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Abstract Regular physical activity is associated with healthier brains and improved cognition among older adults. Yet, the impact of a short bout of exercise on older adults’ cognition still is not fully clarified. The present study explored the effects of 20 min of moderate-intensity aerobic exercise (on a cycle ergometer) on cognition. Forty-eight healthy older adults were randomly assigned to an exercise or a control group and completed four cognitive tests: Affective Go/No-Go (AGN), Simple Reaction Time (SRT), Spatial Working Memory (SWM) and a Backward Counting task. Tests were administered prior to and immediately after 20 min of cycling (exercise group) or rest (control group). Mixed-design 2 × 2 ANOVAs indicated a significant interaction of Group x Session, for commission errors on the positive valence of the Affective Go/No-go task, indicating that the exercise group performed better on one aspect of this inhibition test after cycling (p = 0.004), while the control group’s performance declined after rest. A similar pattern was found for the SWM, with the exercise group showing a significantly better performance after the exercise both for total error (p = 0.027) and the strategy (p = 0.002), while no improvement was observed after rest (controls). The study suggests that inhibitory control functions and working memory may be improved by a single relatively short bout of moderate exercise. However, the null effects of exercise on the other cognitive measures indicate that the neurocognitive benefits of acute exercise for older adults may be selectively sensitive to exercise parameters and to specific aspects of cognition.

Abstract Higher cardiorespiratory fitness has been associated with improved cognitive control in preadolescent children, with various studies highlighting related brain health benefits. This cross-sectional study aimed to provide novel insights into the fitness-cognition relationship by investigating task-related changes in effective connectivity within two brain networks involved in cognitive control: the cingulo-opercular and fronto-parietal networks. Twenty-four higher-fit and twenty-four lower-fit preadolescent children completed a modified flanker task that modulated inhibitory control demand while their EEG and task performance were concurrently recorded. Effective connectivity for correct trials in the theta band was estimated using directed transfer function. The results indicate that children with higher fitness levels demonstrated greater connectivity in specific directions within the cingulo-opercular network (average effect size, d = 0.72). Brain-behavior correlations demonstrated a positive association between the majority of these connections and general task accuracy, which was also higher in higher fit children (average correlation coefficient, ρ = 0.34). The findings further support a positive relationship between fitness and cognitive performance in children. EEG findings offer novel insights into the potential brain mechanisms underlying the fitness-cognition relationship. The study suggests that increased task-related connectivity within the cingulo-opercular network may mediate the cognitive benefits associated with higher fitness levels in preadolescent children.

BackgroundCognitive errors involve negatively biased or distorted thinking patterns that can hinder effective decision-making. When such a phenomenon occurs in the exercise domain, this is referred to as exercise-related cognitive error. Such exercise-related cognitive errors are typically assessed via a questionnaire, but a validated instrument for the application in Chinese-speaking populations is lacking. Thus, this study aims to validate the Chinese version of the Exercise-related Cognitive Errors Questionnaire (E-CEQ-C) among Chinese emerging adults, a self-report measure to evaluate cognitive errors of context-relevant information related to exercise.MethodsFollowing a forward-backward translation of the E-CEQ (N = 24 items), the E-CEQ-C and the Chinese version of the Cognitive Distortions Questionnaire (CD-Quest-C) for gathering evidence of criterion-related validity were administered among a sample of Chinese emerging adults (N = 376, 29.0% male) through an online survey. After a two-week interval, 105 out of 376 participants attended a re-test of the E-CEQ-C. Item analysis, confirmatory factor analysis (CFA), internal consistency, test–retest reliability, and concurrent validity were analyzed.ResultsThe findings from the CFA support the 24-item informed six-factor structure among Chinese emerging adults (χ2 = 699.038, RMSEA = 0.073, CFI = 0.919, TLI = 0.904, and SRMR = 0.055). Cronbach’s α of the six dimensions of the E-CEQ-C were all above 0.7. The test–retest reliability coefficients of each subscale and total scale were acceptable, ranging from 0.60 to 0.81. In accordance with the literature, we also observed positive associations between the six dimensions of E-CEQ-C and the constructs of the CD-Quest-C, which provided concurrent validity evidence for the E-CEQ-C.ConclusionThis study showed that E-CEQ-C is a psychometrically sound measure to assess exercise-related cognitive errors in Chinese-speaking populations.

Abstract Acknowledging the detrimental effects of prolonged sitting, this study examined the effects of an acute exercise break during prolonged sitting on executive function, cortical hemodynamics, and microvascular status. In this randomized crossover study, 71 college students completed three conditions: (i) uninterrupted sitting (SIT); (ii) SIT with a 15 min moderate‐intensity cycling break (MIC); and (iii) SIT with a 15 min vigorous‐intensity cycling break (VIC). Behavioral outcomes, retinal vessel diameters (central retinal artery equivalents [CRAE], retinal vein equivalents [CRVE], arteriovenous ratio [AVR]), cortical activation, and effective connectivity were evaluated. Linear mixed models identified significant positive effects of exercise conditions on behavioral reaction time (RT), error rate, and inverse efficiency score (β = −2.62, −0.19, −3.04: ps < 0.05). MIC and VIC conditions produced pre‐to‐post‐intervention increases in CRAE and CRVE (β = 4.46, 6.34), frontal activation, and resting‐state and task‐state causal density (β = 0.37, 0.06) (ps < 0.05) compared to SIT; VIC was more beneficial for executive function and neurobiological parameters. The effect of AVR on average RT was mediated through task‐based causal density (indirect effect: −0.82). Acutely interrupting prolonged sitting improves executive function, microvascular status, and cortical activation and connectivity, with causal density mediating the microvascular‐executive function link.

ObjectiveAge-related hippocampal atrophy is associated with memory loss in older adults, and certain hippocampal subfields are more vulnerable to age-related atrophy than others. Cardiorespiratory fitness (CRF) may be an important protective factor for preserving hippocampal volume, but little is known about how CRF relates to the volume of specific hippocampal subfields, and whether associations between CRF and hippocampal subfield volumes are related to episodic memory performance. To address these gaps, the current study evaluates the associations among baseline CRF, hippocampal subfield volumes, and episodic memory performance in cognitively unimpaired older adults from the Investigating Gains in Neurocognition Trial of Exercise (IGNITE) (NCT02875301).MethodsParticipants (N = 601, ages 65–80, 72% female) completed assessments including a graded exercise test measuring peak oxygen comsumption (VO2peak) to assess CRF, cognitive testing, and high-resolution magnetic resonance imaging of the hippocampus processed with Automated Segmentation of Hippocampal Subfields (ASHS). Separate linear regression models examined whether CRF was associated with hippocampal subfield volumes and whether those assocations were moderated by age or sex. Mediation models examined whether hippocampal volumes statistically mediated the relationship between CRF and episodic memory performance. Covariates included age, sex, years of education, body mass index, estimated intracranial volume, and study site.ResultsHigher CRF was significantly associated with greater total left (B = 5.82, p = 0.039) and total right (B = 7.64, p = 0.006) hippocampal volume, as well as greater left CA2 (B = 0.14, p = 0.022) and dentate gyrus (DG; B = 2.34, p = 0.031) volume, and greater right CA1 (B = 3.99, p = 0.011), CA2 (B = 0.15, p = 0.002), and subiculum (B = 1.56, p = 0.004) volume. Sex significantly moderated left DG volume (B = −4.26, p = 0.017), such that the association was positive and significant only for males. Total left hippocampal volume [indirect effect = 0.002, 95% CI (0.0002, 0.00), p = 0.027] and right subiculum volume [indirect effect = 0.002, 95% CI (0.0007, 0.01), p = 0.006] statistically mediated the relationship between CRF and episodic memory performance.DiscussionWhile higher CRF was significantly associated with greater total hippocampal volume, CRF was not associated with all underlying subfield volumes. Our results further demonstrate the relevance of the associations between CRF and hippocampal volume for episodic memory performance. Finally, our results suggest that the regionally-specific effects of aging and Alzheimer’s disease on hippocampal subfields could be mitigated by maintaining higher CRF in older adulthood.

BackgroundThe study aimed to validate the Cravings for Rest and Volitional Energy Expenditure (CRAVE) scale among Chinese adults with different health conditions (healthy control, chronic illnesses, and psychiatric disorders) and skill levels (athletes vs. non-athletes).MethodsIn Study 1, a confirmatory factor analysis (CFA) using the Maximum Likelihood Method (MLM) was performed on a Chinese sample of emerging adults (N = 481) to evaluate the structural validity of the Cravings for Rest and Volitional Energy Expenditure-Chinese version (CRAVE-C). In Study 2, differences in “Move” and “Rest” desires were examined among patients with psychiatric disorders, patients with chronic illnesses, and healthy controls. In study 3, investigated the relationship between cardiorespiratory fitness and exercise motivation using the CRAVE-C (N = 83). In Study 4, the changes in “Move” desire from baseline to post-training were compared between athletes and non-athletes.ResultsResults from Study 1 indicated that the 10-item CRAVE-C showed good fit indices (Chi2 (34) = 118.769, CFI = 0.95, TLI = 0.934, SRMR = 0.053, RMSEA = 0.072). “Move” positively correlated with various factors of the Affective Exercise Experiences Questionnaire-Chinese and the Physical Effort Scale-Chinese, while “Rest” correlated negatively. In Study 2, Patients with psychiatric disorders had a significantly higher “Move” desire than healthy controls. Patients with chronic illnesses had a significantly higher “Rest” desire than healthy controls. In Study 3, higher cardiorespiratory fitness was associated with a slight increase in “Move” desire (3.26% ± 37.35%) and a decrease in “Rest” desire (18.94% ± 66.99%). Lower fitness was linked to a significant decline in “Move” desire (−54.61% ± 111.33%) and an increase in “Rest” desire (43.62% ± 63.64%). In Study 4, the athlete group demonstrated a significant increase in “Move” desire from baseline to post-training, whereas the non-athlete group reported a significant decrease in “Move” desire from baseline to post-training.ConclusionThe 10-item CRAVE-C has good reliability and validity in the Chinese cultural context and can be used among Chinese adults with different health conditions and skill levels.

The motoric cognitive risk syndrome (MCR) is a syndrome characterized by subjective memory complaints and slow walking speeds that can identify older adults at increased risk for developing Alzheimer’s disease or a related dementia (ADRD). To date, the feasibility of community-based physical activity (PA) programs for improving outcomes in MCR have yet to be examined. To address this knowledge gap, we conducted a translational randomized controlled trial (RCT) comparing 24-weeks of PA to a healthy aging education (HE) control intervention delivered within the infrastructure of an urban senior center in Greater Boston (clincaltrials.gov identifier: NCT03750682). An existing senior center employee was trained to administer the multimodal group-based PA program that included moderate-intensity aerobic walking, strength, flexibility and balance training. A total of 79 older adults attended the senior center for a screening visit, of whom 29 met the MCR criteria and 25 were randomized to PA or HE (mean age: 74.4 ± 7 years; BMI: 32.4 ± 7 kg/m2; 85% female; 3MSE score: 92.4 ± 7; gait speed: 0.52 ± 0.1 m/s; SPPB score 4.8 ± 1.9). Due to the Covid-19 pandemic the study was stopped prematurely. Participants could successfully adhere to the study interventions (overall attendance rate: PA: 69% vs. HE:70% at study termination). Participants also successfully completed baseline and follow-up study assessments that included a computerized cognitive testing battery and objective tests of physical performance and functional exercise capacity. No study-related adverse events occurred. Notable trends for improved cognitive performance, gait speed and 6-min walk distance were exhibited in PA compared to HE. Our study provides important preliminary information to aid the design of larger-scale RCTs of PA that may help to preserve the independence of vulnerable older adults at high risk for ADRD in community-based settings.

Background: There is a growing interest to understand the neurobiological mechanisms that drive the positive associations of physical activity and fitness with measures of cognitive performance. To better understand those mechanisms, several studies have employed eye-based measures (e.g., eye movement measures such as saccades, pupillary measures such as pupil dilation, and vascular measures such as retinal vessel diameter) deemed to be proxies for specific neurobiological mechanisms. However, there is currently no systematic review providing a comprehensive overview of these studies in the field of exercise-cognition science. Thus, this review aimed to address that gap in the literature. Methods: To identify eligible studies, we searched 5 electronic databases on October 23, 2022. Two researchers independently extracted data and assessed the risk of bias using a modified version of the Tool for the assEssment of Study qualiTy and reporting in EXercise (TESTEX scale, for interventional studies) and the critical appraisal tool from the Joanna Briggs Institute (for cross-sectional studies). Results: Our systematic review (n = 35 studies) offers the following main findings: (a) there is insufficient evidence available to draw solid conclusions concerning gaze-fixation-based measures; (b) the evidence that pupillometric measures, which are a proxy for the noradrenergic system, can explain the positive effect of acute exercise and cardiorespiratory fitness on cognitive performance is mixed; (c) physical training- or fitness-related changes of the cerebrovascular system (operationalized via changes in retinal vasculature) are, in general, positively associated with cognitive performance improvements; (d) acute and chronic physical exercises show a positive effect based on an oculomotor-based measure of executive function (operationalized via antisaccade tasks); and (e) the positive association between cardiorespiratory fitness and cognitive performance is partly mediated by the dopaminergic system (operationalized via spontaneous eye-blink rate). Conclusion: This systematic review offers confirmation that eye-based measures can provide valuable insight into the neurobiological mechanisms that may drive positive associations between physical activity and fitness and measures of cognitive performance. However, due to the limited number of studies utilizing specific methods for obtaining eye-based measures (e.g., pupillometry, retinal vessel analysis, spontaneous eye blink rate) or investigating a possible dose–response relationship, further research is necessary before more nuanced conclusions can be drawn. Given that eye-based measures are economical and non-invasive, we hope this review will foster the future application of eye-based measures in the field of exercise-cognition science.

Aging contributes significantly to cognitive decline. Aerobic exercise (AE) has been shown to induce substantial neuroplasticity changes, enhancing cognitive and brain health. Likewise, recent research underscores the cognitive benefits of foreign language learning (FLL), indicating improvements in brain structure and function across age groups. However, the lack of a comprehensive paradigm integrating language learning with exercise limits research on combined effects in older adults. In order to address this gap, we devised a novel approach using a virtual world tourism scenario for auditory-based language learning combined with aerobic cycling. Our study examines the impact of simultaneous AE and FLL integration on cognitive and language learning outcomes compared to FLL alone. A total of 20 older adults were randomly assigned to AE + FLL and FLL-only groups. The results revealed significantly improved Spanish language learning outcomes in both combined and language learning-only groups. Additionally, significant cognitive function improvement was observed in the FLL group following short-term language learning.

As the emerging treatments that target grey matter pathology in Alzheimer's Disease have limited effectiveness, there is a critical need to identify new neural targets for treatments. White matter's (WM) metabolic vulnerability makes it a promising candidate for new interventions. This study examined the age and sex differences in estimates of axonal content, as well the associations of with highly prevalent modifiable health risk factors such as metabolic syndrome and adiposity. We estimated intra-axonal volume fraction (ICVF) using the Neurite Orientation Dispersion and Density Imaging (NODDI) in a sample of 89 cognitively and neurologically healthy adults (20–79 years). We showed that ICVF correlated positively with age and estimates of myelin content. The ICVF was also lower in women than men, across all ages, which difference was accounted for by intracranial volume. Finally, we found no association of metabolic risk or adiposity scores with the current estimates of ICVF. In addition, the previously observed adiposity-myelin associations (Burzynska et al., 2023) were independent of ICVF. Although our findings confirm the vulnerability of axons to aging, they suggest that metabolic dysfunction may selectively affect myelin content, at least in cognitively and neurologically healthy adults with low metabolic risk, and when using the specific MRI techniques. Future studies need to revisit our findings using larger samples and different MRI approaches, and identify modifiable factors that accelerate axonal deterioration as well as mechanisms linking peripheral metabolism with the health of myelin.

The COVID-19 pandemic altered everyday life starting in March 2020. These alterations extended to the lives of children as their normal routines were disrupted by community lockdowns, online learning, limited in-person social contact, increased screen time, and reduced physical activity. Considerable research has investigated the physical health impact of COVID-19 infection, but far fewer studies have investigated the physiological impact of stressful pandemic-related changes to daily life, especially in children. The purpose of this study was to leverage an ongoing clinical trial to investigate physiological consequences associated with chronic stress of pandemic community lockdown on children. As a part of the clinical trial, children provided saliva samples. Saliva samples were analyzed for cortisol and salivary alpha amylase (sAA) content. This secondary cross-sectional analysis included 94 preadolescent children located within the Greater Boston, Massachusetts community. Children participated in the study either before, during, or following the pandemic community lockdown to form three groups for comparison. In response to chronic stress caused by the pandemic community lockdown, participants demonstrated dysregulation of fast-acting catecholamine response of the locus-coeruleus-norepinephrine system and slower-acting glucocorticoid response, resulting in an asymmetrical relationship of hypocortisolism (M = 0.78 ± 0.19 μg/mL, p

Abstract Prior research has demonstrated the importance of a healthy lifestyle to protect brain health and diminish dementia risk in later life. While a multidomain lifestyle provides an ecological perspective to voluntary engagement, its association with brain health is still under-investigated. Therefore, understanding the neural mechanisms underlying multidomain lifestyle engagement, particularly in older adults at risk for Alzheimer’s disease (AD), gives valuable insights into providing lifestyle advice and intervention for those in need. The current study included 139 healthy older adults with familial risk for AD from the Prevent-AD longitudinal aging cohort. Self-reported exercise engagement, cognitive activity engagement, healthy diet adherence, and social activity engagement were included to examine potential phenotypes of an individual’s lifestyle adherence. Two adherence profiles were discovered using data-driven clustering methodology [i.e., Adherence to healthy lifestyle (AL) group and Non-adherence to healthy lifestyle group]. Resting-state functional connectivity matrices and grey matter brain features obtained from magnetic resonance imaging were used to classify the two groups using a support vector machine (SVM). The SVM classifier was 75% accurate in separating groups. The features that show consistently high importance to the classification model were functional connectivity mainly between nodes located in different prior-defined functional networks. Most nodes were located in the default mode network, dorsal attention network, and visual network. Our results provide preliminary evidence of neurobiological characteristics underlying multidomain healthy lifestyle choices.

Highlights 1. Meeting the combination of all three 24-HMB guidelines, or a combination of screen time and physical activity, was associated with reduced odds of serious difficulties in concentrating, remembering, or making decisions. 2. Meeting the combination of all three 24-HMB guidelines was associated with reduced odds of difficulties making and keeping friends. 3. Meeting the 24-HMB guideline for screen time was associated with reduced odds of being bullied. 4. Meeting the individual guidelines for screen time or sleep duration or a combination of both was associated with reduced odds of bullying others.

Background: The Canadian 24-hour movement behavior (24-HMB) guidelines suggest that a limited amount of screen time use, an adequate level of physical activity (PA), and sufficient sleep duration are beneficial for ensuring and optimizing the health and quality of life (QoL) of children and adolescents. However, this topic has yet to be examined for children and adolescents with autism spectrum disorder (ASD) specifically. The aim of this cross-sectional observational study was to examine the associations between meeting 24-HMB guidelines and several QoL-related indicators among a national sample of American children and adolescents with ASD. Methods: Data were taken from the 2020 U.S. National Survey of Children's Health dataset. Participants (n = 956) aged 6–17 years and currently diagnosed with ASD were included. The exposure of interest was adherence to the 24-HMB guidelines. Outcomes were QoL indicators, including learning interest/curiosity, repeating grades, adaptive ability, victimization by bullying, and behavioral problems. Categorical variables were described with unweighted sample counts and weighted percentages. Age, sex, race, preterm birth status, medication, behavioral treatment, household poverty level, and the educational level of the primary caregivers were included as covariates. Odds ratio (OR) and 95% confidence interval (95%CI) were used to present the strength of association between adherence to 24-HMB guidelines and QoL-related indicators. Results: Overall, 452 participants (45.34%) met 1 of the 3 recommendations, 216 (22.65%) met 2 recommendations, whereas only 39 participants (5.04%) met all 3 recommendations. Compared with meeting none of the recommendations, meeting both sleep duration and PA recommendations (OR = 3.92, 95%CI: 1.63–9.48, p < 0.001) or all 3 recommendations (OR = 2.11, 95%CI: 1.03–4.35, p = 0.04) was associated with higher odds of showing learning interest/curiosity. Meeting both screen time and PA recommendations (OR = 0.15, 95%CI: 0.04–0.61, p < 0.05) or both sleep duration and PA recommendations (OR = 0.24, 95%CI: 0.07–0.87, p < 0.05) was associated with lower odds of repeating any grades. With respect to adaptive ability, participants who met only the PA recommendation of the 24-HMB were less likely to have difficulties dressing or bathing (OR = 0.11, 95%CI: 0.02–0.66, p < 0.05) than those who did not. For participants who met all 3 recommendations (OR = 0.38, 95%CI: 0.15–0.99, p = 0.05), the odds of being victimized by bullying was lower. Participants who adhered to both sleep duration and PA recommendations were less likely to present with severe behavioral problems (OR = 0.17, 95%CI: 0.04–0.71, p < 0.05) than those who did not meet those guidelines. Conclusion: Significant associations were found between adhering to 24-HMB guidelines and selected QoL indicators. These findings highlight the importance of maintaining a healthy lifestyle as a key factor in promoting and preserving the QoL of children with ASD.

Abstract Background Targeted exercise training is a promising strategy for promoting cognitive function and preventing dementia in older age. Despite the utility of exercise as an intervention, variation still exists in exercise-induced cognitive gains and questions remain regarding the type of training (i.e., what), as well as moderators (i.e., for whom) and mechanisms (i.e., how) of benefit. Both aerobic training (AT) and resistance training (RT) enhance cognitive function in older adults without cognitive impairment; however, the vast majority of trials have focused exclusively on AT. Thus, more research is needed on RT, as well as on the combination of AT and RT, in older adults with mild cognitive impairment (MCI), a prodromal stage of dementia. Therefore, we aim to conduct a 6-month, 2 × 2 factorial randomized controlled trial in older adults with MCI to assess the individual effects of AT and RT, and the combined effect of AT and RT on cognitive function and to determine the possible underlying biological mechanisms. Methods Two hundred and sixteen community-dwelling adults, aged 65 to 85 years, with MCI from metropolitan Vancouver will be recruited to participate in this study. Randomization will be stratified by biological sex and participants will be randomly allocated to one of the four experimental groups: (1) 4×/week balance and tone (BAT; i.e., active control); (2) combined 2×/week AT + 2×/week RT; (3) 2×/week AT + 2×/week BAT; or (4) 2×/week RT + 2×/week BAT. The primary outcome is cognitive function as measured by the Alzheimer’s Disease Assessment Scale-Cognitive-Plus. Secondary outcomes include cognitive function, health-related quality of life, physical function, actigraphy measures, questionnaires, and falls. Outcomes will be measured at baseline, 6 months (i.e., trial completion), and 18 months (i.e., 12-month follow-up). Discussion Establishing the efficacy of different types and combinations of exercise training to minimize cognitive decline will advance our ability to prescribe exercise as “medicine” to treat MCI and delay the onset and progression of dementia. This trial is extremely timely as cognitive impairment and dementia pose a growing threat to global public health. Trial registration ClinicalTrials.gov NCT02737878 . Registered on April 14, 2016.

Abstract Background The allergists´ tool box in cat allergy management is limited. Clinical studies have shown that holo beta‐lactoglobulin (holoBLG) can restore micronutritional deficits in atopic immune cells and alleviate allergic symptoms in a completely allergen‐nonspecific manner. With this study, we aimed to provide proof of principle in cat allergy. Methods A novel challenge protocol for cat allergy in a standardized ECARF allergen exposure chamber (AEC) was developed. In an open pilot study (NCT05455749), patients with clinically relevant cat allergy were provoked with cat allergen for 120 min in the AEC before and after a 3‐month intervention phase (holoBLG lozenge 2x daily). Nasal, conjunctival, bronchial, and pruritus symptoms were scored every 10 min– constituting the total symptom score (TSS). Peak nasal inspiratory flow (PNIF) was measured every 30 min. In addition, a titrated nasal provocation test (NPT) was performed before and after the intervention. Primary endpoint was change in TSS at the end of final exposure compared to baseline. Secondary endpoints included changes in PNIF, NPT, and occurrence of late reactions up to 24 h after exposure. Results 35 patients (mean age: 40 years) completed the study. Compared to baseline, holoBLG supplementation resulted in significant improvement in median TSS of 50% (p

PurposeAging is associated with a reduction in brain modularity as well as aspects of executive function, namely, updating, shifting, and inhibition. Previous research has suggested that the aging brain exhibits plasticity. Further, it has been hypothesized that broad-based intervention models may be more effective in eliciting overall gains in executive function than interventions targeted at specific executive skills (e.g., computer-based training). To this end, we designed a 4-week theater-based acting intervention in older adults within an RCT framework. We hypothesized that older adults would show improvements in brain modularity and aspects of executive function, ascribed to the acting intervention.Materials and methodsThe participants were 179 adults from the community, aged 60–89 years and on average, college educated. They completed a battery of executive function tasks and resting state functional MRI scans to measure brain network modularity pre- and post-intervention. Participants in the active intervention group (n = 93) enacted scenes with a partner that involved executive function, whereas the active control group (n = 86) learned about the history and styles of acting. Both groups met two times/week for 75-min for 4 weeks. A mixed model was used to evaluate intervention effects related to brain modularity. Discriminant-analysis was used to determine the role of seven executive functioning tasks in discriminating the two groups. These tasks indexed subdomains of updating, switching, and inhibition. Discriminant tasks were subject to a logistic regression analysis to determine how post-intervention executive function performance interacted with changes in modularity to predict group membership.ResultsWe noted an increase in brain modularity in the acting group, relative to pre-intervention and controls. Performance on updating tasks were representative of the intervention group. However, post-intervention performance on updating did not interact with the observed increase in brain modularity to distinguish groups.ConclusionAn acting intervention can facilitate improvements in modularity and updating, both of which are sensitive to aging and may confer benefits to daily functioning and the ability to learn.

Alzheimer’s disease is currently the leading cause of dementia and one of the most expensive, lethal and severe diseases worldwide. Age-related decline in executive function is widespread and plays a key role in subsequent dementia risk. Physical exercise has been proposed as one of the leading non-pharmaceutical approaches to improve executive function and ameliorate cognitive decline. This single-site, two-arm, single-blinded, randomized controlled trial (RCT) will include 90 cognitively normal older adults, aged 65–80 years old. Participants will be randomized to a 24-week resistance exercise program (3 sessions/week, 60 min/session, n = 45), or a wait-list control group (n = 45) which will be asked to maintain their usual lifestyle. All study outcomes will be assessed at baseline and at 24-weeks after the exercise program, with a subset of selected outcomes assessed at 12-weeks. The primary outcome will be indicated by the change in an executive function composite score assessed with a comprehensive neuropsychological battery and the National Institutes of Health Toolbox Cognition Battery. Secondary outcomes will include changes in brain structure and function and amyloid deposition, other cognitive outcomes, and changes in molecular biomarkers assessed in blood, saliva, and fecal samples, physical function, muscular strength, body composition, mental health, and psychosocial parameters. We expect that the resistance exercise program will have positive effects on executive function and related brain structure and function, and will help to understand the molecular, structural, functional, and psychosocial mechanisms involved.

EEG alpha power varies under many circumstances requiring visual attention. However, mounting evidence indicates that alpha may not only serve visual processing, but also the processing of stimuli presented in other sensory modalities, including hearing. We previously showed that alpha dynamics during an auditory task vary as a function of competition from the visual modality (Clements et al., 2022) suggesting that alpha may be engaged in multimodal processing. Here we assessed the impact of allocating attention to the visual or auditory modality on alpha dynamics at parietal and occipital electrodes, during the preparatory period of a cued-conflict task. In this task, bimodal precues indicated the modality (vision, hearing) relevant to a subsequent reaction stimulus, allowing us to assess alpha during modality-specific preparation and while switching between modalities. Alpha suppression following the precue occurred in all conditions, indicating that it may reflect general preparatory mechanisms. However, we observed a switch effect when preparing to attend to the auditory modality, in which greater alpha suppression was elicited when switching to the auditory modality compared to repeating. No switch effect was evident when preparing to attend to visual information (although robust suppression did occur in both conditions). In addition, waning alpha suppression preceded error trials, irrespective of sensory modality. These findings indicate that alpha can be used to monitor the level of preparatory attention to process both visual and auditory information, and support the emerging view that alpha band activity may index a general attention control mechanism used across modalities.

In the past 20 years, white matter (WM) microstructure has been studied predominantly using diffusion tensor imaging (DTI). Decreases in fractional anisotropy (FA) and increases in mean (MD) and radial diffusivity (RD) have been consistently reported in healthy aging and neurodegenerative diseases. To date, DTI parameters have been studied individually (e.g., only FA) and separately (i.e., without using the joint information across them). This approach gives limited insights into WM pathology, increases the number of multiple comparisons, and yields inconsistent correlations with cognition. To take full advantage of the information in a DTI dataset, we present the first application of symmetric fusion to study healthy aging WM. This data-driven approach allows simultaneous examination of age differences in all four DTI parameters. We used multiset canonical correlation analysis with joint independent component analysis (mCCA + jICA) in cognitively healthy adults (age 20–33, n = 51 and age 60–79, n = 170). Four-way mCCA + jICA yielded one high-stability modality-shared component with co-variant patterns of age differences in RD and AD in the corpus callosum, internal capsule, and prefrontal WM. The mixing coefficients (or loading parameters) showed correlations with processing speed and fluid abilities that were not detected by unimodal analyses. In sum, mCCA + jICA allows data-driven identification of cognitively relevant multimodal components within the WM. The presented method should be further extended to clinical samples and other MR techniques (e.g., myelin water imaging) to test the potential of mCCA+jICA to discriminate between different WM disease etiologies and improve the diagnostic classification of WM diseases.

Abstract Sedentary behaviors are increasing at the cost of millions of dollars spent in health care and productivity losses due to physical inactivity-related deaths worldwide. Understanding the mechanistic predictors of sedentary behaviors will improve future intervention development and precision medicine approaches. It has been posited that humans have an innate attraction towards effort minimization and that inhibitory control is required to overcome this prepotent disposition. Consequently, we hypothesized that individual differences in the functional connectivity of brain regions implicated in inhibitory control and physical effort decision making at the beginning of an exercise intervention in older adults would predict the change in time spent sedentary over the course of that intervention. In 143 healthy, low-active older adults participating in a 6-month aerobic exercise intervention (with three conditions: walking, dance, stretching), we aimed to use baseline neuroimaging (resting state functional connectivity of two a priori defined seed regions), and baseline accelerometer measures of time spent sedentary to predict future pre-post changes in objectively measured time spent sedentary in daily life over the 6-month intervention. Our results demonstrated that functional connectivity between (1) the anterior cingulate cortex and the supplementary motor area and (2) the right anterior insula and the left temporoparietal/temporooccipital junction, predicted changes in time spent sedentary in the walking group. Functional connectivity of these brain regions did not predict changes in time spent sedentary in the dance nor stretch and tone conditions, but baseline time spent sedentary was predictive in these conditions. Our results add important knowledge toward understanding mechanistic associations underlying complex out-of-session sedentary behaviors within a walking intervention setting in older adults.

IntroductionThe social and behavioral effects of the COVID-19 pandemic have impacted the health and physiology of most people, including those never diagnosed with COVID-19. While the impact of the pandemic has been felt across the lifespan, its effects on cardiorespiratory fitness (commonly considered a reflection of total body health) of older adults and children may be particularly profound due to social distancing and stay-at-home advisories, as well as the closure of sport facilities and non-essential businesses. The objective of this investigation was to leverage baseline data from two ongoing clinical trials to determine if cardiorespiratory fitness and body mass index were different during COVID-19 relative to before COVID-19 in older adults and children.MethodsHealthy older individuals (N = 593; 65–80 years) and 200 typically developing children (8–10 years) completed a graded maximal exercise test and had their height and weight measured.ResultsResults revealed that older adults and children tested during COVID-19 had significantly lower cardiorespiratory fitness levels than those tested before COVID-19 shutdowns (older adults: 30% lower; children: 53% lower; p's ≤ 0.001). In addition, older adults and children tested during COVID-19 had significantly higher BMI (older adults: 31.34 ± 0.57 kg/m2, p = 0.004; children: 19.27 ± 0.44 kg/m2, p = 0.05) than those tested before COVID-19 shutdowns (older adults: 29.51 ± 0.26 kg/m2, children: 18.13 ± 0.35 kg/m2). However, these differences in BMI did not remain significant when controlling for cardiorespiratory fitness.DiscussionResults from this investigation indicate that the COVID-19 pandemic, and behavior changes taken to reduce potential exposure, may have led to lower cardiorespiratory fitness levels in older adults and children, as well as higher body mass index. These findings provide relevant public health information as lower cardiorespiratory fitness levels and higher body mass indexes recorded during the pandemic could have far-reaching and protracted health consequences. Public health guidance is needed to encourage physical activity to maintain cardiorespiratory fitness and healthy body composition.Clinical trial registrationOlder adults: https://clinicaltrials.gov/ct2/show/NCT02875301, identifier: NCT02875301; Children: https://clinicaltrials.gov/ct2/show/NCT03592238, identifier: NCT03592238.

Purpose Increasing evidence suggests rural breast cancer survivors (BCS) may experience greater burden in symptoms known to be associated with cancer-associated cognitive decline (CACD). Yet, little is known about CACD in rural BCS. This study (1) examined differences in cognitive function, moderate-to-vigorous physical activity (MVPA), and other CACD correlates and (2) tested the effects of MVPA on cognitive function in rural versus urban BCS. Methods Rural and urban BCS (N = 80), matched on age, education, and time since diagnosis from a larger study, completed cognitive tasks assessing processing speed (Trails-B, Mazes, Task-Switch) and working memory (spatial working memory) and questionnaires assessing subjective memory impairment (SMI), MVPA, and CACD correlates (i.e., sleep quality, fatigue, anxiety/depression). Some participants (n = 62) wore an accelerometer to objectively estimate MVPA. Multiple linear regression and multivariate analysis of covariance were used to test study aims. Results Rural BCS (n = 40, M = 61.1±8.4 years-old) performed significantly slower on Trails-B (p0.28). Regression models did not reveal a significant interaction between MVPA and cognitive performance (all p>0.1); however, estimated marginal means models indicated that the effect of MVPA on processing speed was evident only among rural BCS (Trails-B, p = 0.04; Mazes, p = 0.03). Conclusions Findings suggest rural BCS may suffer greater CACD and engage in less MVPA. Additional research is warranted to further examine CACD and more effectively promote MVPA in rural BCS.

Metabolic syndrome (MetS) is a cluster of conditions that affects ∼25% of the global population, including excess adiposity, hyperglycemia, dyslipidemia, and elevated blood pressure. MetS is one of major risk factors not only for chronic diseases, but also for dementia and cognitive dysfunction, although the underlying mechanisms remain poorly understood. White matter is of particular interest in the context of MetS due to the metabolic vulnerability of myelin maintenance, and the accumulating evidence for the importance of the white matter in the pathophysiology of dementia. Therefore, we investigated the associations of MetS risk score and adiposity (combined body mass index and waist circumference) with myelin water fraction measured with myelin water imaging. In 90 cognitively and neurologically healthy adults (20–79 years), we found that both high MetS risk score and adiposity were correlated with lower myelin water fraction in late-myelinating prefrontal and associative fibers, controlling for age, sex, race, ethnicity, education and income. Our findings call for randomized clinical trials to establish causality between MetS, adiposity, and myelin content, and to explore the potential of weight loss and visceral adiposity reduction as means to support maintenance of myelin integrity throughout adulthood, which could open new avenues for prevention or treatment of cognitive decline and dementia.

Objective: The mitochondrial fission protein Drp1 was proposed to promote NAFLD, as inhibition of hepatocyte Drp1 early in life prevents liver steatosis induced by high-fat diet in mice. However, whether Drp1-knockdown in older mice can reverse established NASH is unknown. Methods: N-acetylgalactosamine-siRNA conjugates, an FDA approved method to deliver siRNA selectively to hepatocytes, were used to knockdown hepatocyte-Drp1 in mice (NAG-Drp1si). NASH was induced in C57BL/6NTac mice by Gubra-Amylin-NASH diet (D09100310, 40% fat, 22% fructose and 2% cholesterol) and treatment with NAG-Drp1si was started at week 24 of diet. Circulating transaminases, liver histology, gene expression of fibrosis and inflammation markers, and hydroxyproline synthesis determined NASH severity. Liver NEFA and triglycerides were quantified by GC/MS. Mitochondrial function was determined by respirometry. Western blots of Oma1, Opa1, p-eIf2α, as well as transcriptional analyses of Atf4-regulated genes determined ISR engagement. Results: NAG-Drp1si treatment decreased body weight and induced liver inflammation in adult healthy mice. Increased hepatic Gdf15 production was the major contributor to body-weight loss caused by NAG-Drp1si treatment, as Gdf15 receptor deletion (Gfral KO) prevented the decrease in food intake and mitigated weight loss. NAG-Drp1si activated the Atf4-controlled integrated stress response (ISR) to increase hepatic Gdf15 expression. NAG-Drp1si in healthy mice caused ER stress and activated the mitochondrial protease Oma1, which are the ER and mitochondrial triggers that activate the Atf4-controlled ISR. Remarkably, induction of NASH was not sufficient to activate Oma1 in liver. However, NAG-Drp1si treatment was sufficient to activate Oma1 in adult mice with NASH, as well as exacerbating NASH-induced ER stress. Consequently, NAG-Drp1si treatment in mice with NASH led to higher ISR activation, exacerbated inflammation, fibrosis and necrosis. Conclusion: Drp1 mitigates NASH by decreasing ER stress, preventing Oma1 activation and ISR exacerbation. The elevation in Gdf15 actions induced by NAG-Drp1si might represent an adaptive response decreasing the nutrient load to liver when mitochondria are misfunctional. Our study argues against blocking Drp1 in hepatocytes to combat NASH.

Introduction Intratumoral injections of novel therapeutics can activate tumor antigen-specific T cells for locoregional tumor control and may even induce durable systemic protection (against distant metastases) via recirculating T cells. Here we explored the possibility of a universal immunotherapy that promotes T-cell responses in situ and beyond, upon intratumoral injection of nanoparticles formulated with micron-sized crystals.Methods Cucumber mosaic virus-like particles containing a tetanus toxin peptide (CuMVTT) were formulated with microcrystalline tyrosine (MCT) adjuvant and injected directly in B16F10 melanoma tumors. To further enhance immunogenicity, we loaded the nanoparticles with a TLR7/8 ligand and incorporated a universal tetanus toxin T-helper cell peptide. We assessed therapeutic efficacy and induction of local and systemic immune responses, including RNA sequencing, providing broad insight into the tumor microenvironment and correlates of protection.Results MCT crystals were successfully decorated with CuMVTT nanoparticles. This ‘immune-enhancer’ formed immunogenic depots in injected tumors, enhanced polyfunctional CD8+ and CD4+ T cells, and inhibited B16F10 tumor growth locally and systemically. Local inflammation and immune responses were associated with upregulation of genes involved in complement activation and collagen formation.Conclusions Our new immune-enhancer turned immunologically cold tumors into hot ones and inhibited local and distant tumor growth. This type of immunotherapy does not require the identification of (patient–individual) relevant tumor antigens. It is well tolerated, non-infectious, and affordable, and can readily be upscaled for future clinical testing and broad application in melanoma and likely other solid tumors.

ObjectiveAdolescents are likely to suffer from negative emotions such as depression and anxiety due to the rapid development of biological, cognitive and social changes. Previous studies have indicated possible risk (rumination) and protective (good social support and high sleep quality) factors for depression and anxiety among this age group. The present study is the first to investigate the association between social support and negative emotions during the Outbreak of Omicron variant, on this basis, to further determine the mediating role of rumination and sleep quality on this link.MethodA total of 1,065 Chinese middle- and high-school students (51.5% female, Mage = 13.80, SD = 1.20) completed a psychosocial battery, including the Social Support Rating Scale (SSRS), the Pittsburgh Sleep Quality Index (PSQI), the Ruminative Responses Scale (RRS), the Depression Anxiety Stress Scale (DASS). Serial multiple mediation analysis was conducted using PROCESS macro based on SPSS.ResultsSocial support, rumination, and sleep quality were significantly negatively correlated with negative emotional states (Ps < 0.05). Further, rumination and sleep quality were found to partially mediate the relationship between social support and negative emotional states.ConclusionsFor early detection and prevention of depression and anxiety, providing sufficient social support is necessary for adolescents, because rumination and sleep problems are reported during stressful periods, such as the COVID-19 pandemic.

Abstract Background There is an increasing prevalence of physical inactivity during childhood, which is associated with a variety of health problems. However, the mechanisms by which acute exercise benefits cognition in childhood remains unknown. Here we describe the protocol for a randomized crossover trial called SNEACY (Sympathetic Nervous System & Exercise Affects Cognition in Youth), a study designed to better understand mechanisms linking acute exercise and cognition in 9–10-year-old healthy, cognitively normal children. Methods Children from the Greater Boston, MA region will be recruited to participate in this single center study. A randomized crossover design will be utilized, such that participants will act as their own controls, through initial randomization to condition assignment and condition counterbalancing across participants. One hundred three children will participate in three randomized acute interventions: moderate intensity treadmill exercise (20 min, 70–75% of their maximal heart rate), seated rest (20 min), and a Trier Social Stress Test for Children (14 min). These visits will occur on 3 three separate days, approximately 5–8 days apart. Before and after each intervention, children complete a variety of cognitive tasks measuring attentional inhibition while their neuroelectric activity is recorded. Variables of interest include EEG data, accuracy and reaction time, academic achievement, and salivary alpha amylase. Academic achievement is also assessed following interventions. In addition, children provide passive drool samples throughout the interventions to measure various biomarkers that may explain the acute exercise benefit on cognition. Discussion The results from this study could influence educational and public health recommendations to enhance cognition and learning in pre-adolescent children. Trial registration ClinicalTrials.gov NCT03592238 . Registered on 19 July 2018

Abstract Background The purpose was to prospectively examine the effects of sedentary behaviors on subjective memory impairment in breast cancer survivors (BCS) and the extent to which sleep disturbances mediated this pathway. Methods BCS (N = 380; Mage = 57.38 ± 9.25 years) completed questionnaires assessing demographics, health history, sitting behaviors, sleep disturbance, subjective memory impairment, and moderate‐to‐vigorous physical activity (MVPA) at baseline and 6‐month follow‐up. A subsample (N = 300) wore an accelerometer to objectively estimate sedentary time and MVPA. Structural equation modeling was used to test direct and indirect effects of self‐reported and objectively estimated sedentary behaviors on memory impairment (through sleep disturbance) across time. Models were adjusted for demographic, clinical, and MVPA covariates. Results At baseline, more total daily sitting (γ = 0.23), occupational sitting (γ = 0.11), television viewing (γ = 0.15), and computer use (γ = 0.22) were associated with greater sleep disturbance, which was associated with greater memory impairment (γ = −0.22). Indirect effects of self‐reported sitting on memory were significant. At follow‐up, increased total daily sitting (γ = 0.08) and computer use (γ = 0.14) predicted increased sleep disturbance, which predicted increased memory impairment (γ = −0.09). The indirect path from increased computer use to memory impairment was significant (β = −0.01). In the accelerometer subsample, greater daily sedentary time at baseline was associated with less sleep disturbance (γ = −0.14) and memory impairment (indirect effect: β = 0.03). Conclusions Findings provide early evidence that sedentary contexts may differentially influence sleep disturbance and memory impairment in BCS. Computer use and television viewing may pose the strongest risks to cognitive health. Disparate findings between objective and subjective sedentary measures warrant further research.

A central aim of research in the psychological and decision sciences is to establish interventions that enhance performance, investigating the efficacy of modern approaches to improve human inference and decision-making. Whereas the decision sciences have established interventions to reduce decision biases by promoting strategies for critical thought and reasoning, methods from psychology have instead focused on enhancing cognition through skill-based training of executive functions. Contemporary research in psychology has engaged these operations through multi-modal interventions designed to enhance cognition and physical health through training of executive functions, mindfulness meditation, and physical fitness. Despite the comparable aims of research in the psychological and decision sciences, the efficacy of multi-modal interventions to enhance decision-making remain to be established. We therefore conducted a comprehensive, 16-week, randomized controlled trial (RCT) to investigate this issue, enrolling 160 healthy adults in one of four interventions: (1) high-intensity cardioresistance fitness training (HICRT); (2) HICRT and cognitive training of core executive functions; (3) HICRT and cognitive training, along with mindfulness meditation training; or (4) active control training. The results of our RCT demonstrate that HICRT training and multi-modal interventions that also incorporate cognitive training and mindfulness meditation have beneficial effects on decision-making competence. The observed pattern of findings motivate the application of modern interventions from psychology and cognitive neuroscience to enhance human judgment and decision-making in complex, real-world environments.

White matter deterioration is associated with cognitive impairment in healthy aging and Alzheimer's disease. It is critical to identify interventions that can slow down white matter deterioration. So far, clinical trials have failed to demonstrate the benefits of aerobic exercise on the adult white matter using diffusion Magnetic Resonance Imaging. Here, we report the effects of a 6-month aerobic walking and dance interventions (clinical trial NCT01472744) on white matter integrity in healthy older adults (n = 180, 60–79 years) measured by changes in the ratio of calibrated T1- to T2-weighted images (T1w/T2w). Specifically, the aerobic walking and social dance interventions resulted in positive changes in the T1w/T2w signal in late-myelinating regions, as compared to widespread decreases in the T1w/T2w signal in the active control. Notably, in the aerobic walking group, positive change in the T1w/T2w signal correlated with improved episodic memory performance. Lastly, intervention-induced increases in cardiorespiratory fitness did not correlate with change in the T1w/T2w signal. Together, our findings suggest that white matter regions that are vulnerable to aging retain some degree of plasticity that can be induced by aerobic exercise training. In addition, we provided evidence that the T1w/T2w signal may be a useful and broadly accessible measure for studying short-term within-person plasticity and deterioration in the adult human white matter.

As target-background similarity increases, search performance declines, but this pattern can be attenuated with training. In the present study we (1) characterized training and transfer effects in visual search for camouflaged targets in naturalistic scenes, (2) evaluated whether transfer effects are preserved 3 months after training, (3) tested the suitability of the perceptual learning hypothesis (i.e., using learned scene statistics to aid camouflaged target detection) for explaining camouflage search improvements over training, and (4) provide guidance for camouflage detection training in practice. Participants were assigned to one of three training groups: adaptive camouflage (difficulty varied by performance), massed camouflage (difficulty increased over time), or an active control (no camouflage), and trained over 14 sessions. Additional sessions measured transfer (immediately post training) and retention of training benefits (10 days and 3 months post training). Both the adaptive and massed training groups showed improved camouflaged target detection up to 3 months following training, relative to the control. These benefits were observed only with backgrounds and targets that were similar to those experienced during training and are broadly consistent with the perceptual learning hypothesis. In practice, training interventions should utilize stimuli similar to the operational environment in which detection is expected to occur.

The concept of treatment of an allergy with the offending allergen was introduced more than a century ago. Allergen immunotherapy (AIT) is the only disease modifying treatment of allergic diseases caused by inhalational allergens and insect venoms. Despite this, only few AIT products have reached licensure in the US or an official marketing authorization status in European countries. Moreover, most of these AIT products are provided on an individual patient basis as named patient products (NPP) in Europe, while individualized preparations of (mixed) allergenic extract vials for subcutaneous administration (compounding) is common practice in the US. AIT products are generally considered safe and well tolerated, but the major practical clinical development challenge is to define the optimal dose and prove the efficacy and safety of these products using state-of-the art Phase II and pivotal Phase III studies. In planning Phase II-III AIT studies, a thorough understanding of the study challenges is essential (e.g. variability and non-validated status of subjective primary endpoints, limitations of pollen season definitions) and dogmas of these products (e.g., for sublingual immunotherapy (SLIT) trials double-blinding conditions cannot be maintained, resulting in stronger placebo responses in the active treatment group and inflated treatment effects in Phase III). There is future promise for more objective biomarker endpoints (e.g. basophil activation (CD63 and CD203c), subsets of regulatory dendritic, T and B cells, IL-10–producing group 2 innate lymphoid cells; alone or in combination) to overcome several of these dogmas and challenges; innovation in AIT clinical trials can only progress with integral biomarker research to complement the traditional endpoints in Phase II-III clinical development. The aim of this paper is to provide an overview of these dogmas, challenges and recommendations based on published data, to facilitate the design of Phase III studies and improve the evidence basis of safe and effective AIT products.

Background: Structured vigorous physical activity (VPA) can improve cognitive control in children, but studies relating daily physical activity (PA) to cognitive control have yielded conflicting findings. While objectively measured daily PA summarizes all occurrences of PA within a registered period, a minimum duration of continuous PA is required for registration of a PA bout. Because brief bouts of high-intensity PA can account for a large proportion of children's daily activity-related energy expenditure, this study assessed whether daily and bouted VPA were selectively related to cognitive control in preadolescents relative to other PA intensities. Methods: A total of 75 children between the ages of 8 and 10 years (49% girls) wore an ActiGraph wGT3X+ on the hip for 7 days. The acceleration signal from the vertical axis was summarized over 1 s, 5 s, and 15 s epochs. Daily and bouted moderate PA, moderate-to-vigorous PA, and VPA were measured. PA bouts were expressed as the frequency and time spent in 2 different continuous PA bouts, one lasting ≥10 s and the other lasting ≥30 s at a given intensity. Inhibitory control was assessed using behavioral responses to a modified flanker task (mean reaction time (RTmean) and accuracy). Attentional resource allocation and cognitive processing speed were measured using the amplitude and latency of the P3 component of event-related brain potentials, respectively. Associations between PA, behavioral indices of inhibitory control, P3 amplitude, and latency were assessed using hierarchical regression models. Results: Daily VPA was not related to RTmean or accuracy on either congruent or incongruent trials. In contrast, more time spent in VPA bouts lasting ≥30 s predicted shorter P3 latency across epochs and flanker congruencies (all β ≤ –0.24, all p ≤ 0.04). The associations between shorter P3 latency and the time spent in moderate-to-vigorous PA bouts lasting ≥30 s were less consistent and largely limited to congruent trials (congruent: β (–0.31, –0.34)). No significant associations were observed upon correction for false discovery rate. Conclusion: The pattern of uncorrected associations aligns with the dose–response literature and suggests that brief VPA bouts may yield the greatest benefits to cognitive processing speed in preadolescents. Future studies using measures of brain structure and function are needed to understand the mechanisms linking bouted VPA to neurocognitive function during childhood. Keywords: Accelerometry, Bouts, Children, ERPs, Inhibitory control, P3, Physical activity

Abstract Background Improving upper limb (UL) motor recovery after stroke represents a major clinical and scientific goal. We aim to complete three systematic reviews to estimate the (1) association between time to start of UL therapy and motor recovery, (2) relative efficacy of different UL therapy approaches post-stroke and (3) cost-effectiveness of UL therapy interventions. Methods We have designed a systematic review protocol to address three systematic review questions that were each registered with PROSPERO. The search will be conducted in MEDLINE, EMBASE, and Cochrane Controlled Register of Trials. We will include randomised controlled trials, non-randomised clinical trials, before-after studies and observational studies of adult stroke survivors with an average stroke onset

Abstract Background Many breast cancer survivors (BCS) report deficits in cognitive function. Physical activity (PA) has been associated with better processing speed and memory in healthy adults and thus may be a useful method for improving cognition in BCS. The purpose of this study was to examine the effects of an acute bout of PA on processing speed and spatial working memory in a sample of BCS. Methods Using a repeated measures, crossover design, BCS [N = 27; M age (SD) = 49.11(8.05)] completed two sessions in counterbalanced order: 30 min of moderate-intensity treadmill walking and 30 min of seated rest. Women completed cognitive tasks immediately before and after each session. Results Within-subjects repeated measures analyses of variance revealed a significant time by session effect for processing speed reaction time [F (1,25) = 5.02, p = .03, η2 = 0.17]. This interaction was driven by significantly reduced reaction time (e.g., faster response) post-exercise and no change post-rest. Further between-subjects analyses indicated a significant time by session by moderate to vigorous physical activity (MVPA) split [F (1,25) = 5.23, p = .03, η2 = 0.17], such that women who engaged in ≥45 min of average daily MVPA reduced their reaction time post-exercise (p = .01) and increased RT post-rest (p = .06). Time by session effects for spatial working memory 3-item accuracy and 4-item reaction time trended towards significance, p = 0.08 and p = 0.10, respectively, again driven by better performance post-exercise. Conclusions The moderate effect of acute exercise on domains of memory and processing speed in BCS is encouraging. Cancer-related cognitive impairment remains largely misunderstood; however, the results from the present study offer preliminary evidence for the positive relationship between acute exercise and cognition in BCS. Trial registration ClinicalTrials.gov NCT02592070. Registered 30 October 2015. Retroactively registered.

Abstract Background Induction of strong T cell responses, in particular cytotoxic T cells, is a key for the generation of efficacious therapeutic cancer vaccines which yet, remains a major challenge for the vaccine developing world. Here we demonstrate that it is possible to harness the physiological properties of the lymphatic system to optimize the induction of a protective T cell response. Indeed, the lymphatic system sharply distinguishes between nanoscale and microscale particles. The former reaches the fenestrated lymphatic system via diffusion, while the latter either need to be transported by dendritic cells or form a local depot. Methods Our previously developed cucumber-mosaic virus-derived nanoparticles termed (CuMVTT-VLPs) incorporating a universal Tetanus toxoid epitope TT830–843 were assessed for their draining kinetics using stereomicroscopic imaging. A nano-vaccine has been generated by coupling p33 epitope as a model antigen to CuMVTT-VLPs using bio-orthogonal Cu-free click chemistry. The CuMVTT-p33 nano-sized vaccine has been next formulated with the micron-sized microcrystalline tyrosine (MCT) adjuvant and the formed depot effect was studied using confocal microscopy and trafficking experiments. The immunogenicity of the nanoparticles combined with the micron-sized adjuvant was next assessed in an aggressive transplanted murine melanoma model. The obtained results were compared to other commonly used adjuvants such as B type CpGs and Alum. Results Our results showed that CuMVTT-VLPs can efficiently and rapidly drain into the lymphatic system due to their nano-size of ~ 30 nm. However, formulating the nanoparticles with the micron-sized MCT adjuvant of ~ 5 μM resulted in a local depot for the nanoparticles and a longer exposure time for the immune system. The preclinical nano-vaccine CuMVTT-p33 formulated with the micron-sized MCT adjuvant has enhanced the specific T cell response in the stringent B16F10p33 murine melanoma model. Furthermore, the micron-sized MCT adjuvant was as potent as B type CpGs and clearly superior to the commonly used Alum adjuvant when total CD8+, specific p33 T cell response or tumour protection were assessed. Conclusion The combination of nano- and micro-particles may optimally harness the physiological properties of the lymphatic system. Since the nanoparticles are well defined virus-like particles and the micron-sized adjuvant MCT has been used for decades in allergen-specific desensitization, this approach may readily be translated to the clinic.

Engaging in musical activities throughout the lifespan may protect against age-related cognitive decline and modify structural and functional connectivity in the brain. Prior research suggests that musical experience modulates brain regions that integrate different modalities of sensory information, such as the insula. Most of this research has been performed in individuals classified as professional musicians; however, general musical experiences across the lifespan may also confer beneficial effects on brain health in older adults. The current study investigated whether general musical experience, characterized using the Goldsmith Music Sophistication Index (Gold-MSI), was associated with functional connectivity in older adults (age = 65.7 ± 4.4, n = 69). We tested whether Gold-MSI was associated with individual differences in the functional connectivity of three a priori hypothesis-defined seed regions in the insula (i.e., dorsal anterior, ventral anterior, and posterior insula). We found that older adults with more musical experience showed greater functional connectivity between the dorsal anterior insula and the precentral and postcentral gyrus, and between the ventral anterior insula and diverse brain regions, including the insula and prefrontal cortex, and decreased functional connectivity between the ventral anterior insula and thalamus (voxel p < 0.01, cluster FWE p < 0.05). Follow-up correlation analyses showed that the singing ability subscale score was key in driving the association between functional connectivity differences and musical experience. Overall, our findings suggest that musical experience, even among non-professional musicians, is related to functional brain reorganization in older adults.

Purpose: Studies of reactive and proactive modes of inhibitory control tend to show age-related declines and are accompanied by abnormalities in the prefrontal cortex. We explored which mode of inhibitory control would be more amenable to change and accrue greater benefits following engagement in a 4-week theater acting intervention in older adults. These gains were evaluated by performance on the AX-CPT task. We hypothesized that an increase in proactive control would relate to an increase in AY errors and a decrease in BX errors. In contrast, an increase in reactive control would be associated with a decrease in AY errors, no change in AY reaction time, and an increase in BX response time. Further, we posited that an increase in behavioral proactive control would accompany greater cue versus probe activity for previously identified regions in the prefrontal cortex. In contrast, an increase in behavioral reactive control would be accompanied by greater probe activation in these identified brain areas.Materials and Methods: The participants were 179 community-dwelling adults aged 60–89 years who were on average, college-educated. Participants were pseudo-randomly assigned to either an active-experiencing acting intervention condition (n = 93) or the active control condition (n = 86); participant assignment was subject to time of enrollment. Participants in both groups were trained by theater-actor researchers with expertise in acting interventions. In contrast to the active control participants who attended a course on theater acting, the acting-intervention group was required to consistently deploy proactive and reactive control mechanisms. Both groups met two times/week for 75-min for 4 weeks. Participant brain-behavioral performance on the AX-CPT task was evaluated prior to and after this four-week period.Results: No intervention effects were found in favor of proactive control. Behavioral evidence in favor of reactive control was weak. Brain-related benefits to reactive control was illustrated by greater probe-activation in Brodmann areas 6 and 8, relative to controls and pre-intervention.Conclusion: We found some evidence for improvements in reactive control via brain measures, attributed to engagement in the acting intervention.

The Stroop task is a traditional measure of cognitive control processes, yet results remain mixed when it comes to assessing age-related differences perhaps in part due to strategies participants use to reduce inhibitory control demands required for success on the task. Thirty-three older adults and 34 younger adults completed a Baseline (traditional, single-task) version of Stroop, followed by two, novel dual-task Stroop variants: Color-Dual (maintain secondary count of prespecified font color regardless the lexical content) and Lexical-Dual (maintain secondary count of prespecified word regardless the font color). With regard to Baseline performance, we predicted an Age x Trial Type interaction in which older adults would be selectively impaired on Incongruent trials compared to younger adults, and this prediction was supported. When we added secondary task demands, we predicted a Trial Type x Dual-Task Type interaction in which performance in the Lexical-Dual condition would be worse than performance in the Color-Dual condition. This prediction was also supported, suggesting that having a secondary task that activated the irrelevant stream of information required more inhibitory control. Finally, we also predicted that Age would interact with Trial Type and Dual-Task Type, which was partially supported in response latencies and more definitively supported in error rates. Overall, our results indicate that Stroop performance is differentially influenced by additional dual-task demands that potentially minimize strategy usage, which has implications for both young and older adult Stroop performance.