Alzheimer's Disease-Related Dementias Summit 2019: National Research Priorities for the Investigation of Traumatic Brain Injury as a Risk Factor for Alzheimer's Disease and Related Dementias.

Traumatic brain injury (TBI) is a risk factor for later-life dementia. Clinical and pre-clinical studies have elucidated multiple mechanisms through which TBI may influence or exacerbate multiple pathological processes underlying Alzheimer's disease and Alzheimer's disease-related dementias (AD/ADRD). The National Institutes of Health hosts triennial ADRD Summits to inform a national research agenda, and the 2019 ADRD Summit was the first to highlight "TBI and AD/ADRD Risk" as an emerging topic in the field.

Understanding Traumatic Brain Injury in Females: A State-of-the-Art Summary and Future Directions.

In this report, we identify existing issues and challenges related to research on traumatic brain injury (TBI) in females and provide future directions for research. In 2017, the National Institutes of Health, in partnership with the Center for Neuroscience and Regenerative Medicine and the Defense and Veterans Brain Injury Center, hosted a workshop that focused on the unique challenges facing researchers, clinicians, patients, and other stakeholders regarding TBI in women. The goal of this "Understanding TBI in Women" workshop was to bring together researchers and clinicians to identify knowledge gaps, best practices, and target populations in research on females and/or sex differences within the field of TBI.

National Institute of Neurological Disorders and Stroke and Department of Defense Sport-Related Concussion Common Data Elements Version 1.0 Recommendations.

Through a partnership with the National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health, and Department of Defense, the development of Sport-Related Concussion (SRC) Common Data Elements (CDEs) was initiated. The aim of this collaboration was to increase the efficiency and effectiveness of clinical research studies and clinical treatment outcomes, increase data quality, facilitate data sharing across studies, reduce study start-up time, more effectively aggregate information into metadata results, and educate new clinical investigators. The SRC CDE Working Group consisted of 32 worldwide experts in concussion from varied fields of related expertise divided into three Subgroups: Acute (<72 h post-concussion), Subacute (3 days-3 months post-concussion) and Persistent/Chronic (>3 months post-concussion).

Military Blast Injury and Chronic Neurodegeneration: Research Presentations from the 2015 International State-of-the-Science Meeting.

Blast-related traumatic brain injury (TBI) is a signature injury of recent military conflicts, leading to increased Department of Defense (DoD) interest in its potential long-term effects, such as chronic traumatic encephalopathy (CTE). The DoD Blast Injury Research Program Coordinating Office convened the 2015 International State-of-the-Science Meeting to discuss the existing evidence regarding a causal relationship between TBI and CTE. Over the course of the meeting, experts across government, academia, and the sports community presented cutting edge research on the unique pathological characteristics of blast-related TBI, blast-related neurodegenerative mechanisms, risk factors for CTE, potential biomarkers for CTE, and treatment strategies for chronic neurodegeneration.

The Biological Basis of Chronic Traumatic Encephalopathy following Blast Injury: A Literature Review.

The United States Department of Defense Blast Injury Research Program Coordinating Office organized the 2015 International State-of-the-Science meeting to explore links between blast-related head injury and the development of chronic traumatic encephalopathy (CTE). Before the meeting, the planning committee examined articles published between 2005 and October 2015 and prepared this literature review, which summarized broadly CTE research and addressed questions about the pathophysiological basis of CTE and its relationship to blast- and nonblast-related head injury. It served to inform participants objectively and help focus meeting discussion on identifying knowledge gaps and priority research areas.

Longitudinal assessment of local and global functional connectivity following sports-related concussion.

Growing evidence suggests that sports-related concussions (SRC) may lead to acute changes in intrinsic functional connectivity, although most studies to date have been cross-sectional in nature with relatively modest sample sizes. We longitudinally assessed changes in local and global resting state functional connectivity using metrics that do not require a priori seed or network selection (regional homogeneity; ReHo and global brain connectivity; GBC, respectively). A large sample of collegiate athletes (N = 43) was assessed approximately one day (1.

Longitudinal assessment of white matter abnormalities following sports-related concussion.

There is great interest in developing physiological-based biomarkers such as diffusion tensor imaging to aid in the management of concussion, which is currently entirely dependent on clinical judgment. However, the time course for recovery of white matter abnormalities following sports-related concussion (SRC) is unknown. We collected diffusion tensor imaging and behavioral data in forty concussed collegiate athletes on average 1.

Smaller Dentate Gyrus and CA2 and CA3 Volumes Are Associated with Kynurenine Metabolites in Collegiate Football Athletes.

An imbalance in kynurenine pathway metabolism is hypothesized to be associated with dysregulated glutamatergic neurotransmission, which has been proposed as a mechanism underlying the hippocampal volume loss observed in a variety of neurological disorders. Pre-clinical models suggest that the CA2-3 and dentate gyrus hippocampal subfields are particularly susceptible to excitotoxicity after experimental traumatic brain injury. We tested the hypothesis that smaller hippocampal volumes in collegiate football athletes with (n = 25) and without (n = 24) a concussion history would be most evident in the dentate gyrus and CA2-3 subfields relative to nonfootball healthy controls (n = 27).

Mood symptoms correlate with kynurenine pathway metabolites following sports-related concussion.

Objective: An imbalance of neuroactive kynurenine pathway metabolites has been proposed as one mechanism behind the neuropsychiatric sequelae of certain neurological disorders. We hypothesized that concussed football players would have elevated plasma levels of neurotoxic kynurenine metabolites and reduced levels of neuroprotective metabolites relative to healthy football players and that altered kynurenine levels would correlate with post-concussion mood symptoms.

Methods: Mood scales and plasma concentrations of kynurenine metabolites were assessed in concussed (N=18; 1.

Thinner Cortex in Collegiate Football Players With, but not Without, a Self-Reported History of Concussion.

Emerging evidence suggests that a history of sports-related concussions can lead to long-term neuroanatomical changes. The extent to which similar changes are present in young athletes is undetermined at this time. Here, we tested the hypothesis that collegiate football athletes with (n = 25) and without (n = 24) a self-reported history of concussion would have cortical thickness differences and altered white matter integrity relative to healthy controls (n = 27) in fronto-temporal regions that appear particularly susceptible to traumatic brain injury.

Autobiographical deficits correlate with gray matter volume in depressed and high risk participants.

Autobiographical memory (AM) overgenerality is a consistent neuropsychological feature of major depressive disorder (MDD) and is present in individuals at high-familial risk (HR) of developing MDD. Structural changes have been found in brain regions implicated in AM recall in MDDs and HRs. However, the relationship between selective regional gray matter volume (GMV) differences and AM recall deficits has not been examined.

Functional neuroimaging correlates of autobiographical memory deficits in subjects at risk for depression.

Overgeneral autobiographical memory (AM) manifests in individuals with major depressive disorder (MDD) tested during depressed (dMDD) or remitted phases (rMDD), and healthy individuals at high-risk (HR) for developing MDD. The current study aimed to elucidate differences in hemodynamic correlates of AM recall between rMDDs, HRs, and controls (HCs) to identify neural changes following previous depressive episodes without the confound of current depressed mood. HCs, HRs, and unmedicated rMDDs (n = 20/group) underwent fMRI while recalling AMs in response to emotionally valenced cue words.

Recovery of cerebral blood flow following sports-related concussion.

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.

Reduction of kynurenic acid to quinolinic acid ratio in both the depressed and remitted phases of major depressive disorder.

Low-grade inflammation is characteristic of a subgroup of currently depressed patients with major depressive disorder (dMDD). It may lead to the activation of the kynurenine-metabolic pathway and the increased synthesis of potentially neurotoxic metabolites such as 3-hydroxykynurenine (3HK) and quinolinic acid (QA), relative to kynurenic acid (KynA). Nevertheless, few studies have examined whether abnormalities in this pathway are present in remitted patients with MDD (rMDD).

Functional magnetic resonance imaging of mild traumatic brain injury.

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 underreporting of self-reported symptoms following sports-related concussion.

Objectives: This cohort study was conducted to examine patterns of symptom reporting in concussed athletes in two different testing environments.

Design: A prospective cohort study was conducted with repeated measures.

Methods: Self-reported symptoms collected by team athletic trainers using the ImPACT Post-Concussion Scale (PCS) were compared to symptoms collected in a confidential setting using structured interviews for depression and anxiety.

Putative neuroprotective and neurotoxic kynurenine pathway metabolites are associated with hippocampal and amygdalar volumes in subjects with major depressive disorder.

Inflammation-related changes in the concentrations of kynurenine pathway metabolites occur in depression secondary to medical conditions but are not firmly established in primary mood disorders. Reductions in hippocampal and amygdalar volume that putatively reflect dendritic atrophy are widely reported in major depressive disorder (MDD). Here we tested whether the relative serum concentrations of putatively neuroprotective (kynurenic acid (KA)) and neurotoxic (3-hydroxykynurenine (3HK) and quinolinic acid (QA)) kynurenine pathway metabolites were altered in primary MDD and whether these metabolites were associated with hippocampal and amygdalar volume.

Relationship of collegiate football experience and concussion with hippocampal volume and cognitive outcomes.

Importance: Concussion and subconcussive impacts have been associated with short-term disrupted cognitive performance in collegiate athletes, but there are limited data on their long-term neuroanatomic and cognitive consequences.

Objective: To assess the relationships of concussion history and years of football experience with hippocampal volume and cognitive performance in collegiate football athletes.

Design, Setting, And Participants: Cross-sectional study conducted between June 2011 and August 2013 at a US psychiatric research institute specializing in neuroimaging among collegiate football players with a history of clinician-diagnosed concussion (n = 25), collegiate football players without a history of concussion (n = 25), and non-football-playing, age-, sex-, and education-matched healthy controls (n = 25).

Trait impulsivity is related to ventral ACC and amygdala activity during primary reward anticipation.

Trait impulsivity is characterized by behavioral disinhibition and rash decision-making that contribute to many maladaptive behaviors. Previous research demonstrates that trait impulsivity is related to the activity of brain regions underlying reward sensitivity and emotion regulation, but little is known about this relationship in the context of immediately available primary reward. This is unfortunate, as impulsivity in these contexts can lead to unhealthy behaviors, including poor food choices, dangerous drug use and risky sexual practices.

Catecholamine depletion in first-degree relatives of individuals with mood disorders: An [(18)F]fluorodeoxyglucose positron emission tomography study.

Catecholamine depletion with alpha-methylparatyrosine (AMPT) has previously been shown to induce depressive symptoms in currently remitted patients with major depressive disorder (MDD) but not healthy controls. Thus sensitivity to catecholamine depletion has been hypothesized to be an endophenotype of MDD. Here we tested this hypothesis in the context of a randomized, double-blinded, placebo-controlled design by measuring changes in mood in a group of psychiatrically-healthy individuals at risk of mood disorders by virtue of family history (high-risk subjects, HRs).

Investigating the properties of the hemodynamic response function after mild traumatic brain injury.

Abstract Although several functional magnetic resonance imaging (fMRI) studies have been conducted in human models of mild traumatic brain injury (mTBI), to date no studies have explicitly examined how injury may differentially affect both the positive phase of the hemodynamic response function (HRF) as well as the post-stimulus undershoot (PSU). Animal models suggest that the acute and semi-acute stages of mTBI are associated with significant disruptions in metabolism and to the microvasculature, both of which could impact on the HRF. Therefore, fMRI data were collected on a cohort of 30 semi-acute patients with mTBI (16 males; 27.

Behavioral and neurophysiological correlates of autobiographical memory deficits in patients with depression and individuals at high risk for depression.

Importance: Individuals with major depressive disorder (MDD) compared with healthy control subjects (HCs) consistently recall fewer specific and more categorical autobiographical memories (AMs). This effect is most pronounced for positive AMs and persists into remission.

Objectives: To determine whether individuals at high familial risk for developing MDD (HR group) also show an AM overgenerality bias and to use functional magnetic resonance imaging to assess differences in functional correlates of AM recall across HR, currently depressed MDD, and HC groups.

Inflammation and neurological disease-related genes are differentially expressed in depressed patients with mood disorders and correlate with morphometric and functional imaging abnormalities.

Depressed patients show evidence of both proinflammatory changes and neurophysiological abnormalities such as increased amygdala reactivity and volumetric decreases of the hippocampus and ventromedial prefrontal cortex (vmPFC). However, very little is known about the relationship between inflammation and neuroimaging abnormalities in mood disorders. A whole genome expression analysis of peripheral blood mononuclear cells yielded 12 protein-coding genes (ADM, APBB3, CD160, CFD, CITED2, CTSZ, IER5, NFKBIZ, NR4A2, NUCKS1, SERTAD1, TNF) that were differentially expressed between 29 unmedicated depressed patients with a mood disorder (8 bipolar disorder, 21 major depressive disorder) and 24 healthy controls (HCs).

The extended functional neuroanatomy of emotional processing biases for masked faces in major depressive disorder.

Background: Major depressive disorder (MDD) is associated with a mood-congruent processing bias in the amygdala toward face stimuli portraying sad expressions that is evident even when such stimuli are presented below the level of conscious awareness. The extended functional anatomical network that maintains this response bias has not been established, however.

Aims: To identify neural network differences in the hemodynamic response to implicitly presented facial expressions between depressed and healthy control participants.