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Meier T.B.,The Mind Research Network Lovelace Biomedical and Environmental Research Institute | Bellgowan P.S.,University of Tulsa | Singh R.,Laureate Institute for Brain Research | Kuplicki R.,Laureate Institute for Brain Research | And 2 more authors.
JAMA neurology | Year: 2015

IMPORTANCE: Animal models suggest that reduced cerebral blood flow (CBF) is one of the most enduring physiological deficits following concussion. Despite this, longitudinal studies documenting serial changes in regional CBF following human concussion have yet to be performed.OBJECTIVE: To longitudinally assess the recovery of CBF in a carefully selected sample of collegiate athletes and compare time course of CBF recovery with that of cognitive and behavioral symptoms.DESIGN, SETTING, AND PARTICIPANTS: A cohort of collegiate football athletes (N = 44) participated in this mixed longitudinal and cross-sectional study at a private research institute specializing in neuroimaging between March 2012 and December 2013. Serial imaging occurred approximately 1 day, 1 week, and 1 month postconcussion for a subset of participants (n = 17). All athletes reported no premorbid mood disorders, anxiety disorders, substance abuse, or alcohol abuse.MAIN OUTCOMES AND MEASURES: Arterial spin labeling magnetic resonance imaging was used to collect voxelwise relative CBF at each visit. Neuropsychiatric evaluations and a brief cognitive screen were also performed at all 3 points. Clinicians trained in sports medicine provided an independent measure of real-world concussion outcome (ie, number of days withheld from competition).RESULTS: The results indicated both cognitive (simple reaction time) and neuropsychiatric symptoms at 1 day postinjury that resolved at either 1 week (cognitive; P < .005) or 1 month (neuropsychiatric; P < .005) postinjury. Imaging data suggested both cross-sectional (ie, healthy vs concussed athletes; P < .05) and longitudinal (1 day and 1 week vs 1 month postinjury; P < .001) evidence of CBF recovery in the right insular and superior temporal cortex. Importantly, CBF in the dorsal midinsular cortex was both decreased at 1 month postconcussion in slower-to-recover athletes (t11 = 3.45; P = .005) and was inversely related to the magnitude of initial psychiatric symptoms (Hamilton Depression Scale: r = -0.64, P = .02; Hamilton Anxiety Scale: r = -0.56, P = .046), suggesting a potential prognostic indication for CBF as a biomarker.CONCLUSIONS AND RELEVANCE: To our knowledge, these results provide the first prospective evidence of reduced CBF in human concussion and subsequent recovery. The resolution of CBF abnormalities closely mirrors previous reports from the animal literature and show real-world validity for predicting outcome following concussion. Source


Mayer A.R.,The Mind Research Network Lovelace Biomedical and Environmental Research Institute
The Journal of neuroscience : the official journal of the Society for Neuroscience | Year: 2012

Pediatric mild traumatic brain injury (pmTBI) is the most prevalent neurological insult in children and is associated with both acute and chronic neurobehavioral sequelae. However, little is known about underlying pathophysiology and how injuries change as a function of recovery. Fractional anisotropy, axial diffusivity, and radial diffusivity were examined in 15 semi-acute pmTBI patients and 15 well-matched controls, with a subset of participants returning for a second visit. A novel analytic strategy was applied to capture spatially heterogeneous white matter injuries (lesions) in addition to standard analyses. Evidence of cognitive dysfunction after pmTBI was observed in the domains of attention (p = 0.02, d = -0.92) and processing speed (p = 0.05, d = -0.73) semi-acutely. Region of interest (ROI) and voxelwise analyses indicated increased anisotropic diffusion for pmTBI patients, with an elevated number of clusters with high anisotropy. Metrics of increased anisotropy were able to objectively classify pmTBI from healthy controls at 90% accuracy but were not associated with neuropsychological deficits. Little evidence of recovery in white matter abnormalities was observed over a 4-month interval in returning patients, indicating that physiological recovery may lag behind subjective reports of normality. Increased anisotropic diffusion has been previously linked with cytotoxic edema after TBI, and the magnitude and duration of these abnormalities appear to be greater in pediatric patients. Current findings suggest that developing white matter may be more susceptible to initial mechanical injury forces and that anisotropic diffusion provides an objective biomarker of pmTBI. Source


Mayer A.R.,The Mind Research Network Lovelace Biomedical and Environmental Research Institute | Mayer A.R.,University of New Mexico | Wilcox C.E.,University of New Mexico | Dodd A.B.,The Mind Research Network Lovelace Biomedical and Environmental Research Institute | And 4 more authors.
American Journal of Drug and Alcohol Abuse | Year: 2016

ABSTRACT: Background: Attentional bias (i.e., differences in reaction time between drug and neutral cues) has been associated with a variety of drug-use behaviors (e.g., craving, abstinence). Reduction of bias may ultimately reduce use. Objective: The current study examined whether attentional bias modification therapy (ABMT) reduced the frequency of drug use behaviors in individuals with cocaine use disorder (CUD). Method: Participants (n = 37) were randomly assigned to ABMT or control therapy, which systematically varied how frequently probes replaced neutral (ABMT = 100%; control therapy = 50%) relative to drug stimuli. Each intervention included 5 training sessions comprising a total of 2640 trials over 4 weeks. Clinical assessments occurred at baseline, post-intervention, 2 weeks and 3 months posttreatment. Results: There were no baseline differences between groups on drug-use behaviors or other clinical measures. Contrary to predictions, both groups exhibited slower rather than faster reaction times for cocaine stimuli (p = 0.005) at baseline, with no relationship between bias and baseline measures of drug-use behavior. Conclusions: ABMT was not more effective than our control therapy at reducing attentional bias, reducing craving or changing other drug use behaviors. Current results suggest additional replication studies are needed to assess ABMT’s efficacy in reducing drug-use behaviors in CUD. © 2016 Taylor & Francis. Source


Mayer A.R.,The Mind Research Network Lovelace Biomedical and Environmental Research Institute | Mayer A.R.,University of New Mexico | Bellgowan P.S.F.,The Laureate Institute for Brain Research | Bellgowan P.S.F.,University of Tulsa | Hanlon F.M.,The Mind Research Network Lovelace Biomedical and Environmental Research Institute
Neuroscience and Biobehavioral Reviews | Year: 2015

Functional magnetic resonance imaging (fMRI) offers great promise for elucidating the neuropathology associated with a single or repetitive mild traumatic brain injury (mTBI). The current review discusses the physiological underpinnings of the blood-oxygen level dependent response and how trauma affects the signal. Methodological challenges associated with fMRI data analyses are considered next, followed by a review of current mTBI findings. The majority of evoked studies have examined working memory and attentional functioning, with results suggesting a complex relationship between cognitive load/attentional demand and neuronal activation. Researchers have more recently investigated how brain trauma affects functional connectivity, and the benefits/drawbacks of evoked and functional connectivity studies are also discussed. The review concludes by discussing the major clinical challenges associated with fMRI studies of brain-injured patients, including patient heterogeneity and variations in scan-time post-injury. We conclude that the fMRI signal represents a complex filter through which researchers can measure the physiological correlates of concussive symptoms, an important goal for the burgeoning field of mTBI research. © 2014 Elsevier Ltd. Source


Mayer A.R.,The Mind Research Network Lovelace Biomedical and Environmental Research Institute | Mayer A.R.,University of New Mexico | Ling J.M.,The Mind Research Network Lovelace Biomedical and Environmental Research Institute | Dodd A.B.,The Mind Research Network Lovelace Biomedical and Environmental Research Institute | And 4 more authors.
Brain Imaging and Behavior | Year: 2016

Although diffusion magnetic resonance imaging (dMRI) has been widely used to characterize the effects of repetitive mild traumatic brain injury (rmTBI), to date no studies have investigated how novel geometric models of microstructure relate to more typical diffusion tensor imaging (DTI) sequences. Moreover, few studies have evaluated the sensitivity of different registration pipelines (non-linear, linear and tract-based spatial statistics) for detecting dMRI abnormalities in clinical populations. Results from single-subject analyses in healthy controls (HC) indicated a strong negative relationship between fractional anisotropy (FA) and orientation dispersion index (ODI) in both white and gray matter. Equally important, only moderate relationships existed between all other estimates of free/intracellular water volume fractions and more traditional DTI metrics (FA, mean, axial and radial diffusivity). These findings suggest that geometric measures provide differential information about the cellular microstructure relative to traditional DTI measures. Results also suggest greater sensitivity for non-linear registration pipelines that maximize the anatomical information available in T1-weighted images. Clinically, rmTBI resulted in a pattern of decreased FA and increased ODI, largely overlapping in space, in conjunction with increased intracellular and free water fractions, highlighting the potential role of edema following repeated head trauma. In summary, current results suggest that geometric models of diffusion can provide relatively unique information regarding potential mechanisms of pathology that contribute to long-term neurological damage. © 2016 Springer Science+Business Media New York Source

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