Cardiorespiratory fitness and hippocampal volume predict faster episodic associative learning in older adults.

Declining episodic memory is common among otherwise healthy older adults, in part due to negative effects of aging on hippocampal circuits. However, there is significant variability between individuals in severity of aging effects on the hippocampus and subsequent memory decline. Importantly, variability may be influenced by modifiable protective physiological factors such as cardiorespiratory fitness (CRF). More research is needed to better understand which aspects of cognition that decline with aging benefit most from CRF. The current study evaluated the relation of CRF with learning rate on the episodic associative learning (EAL) task, a task designed specifically to target hippocampal-dependent relational binding and to evaluate learning with repeated occurrences. Results show higher CRF was associated with faster learning rate. Larger hippocampal volume was also associated with faster learning rate, though hippocampal volume did not mediate the relationship between CRF and learning rate. Furthermore, to support the distinction between learning item relations and learning higher-order sequences, which declines with aging but is largely reliant on extra-hippocampal learning systems, we found learning rate on the EAL task was not related to motor sequence learning on the alternating serial reaction time task. Motor sequence learning was also not correlated with hippocampal volume. Thus, for the first time, we show that both higher CRF and larger hippocampal volume in healthy older adults are related to enhanced rate of relational memory acquisition.

Fitness, but not physical activity, is related to functional integrity of brain networks associated with aging.

Greater physical activity and cardiorespiratory fitness are associated with reduced age-related cognitive decline and lower risk for dementia. However, significant gaps remain in the understanding of how physical activity and fitness protect the brain from adverse effects of brain aging. The primary goal of the current study was to empirically evaluate the independent relationships between physical activity and fitness with functional brain health among healthy older adults, as measured by the functional connectivity of cognitively and clinically relevant resting state networks. To build context for fitness and physical activity associations in older adults, we first demonstrate that young adults have greater within-network functional connectivity across a broad range of cortical association networks. Based on these results and previous research, we predicted that individual differences in fitness and physical activity would be most strongly associated with functional integrity of the networks most sensitive to aging. Consistent with this prediction, and extending on previous research, we showed that cardiorespiratory fitness has a positive relationship with functional connectivity of several cortical networks associated with age-related decline, and effects were strongest in the default mode network (DMN). Furthermore, our results suggest that the positive association of fitness with brain function can occur independent of habitual physical activity. Overall, our findings provide further support that cardiorespiratory fitness is an important factor in moderating the adverse effects of aging on cognitively and clinically relevant functional brain networks.

Data-driven biomarkers outperform theory-based biomarkers in predicting stroke motor outcomes.

Chronic motor impairments are a leading cause of disability after stroke. Previous studies have predicted motor outcomes based on the degree of damage to predefined structures in the motor system, such as the corticospinal tract. However, such theory-based approaches may not take full advantage of the information contained in clinical imaging data. The present study uses data-driven approaches to predict chronic motor outcomes after stroke and compares the accuracy of these predictions to previously-identified theory-based biomarkers. Using a cross-validation framework, regression models were trained using lesion masks and motor outcomes data from 789 stroke patients (293 female/496 male) from the ENIGMA Stroke Recovery Working Group (age 64.9±18.0 years; time since stroke 12.2±0.2 months; normalised motor score 0.7±0.5 (range [0,1]). The out-of-sample prediction accuracy of two theory-based biomarkers was assessed: lesion load of the corticospinal tract, and lesion load of multiple descending motor tracts. These theory-based prediction accuracies were compared to the prediction accuracy from three data-driven biomarkers: lesion load of lesion-behaviour maps, lesion load of structural networks associated with lesion-behaviour maps, and measures of regional structural disconnection. In general, data-driven biomarkers had better prediction accuracy - as measured by higher explained variance in chronic motor outcomes - than theory-based biomarkers. Data-driven models of regional structural disconnection performed the best of all models tested (R2 = 0.210, p < 0.001), performing significantly better than predictions using the theory-based biomarkers of lesion load of the corticospinal tract (R2 = 0.132, p< 0.001) and of multiple descending motor tracts (R2 = 0.180, p < 0.001). They also performed slightly, but significantly, better than other data-driven biomarkers including lesion load of lesion-behaviour maps (R2 =0.200, p < 0.001) and lesion load of structural networks associated with lesion-behaviour maps (R2 =0.167, p < 0.001). Ensemble models - combining basic demographic variables like age, sex, and time since stroke - improved prediction accuracy for theory-based and data-driven biomarkers. Finally, combining both theory-based and data-driven biomarkers with demographic variables improved predictions, and the best ensemble model achieved R2 = 0.241, p < 0.001. Overall, these results demonstrate that models that predict chronic motor outcomes using data-driven features, particularly when lesion data is represented in terms of structural disconnection, perform better than models that predict chronic motor outcomes using theory-based features from the motor system. However, combining both theory-based and data-driven models provides the best predictions.

Association between cardiorespiratory fitness and cerebrovascular reactivity to a breath-hold stimulus in older adults: influence of aerobic exercise training.

Cerebrovascular reactivity (CVR) to a physiological stimulus is a commonly used surrogate of cerebrovascular health. Cross-sectional studies using blood oxygen level dependent (BOLD) neuroimaging demonstrated lower BOLD-CVR to hypercapnia among adults with high compared with lower cardiorespiratory fitness (CRF) in contrast to transcranial Doppler studies. However, whether BOLD-CVR changes following chronic aerobic exercise in older, cognitively intact adults is unclear. This study evaluated relations between BOLD-CVR with CRF (V̇o2peak) using a cross-sectional and interventional study design. We hypothesized that 1) greater CRF would be associated with lower BOLD-CVR in older adults (n = 114; 65 ± 6.5 yr) with a wide range of CRF and 2) BOLD-CVR would be attenuated after exercise training in a subset (n = 33) randomized to 3-mo of moderate- or light-intensity cycling. CVR was quantified as the change in the BOLD signal in response to acute hypercapnia using a blocked breath-hold design from a region-of-interest analysis for cortical networks. In the cross-sectional analysis, there was a quadratic relation between V̇o2peak (P = 0.03), but not linear (P = 0.87) and cortical BOLD-CVR. BOLD-CVR increased until a V̇o2peak ∼28 mL/kg/min after which BOLD-CVR declined. The nonlinear trend was consistent across all networks (P = 0.04-0.07). In the intervention, both the active and light-intensity exercise groups improved CRF similarly (6% vs. 10.8%, P = 0.28). The percent change in CRF was positively associated with change in BOLD-CVR in the default mode network only. These data suggest that BOLD-CVR is nonlinearly associated with CRF and that in lower-fit adults default mode network may be most sensitive to CRF-related increases in BOLD-CVR.NEW & NOTEWORTHY Earlier studies evaluating associations between cardiorespiratory fitness (CRF) and cerebrovascular reactivity (CVR) have demonstrated conflicting findings dependent on imaging modality or subject characteristics in individuals across a narrow range of CRF. This study demonstrates that CRF is nonlinearly associated with CVR measured by blood oxygen level dependent (BOLD) fMRI in a large sample of middle-aged and older adults across a wide range of CRF, suggesting that conflicting prior findings are related to the range of CRFs studied.

Musical Training and Brain Volume in Older Adults.

Musical practice, including musical training and musical performance, has been found to benefit cognitive function in older adults. Less is known about the role of musical experiences on brain structure in older adults. The present study examined the role of different types of musical behaviors on brain structure in older adults. We administered the Goldsmiths Musical Sophistication Index, a questionnaire that includes questions about a variety of musical behaviors, including performance on an instrument, musical practice, allocation of time to music, musical listening expertise, and emotional responses to music. We demonstrated that musical training, defined as the extent of musical training, musical practice, and musicianship, was positively and significantly associated with the volume of the inferior frontal cortex and parahippocampus. In addition, musical training was positively associated with volume of the posterior cingulate cortex, insula, and medial orbitofrontal cortex. Together, the present study suggests that musical behaviors relate to a circuit of brain regions involved in executive function, memory, language, and emotion. As gray matter often declines with age, our study has promising implications for the positive role of musical practice on aging brain health.

Brain network modularity predicts changes in cortical thickness in children involved in a physical activity intervention.

Individual differences in brain network modularity at baseline can predict improvements in cognitive performance after cognitive and physical interventions. This study is the first to explore whether brain network modularity predicts changes in cortical brain structure in 8- to 9-year-old children involved in an after-school physical activity intervention (N = 62), relative to children randomized to a wait-list control group (N = 53). For children involved in the physical activity intervention, brain network modularity at baseline predicted greater decreases in cortical thickness in the anterior frontal cortex and parahippocampus. Further, for children involved in the physical activity intervention, greater decrease in cortical thickness was associated with improvements in cognitive efficiency. The relationships among baseline modularity, changes in cortical thickness, and changes in cognitive performance were not present in the wait-list control group. Our exploratory study has promising implications for the understanding of brain network modularity as a biomarker of intervention-related improvements with physical activity.

Brain Network Modularity Predicts Improvements in Cognitive and Scholastic Performance in Children Involved in a Physical Activity Intervention.

Introduction: Brain network modularity is a principle that quantifies the degree to which functional brain networks are divided into subnetworks. Higher modularity reflects a greater number of within-module connections and fewer connections between modules, and a highly modular brain is often interpreted as a brain that contains highly specialized brain networks with less integration between networks. Recent work in younger and older adults has demonstrated that individual differences in brain network modularity at baseline can predict improvements in performance after cognitive and physical interventions. The use of brain network modularity as a predictor of training outcomes has not yet been examined in children. Method: In the present study, we examined the relationship between baseline brain network modularity and changes (post-intervention performance minus pre-intervention performance) in cognitive and academic performance in 8- to 9-year-old children who participated in an after-school physical activity intervention for 9 months (N = 78) as well as in children in a wait-list control group (N = 72). Results: In children involved in the after-school physical activity intervention, higher modularity of brain networks at baseline predicted greater improvements in cognitive performance for tasks of executive function, cognitive efficiency, and mathematics achievement. There were no associations between baseline brain network modularity and performance changes in the wait-list control group. Discussion: Our study has implications for biomarkers of cognitive plasticity in children. Understanding predictors of cognitive performance and academic progress during child development may facilitate the effectiveness of interventions aimed to improve cognitive and brain health.

Acute Exercise Effects Predict Training Change in Cognition and Connectivity.

PURPOSE: Previous studies report memory and functional connectivity of memory systems improve acutely after a single aerobic exercise session or with training, suggesting that the acute effects of aerobic exercise may reflect initial changes that adapt over time. In this trial, for the first time, we test the proof-of-concept of whether the acute and training effects of aerobic exercise on working memory and brain network connectivity are related in the same participants. METHODS: Cognitively normal older participants (N = 34) were enrolled in a randomized clinical trial (NCT02453178). Participants completed fMRI resting state and a face working memory N-back task acutely after light- and moderate-intensity exercises and after a 12-wk aerobic training intervention. RESULTS: Functional connectivity did not change more after moderate-intensity training compared with light-intensity training. However, both training groups showed similar changes in cardiorespiratory fitness (CRF) (maximal exercise oxygen uptake, V˙O2peak), limiting group-level comparisons. Acute effects of moderate-intensity aerobic exercise on connections primarily in the default network predicted training enhancements in the same connections. Working memory also improved acutely, especially after moderate-intensity, and greater acute improvements predicted greater working memory improvement with training. Exercise effects on functional connectivity of right lateralized frontoparietal connections were related to both acute and training gains in working memory. CONCLUSIONS: Our data support the concept of acute aerobic exercise effects on functional brain systems and performance as an activity-evoked biomarker for exercise training benefits in the same outcomes. These findings may lead to new insights and methods for improving memory outcomes with aerobic exercise training.

Nutritional supplementation boosts aerobic exercise effects on functional brain systems.

There is growing evidence that aerobic exercise protects against age-related cognitive decline and that cardiorespiratory fitness is an important factor for these benefits. Studies also suggest that combining physical activity with cognitive enrichment is beneficial. We further examine these predictions by comparing effects of a nutritional supplement promoting exercise capacity to a lower-intensity activity with cognitive enrichment on functional network and cognitive outcomes that otherwise decline with aging. Inactive healthy older adults were randomized to one of four groups including a low-intensity activity with complex cognitive demands (dancing), walking, walking+supplement, or an active control. Results showed that walking+supplement increased salience network functional connectivity (FC), with less training benefit for default mode network FC. Although cognitive performance did not increase for any training group, participants in the walking+supplement group who were on medication that boosted key neurotransmitters (e.g., selective serotonin reuptake inhibitors) showed improved processing speed. Overall, this study provides new insight into how to boost the protective effects of exercise on brain systems that otherwise deteriorate with aging. NEW & NOTEWORTHY Aerobic exercise effects on brain networks that otherwise decline with aging can be boosted with a nutritional supplement including beta-alanine. Beta-alanine supplementation could enhance the extent to which aerobic adaptations benefit the brain. In contrast, cognitive enrichment with low-intensity physical activity through dance did not affect functional networks. Medications that modulate neurotransmitters affected by aging (e.g., selective serotonin reuptake inhibitors) may modify effects of exercise on cognition.

Cerebral blood flow is not modulated following acute aerobic exercise in preadolescent children.

Cognitive enhancements following a single bout of exercise are frequently attributed to increases in cerebral blood flow, however to date we have little understanding of the extent to which such bouts of exercise actually even influence cerebral blood flow following the cessation of exercise. To gain such insight, both regional and global changes in cerebral blood flow were assessed using 3D pseudo-continuous arterial spin-labeled magnetic resonance imaging in a sample of 41 preadolescent children. Using a within-participants randomized crossover design, cerebral blood flow as assessed prior to and following 20-min of either aerobic exercise or an active-control condition during two separate, counterbalanced sessions. The aerobic exercise condition consisted of walking/jogging on a motor driven treadmill at an intensity of approximately 70% of age-predicted maximum heart rate (HR = 136.1 ±â€¯11.1 bpm). The active control condition consisted of walking on the treadmill at the lowest possible intensity (0.5 mph and 0% grade; HR = 92.0 ±â€¯12.2 bpm). Findings revealed no differences in cerebral blood flow following the cessation of exercise relative to the active control condition. These findings demonstrate that cerebral blood flow may not be altered in preadolescent children following the termination of the exercise stimulus during the period when cognitive enhancements have previously been observed.

Scholastic performance and functional connectivity of brain networks in children.

One of the keys to understanding scholastic success is to determine the neural processes involved in school performance. The present study is the first to use a whole-brain connectivity approach to explore whether functional connectivity of resting state brain networks is associated with scholastic performance in seventy-four 7- to 9-year-old children. We demonstrate that children with higher scholastic performance across reading, math and language have more integrated and interconnected resting state networks, specifically the default mode network, salience network, and frontoparietal network. To add specificity, core regions of the dorsal attention and visual networks did not relate to scholastic performance. The results extend the cognitive role of brain networks in children as well as suggest the importance of network connectivity in scholastic success.

The Acute Effects of Aerobic Exercise on the Functional Connectivity of Human Brain Networks.

Although there is promising evidence that regular physical activity could counteract age-related decline in cognitive and brain function, the mechanisms for this neuroprotection remain unclear. The acute effects of exercise can provide insight into the mechanisms by which the brain adapts to habitual exercise by reflecting transient modulations of systems that would subsequently accumulate long-term adaptations through repeated training sessions. However, methodological limitations have hindered the mechanistic insight gained from previous studies examining acute exercise effects on the human brain. In the current study, we tested the plasticity of functional brain networks in response to a single stimulus of aerobic exercise using resting-state functional connectivity analyses. In a sample of healthy younger (N = 12; age = 23.2 years; 6 females) and older adults (N = 13; age = 66.3 years; 6 females), we found that 30 minutes of moderate-intensity aerobic cycling selectively increased synchrony among brain regions associated with affect and reward processing, learning and memory, and in regions important for attention and executive control. Importantly, these changes did not occur when the same participants completed a passive, motor-driven control condition. Our results suggest that these transient increases in synchrony serve as a possible avenue for systematically investigating the effects of various exercise parameters on specific brain systems, which may accelerate mechanistic discoveries about the benefits of exercise on brain and cognitive function.

Carotid ß-stiffness index is associated with slower processing speed but not working memory or white matter integrity in healthy middle-aged/older adults.

Aging is associated with increased carotid artery stiffness, a predictor of incident stroke, and reduced cognitive performance and brain white matter integrity (WMI) in humans. Therefore, we hypothesized that higher carotid stiffness/lower compliance would be independently associated with slower processing speed, higher working memory cost, and lower WMI in healthy middle-aged/older (MA/O) adults. Carotid ß-stiffness (P < 0.001) was greater and compliance (P < 0.001) was lower in MA/O (n = 32; 64.4 ± 4.3 yr) vs. young (n = 19; 23.8 ± 2.9 yr) adults. MA/O adults demonstrated slower processing speed (27.4 ± 4.6 vs. 35.4 ± 5.0 U/60 s, P < 0.001) and higher working memory cost (-15.4 ± 0.14 vs. -2.2 ± 0.05%, P < 0.001) vs. young adults. Global WMI was lower in MA/O adults (P < 0.001) and regionally in the frontal lobe (P = 0.020) and genu (P = 0.009). In the entire cohort, multiple regression analysis that included education, sex, and body mass index, carotid ß-stiffness index (B = -0.53 ± 0.15 U, P = 0.001) and age group (B = -4.61 ± 1.7, P = 0.012, adjusted R2 = 0.4) predicted processing speed but not working memory cost or WMI. Among MA/O adults, higher ß-stiffness (B = -0.60 ± 0.18, P = 0.002) and lower compliance (B = 0.93 ± 0.26, P = 0.002) were associated with slower processing speed but not working memory cost or WMI. These data suggest that greater carotid artery stiffness is independently and selectively associated with slower processing speed but not working memory among MA/O adults. Carotid artery stiffening may modulate reductions in processing speed earlier than working memory with healthy aging in humans.NEW & NOTEWORTHY Previously, studies investigating the relation between large elastic artery stiffness, cognition, and brain structure have focused mainly on aortic stiffness in aged individuals with cardiovascular disease risk factors and other comorbidities. This study adds to the field by demonstrating that the age-related increases in carotid artery stiffness, but not aortic stiffness, is independently and selectively associated with slower processing speed but not working memory among middle-aged/older adults with low cardiovascular disease risk factor burden.

Differential Effects of Acute Exercise on Distinct Aspects of Executive Function.

PURPOSE: To increase understanding about the effects of moderate-intensity physical activity on cognitive function, the current study examined whether a single bout of aerobic exercise exerts differential effects on distinct aspects of executive function in healthy young adults. METHODS: A within-subjects study was designed where 26 young adult participants (mean age = 25.23 yr, 12 males) engaged in a 30-min bout of both (a) moderate-intensity aerobic cycling and (b) passive motor-driven cycling, occurring on two separate occasions and counterbalanced in their order. To assess changes in cognitive function, performance on two tasks of executive function-working memory and inhibitory control, counterbalanced in the order of administration-was collected before and immediately after each exercise session. RESULTS: Results indicate that working memory performance on the 2-back condition of a facial n-back task was acutely enhanced by moderate-intensity exercise (mean increase in accuracy = 6.4% ± 1.1%), which was significantly greater than the changes after passive exercise control (P < 0.05). This finding was not observed for inhibitory control in which neither of the exercise sessions elicited significant changes in performance on a flanker task. CONCLUSIONS: Acute aerobic exercise evokes differential effects on executive functions. This specificity in behavioral outcomes leads to the prediction that brain mechanisms related to working memory, compared to inhibitory control, are selectively benefited by moderate-intensity exercise.