Stressor-evoked brain activity, cardiovascular reactivity, and subclinical atherosclerosis in midlife adults.

Background: Cardiovascular responses to psychological stressors have been separately associated with preclinical atherosclerosis and hemodynamic brain activity patterns across different studies and cohorts; however, what has not been established is whether cardiovascular stress responses reliably link indicators of stressor-evoked brain activity and preclinical atherosclerosis that have been measured in the same individuals. Accordingly, the present study used cross-validation and predictive modeling to test for the first time whether stressor-evoked systolic blood pressure (SBP) responses statistically mediated the association between concurrently measured brain activity and a vascular marker of preclinical atherosclerosis in the carotid arteries. Methods: 624 midlife adults (aged 28-56 years, 54.97% female) from two different cohorts underwent two information-conflict fMRI tasks, with concurrent SBP measures collected. Carotid artery intima-media thickness (CA-IMT) was measured by ultrasonography. A mediation framework that included harmonization, cross-validation, and penalized principal component regression was then employed, while significant areas in possible direct and indirect effects were identified through bootstrapping. Sensitivity analysis further tested the robustness of findings after accounting for prevailing levels of cardiovascular disease risk and brain imaging data quality control. Results: Task-averaged patterns of hemodynamic brain responses exhibited a generalizable association with CA-IMT, which was mediated by an area-under-the-curve measure of aggregate SBP reactivity. Importantly, this effect held in sensitivity analyses. Implicated brain areas in this mediation included the ventromedial prefrontal cortex, anterior cingulate cortex, insula and amygdala. Conclusions: These novel findings support a link between stressor-evoked brain activity and preclinical atherosclerosis accounted for by individual differences in corresponding levels of stressor-evoked cardiovascular reactivity.

Effects of a laboratory-based aerobic exercise intervention on brain volume and cardiovascular health markers: protocol for a randomised clinical trial.

INTRODUCTION: Physical activity (PA) has beneficial effects on brain health and cardiovascular disease (CVD) risk. Yet, we know little about whether PA-induced changes to physiological mediators of CVD risk influence brain health and whether benefits to brain health may also explain PA-induced improvements to CVD risk. This study combines neurobiological and peripheral physiological methods in the context of a randomised clinical trial to better understand the links between exercise, brain health and CVD risk. METHODS AND ANALYSIS: In this 12-month trial, 130 healthy individuals between the ages of 26 and 58 will be randomly assigned to either: (1) moderate-intensity aerobic PA for 150 min/week or (2) a health information control group. Cardiovascular, neuroimaging and PA measurements will occur for both groups before and after the intervention. Primary outcomes include changes in (1) brain structural areas (ie, hippocampal volume); (2) systolic blood pressure (SBP) responses to functional MRI cognitive stressor tasks and (3) heart rate variability. The main secondary outcomes include changes in (1) brain activity, resting state connectivity, cortical thickness and cortical volume; (2) daily life SBP stress reactivity; (3) negative and positive affect; (4) baroreflex sensitivity; (5) pulse wave velocity; (6) endothelial function and (7) daily life positive and negative affect. Our results are expected to have both mechanistic and public health implications regarding brain-body interactions in the context of cardiovascular health. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the University of Pittsburgh Institutional Review Board (IRB ID: 19020218). This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. TRIAL REGISTRATION NUMBER: NCT03841669.

Dual impedance cardiography: An inexpensive and reliable method to assess arterial stiffness.

Pulse wave velocity (PWV) is a common measure of arterial stiffness. Non-invasive methods to measure PWV are widely used in biomedical studies of aging and cardiovascular disease, but they are rarely used in psychophysiology. Barriers to wider use include the prohibitive costs of specialized equipment and need for trained technicians (e.g., ultrasonographers). Here, we describe an impedance cardiography method to measure PWV. By this method, impedance signals are dually collected from the thorax and calf. Combined with ensemble averaging of vascular signals, this dual impedance cardiography (d-ICG) method allows for the measurement of aortic flow onset and the arrival time of peripheral pulse waveforms to compute PWV. In a community sample of adults (aged 19-78 years), PWV measured with d-ICG exhibited a strong positive correlation with age. Moreover, age-specific mean PWV values were within the normative reference intervals established by large scale studies using other techniques. PWV derived from d-ICG exhibited high test-retest reliability across several days, as well as excellent inter-rater reliability. Last, PWV exhibited expected associations with known cardiovascular disease risk factors and indicators of autonomic cardiovascular control. d-ICG is an inexpensive and reliable method to assess arterial stiffness.

The Negative Influence of Adiposity Extends to Intraindividual Variability in Cognitive Control Among Preadolescent Children.

OBJECTIVE: The objective of this study was to investigate the relationship between adiposity and cognition by using mean accuracy, mean reaction time, and intraindividual variability (IIV) among preadolescents. METHODS: Children 7 to 9 years old (N = 233, 133 females) underwent dual-energy x-ray absorptiometry and a maximal oxygen consumption test to assess whole-body adiposity and aerobic fitness relative to fat-free mass (VO2 FF), respectively. Attentional inhibition was assessed by using a modified flanker task. IIV was assessed as standard deviation of reaction time and as a coefficient of variation of reaction time (CVRT). Hierarchical linear regression analyses were performed to examine the relationships between adiposity and cognitive measures following the adjustment of significant demographic factors, intelligence quotient, and VO2 FF. RESULTS: Whole-body adiposity was negatively related to congruent trial mean accuracy and reaction time and to CVRT in both the congruent and incongruent trials. Differences in cognitive function across weight status were selectively evident for measures of IIV, such that children with overweight/obesity (≥ 85th BMI-for-age percentile) exhibited higher CVRT for both the congruent and incongruent trials. CONCLUSIONS: This work provides additional evidence linking childhood obesity to poorer cognitive function and includes novel data extending the negative influence of adiposity to measures of intraindividual response variability in cognitive control, even after accounting for intellectual abilities, aerobic fitness, and demographic factors.

Effects of the FITKids physical activity randomized controlled trial on conflict monitoring in youth.

The present study investigated the effect of a 9-month physical activity (PA) intervention on children's cardiorespiratory fitness levels and neuroelectric indices of conflict monitoring (i.e., error-related negativity, ERN). Four hundred twenty-eight preadolescent children (8-9 years old) were randomized into a PA intervention or wait-list control group, and completed a fitness and cognitive control assessment (i.e., modified flanker task) at pre- and posttest. Following exclusion criterion, 308 children were included in the analyses (PA intervention: n = 139; wait-list control: n = 169). Children in the intervention displayed greater improvements in fitness and response accuracy, which were accompanied by stability of ERN amplitude from pre- to posttest. In contrast, the control group revealed increased ERN amplitude at posttest compared to pretest, despite no change in fitness or task performance. These findings demonstrate the efficacy of daily PA for promoting children's fitness and underlying neural processes associated with effective conflict monitoring. Such findings have significant implications for promoting organized PA programs intended to foster overall physical and brain health in school age children.

Physical activity and academic achievement across the curriculum: Results from a 3-year cluster-randomized trial.

We compared changes in academic achievement across 3years between children in elementary schools receiving the Academic Achievement and Physical Activity Across the Curriculum intervention (A+PAAC), in which classroom teachers were trained to deliver academic lessons using moderate-to-vigorous physical activity (MVPA) compared to a non-intervention control. Elementary schools in eastern Kansas (n=17) were cluster randomized to A+PAAC (N=9, target ≥100min/week) or control (N=8). Academic achievement (math, reading, spelling) was assessed using the Wechsler Individual Achievement Test-Third Edition (WIAT-III) in a sample of children (A+PAAC=316, Control=268) in grades 2 and 3 at baseline (Fall 2011) and repeated each spring across 3years. On average 55min/week of A+PACC lessons were delivered each week across the intervention. Baseline WIAT-III scores (math, reading, spelling) were significantly higher in students in A+PAAC compared with control schools and improved in both groups across 3years. However, linear mixed modeling, accounting for baseline between group differences in WIAT-III scores, ethnicity, family income, and cardiovascular fitness, found no significant impact of A+PAAC on any of the academic achievement outcomes as determined by non-significant group by time interactions. A+PAAC neither diminished or improved academic achievement across 3-years in elementary school children compared with controls. Our target of 100min/week of active lessons was not achieved; however, students attending A+PAAC schools received an additional 55min/week of MVPA which may be associated with both physical and mental health benefits, without a reduction in time devoted to academic instruction.

The association between aerobic fitness and congruency sequence effects in preadolescent children.

Aerobic fitness has previously been related to cognitive control in preadolescents; however, these investigations have generally relied on global measures of performance. Thus, we have little understanding of how aerobic fitness may relate to trial-by-trial modulations in cognitive control. This study utilized congruency sequence effects (CSEs), which characterize how behavior on the current trial is influenced by the previous trial, to investigate the relation of aerobic fitness on varying levels of cognitive control. One hundred eighty-seven children completed tests of aerobic fitness and a flanker task. Regressions were performed to determine relationships between CSE sequences and aerobic fitness while controlling for other potential confounding factors (e.g., age, sex, IQ). Lower-fit children were less able to modulate cognitive control during sequences requiring relatively less cognitive control. Additionally, lower-fit children were less able to adjust for variable levels of cognitive control during relatively more difficult sequences. Lastly, lower-fit children had longer reaction times (RTs) for all sequences in the condition requiring greater amounts of cognitive control. These findings corroborate the importance of aerobic fitness for cognitive control in school-aged children, and extend the literature by demonstrating a relationship between fitness and trial-by-trial modulations in control demands.

Aerobic Fitness Is Associated With Cognitive Control Strategy in Preadolescent Children.

The authors used a conditional accuracy function (CAF) method to compute the mean accuracy of multiple reaction time ranges, to investigate the association between aerobic fitness and the utilization of cognitive control strategy during preadolescence. Thirty-eight higher- and lower-fit children were grouped according to their cardiorespiratory capacity (VO2max) and completed a modified flanker task. Seventeen young adults were recruited as a reference group of maturation. The results showed that higher-fit children exhibited an adult-like performance pattern, and demonstrated increased overall response accuracy compared to lower-fit children, with a disproportionally larger increase in individual responses when the time allowed for discriminative processing was constrained. These findings suggest that aerobic fitness is associated with enhanced cognitive control and development of a more proactive control strategy during flanker task in preadolescent children.

Systematic, Evidence-Based Review of Exercise, Physical Activity, and Physical Fitness Effects on Cognition in Persons with Multiple Sclerosis.

Cognitive dysfunction is highly prevalent, disabling, and poorly-managed in persons with multiple sclerosis (MS). Recent evidence suggests that exercise might have beneficial effects on cognition in this population. The current systematic, evidence-based review examined the existing literature on exercise, physical activity, and physical fitness effects on cognition in MS to accurately describe the current status of the field, offer recommendations for clinicians, and identify study-specific and participant-specific characteristics for providing future direction for ongoing MS research. We performed an open-dated search of Medline, PsychInfo, and CINAHL in December 2015. The search strategy involved using the terms 'exercise' OR 'physical activity' OR 'physical fitness' OR 'aerobic' OR 'resistance' OR 'balance' OR 'walking' OR 'yoga' OR 'training' OR 'rehabilitation' AND 'multiple sclerosis'. Articles were eliminated from the systematic review if it was a review article, theoretical paper, or textbook chapter; did not involve persons with MS; involved only persons with pediatric-onset MS; did not involve neuropsychological outcomes; did not include empirical data to evaluate outcomes; involved pharmacological interventions; or was not available in English. The selected articles were first classified as examining exercise, physical activity, or physical fitness, and were then randomly assigned to 2 independent reviewers who rated each article for level of evidence based on American Academy of Neurology criteria. Reviewers further completed a table to characterize important elements of each study (i.e., intervention characteristics), the cognitive domain(s) that were targeted, participant-specific characteristics, outcome measures, and study results. The present review resulted in 26 studies on the effects of exercise, physical activity, and physical fitness on cognition in persons with MS. This included 1 Class I study, 3 Class II studies, 8 Class III studies, and 14 Class IV studies. Of the 26 total studies, 6 were randomized controlled trials. Overall, there is conflicting evidence for the effects of exercise on cognition in MS, and overall positive, but not definitive evidence for the effects of physical activity and physical fitness, respectively, on cognition in this population. Collectively, there is insufficient well-designed research to definitively conclude that exercise, physical activity, and physical fitness are effective for improving cognition in MS. This is based, in part, on methodological issues of Class I and II studies, such as inclusion of cognition as a secondary outcome (35 % of reviewed studies), poorly-developed exercise interventions, and paucity of research that included cognitively-impaired MS samples. However, promising evidence from Class III and Class IV studies may be useful for informing the development of better intervention research.

Aerobic fitness is associated with greater hippocampal cerebral blood flow in children.

The present study is the first to investigate whether cerebral blood flow in the hippocampus relates to aerobic fitness in children. In particular, we used arterial spin labeling (ASL) perfusion MRI to provide a quantitative measure of blood flow in the hippocampus in 73 7- to 9-year-old preadolescent children. Indeed, aerobic fitness was found to relate to greater perfusion in the hippocampus, independent of age, sex, and hippocampal volume. Such results suggest improved microcirculation and cerebral vasculature in preadolescent children with higher levels of aerobic fitness. Further, aerobic fitness may influence how the brain regulates its metabolic demands via blood flow in a region of the brain important for learning and memory. To add specificity to the relationship of fitness to the hippocampus, we demonstrate no significant association between aerobic fitness and cerebral blood flow in the brainstem. Our results reinforce the importance of aerobic fitness during a critical period of child development.

Tracking the relationship between children's aerobic fitness and cognitive control.

OBJECTIVE: To investigate if changes in aerobic fitness over a 3-year period are associated with modulations in children's cognitive control. METHOD: A sample of 2nd/3rd-grade children (N = 290) completed baseline measures in Fall of 2011, and again in Spring of 2014 at the end of 4th/5th grade. Children completed the Progressive Aerobic Cardiovascular Endurance Run (PACER) test to measure aerobic capacity, a flanker task to evaluate inhibitory control, and an n-back task to assess working memory. Aerobic fitness was included as an independent variable in hierarchical regression analyses conducted at both time points, in addition to analyses examining changes in cognition over time. RESULTS: At baseline, higher fit children exhibited shorter overall flanker reaction time (RT), as well as superior accuracy and d' scores (i.e., target discrimination) for both 1- and 2-back conditions. Approximately 3 years later, higher levels of fitness were associated with better performance for only the most difficult conditions of each task, including greater incongruent flanker accuracy and less interference during the compatible condition, as well as better accuracy and target discrimination for the 2-back condition of the n-back task. Importantly, increases in fitness were independently related to improvements in incongruent flanker accuracy and 2-back d' scores. CONCLUSIONS: The current findings indicate that both higher aerobic fitness levels as well as increases in children's fitness are associated with better performance for task conditions eliciting greater cognitive demand. Such evidence is vital for implementing future health recommendations intended to foster improved cognitive performance in children. (PsycINFO Database Record

Moderate-to-Vigorous Physical Activity, Indices of Cognitive Control, and Academic Achievement in Preadolescents.

OBJECTIVE: To assess whether preadolescents' objectively measured moderate-to-vigorous physical activity (MVPA) is associated with cognitive control and academic achievement, independent of aerobic fitness. STUDY DESIGN: A sample of 74 children (Meanage = 8.64 years, SD = .58, 46% girls) were included in the analyses. Daily MVPA (min/d) was measured over 7 days using ActiGraph wGT3X+ accelerometer. Aerobic fitness was measured using a maximal graded exercise test and expressed as maximal oxygen uptake (mL*kg(-1)*min(-1)). Inhibitory control was measured with a modified Eriksen flanker task (reaction time and accuracy), and working memory with an Operation Span Task (accuracy scores). Academic achievement (in reading, mathematics, and spelling) was expressed as standardized scores on the Kaufman Test of Educational Achievement. The relationships were assessed using hierarchical regression models adjusting for aerobic fitness and other covariates. RESULTS: No significant associations were found between MVPA and inhibition, working memory, or academic achievement. Aerobic fitness was positively associated with inhibitory control (P = .02) and spelling (P = .04) but not with other cognitive or academic variables (all P > .05). CONCLUSIONS: Aerobic fitness, rather than daily MVPA, is positively associated with childhood ability to manage perceptual interference and spelling. Further research into the associations between objectively measured MVPA and cognitive and academic outcomes in children while controlling for important covariates is needed.

The sexual dimorphic association of cardiorespiratory fitness to working memory in children.

The present investigation examined the sexual dimorphic patterns of cardiorespiratory fitness to working memory in preadolescent children (age range: 7.7-10.9). Data were collected in three separate studies (Study 1: n = 97, 42 females; Study 2: n = 95, 45 females; Study 3: n = 84, 37 females). All participants completed a cardiorespiratory fitness assessment in addition to a specific measure of working memory (i.e. the operation span task, the n-back task, or the Sternberg task). Results from all three samples revealed that higher cardiorespiratory fitness levels were associated with better working memory performance only for males with no such relation observed for females. In addition, the sexually dimorphic pattern was selective for the most challenging working memory conditions in each task. Together, these findings reveal new evidence that cardiorespiratory fitness is selectively related to better working memory performance for male children. This investigation provides additional insight into how interventions aimed at improving fitness may influence cognitive development differentially among preadolescent children.

The persistent influence of concussion on attention, executive control and neuroelectric function in preadolescent children.

The aim of this investigation was to examine the influence of pediatric sport-related concussion on brain and cognitive function. To do so, we used a between-participants design, measures of executive control, and event-related potentials (ERPs). The findings demonstrate that children with a history of concussion exhibit behavioral deficits in attention, working memory and impulse control, as well as neuroelectric alterations in ERP indices of visual attention (N1), conflict resolution (N2) and attentional resource allocation (P3). Furthermore, the age at injury related to the magnitude of several concussion-related deficits. Accordingly, a single sports-related concussive incident during childhood (m=2.1years prior to testing) may lead to subtle, yet pervasive alterations in the behavioral and neural indices of attention and executive control, and age at injury may moderate injury outcomes.

Aerobic Fitness and Context Processing in Preadolescent Children.

BACKGROUND: There is a growing trend of inactivity among children, which may not only result in poorer physical health but also poorer cognitive health. The purpose of this study was to investigate the relationship between aerobic fitness and proactive and reactive cognitive control using a continuous performance task (CPT). METHODS: Forty-eight 9- to 10-year-old children (n = 24 higher fit [HF] and n = 24 lower fit [LF]) performed an AX-CPT requiring them to respond to target cue-probe pairs (AX) or nontarget pairs (AY, BX, BY) under 2 different trial duration conditions, which modulated working memory demands. RESULTS: Across trials and conditions, HF children had greater accuracy than LF children. For target trials, the long duration resulted in lower accuracy than the short duration. For nontarget trials, an interaction of duration and trial was observed, indicating that the long duration resulted in decreased BX and BY accuracy relative to the short duration. AY trials had greater accuracy during the long duration compared with the short duration. CONCLUSIONS: These data suggest that fitness may modulate cognitive control strategies during tasks requiring context updating and maintenance, key components of working memory and further support aerobic fitness as a marker of cognitive and brain health in children.

The persistent influence of pediatric concussion on attention and cognitive control during flanker performance.

This study investigated the influence of concussion history on children's neurocognitive processing. Thirty-two children ages 8-10 years (16 with a concussion history, 16 controls) completed compatible and incompatible conditions of a flanker task while behavioral and neuroelectric data were collected. Relative to controls, children with a concussion history exhibited alterations in the sequential congruency effect, committed more omission errors, and exhibited decreased post-error accuracy. Children with a concussion history exhibited longer N2 latency across task conditions, increased N2 amplitude during the incompatible condition of the task, and decreased P3b amplitude across task conditions. Children with a history of concussion also exhibited decreased ERN and Pe amplitudes, with group difference increasing for the incompatible condition of the task. The current results indicate that pediatric concussion may lead to subtle, but pervasive deficits in attention and cognitive control. These results serve to inform a poorly understood but significant public health concern.

The relation of saturated fats and dietary cholesterol to childhood cognitive flexibility.

Identification of health behaviors and markers of physiological health associated with childhood cognitive function has important implications for public health policy targeted toward cognitive health throughout the life span. Although previous studies have shown that aerobic fitness and obesity exert contrasting effects on cognitive flexibility among prepubertal children, the extent to which diet plays a role in cognitive flexibility has received little attention. Accordingly, this study examined associations between saturated fats and cholesterol intake and cognitive flexibility, assessed using a task switching paradigm, among prepubertal children between 7 and 10 years (N = 150). Following adjustment of confounding variables (age, sex, socioeconomic status, IQ, VO2max, and BMI), children consuming diets higher in saturated fats exhibited longer reaction time during the task condition requiring greater amounts of cognitive flexibility. Further, increasing saturated fat intake and dietary cholesterol were correlated with greater switch costs, reflecting impaired ability to maintain multiple task sets in working memory and poorer efficiency of cognitive control processes involved in task switching. These data are among the first to indicate that children consuming diets higher in saturated fats and cholesterol exhibit compromised ability to flexibly modulate their cognitive operations, particularly when faced with greater cognitive challenge. Future longitudinal and intervention studies are necessary to comprehensively characterize the interrelationships between diet, aerobic fitness, obesity, and children's cognitive abilities.

Central adiposity is negatively associated with hippocampal-dependent relational memory among overweight and obese children.

OBJECTIVE: To assess associations between adiposity and hippocampal-dependent and hippocampal-independent memory forms among prepubertal children. STUDY DESIGN: Prepubertal children (age 7-9 years; n = 126), classified as non-overweight (<85th percentile body mass index [BMI]-for-age [n = 73]) or overweight/obese (≥85th percentile BMI-for-age [n = 53]), completed relational (hippocampal-dependent) and item (hippocampal-independent) memory tasks. Performance was assessed with both direct (behavioral accuracy) and indirect (preferential disproportionate viewing [PDV]) measures. Adiposity (ie, percent whole-body fat mass, subcutaneous abdominal adipose tissue, visceral adipose tissue, and total abdominal adipose tissue) was assessed by dual-energy X-ray absorptiometry. Backward regression identified significant (P < .05) predictive models of memory performance. Covariates included age, sex, pubertal timing, socioeconomic status (SES), IQ, oxygen consumption, and BMI z-score. RESULTS: Among overweight/obese children, total abdominal adipose tissue was a significant negative predictor of relational memory behavioral accuracy, and pubertal timing together with SES jointly predicted the PDV measure of relational memory. In contrast, among non-overweight children, male sex predicted item memory behavioral accuracy, and a model consisting of SES and BMI z-score jointly predicted the PDV measure of relational memory. CONCLUSION: Regional, but not whole-body, fat deposition was selectively and negatively associated with hippocampal-dependent relational memory among overweight/obese prepubertal children.

Cognitive control in preadolescent children with risk factors for metabolic syndrome.

OBJECTIVE: To investigate the relationship between cognitive control and metabolic syndrome (MetS) risk factors in preadolescent children while controlling for aerobic fitness and weight status. METHODS: Hierarchical regression analyses were conducted using aerobic fitness, demographic, and MetS risk-factor variables in a sample of 2nd- and 3rd-grade children (n = 139) who performed a modified version of a flanker task to assess cognitive control. Flanker performance was also compared between children that met no MetS risk-factor criteria (n = 70), and children who met 1 criterion or more (n = 69). RESULTS: Regression analyses indicated that after controlling for demographic variables and fitness, HDL cholesterol exhibited an independent negative association with flanker reaction time (RT). Group comparisons further revealed that children with no risk factors demonstrated overall shorter RT than the at-risk group. In addition, at-risk children exhibited larger accuracy-interference scores (i.e., poorer performance) for the more difficult conditions of the flanker task that required the up-regulation of cognitive control to meet elevated task demands. CONCLUSIONS: These findings are consonant with the previous literature reporting a beneficial influence of aerobic fitness on cognitive control, and reveal new evidence that children without risk factors for MetS exhibit better inhibitory control and increased cognitive flexibility than do at-risk children. In addition to aerobic fitness, these risk factors may serve as important biomarkers for understanding the potential cognitive implications of MetS risk in younger generations.