Accelerated Aging after Traumatic Brain Injury: An ENIGMA Multi-Cohort Mega-Analysis.

OBJECTIVE: The long-term consequences of traumatic brain injury (TBI) on brain structure remain uncertain. Given evidence that a single significant brain injury event increases the risk of dementia, brain-age estimation could provide a novel and efficient indexing of the long-term consequences of TBI. Brain-age procedures use predictive modeling to calculate brain-age scores for an individual using structural magnetic resonance imaging (MRI) data. Complicated mild, moderate, and severe TBI (cmsTBI) is associated with a higher predicted age difference (PAD), but the progression of PAD over time remains unclear. We sought to examine whether PAD increases as a function of time since injury (TSI) and if injury severity and sex interacted to influence this progression. METHODS: Through the ENIGMA Adult Moderate and Severe (AMS)-TBI working group, we examine the largest TBI sample to date (n = 343), along with controls, for a total sample size of n = 540, to replicate and extend prior findings in the study of TBI brain age. Cross-sectional T1w-MRI data were aggregated across 7 cohorts, and brain age was established using a similar brain age algorithm to prior work in TBI. RESULTS: Findings show that PAD widens with longer TSI, and there was evidence for differences between sexes in PAD, with men showing more advanced brain age. We did not find strong evidence supporting a link between PAD and cognitive performance. INTERPRETATION: This work provides evidence that changes in brain structure after cmsTBI are dynamic, with an initial period of change, followed by relative stability in brain morphometry, eventually leading to further changes in the decades after a single cmsTBI. ANN NEUROL 2024.

Establishing ground truth in the traumatic brain injury literature: if replication is the answer, then what are the questions?

The replication crisis poses important challenges to modern science. Central to this challenge is re-establishing ground truths or the most fundamental theories that serve as the bedrock to a scientific community. However, the goal to identify hypotheses with the greatest support is non-trivial given the unprecedented rate of scientific publishing. In this era of high-volume science, the goal of this study is to sample from one research community within clinical neuroscience (traumatic brain injury) and track major trends that have shaped this literature over the past 50 years. To do so, we first conduct a decade-wise (1980-2019) network analysis to examine the scientific communities that shape this literature. To establish the robustness of our findings, we utilized searches from separate search engines (Web of Science; Semantic Scholar). As a second goal, we sought to determine the most highly cited hypotheses influencing the literature in each decade. In a third goal, we then searched for any papers referring to 'replication' or efforts to reproduce findings within our >50 000 paper dataset. From this search, 550 papers were analysed to determine the frequency and nature of formal replication studies over time. Finally, to maximize transparency, we provide a detailed procedure for the creation and analysis of our dataset, including a discussion of each of our major decision points, to facilitate similar efforts in other areas of neuroscience. We found that the unparalleled rate of scientific publishing within the brain injury literature combined with the scarcity of clear hypotheses in individual publications is a challenge to both evaluating accepted findings and determining paths forward to accelerate science. Additionally, while the conversation about reproducibility has increased over the past decade, the rate of published replication studies continues to be a negligible proportion of the research. Meta-science and computational methods offer the critical opportunity to assess the state of the science and illuminate pathways forward, but ultimately there is structural change needed in the brain injury literature and perhaps others.

Effects of preexisting stroke on acute hospital outcomes for older adults admitted with neurotrauma and orthopedic injury.

OBJECTIVE: We aimed to examine acute trauma outcomes, specifically among those with neurotrauma (NT), in patients with preexisting cerebrovascular accident (CVA). METHODS: We identified patients treated for neurotrauma or orthopedic trauma at hospitals in Pennsylvania with and without an identified history of stroke with residual deficits, aged 50-99 across four groups of N = 11,648 each. We assessed mortality, craniotomy, and total hospital, ICU, step-down, and ventilator days, functional status at discharge (FSD), and discharge destination. RESULTS: Stroke history did not influence mortality but was predictive of patients undergoing craniotomy (OR = 1.25, p = 0.008). There was a moderate group effect on total ICU days, with the CVA+NT group in the ICU the longest (η2 = 0.10, p < 0.001). Patients with stroke history were less likely to be discharged to home (OR = 0.65, p < 0.001) and had poorer FSD scores across the various domains assessed. CONCLUSIONS: Trauma patients with preexisting CVA were found to have poorer outcomes on a number of different metrics when compared to those without stroke history. While it is possible that functional differences pre-injury influenced FSD and discharge destination, given these results, clinicians should assess for possible comorbidities that may influence treatment.

Avoidant Coping Is Associated with Quality of Life in Persons with Multiple Sclerosis with High Cognitive Reserve.

OBJECTIVE: The goal of this study was to determine the impact of the relationship between cognitive reserve and coping strategy on quality of life (QoL) outcomes in persons with MS (PwMS) across multiple domains. METHODS: We examined the effect of the interactions between coping style and cognitive reserve on QoL and disease burden in 97 persons with MS (PwMS). Coping strategy, either active or avoidant, was measured using the COPE inventory. We defined cognitive reserve as a composite measure of years of education and scores on the Shipley-2 Vocabulary subtest. QoL and disease burden were assessed using the Functional Assessment of MS (FAMS) scale and the Expanded Disability Status Scale, respectively. We examined both the FAMS individual subscales and the overall QoL score. RESULTS: For those with higher cognitive reserve, greater avoidant coping was associated with lower QoL for the thinking and fatigue subscale (p < 0.001) and poorer overall QoL (p = 0.03); greater active coping was associated with poorer QoL for mobility (p = 0.001). However, these associations did not hold for those with lower cognitive reserve. Furthermore, there were no associations between coping strategy and cognitive reserve with disease burden. CONCLUSIONS: This study extends previous findings by demonstrating that avoidant coping, rather than active coping, is associated with poorer thinking and fatigue and overall QoL only for PwMS with greater cognitive reserve. Counseling PwMS on the impact of coping strategies on QoL outcomes, especially for those with greater cognitive reserve, may improve quality of life outcomes in this population.

Basolateral amygdala to posterior piriform cortex connectivity ensures precision in learned odor threat.

Odor perception can both evoke emotional states and be shaped by emotional or hedonic states. The amygdala complex plays an important role in recognition of, and response to, hedonically valenced stimuli, and has strong, reciprocal connectivity with the primary olfactory (piriform) cortex. Here, we used differential odor-threat conditioning in rats to test the role of basolateral amygdala (BLA) input to the piriform cortex in acquisition and expression of learned olfactory threat responses. Using local field potential recordings, we demonstrated that functional connectivity (high gamma band coherence) between the BLA and posterior piriform cortex (pPCX) is enhanced after differential threat conditioning. Optogenetic suppression of activity within the BLA prevents learned threat acquisition, as do lesions of the pPCX prior to threat conditioning (without inducing anosmia), suggesting that both regions are critical for acquisition of learned odor threat responses. However, optogenetic BLA suppression during testing did not impair threat response to the CS+ , but did induce generalization to the CS-. A similar loss of stimulus control and threat generalization was induced by selective optogenetic suppression of BLA input to pPCX. These results suggest an important role for amygdala-sensory cortical connectivity in shaping responses to threatening stimuli.

Depression associated with APOE status and hippocampal volume but not cognitive decline in older adults aging with traumatic brain injury.

OBJECTIVE: To examine the relationship between depression and cognition, genetic risk, and hippocampal differences in a sample of older adults with a history of traumatic brain injury (TBI). METHOD: Participants were 85 males and 35 females (91 Caucasian, 29 African-American) with a mean age of 65.04 (±8.27) years and a history of moderate, severe, or complicated mild TBI. Participants were an average of 9.33 (±7.27) years post injury (range: 0.78-45.63). Participants underwent genetic testing, a comprehensive neuropsychological battery, surveys, and a subset underwent MRI scanning. RESULTS: Apolipoprotein E (APOE) e4 carrier status predicted clinically significant depressive symptomatology on the Geriatric Depression Scale (GDS) with an odds ratio of 3.63, 95% CI [1.33, 9.29]. GDS was not associated with scores on measures of executive function, list learning recall, or retention. Although GDS score was initially associated with poorer confrontation naming scores and story memory recall, these effect sizes were small, and this variance was better accounted for by age and cognitive reserve. Higher GDS scores were also associated with decreased hippocampal volume. CONCLUSIONS: APOE carrier status was predictive of depression in a sample of older adults with a history of TBI. Depressive symptoms were also associated with decreased hippocampal volume but did not predict cognitive deficits in the examined domains beyond the effects of cognitive reserve. Despite the relationship between GDS and biological risks for decline, depressive symptoms in this population showed no direct relationship with cognitive decline. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Cortical processing of configurally perceived odor mixtures.

Most odors are not composed of a single volatile chemical species, but rather are mixtures of many different volatile molecules, the perception of which is dependent on the identity and relative concentrations of the components. Changing either the identity or ratio of components can lead to shifts between configural and elemental perception of the mixture. For example, a 30/70 ratio of ethyl isobutyrate (odorant A, a strawberry scent) and ethyl maltol (odorant B, a caramel scent) is perceived as pineapple by humans - a configural percept distinct from the components. In contrast, a 68/32 ratio of the same odorants is perceived elementally, and is identified as the component odors. Here, we examined single-unit responses in the anterior and posterior piriform cortex (aPCX and pPCX) of mice to these A and B mixtures. We first demonstrate that mouse behavior is consistent with a configural/elemental perceptual shift as concentration ratio varies. We then compared responses to the configural mixture to those evoked by the elemental mixture, as well as to the individual components. Hierarchical cluster analyses suggest that in the mouse aPCX, the configural mixture was coded as distinct from both components, while the elemental mixture was coded as similar to the components. In contrast, mixture perception did not predict pPCX ensemble coding. Similar electrophysiological results were also observed in rats. The results suggest similar perceptual characteristics of the AB mixture across species, and a division in the roles of aPCX and pPCX in the coding of configural and elemental odor mixtures.