Proximal threats promote enhanced acquisition and persistence of reactive fear-learning circuits.

Physical proximity to a traumatic event increases the severity of accompanying stress symptoms, an effect that is reminiscent of evolutionarily configured fear responses based on threat imminence. Despite being widely adopted as a model system for stress and anxiety disorders, fear-conditioning research has not yet characterized how threat proximity impacts the mechanisms of fear acquisition and extinction in the human brain. We used three-dimensional (3D) virtual reality technology to manipulate the egocentric distance of conspecific threats while healthy adult participants navigated virtual worlds during functional magnetic resonance imaging (fMRI). Consistent with theoretical predictions, proximal threats enhanced fear acquisition by shifting conditioned learning from cognitive to reactive fear circuits in the brain and reducing amygdala-cortical connectivity during both fear acquisition and extinction. With an analysis of representational pattern similarity between the acquisition and extinction phases, we further demonstrate that proximal threats impaired extinction efficacy via persistent multivariate representations of conditioned learning in the cerebellum, which predicted susceptibility to later fear reinstatement. These results show that conditioned threats encountered in close proximity are more resistant to extinction learning and suggest that the canonical neural circuitry typically associated with fear learning requires additional consideration of a more reactive neural fear system to fully account for this effect.

Multivariate Patterns of Posterior Cortical Activity Differentiate Forms of Emotional Distancing.

Distancing is an effective tactic for emotion regulation, which can take several forms depending on the type(s) of psychological distance being manipulated to modify affect. We recently proposed a neurocognitive model of emotional distancing, but it is unknown how its specific forms are instantiated in the brain. Here, we presented healthy young adults (N = 34) with aversive pictures during functional magnetic resonance imaging to directly compare behavioral performance and brain activity across spatial, temporal, and objective forms of distancing. We found emotion regulation performance to be largely comparable across these forms. A conjunction analysis of activity associated with these forms yielded a high degree of overlap, encompassing regions of the default mode and frontoparietal networks as predicted by our model. A multivariate pattern classification further revealed distributed patches of posterior cortical activation that discriminated each form from one another. These findings not only confirm aspects of our overarching model but also elucidate a novel role for cortical regions in and around the parietal lobe in selectively supporting spatial, temporal, and social cognitive processes to distance oneself from an emotional encounter. These regions may provide new targets for brain-based interventions for emotion dysregulation.

Extinction learning alters the neural representation of conditioned fear.

Extinction learning is a primary means by which conditioned associations to threats are controlled and is a model system for emotion dysregulation in anxiety disorders. Recent work has called for new approaches to track extinction-related changes in conditioned stimulus (CS) representations. We applied a multivariate analysis to previously -collected functional magnetic resonance imaging data on extinction learning, in which healthy young adult participants (N = 43; 21 males, 22 females) encountered dynamic snake and spider CSs while passively navigating 3D virtual environments. We used representational similarity analysis to compare voxel-wise activation t-statistic maps for the shock-reinforced CS (CS+) from the late phase of fear acquisition to the early and late phases of extinction learning within subjects. These patterns became more dissimilar from early to late extinction in a priori regions of interest: subgenual and dorsal anterior cingulate gyrus, amygdala and hippocampus. A whole-brain searchlight analysis revealed similar findings in the insula, mid-cingulate cortex, ventrolateral prefrontal cortex, somatosensory cortex, cerebellum, and visual cortex. High state anxiety attenuated extinction-related changes to the CS+ patterning in the amygdala, which suggests an enduring threat representation. None of these effects generalized to an unreinforced control cue, nor were they evident in traditional univariate analyses. Our approach extends previous neuroimaging work by emphasizing how evoked neural patterns change from late acquisition through phases of extinction learning, including those in brain regions not traditionally implicated in animal models. Finally, the findings provide additional support for a role of the amygdala in anxiety-related persistence of conditioned fears.

Findings from Structural MR Imaging in Military Traumatic Brain Injury.

PURPOSE: To describe the initial neuroradiology findings in a cohort of military service members with primarily chronic mild traumatic brain injury (TBI) from blast by using an integrated magnetic resonance (MR) imaging protocol. MATERIALS AND METHODS: This study was approved by the Walter Reed National Military Medical Center institutional review board and is compliant with HIPAA guidelines. All participants were military service members or dependents recruited between August 2009 and August 2014. There were 834 participants with a history of TBI and 42 participants in a control group without TBI (not explicitly age- and sex-matched). MR examinations were performed at 3 T primarily with three-dimensional volume imaging at smaller than 1 mm(3) voxels for the structural portion of the examination. The structural portion of this examination, including T1-weighted, T2-weighted, before and after contrast agent administrtion T2 fluid attenuation inversion recovery, and susceptibility-weighted images, was evaluated by neuroradiologists by using a modified version of the neuroradiology TBI common data elements (CDEs). Incident odds ratios (ORs) between the TBI participants and a comparison group without TBI were calculated. RESULTS: The 834 participants were diagnosed with predominantly chronic (mean, 1381 days; median, 888 days after injury) and mild (92% [768 of 834]) TBI. Of these participants, 84.2% (688 of 817) reported one or more blast-related incident and 63.0% (515 of 817) reported loss of consciousness at the time of injury. The presence of white matter T2-weighted hyperintense areas was the most common pathologic finding, observed in 51.8% (432 of 834; OR, 1.75) of TBI participants. Cerebral microhemorrhages were observed in a small percentage of participants (7.2% [60 of 834]; OR, 6.64) and showed increased incidence with TBI severity (P < .001, moderate and severe vs mild). T2-weighted hyperintense areas and microhemorrhages did not collocate by visual inspection. Pituitary abnormalities were identified in a large proportion (29.0% [242 of 834]; OR, 16.8) of TBI participants. CONCLUSION: Blast-related injury and loss of consciousness is common in military TBI. Structural MR imaging demonstrates a high incidence of white matter T2-weighted hyperintense areas and pituitary abnormalities, with a low incidence of microhemorrhage in the chronic phase.

Postconcussional disorder and PTSD symptoms of military-related traumatic brain injury associated with compromised neurocircuitry.

Traumatic brain injury (TBI) is a common combat injury, often through explosive blast, and produces heterogeneous brain changes due to various mechanisms of injury. It is unclear whether the vulnerability of white matter differs between blast and impact injury, and the consequences of microstructural changes on neuropsychological function are poorly understood in military TBI patients. Diffusion tensor imaging (DTI) techniques were used to assess the neurocircuitry in 37 U.S. service members (29 mild, 7 moderate, 1 severe; 17 blast and 20 nonblast), who sustained a TBI while deployed, compared to 14 nondeployed, military controls. High-dimensional deformable registration of MRI diffusion tensor data was followed by fiber tracking and tract-specific analysis along with region-of-interest analysis. DTI results were examined in relation to post-concussion and post-traumatic stress disorder (PTSD) symptoms. The most prominent white matter microstructural injury for both blast and nonblast patients was in the frontal fibers within the fronto-striatal (corona radiata, internal capsule) and fronto-limbic circuits (fornix, cingulum), the fronto-parieto-occipital association fibers, in brainstem fibers, and in callosal fibers. Subcortical superior-inferiorly oriented tracts were more vulnerable to blast injury than nonblast injury, while direct impact force had more detrimental effects on anterior-posteriorly oriented tracts, which tended to cause heterogeneous left and right hemispheric asymmetries of white matter connectivity. The tractography using diffusion anisotropy deficits revealed the cortico-striatal-thalamic-cerebellar-cortical (CSTCC) networks, where increased post-concussion and PTSD symptoms were associated with low fractional anisotropy in the major nodes of compromised CSTCC neurocircuitry, and the consequences on cognitive function were explored as well.

A pilot study exploring the relationship between internists' self-reported sleepiness, performance on multiple-choice exam items and prefrontal cortex activity.

BACKGROUND: Studies of resident fatigue and performance have shown mixed results. However, research has not examined daytime sleepiness and performance among attending physicians. The purpose of this study was to explore the relationship between sleep, performance and prefrontal cortex (PFC) activity. We hypothesized that sleepiness scores would negatively correlate with multiple-choice question (MCQ) performance and would also correlate with PFC activity. METHODS: Board-certified physicians completed an Epworth Sleepiness Scale (ESS) and then answered MCQs from licensing examinations while in a functional Magnetic Resonance Imaging (fMRI) scanner. RESULTS: Seventeen board-certified internists completed the study. The mean number of correct responses was 18.5/32. The correlation between the ESS and MCQ score was -0.30, and higher ESS scores were negatively associated with statistically significant changes in medial PFC (mPFC) activity. CONCLUSIONS: Attending physicians who reported higher sleepiness scores performed worse on licensing exam questions. Notably, our cohort had normal to mild sleepiness scores. Moreover, higher sleepiness scores were negatively associated with changes in mPFC activity on fMRI, which is consistent with emerging work implicating the PFC in fatigue-related cognitive impairment. Our findings have implications regarding the impact of sleep on physician performance during examinations and potentially on their care of patients.

Perfusion deficits in patients with mild traumatic brain injury characterized by dynamic susceptibility contrast MRI.

Perfusion deficits in patients with mild traumatic brain injury (TBI) from a military population were characterized by dynamic susceptibility contrast perfusion imaging. Relative cerebral blood flow (rCBF) was calculated by a model-independent deconvolution approach from the tracer concentration curves following a bolus injection of gadolinium diethylenetriaminepentaacetate (Gd-DTPA) using both manually and automatically selected arterial input functions (AIFs). Linear regression analysis of the mean values of rCBF from selected regions of interest showed a very good agreement between the two approaches, with a regression coefficient of R = 0.88 and a slope of 0.88. The Bland-Altman plot also illustrated the good agreement between the two approaches, with a mean difference of 0.6 ± 12.4 mL/100 g/min. Voxelwise analysis of rCBF maps from both approaches demonstrated multiple clusters of decreased perfusion (p < 0.01) in the cerebellum, cuneus, cingulate and temporal gyrus in the group with mild TBI relative to the controls. MRI perfusion deficits in the cerebellum and anterior cingulate also correlated (p < 0.01) with neurocognitive results, including the mean reaction time in the Automated Neuropsychological Assessment Metrics and commission error and detection T-scores in the Continuous Performance Test, as well as neurobehavioral scores in the Post-traumatic Stress Disorder Checklist-Civilian Version. In conclusion, rCBF calculated using AIFs selected from an automated approach demonstrated a good agreement with the corresponding results using manually selected AIFs. Group analysis of patients with mild TBI from a military population demonstrated scattered perfusion deficits, which showed significant correlations with measures of verbal memory, speed of reaction time and self-report of stress symptoms.

Does the think-aloud protocol reflect thinking? Exploring functional neuroimaging differences with thinking (answering multiple choice questions) versus thinking aloud.

BACKGROUND: Whether the think-aloud protocol is a valid measure of thinking remains uncertain. Therefore, we used functional magnetic resonance imaging (fMRI) to investigate potential functional neuroanatomic differences between thinking (answering multiple-choice questions in real time) versus thinking aloud (on review of items). METHODS: Board-certified internal medicine physicians underwent formal think-aloud training. Next, they answered validated multiple-choice questions in an fMRI scanner while both answering (thinking) and thinking aloud about the questions, and we compared fMRI images obtained during both periods. RESULTS: Seventeen physicians (15 men and 2 women) participated in the study. Mean physician age was 39.5 + 7 (range: 32-51 years). The mean number of correct responses was 18.5/32 questions (range: 15-25). Statistically significant differences were found between answering (thinking) and thinking aloud in the following regions: motor cortex, bilateral prefrontal cortex, bilateral cerebellum, and the basal ganglia (p < 0.01). DISCUSSION: We identified significant differences between answering and thinking aloud within the motor cortex, prefrontal cortex, cerebellum, and basal ganglia. These differences were by degree (more focal activation in these areas with thinking aloud as opposed to answering). Prefrontal cortex and cerebellum activity was attributable to working memory. Basal ganglia activity was attributed to the reward of answering a question. The identified neuroimaging differences between answering and thinking aloud were expected based on existing theory and research in other fields. These findings add evidence to the notion that the think-aloud protocol is a reasonable measure of thinking.

Using functional neuroimaging combined with a think-aloud protocol to explore clinical reasoning expertise in internal medicine.

BACKGROUND: Clinical reasoning is essential to medical practice, but because it entails internal mental processes, it is difficult to assess. Functional magnetic resonance imaging (fMRI) and think-aloud protocols may improve understanding of clinical reasoning as these methods can more directly assess these processes. The objective of our study was to use a combination of fMRI and think-aloud procedures to examine fMRI correlates of a leading theoretical model in clinical reasoning based on experimental findings to date: analytic (i.e., actively comparing and contrasting diagnostic entities) and nonanalytic (i.e., pattern recognition) reasoning. We hypothesized that there would be functional neuroimaging differences between analytic and nonanalytic reasoning theory. METHODS: 17 board-certified experts in internal medicine answered and reflected on validated U.S. Medical Licensing Exam and American Board of Internal Medicine multiple-choice questions (easy and difficult) during an fMRI scan. This procedure was followed by completion of a formal think-aloud procedure. RESULTS: fMRI findings provide some support for the presence of analytic and nonanalytic reasoning systems. Statistically significant activation of prefrontal cortex distinguished answering incorrectly versus correctly (p < 0.01), whereas activation of precuneus and midtemporal gyrus distinguished not guessing from guessing (p < 0.01). CONCLUSIONS: We found limited fMRI evidence to support analytic and nonanalytic reasoning theory, as our results indicate functional differences with correct vs. incorrect answers and guessing vs. not guessing. However, our findings did not suggest one consistent fMRI activation pattern of internal medicine expertise. This model of employing fMRI correlates offers opportunities to enhance our understanding of theory, as well as improve our teaching and assessment of clinical reasoning, a key outcome of medical education.

Psychosocial determinants of anxiety about the COVID-19 pandemic.

Pandemic health threats can cause considerable anxiety, but not all individuals react similarly. To understand the sources of this variability, we applied a theoretical model developed during the H1N1 pandemic of 2009 to quantify relationships among intolerance of uncertainty, stress appraisals, and coping style that predict anxiety about the COVID-19 pandemic. We surveyed 1579 U.S. Amazon Mechanical Turk workers in April 2020. Using structural equation modeling, we found that individuals who were more intolerant of uncertainty reported higher appraisals of threat, stress, and other-control, which predicted higher anxiety when emotion-focused coping was engaged, and lower anxiety when problem-focused coping was engaged. Political affiliation moderated these effects, such that conservatives relied more on self-control and other-control appraisals to mitigate anxiety than independents or liberals. These results show that how people appraise and cope with their stress interacts with political ideology to shape anxiety in the face of a global health threat.

Enhancing cognitive restructuring with concurrent fMRI-guided neurostimulation for emotional dysregulation-A randomized controlled trial.

BACKGROUND: Transdiagnostic clinical emotional dysregulation is a key component of many mental health disorders and offers an avenue to address multiple disorders with one transdiagnostic treatment. In the current study, we pilot an intervention that combines a one-time teaching and practice of cognitive restructuring (CR) with repetitive transcranial magnetic stimulation (rTMS), targeted based on functional magnetic resonance imaging (fMRI). METHODS: Thirty-seven clinical adults who self-reported high emotional dysregulation were enrolled in this randomized, double-blind, placebo-controlled trial. fMRI was collected as participants were reminded of lifetime stressors and asked to downregulate their distress using CR tactics. fMRI BOLD data were analyzed to identify the cluster of voxels within the left dorsolateral prefrontal cortex (dlPFC) with the highest activation when participants attempted to downregulate, versus passively remember, distressing memories. Participants underwent active or sham rTMS (10 Hz) over the left dlPFC target while practicing CR following emotional induction using recent autobiographical stressors. RESULTS: Receiving active versus sham rTMS led to significantly higher high frequency heart rate variability during regulation, lower regulation duration during the intervention, and higher likelihood to use CR during the week following the intervention. There were no differences between conditions when administering neurostimulation alone without the CR skill and compared to sham. Participants in the sham versus active condition experienced less distress the week after the intervention. There were no differences between conditions at the one-month follow up. CONCLUSION: This study demonstrated that combining active rTMS with emotion regulation training for one session significantly enhances emotion regulation and augments the impact of training for as long as a week. These findings are a promising step towards a combined intervention for transdiagnostic emotion dysregulation.

Complex functional brain network properties in anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a disorder characterized by an incapacitating fear of weight gain and by a disturbance in the way the body is experienced, facets that motivate dangerous weight loss behaviors. Multimodal neuroimaging studies highlight atypical neural activity in brain networks involved in interoceptive awareness and reward processing. METHODS: The current study used resting-state neuroimaging to model the architecture of large-scale functional brain networks and characterize network properties of individual brain regions to clinical measures. Resting-state neuroimaging was conducted in 62 adolescents, 22 (21 female) with a history of AN and 40 (39 female) healthy controls (HCs). Sensorimotor and basal ganglia regions, as part of a 165-region whole-brain network, were investigated. Subject-specific functional brain networks were computed to index centrality. A contrast analysis within the general linear model covarying for age was performed. Correlations between network properties and behavioral measures were conducted (significance q < .05). RESULTS: Compared to HCs, AN had lower connectivity from sensorimotor regions, and greater connectivity from the left caudate nucleus to the right postcentral gyrus. AN demonstrated lower sensorimotor centrality, but higher basal ganglia centrality. Sensorimotor connectivity dyads and centrality exhibited negative correlations with body dissatisfaction and drive for thinness, two essential features of AN. CONCLUSIONS: These findings suggest that AN is associated with greater communication from the basal ganglia, and lower information propagation in sensorimotor cortices. This is consistent with the clinical presentation of AN, where individuals exhibit patterns of rigid habitual behavior that is not responsive to bodily needs, and seem "disconnected" from their bodies.

Individuals with anorexia nervosa (AN) usually report a fear of gaining weight. They often develop a dislike and distrust of their bodies, feeling that their bodies had somehow let them down. These fears can in turn lead to dangerous weight loss behaviors. Magnetic resonance imaging of the brain is a tool that helps highlight the underlying biological processes associated with AN. In the current study we aim to investigate how the connections in key regions of the brain are related to clinical and behavioral factors associated with AN. We found regions of two main networks were associated with body dissatisfaction and drive for thinness, which are key features of AN. The brain regions involved help explain why patients with AN have characteristics of feeling disconnected from their bodies, having difficulty labeling and regulating emotions, responding to biological needs such as hunger and fatigue, and differentiating experiences that will be rewarding. These results can help guide interventions that will be directed towards helping individuals with AN to better sense, decipher, and act on the various signals being communicated by their body.

Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group.

BACKGROUND: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. METHODS: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). RESULTS: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. CONCLUSIONS: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.

Exploring variations in functional connectivity of the resting state default mode network in mild traumatic brain injury.

A definitive diagnosis of mild traumatic brain injury (mTBI) is difficult due to the absence of biomarkers in standard clinical imaging. The brain is a complex network of interconnected neurons and subtle changes can modulate key networks of cognitive function. The resting state default mode network (DMN) has been shown to be sensitive to changes induced by pathology. This study seeks to determine whether quantitative measures of the DMN are sensitive in distinguishing mTBI subjects. Resting state functional magnetic resonance imaging data were obtained for healthy (n=12) and mTBI subjects (n=15). DMN maps were computed using dual-regression Independent Component Analysis (ICA). A goodness-of-fit (GOF) index was calculated to assess the degree of spatial specificity and sensitivity between healthy controls and mTBI subjects. DMN regions and neuropsychological assessments were examined to identify potential relationships. The resting state DMN maps indicate an increase in spatial coactivity in mTBI subjects within key regions of the DMN. Significant coactivity within the cerebellum and supplementary motor areas of mTBI subjects were also observed. This has not been previously reported in seed-based resting state network analysis. The GOF suggested the presence of high variability within the mTBI subject group, with poor sensitivity and specificity. The neuropsychological data showed correlations between areas of coactivity within the resting state network in the brain with a number of measures of emotion and cognitive functioning. The poor performance of the GOF highlights the key challenge associated with mTBI injury: the high variability in injury mechanisms and subsequent recovery. However, the quantification of the DMN using dual-regression ICA has potential to distinguish mTBI from healthy subjects, and provide information on the relationship of aspects of cognitive and emotional functioning with their potential neural correlates.

Neural basis of nonanalytical reasoning expertise during clinical evaluation.

INTRODUCTION: Understanding clinical reasoning is essential for patient care and medical education. Dual-processing theory suggests that nonanalytic reasoning is an essential aspect of expertise; however, assessing nonanalytic reasoning is challenging because it is believed to occur on the subconscious level. This assumption makes concurrent verbal protocols less reliable assessment tools. METHODS: Functional magnetic resonance imaging was used to explore the neural basis of nonanalytic reasoning in internal medicine interns (novices) and board-certified staff internists (experts) while completing United States Medical Licensing Examination and American Board of Internal Medicine multiple-choice questions. RESULTS: The results demonstrated that novices and experts share a common neural network in addition to nonoverlapping neural resources. However, experts manifested greater neural processing efficiency in regions such as the prefrontal cortex during nonanalytical reasoning. CONCLUSIONS: These findings reveal a multinetwork system that supports the dual-process mode of expert clinical reasoning during medical evaluation.

Functional MRI in the investigation of blast-related traumatic brain injury.

This review focuses on the application of functional magnetic resonance imaging (fMRI) to the investigation of blast-related traumatic brain injury (bTBI). Relatively little is known about the exact mechanisms of neurophysiological injury and pathological and functional sequelae of bTBI. Furthermore, in mild bTBI, standard anatomical imaging techniques (MRI and computed tomography) generally fail to show focal lesions and most of the symptoms present as subjective clinical functional deficits. Therefore, an objective test of brain functionality has great potential to aid in patient diagnosis and provide a sensitive measurement to monitor disease progression and treatment. The goal of this review is to highlight the relevant body of blast-related TBI literature and present suggestions and considerations in the development of fMRI studies for the investigation of bTBI. The review begins with a summary of recent bTBI publications followed by discussions of various elements of blast-related injury. Brief reviews of some fMRI techniques that focus on mental processes commonly disrupted by bTBI, including working memory, selective attention, and emotional processing, are presented in addition to a short review of resting state fMRI. Potential strengths and weaknesses of these approaches as regards bTBI are discussed. Finally, this review presents considerations that must be made when designing fMRI studies for bTBI populations, given the heterogeneous nature of bTBI and its high rate of comorbidity with other physical and psychological injuries.

Examining intrinsic thalamic resting state networks using graph theory analysis: implications for mTBI detection.

A major challenge associated with understanding mild traumatic brain injury (mTBI) is the absence of biomarkers in standard clinical imaging modalities. Furthermore, the inhomogeneity of mTBI location and intensity, combined with latent symptoms further complicates identification and treatment. A growing body of evidence suggests that the thalamus may be injured or susceptible to change as the result of mTBI. A significant number of connections to and from cortical, subcortical, cerebellar and brain stem regions converge at the thalamus. Furthermore, the thalamus is also involved with information processing, integration and the regulation of specific behaviors. We use graph theory analysis to evaluate intrinsic functional networks of the left and right thalamus in mTBI subjects (N=15) and neurologically intact healthy controls (N=12). We also explore neural correlates of the thalamic network architecture with clinical assessments. Our results suggest the presence of distinct unilateral thalamic differences in mTBI subjects. We also observe correlations of the thalamic changes with clinical assessments. The findings from this study have implications for functional networks in the thalamus and its projections for application as a potential biomarker for mTBI detection.

Fetal dopamine receptor characteristics assessed in utero.

Any tracer in fetal tissue comes from maternal arterial blood. Provided steady state is achieved and intermediate compartments are reversible, the Logan graphical methods should be applicable to the assessment of binding parameters in the fetal brain. Two pregnant rhesus macaques were studied with fallypride and the Logan method was used to assess dopamine receptor distribution volume ratios (DVRs) in both maternal and fetal striatum. The agreement between fetal striatal DVRs using maternal arterial blood and maternal and fetal cerebellum as input functions strongly supports our hypothesis that the conditions necessary for graphical analysis have been met.