Adolescent Engagement in Dangerous Behaviors Is Associated with Increased White Matter Maturity of Frontal Cortex

Background: Myelination of white matter in the brain continues throughout adolescence and early adulthood. This cortical immaturity has been suggested as a potential cause of dangerous and impulsive behaviors in adolescence. Methodology/Principal Findings: We tested this hypothesis in a group of healthy adolescents, age 12–18 (N = 91), who underwent diffusion tensor imaging (DTI) to delineate cortical white matter tracts. As a measure of real-world risk taking, participants completed the Adolescent Risk Questionnaire (ARQ) which measures engagement in dangerous activities. After adjusting for age-related changes in both DTI and ARQ, engagement in dangerous behaviors was found to be positively correlated with fractional anisotropy and negatively correlated with transverse diffusivity in frontal white matter tracts, indicative of increased myelination and/or density of fibers (ages 14–18, N = 60). Conclusions/Significance: The direction of correlation suggests that rather than having immature cortices, adolescents who engage in dangerous activities have frontal white matter tracts that are more adult in form than their more conservative peers

Effects of traumatic brain injury and posttraumatic stress disorder on Alzheimer's disease in veterans, using the Alzheimer's Disease Neuroimaging Initiative

Both traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) are common problems resulting from military service, and both have been associated with increased risk of cognitive decline and dementia resulting from Alzheimer's disease (AD) or other causes. This study aims to use imaging techniques and biomarker analysis to determine whether traumatic brain injury (TBI) and/or PTSD resulting from combat or other traumas increase the risk for AD and decrease cognitive reserve in Veteran subjects, after accounting for age. Using military and Department of Veterans Affairs records, 65 Vietnam War veterans with a history of moderate or severe TBI with or without PTSD, 65 with ongoing PTSD without TBI, and 65 control subjects are being enrolled in this study at 19 sites. The study aims to select subject groups that are comparable in age, gender, ethnicity, and education. Subjects with mild cognitive impairment (MCI) or dementia are being excluded. However, a new study just beginning, and similar in size, will study subjects with TBI, subjects with PTSD, and control subjects with MCI. Baseline measurements of cognition, function, blood, and cerebrospinal fluid biomarkers; magnetic resonance images (structural, diffusion tensor, and resting state blood-level oxygen dependent (BOLD) functional magnetic resonance imaging); and amyloid positron emission tomographic (PET) images with florbetapir are being obtained. One-year follow-up measurements will be collected for most of the baseline procedures, with the exception of the lumbar puncture, the PET imaging, and apolipoprotein E genotyping. To date, 19 subjects with TBI only, 46 with PTSD only, and 15 with TBI and PTSD have been recruited and referred to 13 clinics to undergo the study protocol. It is expected that cohorts will be fully recruited by October 2014. This study is a first step toward the design and statistical powering of an AD prevention trial using at-risk veterans as subjects, and provides the basis for a larger, more comprehensive study of dementia risk factors in veterans

Microstructure Abnormalities in Adolescents with Internet Addiction Disorder

BACKGROUND: Recent studies suggest that internet addiction disorder (IAD) is associated with structural abnormalities in brain gray matter. However, few studies have investigated the effects of internet addiction on the microstructural integrity of major neuronal fiber pathways, and almost no studies have assessed the microstructural changes with the duration of internet addiction. METHODOLOGY/PRINCIPAL FINDINGS: We investigated the morphology of the brain in adolescents with IAD (N = 18) using an optimized voxel-based morphometry (VBM) technique, and studied the white matter fractional anisotropy (FA) changes using the diffusion tensor imaging (DTI) method, linking these brain structural measures to the duration of IAD. We provided evidences demonstrating the multiple structural changes of the brain in IAD subjects. VBM results indicated the decreased gray matter volume in the bilateral dorsolateral prefrontal cortex (DLPFC), the supplementary motor area (SMA), the orbitofrontal cortex (OFC), the cerebellum and the left rostral ACC (rACC). DTI analysis revealed the enhanced FA value of the left posterior limb of the internal capsule (PLIC) and reduced FA value in the white matter within the right parahippocampal gyrus (PHG). Gray matter volumes of the DLPFC, rACC, SMA, and white matter FA changes of the PLIC were significantly correlated with the duration of internet addiction in the adolescents with IAD. CONCLUSIONS: Our results suggested that long-term internet addiction would result in brain structural alterations, which probably contributed to chronic dysfunction in subjects with IAD. The current study may shed further light on the potential brain effects of IAD

Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after traumatic brain injury

<p>Abstract</p> <p>Background</p> <p>Traumatic brain injury initiates biochemical processes that lead to secondary neurodegeneration. Imaging studies suggest that tissue loss may continue for months or years after traumatic brain injury in association with chronic microglial activation. Recently we found that metabotropic glutamate receptor 5 (mGluR5) activation by (<it>RS</it>)-2-chloro-5-hydroxyphenylglycine (CHPG) decreases microglial activation and release of associated pro-inflammatory factors <it>in vitro</it>, which is mediated in part through inhibition of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Here we examined whether delayed CHPG administration reduces chronic neuroinflammation and associated neurodegeneration after experimental traumatic brain injury in mice.</p> <p>Methods</p> <p>One month after controlled cortical impact traumatic brain injury, C57Bl/6 mice were randomly assigned to treatment with single dose intracerebroventricular CHPG, vehicle or CHPG plus a selective mGluR5 antagonist, 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine. Lesion volume, white matter tract integrity and neurological recovery were assessed over the following three months.</p> <p>Results</p> <p>Traumatic brain injury resulted in mGluR5 expression in reactive microglia of the cortex and hippocampus at one month post-injury. Delayed CHPG treatment reduced expression of reactive microglia expressing NADPH oxidase subunits; decreased hippocampal neuronal loss; limited lesion progression, as measured by repeated T2-weighted magnetic resonance imaging (at one, two and three months) and white matter loss, as measured by high field <it>ex vivo </it>diffusion tensor imaging at four months; and significantly improved motor and cognitive recovery in comparison to the other treatment groups.</p> <p>Conclusion</p> <p>Markedly delayed, single dose treatment with CHPG significantly improves functional recovery and limits lesion progression after experimental traumatic brain injury, likely in part through actions at mGluR5 receptors that modulate neuroinflammation.</p

Physiological and histopathological responses following closed rotational head injury depend on direction of head motion

Rotational inertial forces are thought to be the underlying mechanism for most severe brain injuries. However, little is known about the effect of head rotation direction on injury outcomes, particularly in the pediatric population. Neonatal piglets were subjected to a single non-impact head rotation in the horizontal, coronal, or sagittal direction, and physiological and histopathological responses were observed. Sagittal rotation produced the longest duration of unconsciousness, highest incidence of apnea, and largest intracranial pressure increase, while coronal rotation produced little change, and horizontal rotation produced intermediate and variable derangements. Significant cerebral blood flow reductions were observed following sagittal but not coronal or horizontal injury compared to sham. Subarachnoid hemorrhage, ischemia, and brainstem pathology were observed in the sagittal and horizontal groups but not in a single coronal animal. Significant axonal injury occurred following both horizontal and sagittal rotations. For both groups, the distribution of injury was greater in the frontal and parietotemporal lobes than in the occipital lobes, frequently occurred in the absence of ischemia, and did not correlate with regional cerebral blood flow reductions. We postulate that these direction-dependent differences in injury outcomes are due to differences in tissue mechanical loading produced during head rotation

Adolescent Brain Development and the Risk for Alcohol and Other Drug Problems

Dynamic changes in neurochemistry, fiber architecture, and tissue composition occur in the adolescent brain. The course of these maturational processes is being charted with greater specificity, owing to advances in neuroimaging and indicate grey matter volume reductions and protracted development of white matter in regions known to support complex cognition and behavior. Though fronto-subcortical circuitry development is notable during adolescence, asynchronous maturation of prefrontal and limbic systems may render youth more vulnerable to risky behaviors such as substance use. Indeed, binge-pattern alcohol consumption and comorbid marijuana use are common among adolescents, and are associated with neural consequences. This review summarizes the unique characteristics of adolescent brain development, particularly aspects that predispose individuals to reward seeking and risky choices during this phase of life, and discusses the influence of substance use on neuromaturation. Together, findings in this arena underscore the importance of refined research and programming efforts in adolescent health and interventional needs

Valsalva maneuver unveils central baroreflex dysfunction with altered blood pressure control in persons with a history of mild traumatic brain injury

BACKGROUND: Patients with a history of mild TBI (post-mTBI-patients) have an unexplained increase in long-term mortality which might be related to central autonomic dysregulation (CAD). We investigated whether standardized baroreflex-loading, induced by a Valsalva maneuver (VM), unveils CAD in otherwise healthy post-mTBI-patients. METHODS: In 29 healthy persons (31.3 ± 12.2 years; 9 women) and 25 post-mTBI-patients (35.0 ± 13.2 years, 7 women, 4–98 months post-injury), we monitored respiration (RESP), RR-intervals (RRI) and systolic blood pressure (BP) at rest and during three VMs. At rest, we calculated parameters of total autonomic modulation [RRI-coefficient-of-variation (CV), RRI-standard-deviation (RRI-SD), RRI-total-powers], of sympathetic [RRI-low-frequency-powers (LF), BP-LF-powers] and parasympathetic modulation [square-root-of-mean-squared-differences-of-successive-RRIs (RMSSD), RRI-high-frequency-powers (HF)], the index of sympatho-vagal balance (RRI LF/HF-ratios), and baroreflex sensitivity (BRS). We calculated Valsalva-ratios (VR) and times from lowest to highest RRIs after strain (VR-time) as indices of parasympathetic activation, intervals from highest systolic BP-values after strain-release to the time when systolic BP had fallen by 90 % of the differences between peak-phase-IV-BP and baseline-BP (90 %-BP-normalization-times), and velocities of BP-normalization (90 %-BP-normalization-velocities) as indices of sympathetic withdrawal. We compared patient- and control-parameters before and during VM (Mann-Whitney-U-tests or t-tests; significance: P < 0.05). RESULTS: At rest, RRI-CVs, RRI-SDs, RRI-total-powers, RRI-LF-powers, BP-LF-powers, RRI-RMSSDs, RRI-HF-powers, and BRS were lower in patients than controls. During VMs, 90 %-BP-normalization-times were longer, and 90 %-BP-normalization-velocities were lower in patients than controls (P < 0.05). CONCLUSIONS: Reduced autonomic modulation at rest and delayed BP-decrease after VM-induced baroreflex-loading indicate subtle CAD with altered baroreflex adjustment to challenge. More severe autonomic challenge might trigger more prominent cardiovascular dysregulation and thus contribute to increased mortality risk in post-mTBI-patients