Measure Of Integrity Research Articles

NOVEL BEHAVIORAL INTERVENTIONS TARGETING COGNITIVE-MOTOR NEUROPLASTICITY IN OLDER ADULTS

Abstract Comparatively little is known about the ability of physical activity to improve or maintain cognitive function in older adults. Our Midwest Roybal Center uses social/behavioral theory to promote engagement in physical activity in order to improve this outcome. In 2019, we received funding to establish a Multimodal Connectomics Core that enabled investigators to examine concurrent changes in cognitive function and brain connectivity by providing access to fMRI imaging. The Connectomics Core enabled investigators for the first time to examine cognitive function and changes in brain connectivity simultaneously by providing access to fMRI imaging as well as MRI data storage and data analysis. It enabled measuring of standardized participant outcomes selected from the NIH toolbox. This Symposium describes findings from the first three completed pilots and discusses their implications for the field. The first pilot by Bronas examined effect of a 6-month home-based walking program in people chronic kidney disease on cognitive function and intervention induced neuroplasticity compared to usual care. The second pilot by Marquez adapted the Fit & Strong! program to test the combined impact of physical activity and interactive health education for managing mood on cognitive function among older adults with depression. The third pilot by Bhatt examined the effectiveness of 4 weeks of exergaming combined explicit cognitive training on behavioral measures of fall-risk (physical and cognitive) and their associations with brain integrity measures. The discussant will initiate discussion based on outcomes of these pilots and future directions for developing them into larger studies or clinical translation.

Longitudinal stability in working memory and frontal activity in relation to general brain maintenance

Cognitive functions are well-preserved for some older individuals, but the underlying brain mechanisms remain disputed. Here, 5-year longitudinal 3-back in-scanner and offline data classified individuals in a healthy older sample (baseline age = 64–68 years) into having stable or declining working-memory (WM). Consistent with a vital role of the prefrontal cortex (PFC), WM stability or decline was related to maintained or reduced longitudinal PFC functional responses. Subsequent analyses of imaging markers of general brain maintenance revealed higher levels in the stable WM group on measures of neurotransmission and vascular health. Also, categorical and continuous analyses showed that rate of WM decline was related to global (ventricles) and local (hippocampus) measures of neuronal integrity. Thus, our findings support a role of the PFC as well as general brain maintenance in explaining heterogeneity in longitudinal WM trajectories in aging.

Premature Cardiovascular Disease and Brain Health in Midlife: The Coronary Artery Risk Development in Young Adults (CARDIA) Study

AbstractBackgroundCardiovascular disease (CVD) is associated with cognitive impairment and dementia risk in late life, yet little is known about the role of premature (defined younger than 60 years) CVD events with cognition and brain health earlier in the life course, including in midlife. As part of the Coronary Artery Risk Development in Young Adults (CARDIA) Study, we investigated the association of premature CVD events in young and middle adulthood with cognition and white‐matter health in midlife.MethodsWe studied 3,146 Black and White participants (57% women, 48% Black) aged 18‐30 years at baseline (1985‐86) who were followed up to Year 30 (mean age 55.1±3.6 years) when 5 cognitive tests measuring different domains were administered. A subset (656 participants) had brain MRI with measures of white matter hyperintensity (WMH) burden and white matter integrity. Premature CVD events were adjudicated based on participants' history and medical records of coronary heart disease, stroke/TIA, cardiac revascularization, congestive heart failure, carotid artery disease, and peripheral artery disease. We conducted linear regression to determine the association of premature CVD with cognitive and structural brain measures.ResultsFive percent (n = 147) of participants had premature CVD events over the 30 years. Having premature CVD events was associated with lower cognitive function in all domains. After adjustment for demographics, education, depressive symptoms, physical activity, diet, APOE ε4, and cardiovascular risk factors (CVRFs), premature CVD was associated with lower cognition (z‐standardized) except for verbal fluency: global cognition (‐0.19, 95% CI ‐0.35 to ‐0.03), verbal memory (‐0.24, 95% CI ‐0.41 to ‐0.07), processing speed (‐0.46, 95% CI ‐0.63 to ‐0.30), and executive function (‐0.38, 95% CI ‐0.56 to ‐0.20). Premature CVD was also associated with greater WMH volumes (total, frontal, temporal, and parietal lobes) and alternations of white matter integrity (higher total and temporal lobe mean diffusivity and lower parietal lobe fractional anisotropy) after adjusting for demographics, total intracranial volume, and CVRFs.ConclusionPremature CVD is associated with worse midlife cognition and white‐matter health independent of CVRFs. Young and middle adulthood is a critical time for CVD prevention, the efforts of which may delay the onset of cognitive decline and dementia later in life.

Language Fluency and Premature Brain Aging

AbstractBackgroundAge‐related changes in the brain are often associated with general cognitive decline. Cognitive aging affects the ability to produce spoken language, with older adults experiencing increased difficulties in word‐finding1 and verbal fluency2,3. Neurodegenerative diseases such as Alzheimer’s disease are often attributed to an acceleration of typical aging processes (i.e., premature aging). Accelerated age‐related atrophy is present in mild cognitive impairment4,5 and premature brain aging may contribute to declining cognitive skills6,7. A recent study demonstrated that the disparity between chronological age and brain age (based on measures of cortical integrity) is a good predictor of early cognitive impairment8. Our aim was to extend these findings by investigating the role of brain age in overall cognition as well as language in particular.MethodParticipants included 216 healthy controls (age range 20–79) from the Aging Brain Cohort at the University of South Carolina9. Structural T1‐weighted MRI scans were collected, and participants completed the Montreal Cognitive Assessment (MoCA10). Brain age was calculated based on T1‐weighted structural data using the BrainAgeR analysis pipeline (github.com/james‐cole/brainageR). A brain age gap estimate (BrainAGE)11 was calculated as the difference between brain age and chronological age. This was used as the primary measure of advanced/delayed brain health, where positive values represent premature brain aging.ResultEstimated brain age differences ranged from 22 years younger to 14 years older than chronological age. Pearson correlations revealed a negative correlation between MoCA total score and chronological age (r(209) = ‐0.41, p<0.001), but not in partial correlations using BrainAGE, accounting for chronological age (r(207) = ‐0.003, p = 0.48.). Regarding our language measure (words generated during the MoCA fluency task), we observed a negative correlation with BrainAGE, corrected for chronological age (r(208) = ‐0.133, p = 0.03), but no correlation with chronological age (r(210) = ‐0.04, p = 0.58).ConclusionOur data support the hypothesis that differences between chronological and brain age are related to cognition and language, and highlight the utility/importance of brain age in understanding cognitive impairment. Interestingly, findings suggest that there may be a particularly strong relationship between the brain age gap estimation and MRI‐based measure of brain aging and language in particular.

Higher allostatic load is associated with poorer structural integrity in the limbic network in cognitively unimpaired elderly

AbstractBackgroundAllostatic load (AL) is a cumulative measure of dysregulations across multiple physiological systems of the body occurring over time. AL was originally developed to explain how chronic stress damages physiologic systems and accelerates aging. Studies exploring the relationship between AL and brain health in older adults using a multimodal approach are limited. Our objective was to provide a comprehensive overview of the brain substrates of AL in cognitively unimpaired elderly using complementary multimodal neuroimaging techniques.MethodBaseline data of 111 cognitively unimpaired older adults (mean age, 68.9years) from the Age‐Well study (NCT02977819) were included. They underwent multimodal neuroimaging (T1‐weighted and diffusion MRI, FDG‐PET and amyloid‐PET). A global measure of brain integrity was obtained for each modality by extracting the averaged signal across the whole gray matter (GM) or white matter (WM) for diffusion. AL was computed based on 19 markers of health. First, we examined the relationships between AL and sex or age. Second, we performed multiple regression and voxel‐wise analyses to predict AL from each neuroimaging modality and to highlight the brain regions involved. Finally, we conducted forward stepwise multiple regressions including the 19 AL‐components to determine the prognostic components of each of these associations; correcting for age, sex and education.ResultAL was associated with sex (men>women) but not with age. Higher AL was associated with lower global GM volume and WM mean diffusivity. Adjusting for alcohol consumption, smoking habits, treatments or comorbidities, these associations remained unchanged. Association with lower GM volume was found in the parahippocampus, hypothalamus, anterior insula and prefrontal gyrus and with WM diffusivity in the corona radiata and corpus callosum. Stepwise regressions revealed that these associations with GM volume and WM diffusivity were mainly explained by the body mass index (BMI) and waist‐hip‐ratio (WHR), respectively.ConclusionHigher AL is associated with poorer structural integrity in regions of the limbic network, which is implicated in memory, emotion and stress processes and known to be particularly vulnerable to Alzheimer’s disease. Our results further suggest that maintenance of a healthy weight (by monitoring BMI and WHR) might help to prevent AL increase, thus promoting brain health.

Spectral signatures associated with cognitive aging, APOE4, amyloid‐β and measures of axonal integrity in cognitively unimpaired adults

AbstractBackgroundOscillatory brain rhythms are a defining feature of neuronal activity that support cognition in humans. Previous studies that showed associations of spectral changes in individuals who harbor high risk for Alzheimer’s disease (AD) were limited to identify abnormalities within select brain regions defined apriori. Comprehensive whole‐brain spatiotemporal patterns of oscillatory changes associated with cognitive‐aging and with AD risk are only partly known. Our main goals were to understand how frequency specific spectral changes relate to cognitive abilities in normal aging and to identify oscillatory signatures that indicate pre‐symptomatic AD pathophysiological processes in cognitively unimpaired elderly.MethodsWe used magnetoencephalography (MEG) to study the spectral signatures within delta‐theta (2‐7Hz), alpha (8‐12Hz) and beta (13‐35Hz) oscillations, in cognitively unimpaired adults (n=70). Using a partial‐least‐square regression, we correlated spectral patterns to executive, memory, and processing‐speed abilities (n=40). Next, we compared the spectral signatures between amyloid‐β (Aβ)+ vs. Aβ‐ and between APOE‐Ɛ4+ vs. APOE‐Ɛ4‐, in sub‐cohorts evaluated with Aβ‐PET (n=46) and APOE4 (n=65), respectively. In a subset of participants (n=19), we also examined associations between spectral signatures and cerebrospinal fluid (CSF) markers indicating damage to: presynaptic (growth‐associated protein‐43, GAP43); postsynaptic (neurogranin, NG); axonal (neurofilament light chain, NFL), levels.ResultsAn age dependent, low‐grade, increase in alpha power and decrease in delta‐theta power were associated with better cognitive performance in memory, executive and processing speed (Figure‐1). APOE4+ individuals showed reduced alpha power within bilateral medial temporal and right precuneus, compared to APOE4‐. Aβ+ individuals showed a dual pattern of alpha change with increased frontal and reduced medial and lateral temporal cortex pattern and a frontally distributed increased delta‐theta power (Figure‐2). Higher CSF‐NFL was correlated with lower alpha power.ConclusionsOur findings demonstrate that higher alpha power indicates a positive spectral change towards better cognitive health in aging. Importantly, a reduced alpha power signature indicated early neurodegenerative changes, as demonstrated by: (1)Aβ+ individuals and APOE‐Ɛ4+ individuals showing reduced alpha power within the regions known for earliest tau accumulations; (2) lower alpha correlating with higher NFL, which reflects Aβ‐independent neurodegeneration. Collectively alpha signatures may indicate tau related neuropathology with aging and in early AD.

Association between real-time strategy video game learning outcomes and pre-training brain white matter structure: preliminary study

In recent years the association between video games, cognition, and the brain has been actively investigated. However, it is still unclear how individual predispositions, such as brain structure characteristics, play a role in the process of acquiring new skills, such as video games. The aim of this preliminary study was to investigate whether acquisition of cognitive-motor skills from the real-time strategy video game (StarCraft II) is associated with pre-training measures of brain white matter integrity. Results show that higher white matter integrity in regions (anterior limb of internal capsule, cingulum/hippocampus) and tracts (inferior longitudinal fasciculus) related with motoric functions, set shifting and visual decision making was associated with better Star Craft II performance. The presented findings inline with previous results and suggest that structural brain predispositions of individuals are related to the video game skill acquisition. Our study highlights the importance of neuroimaging studies that focus on white matter in predicting the outcomes of intervention studies and has implications for understanding the neural basis of the skill learning process.

C‐reactive protein (CRP) blood concentrations associate with reduced global system segregation in middle‐aged individuals

AbstractBackgroundHigh concentrations of circulating C‐reactive protein (CRP) have been related to poorer cognition in adults (Lewis et al. Age Ageing. 2021;50:2199). Within the Lifebrain consortium (Walhovd et al. Eur Psychiatry. 2018;50:47), we recently reported overall lifespan associations between increased CRP and smaller hippocampal (HPC) volumes, albeit these could not be observed in one subsample of middle‐aged individuals (Wang et al. Brain Behav Immun. 2022;100:243). Here we hypothesized that functional brain integrity measures would be sensitive to predict CRP levels in this group. We focused on global system segregation (SyS) a graph theory‐based metric which quantifies the extent to which major functional networks are segregated from each other.MethodWe included 336 volunteers (mean age 53.8; SD: 7.1; 47.9% women) from the Barcelona Brain Health Initiative (Cattaneo et al. Front Aging Neurosci. 2018;10:321). High‐sensitive CRP (hsCRP) concentrations were determined through dry blood samples and log10 transformed (Wang et al. Brain Behav Immun. 2022;100:243). Adjusted HPC volumes were estimated from T1‐wheigthed 3T MRI acquisitions (Raz et al. Cereb Cortex 2005;15:1676). SyS values were calculated (Ewers et al. Brain. 2021;144:2176) from 100 nodes defined by the Schaefer‐Yeo atlas (Fig 1a). Multiple linear regression investigated the associations between age, gender, cognitive function (MMSE and episodic memory), HPC volumes, APOE status and SyS as predictor variables and hs‐CRP as the dependent measure.ResultIn the adjusted model only SyS (β= ‐0.56, p<0.05) and APOE (β= ‐0.21, p=0.003) predicted hsCRP concentrations. Global SyS was negatively related to hsCRP (Fig 1b). As in Wang et al (2022), APOE E4 carriers (N=71; mean:‐0.43; SD=0.62) exhibited lower CRP circulating levels than non‐E4 bearers (N=265; mean: ‐0.20; SD=0.51; t=3.23, p<0.001), however there were no differences in SyS according to APOE genotypes (t=0.95, p=0.34).Conclusionhs‐CRP blood concentrations were predicted by global segregation of functional networks in absence of HPC volume or cognitive status effects. As such, blood derived hsCRP levels may represent an early indicator of middle‐age individual variations in a measure recently reported to predict future cognitive decline (Chan et al. Nat Aging 2021;1:1053) and represent a cognitive resilience mechanism in the face of AD pathology (Ewers et al. Brain. 2021;144:2176).

Substantia nigra integrity is associated with poorer recognition memory for novel stimuli in early Alzheimer’s disease

AbstractBackgroundThe substantia nigra/ventral tegmental area (SN/VTA), the brain’s most prominent dopamine source, is involved in novelty exploration and episodic memory. Using a novelty detection task combined with neuromelanin‐sensitive MRI, this work aimed to investigate the relationship between SN integrity, neural novelty response and subsequent recognition memory performance in individuals with early Alzheimer’s disease.Method79 healthy subjects, 54 participants with subjective cognitive decline (SCD), 18 with mild cognitive impairment (MCI), and 10 individuals with ADD from the DZNE Longitudinal Cognitive Impairment and Dementia (DELCODE) study performed a previously published scene novelty and encoding task (“FADE”) using 3T fMRI. Additional 3D T1‐weighted FLASH images were collected to visualize and quantify the volume and MRI contrast in the SN.Linear regression models were generated to assess for associations between either SN volume and median MRI contrast, considered as proxy integrity measures, with functional activity during novelty and subsequent recognition memory performance (dprime). We used site, gender, age and years of education as covariates. We assessed AD pathology in a subsample of individuals with CSF biomarkers (n = 71).ResultWe observed a significant decline in SN volume (p = 0.003) but not MRI contrast in ADD compared to healthy controls. The SN volume in the whole sample correlated positively with recognition memory for novel stimuli (r = 0.35; p = 0.02,). This association held in the CSF subsample (r = 0.31; p = 0.034) and also after correcting for levels of both tau (phosphotau, r = 0.57; p = 0.0284,) and amyloid (Abeta 42/40 ratio, r = 0.46; p = 0.03,). Additionally, SN median MRI contrast significantly correlated with novelty responses in the hippocampus in the CSF subsample and also in amyloid positive but not negative (Abeta 42/40 ratio<0.08, n = 26) individuals. Finally, recognition memory (p<0.001) was significantly decreased in Abeta positive compared to negative individuals.ConclusionWe show that significant degeneration to the SN in AD dementia and pathological Abeta 42/40 levels are associated with poorer recognition memory for novel stimuli. Moreover, associations between SN median MRI contrast and novelty responses differed between amyloid positive and negative individuals. These results indicate that degeneration to the SN may contribute to memory dysfunction in AD dementia which may be linked to pathological amyloid levels.

White matter integrity as a mediator between socioeconomic status and executive function.

Lower socioeconomic status (SES) is associated with poorer executive function, but the neural mechanisms of this association remain unclear. As healthy brain communication is essential to our cognitive abilities, white matter integrity may be key to understanding socioeconomic disparities. Participants were 201 African American and White adults (ages 33-72) from the Healthy Aging in Neighborhoods of Diversity across the Life Span (HANDLS) SCAN study. Diffusion tensor imaging was used to estimate regional fractional anisotropy as a measure of white matter integrity. Adjusting for age, analyses examined if integrity of the anterior limb of the internal capsule (ALIC), external capsule (EC), superior longitudinal fasciculus (SLF), and cingulum mediated SES-executive function relations. Lower SES was related to poorer cognitive performance and white matter integrity. Lower Trails B performance was related to poorer integrity of the ALIC, EC, and SLF, and lower Stroop performance was associated with poorer integrity of the ALIC and EC. ALIC mediated the SES-Trails B relation, and EC mediated the SES-Trails B and SES-Stroop relations. Sensitivity analyses revealed that (1) adjustment for race rendered the EC mediations non-significant, (2) when using poverty status and continuous education as predictors, results were largely the same, (3) at least some of the study's findings may generalize to processing speed, (4) mediations are not age-dependent in our sample, and (5) more research is needed to understand the role of cardiovascular risk factors in these models. Findings demonstrate that poorer white matter integrity helps explain SES disparities in executive function and highlight the need for further clarification of the biopsychosocial mechanisms of the SES-cognition association.

Effects of a nutritional intervention on impaired behavior and cognitive function in an emphysematous murine model of COPD with endotoxin-induced lung inflammation.

One cluster of the extrapulmonary manifestations in chronic obstructive pulmonary disease (COPD) is related to the brain, which includes anxiety, depression and cognitive impairment. Brain-related comorbidities are related to worsening of symptoms and increased mortality in COPD patients. In this study, a murine model of COPD was used to examine the effects of emphysema and repetitive pulmonary inflammatory events on systemic inflammatory outcomes and brain function. In addition, the effect of a dietary intervention on brain-related parameters was assessed. Adult male C57Bl/6J mice were exposed to elastase or vehicle intratracheally (i.t.) once a week on three consecutive weeks. Two weeks after the final administration, mice were i.t. exposed to lipopolysaccharide (LPS) or vehicle for three times with a 10 day interval. A dietary intervention enriched with omega-3 PUFAs, prebiotic fibers, tryptophan and vitamin D was administered from the first LPS exposure onward. Behavior and cognitive function, the degree of emphysema and both pulmonary and systemic inflammation as well as blood-brain barrier (BBB) integrity and neuroinflammation in the brain were assessed. A lower score in the cognitive test was observed in elastase-exposed mice. Mice exposed to elastase plus LPS showed less locomotion in the behavior test. The enriched diet seemed to reduce anxiety-like behavior over time and cognitive impairments associated with the presented COPD model, without affecting locomotion. In addition, the enriched diet restored the disbalance in splenic T-helper 1 (Th1) and Th2 cells. There was a trend toward recovering elastase plus LPS-induced decreased expression of occludin in brain microvessels, a measure of BBB integrity, as well as improving expression levels of kynurenine pathway markers in the brain by the enriched diet. The findings of this study demonstrate brain-associated comorbidities - including cognitive and behavioral impairments - in this murine model for COPD. Although no changes in lung parameters were observed, exposure to the specific enriched diet in this model appeared to improve systemic immune disbalance, BBB integrity and derailed kynurenine pathway which may lead to reduction of anxiety-like behavior and improved cognition.

Multimodal-neuroimaging machine-learning analysis of motor disability in multiple sclerosis.

Motor disability is a dominant and restricting symptom in multiple sclerosis, yet its neuroimaging correlates are not fully understood. We apply statistical and machine learning techniques on multimodal neuroimaging data to discriminate between multiple sclerosis patients and healthy controls and to predict motor disability scores in the patients. We examine the data of sixty-four multiple sclerosis patients and sixty-five controls, who underwent the MRI examination and the evaluation of motor disability scales. The modalities used comprised regional fractional anisotropy, regional grey matter volumes, and functional connectivity. For analysis, we employ two approaches: high-dimensional support vector machines run on features selected by Fisher Score (aiming for maximal classification accuracy), and low-dimensional logistic regression on the principal components of data (aiming for increased interpretability). We apply analogous regression methods to predict symptom severity. While fractional anisotropy provides the classification accuracy of 96.1% and 89.9% with both approaches respectively, including other modalities did not bring further improvement. Concerning the prediction of motor impairment, the low-dimensional approach performed more reliably. The first grey matter volume component was significantly correlated (R = 0.28-0.46, p < 0.05) with most clinical scales. In summary, we identified the relationship between both white and grey matter changes and motor impairment in multiple sclerosis. Furthermore, we were able to achieve the highest classification accuracy based on quantitative MRI measures of tissue integrity between patients and controls yet reported, while also providing a low-dimensional classification approach with comparable results, paving the way to interpretable machine learning models of brain changes in multiple sclerosis.

Abstract 10514: Compromised Cerebral Artery Integrity is Associated With Brain Tissue Injury and Cognition Deficits in Adolescents With Complex Congenital Heart Disease

Introduction: Adolescents with complex congenital heart disease (CCHD) show brain tissue injury in regions associated with cognitive deficits. Alteration in cerebral artery integrity (CAI), as measured by arterial transit time (ATT), may lead to perfusion deficits, and be a potential cause of brain injury in CCHD. To date, there are no reports of CAI in CCHD or associations between CAI, brain tissue integrity, and cognition in CCHD. Methods: 70 subjects (37 CCHD / 33 controls), 14-18 years of age, undergone surgical palliation (CCHD), and no contraindications for a magnetic resonance imaging (MRI) and healthy controls (age- and sex-matched) participated. Participants completed cognitive testing (Montreal Assessment of Cognition [MoCA] and the Wide Range Assessment of Memory and Learning [General Memory Index, GMI]) and brain MRI using 3.0 Tesla scanner. ATT values (via diffusion-weighted pseudo-continuous arterial spin labeling [pCASL] procedures), and regional brain mean diffusivity [MD] (measure of tissue integrity) were computed in whole brain. Descriptive, partial correlations, and ANCOVA analyses used (covariates, age and sex). Results: Mean MoCA [23.1 ± 4.1 vs. 28.1 ± 2.3; p &lt;.001] and GMI scores [86.8 ± 15.4 vs. 110.3 ± 14.5; p&lt;.001] show significant cognitive deficits in CCHD compared to controls. ATT was significantly increased in CCHD vs controls (mean ± SD, sec, 1.3±0.13 vs 1.22±0.13, p=0.02), respectively, indicating compromised CAI. Partial correlations between ATT, MD values, and cognition (covariates, age and sex, p&lt; 0.005) showed significant associations in various areas including the hippocampus, prefrontal cortices, cerebellum, frontal white matter, anterior and posterior cingulate, frontal cortex, temporal cortices, and midbrain. Conclusion: Adolescents with CCHD have prolonged ATTs compared to controls indicative of compromised CAI and altered cerebral perfusion. CAI is significantly associated with alterations in regional brain tissue integrity and cognitive impairment. Further evaluation is needed to test interventions to increase cerebral perfusion and to protect neural tissue.

Exploring stop signal reaction time over two sessions of the anticipatory response inhibition task

Various behavioural tasks measure response inhibition encompassing the ability to cancel unwanted actions, evaluated via stop signal reaction time (SSRT). It is unclear whether SSRT is an unchangeable inherent measure of inhibitory network integrity or whether it can improve with repetition. The current study explored if and how SSRT changed over two sessions for the Anticipatory Response Inhibition Task (ARIT), and how this compared with the Stop Signal Task (SST). Forty-four participants repeated the ARIT and SST over two sessions. SSRT and its constituent measures (Go trial reaction time, stop signal delay) were calculated. SSRT reflecting non-selective response inhibition was consistent between sessions in the ARIT and SST (both p > 0.293). Reaction time and stop signal delay also remained stable across sessions in the ARIT (all p > 0.063), whereas in the SST, reaction time (p = 0.013) and stop signal delay (p = 0.009) increased. SSRT reflecting behaviourally selective stopping on the ARIT improved (p < 0.001) over two sessions, which was underpinned by changes to reaction time (p < 0.001) and stop signal delay (p < 0.001). Overall, the maximal efficiency of non-selective inhibition remained stable across two sessions in the ARIT. Results of the SST confirmed that non-selective inhibition can, however, be affected by more than inhibitory network integrity. Behaviourally selective stopping on the ARIT changed across sessions, suggesting the sequential neural process captured by the SSRT occurred more quickly in session two. These findings have implications for future studies that necessitate behavioural measures over multiple sessions.

Neurophysiologic predictors of individual risk for post-operative delirium after elective surgery.

Post-surgical delirium is associated with increased morbidity, lasting cognitive decline, and loss of functional independence. Within a conceptual framework that delirium is triggered by stressors when vulnerabilities exist in cerebral connectivity and plasticity, we previously suggested that neurophysiologic measures might identify individuals at risk for post-surgical delirium. Here we demonstrate the feasibility of the approach and provide preliminary experimental evidence of the predictive value of such neurophysiologic measures for the risk of delirium in older persons undergoing elective surgery. Electroencephalography (EEG) and transcranial magnetic stimulation (TMS) were collected from 23 patients prior to elective surgery. Resting-state EEG spectral power ratio (SPR) served as a measure of integrity of neural circuits. TMS-EEG metrics of plasticity (TMS-plasticity) were used as indicators of brain capacity to respond to stressors. Presence or absence of delirium was assessed using the confusion assessment method (CAM). We included individuals with no baseline clinically relevant cognitive impairment (MoCA scores ≥21) in order to focus on subclinical neurophysiological measures. In patients with no baseline cognitive impairment (N=20, age=72 ± 6), 3 developed post-surgical delirium (MoCA=24 ± 2.6) and 17 did not (controls; MoCA=25 ± 2.4). Patients who developed delirium had pre-surgical resting-state EEG power ratios outside the 95% confidence interval of controls, and 2/3 had TMS-plasticity measures outside the 95% CI of controls. Consistent with our proposed conceptual framework, this pilot study suggests that non-invasive and scalable neurophysiologic measures can identify individuals at risk of post-operative delirium. Specifically, abnormalities in resting-state EEG spectral power or TMS-plasticity may indicate sub-clinical risk for post-surgery delirium. Extension and confirmation of these findings in a larger sample is needed to assess the clinical utility of the proposed neurophysiologic markers, and to identify specific connectivity and plasticity targets for therapeutic interventions that might minimize the risk of delirium.

Alpha-Lipoic Acid Ameliorates Sperm DNA Damage and Chromatin Integrity in Men with High DNA Damage: A Triple Blind Randomized Clinical Trial.

Evidence suggests the contributory role of oxidative stress (OS) to sperm DNA damage and eventually, male infertility. Antioxidant supplementation has exhibited favorable results regarding seminal OS, sperm DNA damage, and chromatin integrity. We aimed to evaluate the effect of alpha-lipoic acid (ALA) supplementation on semen analysis, sperm DNA damage, chromatin integrity, and seminal/intracellular OS in infertile men with high sperm DNA damage. In this randomized triple-blind placebo-controlled clinical trial study, we opted for a triple-blind controlled clinical trial design. Considering the study's inclusion criteria for the level of sperm DNA fragmentation (higher than the threshold of 30 and 15%), 70% of participants were selected for this clinical research study. Subjects were divided into case and control groups receiving oral ALA (600 mg/day) and placebo for eighty days, respectively. Sperm parameters and functional tests were examined and compared before and after treatment. The final sample size was 34 and 29 for ALA and placebo receivers, respectively. No significant differences were observed about anthropometrics and baseline measures of semen analysis, DNA damage, OS, and chromatin integrity between the two groups. Conventional semen parameters were enhanced insignificantly in both groups (P>0.05). DNA damage decreased significantly in the ALA group, as per sperm chromatin structure assay (SCSA, P<0.001). Moreover, chromomycin A3 (CMA3) staining results indicated a decrease in nuclear protamine deficiency post-ALA therapy (P=0.004). Lipid peroxidation decreased significantly after treatment with ALA (P=0.003). Further, seminal antioxidant capacity/activity did not differ significantly in either of the groups (registration number: IRCT20190406043177N1). An 80-day course of oral ALA supplementation (600 mg/day) alleviates sperm OS, DNA damage, and chromatin integrity in men with high sperm DNA damage.

Predicting to Improve: Integrity Measures for Assessing Visual Localization Performance

Visual Place Recognition (VPR) is a key component of many robot localization and mapping system processing pipelines, providing loop closure and coarse topological localization priors for pose refinement stages. When deploying these systems in the real-world, system self-characterization of when it is performing well or poorly can be more important than absolute performance. In this research, we demonstrate a new supervised learning approach to predicting localization integrity on a frame-by-frame basis along a route, using artefacts from the localization technique itself. Our method involves a lightweight post-processing step that is VPR technique-agnostic; it can be calibrated for any given place recognition technique, such that inaccurate localization points along a route can be identified and discarded. Unlike the normal parameter sweeping evaluation of a VPR system, which directly trades precision for recall, when deployed on a baseline VPR system our approach improves the precision without significantly reducing recall, resulting in improved average localization performance. Over twelve combinations of varied datasets and VPR techniques, we demonstrate our approach is able to predict localization errors with an average precision of 74%, resulting in an improvement in mean localization accuracy.

PSV-A-7 Quality Assessments of Sperm from Gnrh-II Receptor Knockdown (KD) Boars

Abstract Pigs are the only livestock species encoding functional proteins for both the second form of gonadotropin-releasing hormone (GnRH-II) and its receptor (GnRHR-II). Previously, we determined that GnRHR-II localizes to the connecting piece of ejaculated sperm, whereas GnRH-II is present within seminal plasma, suggesting an autocrine/paracrine interaction influencing porcine sperm function. To examine the GnRH-II/GnRHR-II system further, we produced a swine line with reduced endogenous expression of GnRHR-II (GnRHR-II KD). Therefore, our objective was to assess sperm quality of ejaculates collected from GnRHR-II KD (n = 3) and littermate control (n = 3) boars. Semen was extended (37.5 x 106 sperm/mL) in Androstar Plus and subjected to flow cytometry (Kuster Research and Consulting, Inc.; Atkinson, IL). Assays measured DNA compaction, membrane fluidity and viability, acrosome integrity, mitochondrial depolarization, and morphology. Data were analyzed using the MIXED procedure of SAS; the model included ejaculate as the experimental unit and line as a fixed effect. DNA compaction, membrane fluidity, acrosome integrity, mitochondrial depolarization, and morphology were not statistically different between lines (P &amp;gt; 0.05). However, the percentage of sperm with a viable (intact) plasma membrane was reduced in GnRHR-II KD boars (87.4 ± 0.8%) compared with controls (89.6 ± 0.8%; P &amp;lt; 0.05). Although differences did not reach significance, DNA compaction (a measure of sperm chromatin integrity when undergoing acid stress) was doubled and mitochondrial depolarization (reflective of mitochondrial function) was 11% greater in sperm from transgenic males relative to littermate controls, indicating that GnRHR-II KD sperm are more susceptible to environmental stressors and have altered energy production. Thus, these initial data suggest disruptions in the function and fertilizing capacity of GnRHR-II KD sperm, implying that GnRHR-II may represent a potential biomarker for boar fertility. Supported by USDA/NIFA AFRI (2017-67015-26508) and Hatch Multistate (NEB-26-244) funds. USDA is an equal opportunity provider and employer.

Correlation between per- and polyfluoroalkyl substances (PFAS) in seminal plasma and semen quality parameters in firefighters

BACKGROUND AND AIM For decades firefighters have used aqueous film-forming foam (AFFF) to extinguish specific types of fires. Some of the AFFF formulations contains per- and polyfluoroalkyl substances (PFASs). PFASs exposure was reported to induce male reproductive toxicity in toxicological studies. Further current epidemiological studies linked increased exposure to PFASs with lowered testosterone and semen quality. As firefighters are exposed during their service to PFASs to a much greater extent than the general population we aim to evaluate the associations between occupational exposure to PFASs and semen quality and spermatozoa DNA damage. METHODS We developed an analytical method based on solid phase extraction followed by liquid chromatography tandem mass spectrometry (LC/MSMS) to detect selected PFASs in human seminal plasma. Subsequently, concentrations of PFASs in seminal plasma were determined among 23 firefighters recruited from a local fire-training center. The relationship between PFASs concentrations with semen quality parameters and DNA integrity will be addressed by statistical methods. RESULTS We screened in total for 16 PFASs in seminal plasma commonly found in AFFF. The highest detection frequency was observed for perfluorooctanoic acid (PFOA). Associations of PFASs concentrations with semen quality parameters, DNA integrity measures will be assessed by logistic or linear regression models with adjustment for potential confounders. CONCLUSIONS Several PFASs were detected in seminal plasma samples of male firefighters. Further we aim to test the potential effect of the substances on semen quality. KEYWORDS Male infertility, occupational exposure, firefighters, per- and polyfluoroalkyl substances, spermatozoa

Association of Cerebral Blood Flow With Longitudinal Changes in Cerebral Microstructural Integrity in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

Decreased cerebral tissue integrity and cerebral blood flow (CBF) are features of neurodegenerative diseases. Brain tissue maintenance is an energy-demanding process, making it particularly sensitive to hypoperfusion. However, little is known about the association between blood flow and brain microstructural integrity, including in normative aging. To assess associations between CBF and changes in cerebral tissue integrity in white matter and gray matter brain regions. In this longitudinal cohort study, magnetic resonance imaging was performed on 732 healthy adults from the Coronary Artery Risk Development in Young Adults (CARDIA) study, a prospective longitudinal study (baseline age of 18-30 years) that examined participants up to 8 times during 30 years (1985-1986 to 2015-2016). Cerebral blood flow was measured at baseline (year 25 of the CARDIA study), and changes in diffusion tensor indices of fractional anisotropy (FA) and mean diffusivity (MD), measures of microstructural tissue integrity, were measured at both baseline and after approximately 5 years of follow-up (year 30). Analyses were conducted from November 5, 2020, to January 29, 2022. Automated algorithms and linear mixed-effects statistical models were used to evaluate the associations between CBF at baseline and changes in FA or MD. After exclusion of participants with missing or low-quality data, 654 at baseline (342 women; mean [SD] age, 50.3 [3.5] years) and 433 at follow-up (230 women; mean [SD] age, 55.1 [3.5] years) were scanned for CBF or FA and MD imaging. In the baseline cohort, 247 participants were Black (37.8%) and 394 were White (60.2%); in the follow-up cohort, 156 were Black (36.0%) and 277 were White (64.0%). Cross-sectionally, FA and MD were associated with CBF in most regions evaluated, with lower CBF values associated with lower FA or higher MD values, including the frontal white matter lobes (for CBF and MD: mean [SE] β = -1.4 [0.5] × 10-6; for CBF and FA: mean [SE] β = 2.9 [1.0] × 10-4) and the parietal white matter lobes (for CBF and MD: mean [SE] β = -2.4 [0.6] × 10-6; for CBF and FA: mean [SE] β = 4.4 [1.1] × 10-4). Lower CBF values at baseline were also significantly associated with steeper regional decreases in FA or increases in MD in most brain regions investigated, including the frontal (for CBF and MD: mean [SE] β = -1.1 [0.6] × 10-6; for CBF and FA: mean [SE] β = 2.9 [1.0] × 10-4) and parietal lobes (for CBF and MD: mean [SE] β = -1.5 [0.7] × 10-6; for CBF and FA: mean [SE] β = 4.4 [1.1] × 10-4). Results of this longitudinal cohort study of the association between CBF and diffusion tensor imaging metrics suggest that blood flow may be significantly associated with brain tissue microstructure. This work may lay the foundation for investigations to clarify the nature of early brain damage in neurodegeneration. Such studies may lead to new neuroimaging biomarkers of brain microstructure and function for disease progression.