in the right temporal pole. Results from these preliminary findings are discussed in terms of injury variables and developmental factors associated with mTBI in childhood.

Relationship between brain stem volume and aggression in children diagnosed with autism spectrum disorder.

BACKGROUND: Aggressive behaviors are common in individuals diagnosed with autism spectrum disorder (ASD) and may be phenotypic indicators of different subtypes within ASD. In current research literature for non-ASD samples, aggression has been linked to several brain structures associated with emotion and behavioral control. However, few if any studies exist investigating brain volume differences in individuals with ASD who have comorbid aggression as indicated by standardized diagnostic and behavioral measures. METHOD: We examined neuroimaging data from individuals rigorously diagnosed with ASD versus typically developing (TD) controls. We began with data from brain volume regions of interest (ROI) taken from previous literature on aggression including the brainstem, amygdala, orbitofrontal cortex, anterior cingulate cortex, and dorsolateral prefrontal cortex. We defined aggression status using the Irritability subscale of the Aberrant Behavior Checklist and used lasso logistic regression to select among these predictor variables. Brainstem volume was the only variable shown to be a predictor of aggression status. RESULTS: We found that smaller brainstem volumes are associated with higher odds of being in the high aggression group. CONCLUSIONS: Understanding brain differences in individuals with ASD who engage in aggressive behavior from those with ASD who do not can inform treatment approaches. Future research should investigate brainstem structure and function in ASD to identify possible mechanisms related to arousal and aggression.

Reaffirmed limitations of meta-analytic methods in the study of mild traumatic brain injury: a response to Rohling et al.

In 2009 Pertab, James, and Bigler published a critique of two prior meta-analyses by Binder, Rohling, and Larrabee (1997) and Frencham, Fox, and Maybery (2005) that showed small effect size difference at least 3 months post-injury in individuals who had sustained a mild traumatic brain injury (mTBI). The Binder et al. and Frencham et al. meta-analyses have been widely cited as showing no lasting effect of mTBI. In their critique Pertab et al. (2009) point out many limitations of these two prior meta-analyses, demonstrating that depending on how inclusion/exclusion criteria were defined different meta-analytic findings occur, some supporting the persistence of neuropsychological impairments beyond 3 months. Rohling et al. (2011) have now critiqued Pertab et al. (2009). Herein we respond to the Rolling et al. (2011) critique reaffirming the original findings of Pertab et al. (2009), providing additional details concerning the flaws in prior meta-analytic mTBI studies and the effects on neuropsychological performance.

Volumetric and voxel-based morphometry findings in autism subjects with and without macrocephaly.

This study sought to replicate Herbert et al. (2003a), which found increased overall white matter (WM) volume in subjects with autism, even after controlling for head size differences. To avoid the possibility that greater WM volume in autism is merely an epiphenomena of macrocephaly overrepresentation associated with the disorder, the current study included control subjects with benign macrocephaly. The control group also included subjects with a reading disability to insure cognitive heterogeneity. WM volume in autism was significantly larger, even when controlling for brain volume, rate of macrocephaly, and other demographic variables. Autism and controls differed little on whole-brain WM voxel-based morphometry (VBM) analyses suggesting that the overall increase in WM volume was non-localized. Autism subjects exhibited a differential pattern of IQ relationships with brain volumetry findings from controls. Current theories of brain overgrowth and their importance in the development of autism are discussed in the context of these findings.