OBJECTIVE: To compare the diagnosis of positive versus negative for mild traumatic brain injury (mTBI) using the Boston Assessment of TBI-Lifetime (BAT-L), a validated forensic clinical interview used to identify TBI in research, to the diagnosis of mTBI in the clinical polytrauma service using the Comprehensive TBI Evaluation (CTBIE). PARTICIPANTS: Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn Veterans who were enrolled in the Translational Research Center for TBI and Stress Disorders longitudinal cohort study and received a CTBIE at a Veterans Health Administration healthcare facility (n = 104). MAIN MEASURES: The BAT-L, CTBIE, and Neurobehavioral Symptom Inventory. RESULTS: There was poor correspondence between the BAT-L and CTBIE mTBI diagnoses (κ = 0.283). The CTBIE showed moderate sensitivity but poor specificity relative to the BAT-L. The agreement did not improve after removing individuals who had failed symptom validity measures, as assessed by the Validity-10 scale of the Neurobehavioral Symptom Inventory. CONCLUSIONS: This lack of correspondence highlights the difficulties in diagnosing mTBI in Veterans using retrospective self-report. Future work is needed to establish a reliable and valid method for identifying military mTBI both for the care of our Veterans and for appropriate distribution of benefits.

Sustained attention is critical for tasks where perceptual information must be continuously processed, like reading or driving; however, the cognitive processes underlying sustained attention remain incompletely characterized. In the experiments that follow, we explore the relationship between sustaining attention and the contents and maintenance of task-relevant features in an attentional template. Specifically, we administered the gradual onset continuous performance task (gradCPT), a sensitive measure of sustained attention, to a large web-based sample (N>20,000) and a smaller laboratory sample for validation and extension. The gradCPT requires participants to respond to most stimuli (city scenes – 90 %) and withhold to rare target images (mountain scenes – 10 %). By using stimulus similarity to probe the representational content of task-relevant features—assuming either exemplar- or category-based feature matching—we predicted that RTs for city stimuli that were more “mountain-like” would be slower and “city-like” mountain stimuli would elicit more erroneous presses. We found that exemplar-based target-nontarget (T-N) similarity predicted both RTs and erroneous button presses, suggesting a stimulus-specific feature matching process was adopted. Importantly, individual differences in the degree of sensitivity to these similarity measures correlated with conventional measures of attentional ability on the gradCPT as well as another CPT that is perceptually less demanding. In other words, individuals with greater sustained attention ability (assessed by two tasks) were more likely to be influenced by stimulus similarity on the gradCPT. These results suggest that sustained attention facilitates the construction and maintenance of an attentional template that is optimal for a given task.

Objective Metabolic syndrome (MetS) refers to a cluster of risk factors for cardiovascular disease, including obesity, hypertension, dyslipidemia, and hyperglycemia. While sizable prior literature has examined associations between individual risk factors and quantitative measures of cortical thickness (CT), only very limited research has investigated such measures in MetS. Furthermore, the relative contributions of these risk factors to MetS-related effects on brain morphology have not yet been studied. The primary goal of this investigation was to examine how MetS may affect CT. A secondary goal was to explore the relative contributions of individual risk factors to regional alterations in CT, with the potential to identify risk factor combinations that may underlie structural changes. Methods Eighteen participants with MetS (mean age=59.78years) were age-matched with 18 healthy control participants (mean age=60.50years). CT measures were generated from T1-weighted images and groups were contrasted using whole-brain general linear modeling. A follow-up multivariate partial least squares correlation (PLS) analysis, including the full study sample with complete risk factor measurements (N=53), was employed to examine which risk factors account for variance in group structural differences. Results Participants with MetS demonstrated significantly reduced CT in left hemisphere inferior parietal, rostral middle frontal, and lateral occipital clusters and in a right hemisphere precentral cluster. The PLS analysis revealed that waist circumference, high-density lipoprotein cholesterol (HDL-C), triglycerides, and glucose were significant contributors to reduced CT in these clusters. In contrast, diastolic blood pressure showed a significantly positive association with CT while systolic blood pressure did not emerge as a significant contributor. Age was not associated with CT. Conclusion These results indicate that MetS can be associated with regionally specific reductions in CT. Importantly, a novel link between a risk factor profile comprising indices of obesity, hyperglycemia, dyslipidemia and diastolic BP and localized alterations in CT emerged. While the pathophysiological mechanisms underlying these associations remain incompletely understood, these findings may be relevant for future investigations of MetS and might have implications for treatment approaches that focus on specific risk factor profiles with the aim to reduce negative consequences on the structural integrity of the brain.

INTRODUCTION: Interpersonal early life trauma (I-ELT) is associated with a myriad of functional impairments in adulthood, increased risk of drug addiction, and neuropsychiatric disorders. While deficits in emotional regulation and amygdala functioning are well characterized, deficits in general cognitive functioning have also been documented. However, the neural underpinnings of cognitive dysfunction in adults with a history of I-ELT and the potential relationship between amygdala-based functional connectivity and behavioral performance are currently poorly understood. This study examined how I-ELT affects the cognitive and neural mechanisms supporting sustained attention. METHODS: A total of 66 Veterans (18 with and 48 without a history of I-ELT) completed a nonemotional sustained attention task during functional MRI. RESULTS: The individuals with I-ELT showed significant impairments in sustained attention (i.e., higher error rates, greater response variability). This cohort exhibited increased amygdala functional connectivity with the prefrontal cortex and decreased functional connectivity with the parahippocampal gyrus when compared to those without I-ELT. These connections were significantly correlated with individual differences in sustained attention performance. Notably, classification analyses revealed that the pattern of amygdala connectivity across the whole brain was able to classify I-ELT status with 70% accuracy. CONCLUSION: These results provide evidence of a lasting negative impact for those with a history of I-ELT on sustained attention ability. They also highlight a critical role for amygdala functioning in cognitive control and sustained attention for those with a history of I-ELT, which may underlie the observed attention deficits in clinical assessments and cognitive tests involving both emotional and nonemotional stimuli.

BACKGROUND: Memory-based alterations are among the hallmark symptoms of posttraumatic stress disorder (PTSD) and may be associated with the integrity of the hippocampus. However, neuroimaging studies of hippocampal volume in individuals with PTSD have yielded inconsistent results, raising the possibility that various moderators, such as genetic factors, may influence this association. We examined whether the catechol-O-methyltransferase (COMT) Val158Met polymorphism, which has previously been shown to be associated with hippocampal volume in healthy individuals, moderates the association between PTSD and hippocampal volume. METHODS: Recent war veterans underwent structural MRI on a 3 T scanner. We extracted volumes of the right and left hippocampus using FreeSurfer and adjusted them for individual differences in intracranial volume. We assessed PTSD severity using the Clinician-Administered PTSD Scale. Hierarchical linear regression was used to model the genotype (Val158Met polymorphism) × PTSD severity interaction and its association with hippocampal volume. RESULTS: We included 146 white, non-Hispanic recent war veterans (90% male, 53% with diagnosed PTSD) in our analyses. A significant genotype × PTSD symptom severity interaction emerged such that individuals with greater current PTSD symptom severity who were homozygous for the Val allele showed significant reductions in left hippocampal volume. LIMITATIONS: The direction of proposed effects is unknown, thus precluding definitive assessment of whether differences in hippocampal volume reflect a consequence of PTSD, a pre-existing characteristic, or both. CONCLUSION: Our findings suggest that the COMT polymorphism moderates the association between PTSD and hippocampal volume. These results highlight the role that the dopaminergic system has in brain structure and suggest a possible mechanism for memory disturbance in individuals with PTSD.

Moderate-to-severe traumatic brain injury is one of the strongest environmental risk factors for the development of neurodegenerative diseases such as late-onset Alzheimer's disease, although it is unclear whether mild traumatic brain injury, or concussion, also confers risk. This study examined mild traumatic brain injury and genetic risk as predictors of reduced cortical thickness in brain regions previously associated with early Alzheimer's disease, and their relationship with episodic memory. Participants were 160 Iraq and Afghanistan War veterans between the ages of 19 and 58, many of whom carried mild traumatic brain injury and post-traumatic stress disorder diagnoses. Whole-genome polygenic risk scores for the development of Alzheimer's disease were calculated using summary statistics from the largest Alzheimer's disease genome-wide association study to date. Results showed that mild traumatic brain injury moderated the relationship between genetic risk for Alzheimer's disease and cortical thickness, such that individuals with mild traumatic brain injury and high genetic risk showed reduced cortical thickness in Alzheimer's disease-vulnerable regions. Among males with mild traumatic brain injury, high genetic risk for Alzheimer's disease was associated with cortical thinning as a function of time since injury. A moderated mediation analysis showed that mild traumatic brain injury and high genetic risk indirectly influenced episodic memory performance through cortical thickness, suggesting that cortical thinning in Alzheimer's disease-vulnerable brain regions is a mechanism for reduced memory performance. Finally, analyses that examined the apolipoprotein E4 allele, post-traumatic stress disorder, and genetic risk for schizophrenia and depression confirmed the specificity of the Alzheimer's disease polygenic risk finding. These results provide evidence that mild traumatic brain injury is associated with greater neurodegeneration and reduced memory performance in individuals at genetic risk for Alzheimer's disease, with the caveat that the order of causal effects cannot be inferred from cross-sectional studies. These results underscore the importance of documenting head injuries even within the mild range as they may interact with genetic risk to produce negative long-term health consequences such as neurodegenerative disease.

ABSTRACTObjective: Veterans from recent military conflicts frequently report persisting symptoms associated with concussion well beyond the expected period of recovery following mild traumatic brain injury. This study examined differences in the reporting of symptoms associated with concussion between clinical and research contexts. Methods: This naturalistic comparison included 91 Veterans from Operations Enduring Freedom (OEF), Iraqi Freedom (OIF) and New Dawn (OND). All participants were enrolled in a longitudinal study focused on traumatic brain injury and stress-related disorders and had also completed a VHA Comprehensive TBI Evaluation. Individuals completed the Neurobehavioral Symptom Inventory (NSI) during their research and clinical evaluations; additional measures of performance and symptom validity were also available for a subset of participants. Results: NSI mean total and subscale scores were significantly higher when assessed in the clinical compared to the research setting, irrespective of the order and duration of time between evaluations. Rates of over-reporting on the NSI and performance validity test failure were also higher during the clinical evaluation. Conclusion: Clinicians and researchers must appreciate the possible effects of context on the reporting of symptoms commonly associated with concussion. Future research identifying and mitigating factors influencing the effect of context on symptom reporting is needed.

OBJECTIVE: This study investigated sleep problems and physical pain as moderators of the relationship between PTSD symptoms and aggression among returning veterans. Prior research has demonstrated associations between PTSD symptoms and aggression, but little work has sought to identify moderators of this relationship. Sleep problems and physical pain are both common clinical problems among veterans and have theoretical links to aggression. METHOD: Participants were 103 returning service members and veterans recruited from the greater Boston area and enrolled in the VA Translational Research Center for Traumatic Brain Injury (TBI) and Stress Disorders (TRACTS). Aggression outcomes included physical and psychological intimate partner aggression (IPA), as well as physical and psychological general aggression (GA). Variables were measured via self-report questionnaires, with the exception of PTSD symptoms, which were assessed via clinician interview. RESULTS: Bivariate correlations revealed significant associations between PTSD symptoms, sleep problems, physical pain, and aggression outcomes. Both sleep problems and physical pain significantly moderated the relationship between PTSD symptoms and physical GA, such that this relationship became stronger at higher levels of these moderator variables. However, moderation was not found for the other aggression outcomes. CONCLUSIONS: Findings suggest that sleep problems and physical pain strengthen the relationship between veterans' PTSD symptoms and physical aggression toward others. Although further replication and elucidation is needed, these factors may disinhibit aggression among those at higher risk due to their PTSD symptoms. (PsycINFO Database Record

The majority of research examining affective attentional bias in posttraumatic stress disorder (PTSD) has not examined the influence of co-occurring psychiatric disorders. This study examined the individual and interactive effects of PTSD symptoms and substance use disorders (SUDs) on affective attentional processing among 323 veterans deployed to Iraq or Afghanistan. Participants were divided into those with SUD (SUD+, n = 46) and those without (SUD-, n = 277). Substance use disorder was determined using the Structured Clinical Interview for DSM-IV. Posttraumatic stress disorder was measured using the Clinician Administered PTSD Scale. A computerized go/no-go task (Robbins et al., 1994, Robbins et al.,1998) assessed affective attentional processing. Relative to those without SUD, those with SUD showed a significant association between PTSD symptoms and increased omission and commission accuracy rates and decreased d prime. No effects of valence were found. Findings suggest the need to consider co-occurring SUD when investigating the effects of PTSD on attentional control.

AIM: We examined concordance of methylation levels across the Illumina Infinium HumanMethylation450 BeadChip and the Infinium MethylationEPIC BeadChip. METHODS: We computed the correlation for 145 whole blood DNA samples at each of the 422,524 CpG sites measured by both chips. RESULTS: The correlation at some sites was high (up to r = 0.95), but many sites had low correlation (55% had r  0.20). The low correspondence between 450K and EPIC measured methylation values at many loci was largely due to the low variability in methylation values for the majority of the CpG sites in blood. CONCLUSION: Filtering out probes based on the observed correlation or low variability may increase reproducibility of BeadChip-based epidemiological studies.