Investigating nutrient biomarkers of healthy brain aging: a multimodal brain imaging study.

The emerging field of Nutritional Cognitive Neuroscience aims to uncover specific foods and nutrients that promote healthy brain aging. Central to this effort is the discovery of nutrient profiles that can be targeted in nutritional interventions designed to promote brain health with respect to multimodal neuroimaging measures of brain structure, function, and metabolism. The present study therefore conducted one of the largest and most comprehensive nutrient biomarker studies examining multimodal neuroimaging measures of brain health within a sample of 100 older adults. To assess brain health, a comprehensive battery of well-established cognitive and brain imaging measures was administered, along with 13 blood-based biomarkers of diet and nutrition. The findings of this study revealed distinct patterns of aging, categorized into two phenotypes of brain health based on hierarchical clustering. One phenotype demonstrated an accelerated rate of aging, while the other exhibited slower-than-expected aging. A t-test analysis of dietary biomarkers that distinguished these phenotypes revealed a nutrient profile with higher concentrations of specific fatty acids, antioxidants, and vitamins. Study participants with this nutrient profile demonstrated better cognitive scores and delayed brain aging, as determined by a t-test of the means. Notably, participant characteristics such as demographics, fitness levels, and anthropometrics did not account for the observed differences in brain aging. Therefore, the nutrient pattern identified by the present study motivates the design of neuroscience-guided dietary interventions to promote healthy brain aging.

Assessing blood oxygen level-dependent signal variability as a biomarker of brain injury in sport-related concussion.

Mild traumatic brain injury is a complex neurological disorder of significant concern among athletes who play contact sports. Athletes who sustain sport-related concussion typically undergo physical examination and neurocognitive evaluation to determine injury severity and return-to-play status. However, traumatic disruption to neurometabolic processes can occur with minimal detectable anatomic pathology or neurocognitive alteration, increasing the risk that athletes may be cleared for return-to-play during a vulnerable period and receive a repetitive injury. This underscores the need for sensitive functional neuroimaging methods to detect altered cerebral physiology in concussed athletes. The present study compared the efficacy of Immediate Post-concussion Assessment and Cognitive Testing composite scores and whole-brain measures of blood oxygen level-dependent signal variability for classifying concussion status and predicting concussion symptomatology in healthy, concussed and repetitively concussed athletes, assessing blood oxygen level-dependent signal variability as a potential diagnostic tool for characterizing functional alterations to cerebral physiology and assisting in the detection of sport-related concussion. We observed significant differences in regional blood oxygen level-dependent signal variability measures for concussed athletes but did not observe significant differences in Immediate Post-concussion Assessment and Cognitive Testing scores of concussed athletes. We further demonstrate that incorporating measures of functional brain alteration alongside Immediate Post-concussion Assessment and Cognitive Testing scores enhances the sensitivity and specificity of supervised random forest machine learning methods when classifying and predicting concussion status and post-concussion symptoms, suggesting that alterations to cerebrovascular status characterize unique variance that may aid in the detection of sport-related concussion and repetitive mild traumatic brain injury. These results indicate that altered blood oxygen level-dependent variability holds promise as a novel neurobiological marker for detecting alterations in cerebral perfusion and neuronal functioning in sport-related concussion, motivating future research to establish and validate clinical assessment protocols that can incorporate advanced neuroimaging methods to characterize altered cerebral physiology following mild traumatic brain injury.

Integrating Nutrient Biomarkers, Cognitive Function, and Structural MRI Data to Build Multivariate Phenotypes of Healthy Aging.

BACKGROUND: Research in the emerging field of nutritional cognitive neuroscience demonstrates that many aspects of nutrition-from entire diets to specific nutrients-affect cognitive performance and brain health. OBJECTIVES: Although previous research has primarily examined the bivariate relationship between nutrition and cognition or nutrition and brain health, this study sought to investigate the joint relationship between these essential and interactive elements of human health. METHODS: We applied a state-of-the-art data fusion method, coupled matrix tensor factorization, to characterize the joint association between measures of nutrition (52 nutrient biomarkers), cognition (Wechsler Abbreviated Test of Intelligence and Wechsler Memory Scale), and brain health (high-resolution MRI measures of structural brain volume) within a cross-sectional sample of 111 healthy older adults, with an average age of 69.1 y, 62% being female, and an average body mass index of 26.0 kg/m2. RESULTS: Data fusion uncovered latent factors that capture the joint association between specific nutrient profiles, cognitive measures, and cortical volumes, demonstrating the respects in which these health domains are coupled. A hierarchical cluster analysis further revealed systematic differences between a subset of variables contributing to the underlying latent factors, providing evidence for multivariate phenotypes that represent high and low levels of performance across multiple health domains. The primary features that distinguish between each phenotype were as follows: 1) nutrient biomarkers for monounsaturated and polyunsaturated fatty acids; 2) cognitive measures of immediate, auditory, and delayed memory; and 3) brain volumes within frontal, temporal, and parietal cortexes. CONCLUSIONS: By incorporating innovations in nutritional epidemiology (nutrient biomarker analysis), cognitive neuroscience (high-resolution structural brain imaging), and statistics (data fusion), this study provides an interdisciplinary synthesis of methods that elucidate how nutrition, cognition, and brain health are integrated through lifestyle choices that affect healthy aging.

Efforts to enhance reproducibility in a human performance research project.

Background: Ensuring the validity of results from funded programs is a critical concern for agencies that sponsor biological research. In recent years, the open science movement has sought to promote reproducibility by encouraging sharing not only of finished manuscripts but also of data and code supporting their findings. While these innovations have lent support to third-party efforts to replicate calculations underlying key results in the scientific literature, fields of inquiry where privacy considerations or other sensitivities preclude the broad distribution of raw data or analysis may require a more targeted approach to promote the quality of research output. Methods: We describe efforts oriented toward this goal that were implemented in one human performance research program, Measuring Biological Aptitude, organized by the Defense Advanced Research Project Agency's Biological Technologies Office. Our team implemented a four-pronged independent verification and validation (IV&V) strategy including 1) a centralized data storage and exchange platform, 2) quality assurance and quality control (QA/QC) of data collection, 3) test and evaluation of performer models, and 4) an archival software and data repository. Results: Our IV&V plan was carried out with assistance from both the funding agency and participating teams of researchers. QA/QC of data acquisition aided in process improvement and the flagging of experimental errors. Holdout validation set tests provided an independent gauge of model performance. Conclusions: In circumstances that do not support a fully open approach to scientific criticism, standing up independent teams to cross-check and validate the results generated by primary investigators can be an important tool to promote reproducibility of results.

Enhanced physical and cognitive performance in active duty Airmen: evidence from a randomized multimodal physical fitness and nutritional intervention.

Achieving military mission objectives requires high levels of performance from Airmen who operate under extreme physical and cognitive demands. Thus, there is a critical need to establish scientific interventions to enhance physical fitness and cognitive performance-promoting the resilience of Airmen and aiding in mission success. We therefore conducted a comprehensive, 12-week randomized controlled trial in active-duty Air Force Airmen (n = 148) to compare the efficacy of a multimodal intervention comprised of high-intensity interval aerobic fitness and strength training paired with a novel nutritional supplement [comprised of ß-hydroxy ß-methylbutyrate (HMB), lutein, phospholipids, DHA and selected micronutrients including B12 and folic acid] to high-intensity interval aerobic fitness and strength training paired with a standard of care placebo beverage. The exercise intervention alone improved several dimensions of physical fitness [strength and endurance (+ 8.3%), power (+ 0.85%), mobility and stability (+ 22%), heart rate (- 1.1%) and lean muscle mass (+ 1.4%)] and cognitive function [(episodic memory (+ 9.5%), processing efficiency (+ 7.5%), executive function reaction time (- 4.8%) and fluid intelligence accuracy (+ 19.5%)]. Relative to exercise training alone, the multimodal fitness and nutritional intervention further improved working memory (+ 9.0%), fluid intelligence reaction time (- 7.7%), processing efficiency (+ 1.8%), heart rate (- 2.4%) and lean muscle mass (+ 1.5%). These findings establish the efficacy of a multimodal intervention that incorporates aerobic fitness and strength training with a novel nutritional supplement to enhance military performance objectives and to provide optimal exercise training and nutritional support for the modern warfighter.

Opposing associations between sedentary time and decision-making competence in young adults revealed by functional connectivity in the dorsal attention network.

How daily physical activity and sedentary time relate to human judgement and functional connectivity (FC) patterns that support them remains underexplored. We investigated the relationships between accelerometer-measured moderate-to-vigorous physical activity (MVPA) and sedentary time to decision-making competence (DMC) in young adults using a comprehensive Adult-Decision Making Competence battery. We applied graph theory measures of global and local efficiency to test the mediating effects of FC in cognitively salient brain networks (fronto-parietal; dorsal attention, DAN; ventral attention; and default mode), assessed from the resting-state fMRI. Sedentary time was related to lower susceptibility to a framing bias. However, once global and local efficiency of the DAN were considered we observed (1) higher susceptibility to framing with more sedentary time, mediated through lower local and global efficiency in the DAN, and (2) lower susceptibility to framing with more sedentary time. MVPA was not related to DMC or graph theory measures. These results suggest that remaining sedentary may reduce neurofunctional readiness for top-down control and decrease engagement of deliberate thought, required to ignore irrelevant aspects of a problem. The positive effect suggests that the relationship between sedentary time and DMC may be moderated by unmeasured factors such as the type of sedentary behavior.

Enhanced decision-making through multimodal training.

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.

Essential Amino Acids, Vitamins, and Minerals Moderate the Relationship between the Right Frontal Pole and Measures of Memory.

SCOPE: Nutrition has increasingly been recognized for its ability to help prevent and protect against disease, inspiring new programs of research that translate findings from nutritional science into innovative assessment tools, technologies, and therapies to advance the practice of modern medicine. A central aim in this effort is to discover specific dietary patterns that promote healthy brain aging and moderate the engagement of neural systems known to facilitate cognitive performance in later life. METHODS AND RESULTS: The present study therefore investigates estimates of nutrient intake derived from food frequency questionnaires, structural measures of brain volume via high-resolution magnetic resonance imaging, and standardized neuropsychological measures of memory performance in nondemented elders (n = 111) using a moderation analysis. The results reveal that the essential amino acids, vitamins, and minerals nutrient pattern moderates the positive relationship between the volume of the right frontal pole and measures of both delayed and auditory memory. CONCLUSIONS: Our findings demonstrate that a nutrient pattern including macro- and micronutrients moderate the effect of brain structure on cognitive function in old age and support the efficacy of interdisciplinary methods in nutritional cognitive neuroscience for the study of healthy brain aging.

Nutrient biomarker patterns, cognitive function, and fMRI measures of network efficiency in the aging brain.

A central aim of research in the psychological and brain sciences is to establish therapeutic interventions to promote healthy brain aging. Accumulating evidence indicates that diet and the many bioactive substances present in food are reasonable interventions to examine for dementia prevention. However, interdisciplinary research that applies methods from nutritional epidemiology and network neuroscience to investigate the role of nutrition in shaping functional brain network efficiency remains to be conducted. The present study therefore sought to combine methods across disciplines, applying nutrient biomarker pattern (NBP) analysis to capture the effects of plasma nutrients in combination and to examine their collective influence on measures of functional brain network efficiency (small-world propensity). We examined the contribution of NBPs to multiple indices of cognition and brain health in non-demented elders (n = 116), investigating performance on measures of general intelligence, executive function, and memory, and resting-state fMRI measures of brain network efficiency within seven intrinsic connectivity networks. Statistical moderation investigated whether NBPs influenced network efficiency and cognitive outcomes. The results revealed five NBPs that were associated with enhanced cognitive performance, including biomarker patterns high in plasma: (1) ω-3 and ω-6 polyunsaturated fatty acids (PUFAs), (2) lycopene, (3) ω-3 PUFAs, (4) carotenoids, and (5) vitamins B (riboflavin, folate, B12) and D. Furthermore, three NBPs were associated with enhanced functional brain network efficiency, including biomarker patterns high in plasma: (1) ω-6 PUFAs, (2) ω-3 PUFAs, and (3) carotene. Finally, ω-3 PUFAs moderated the fronto-parietal network and general intelligence, while ω-6 PUFAs and lycopene moderated the dorsal attention network and executive function. In sum, NBPs account for a significant proportion of variance in measures of cognitive performance and functional brain network efficiency. The results motivate a multidisciplinary approach that applies methods from nutritional epidemiology (NBP analysis) and cognitive neuroscience (functional brain network efficiency) to characterize the impact of nutrition on human health, aging, and disease.

Nutrient biomarkers shape individual differences in functional brain connectivity: Evidence from omega-3 PUFAs.

A wealth of neuroscience evidence demonstrates that diet and nutrition play an important role in structural brain plasticity, promoting the development of gray matter volume and maintenance of white matter integrity across the lifespan. However, the role of nutrition in shaping individual differences in the functional brain connectome remains to be well established. We therefore investigated whether nutrient biomarkers known to have beneficial effects on brain structure (i.e., the omega-3 polyunsaturated fatty acids; ω-3 PUFAs), explain individual differences in functional brain connectivity within healthy older adults (N = 96). Our findings demonstrate that ω-3 PUFAs are associated with individual differences in functional connectivity within regions that support executive function (prefrontal cortex), memory (hippocampus), and emotion (amygdala), and provide key evidence that the influence of these regions on global network connectivity reliably predict general, fluid, and crystallized intelligence. The observed findings not only elucidate the role of ω-3 PUFAs in functional brain plasticity and intelligence, but also motivate future studies to examine their impact on psychological health, aging, and disease.

Individual differences in decision making competence revealed by multivariate fMRI.

While an extensive literature in decision neuroscience has elucidated the neurobiological foundations of decision making, prior research has focused primarily on group-level effects in a sample population. Due to the presence of inherent differences between individuals' cognitive abilities, it is also important to examine the neural correlates of decision making that explain interindividual variability in cognitive performance. This study therefore investigated how individual differences in decision making competence, as measured by the Adult Decision Making Competence (A-DMC) battery, are related to functional brain connectivity patterns derived from resting-state fMRI data in a sample of 304 healthy participants. We examined connectome-wide associations, identifying regions within frontal, parietal, temporal, and occipital cortex that demonstrated significant associations with decision making competence. We then assessed whether the functional interactions between brain regions sensitive to decision making competence and seven intrinsic connectivity networks (ICNs) were predictive of specific facets of decision making assessed by subtests of the A-DMC battery. Our findings suggest that individual differences in specific facets of decision making competence are mediated by ICNs that support executive, social, and perceptual processes, and motivate an integrative framework for understanding the neural basis of individual differences in decision making competence.

Seven-year-olds allocate attention like adults unless working memory is overloaded.

Previous studies have indicated that visual working memory performance increases with age in childhood, but it is not clear why. One main hypothesis has been that younger children are less efficient in their attention; specifically, they are less able to exclude irrelevant items from working memory to make room for relevant items. We examined this hypothesis by measuring visual working memory capacity under a continuum of five attention conditions. A recognition advantage was found for items to be attended as opposed to ignored. The size of this attention-related effect was adult-like in young children with small arrays, suggesting that their attention processes are efficient even though their working memory capacity is smaller than that of older children and adults. With a larger working memory load, this efficiency in young children was compromised. The efficiency of attention cannot be the sole explanation for the capacity difference.

An assessment of fixed-capacity models of visual working memory.

Visual working memory is often modeled as having a fixed number of slots. We test this model by assessing the receiver operating characteristics (ROC) of participants in a visual-working-memory change-detection task. ROC plots yielded straight lines with a slope of 1.0, a tell-tale characteristic of all-or-none mnemonic representations. Formal model assessment yielded evidence highly consistent with a discrete fixed-capacity model of working memory for this task.