Cognitive health is a life-long concern affected by modifiable risk factors, including lifestyle choices, such as dietary intake, with serious implications for quality of life, morbidity, and mortality worldwide. In addition, nuts are a nutrient-dense food that contain a number of potentially neuroprotective components, including monounsaturated and polyunsaturated fatty acids, fiber, B-vitamins, non-sodium minerals, and highly bioactive polyphenols. However, increased nut consumption relates to a lower cardiovascular risk and a lower burden of cardiovascular risk factors that are shared with neurodegenerative disorders, which is why nuts have been hypothesized to be beneficial for brain health. The present narrative review discusses up-to-date epidemiological, clinical trial, and mechanistic evidence of the effect of exposure to nuts on cognitive performance. While limited and inconclusive, available evidence suggests a possible role for nuts in the maintenance of cognitive health and prevention of cognitive decline in individuals across the lifespan, particularly in older adults and those at higher risk. Walnuts, as a rich source of the plant-based polyunsaturated omega-3 fatty acid alpha-linolenic acid, are the nut type most promising for cognitive health. Given the limited definitive evidence available to date, especially regarding cognitive health biomarkers and hard outcomes, future studies are needed to better elucidate the impact of nuts on the maintenance of cognitive health, as well as the prevention and management of cognitive decline and dementia, including Alzheimer disease.

Multimodal brain magnetic resonance imaging (MRI) can provide biomarkers of early influences on neurodevelopment such as nutrition, environmental and genetic factors. As the exposure to early influences can be separated from neurodevelopmental outcomes by many months or years, MRI markers can serve as an important intermediate outcome in multivariate analyses of neurodevelopmental determinants. Key to the success of such work are recent advances in data science as well as the growth of relevant data resources. Multimodal MRI assessment of neurodevelopment can be supplemented with other biomarkers of neurodevelopment such as electroencephalograms, magnetoencephalogram, and non-imaging biomarkers. This review focuses on how maternal nutrition impacts infant brain development, with three purposes: (1) to summarize the current knowledge about how nutrition in stages of pregnancy and breastfeeding impact infant brain development; (2) to discuss multimodal MRI and other measures of early neurodevelopment; and (3) to discuss potential opportunities for data science and artificial intelligence to advance precision nutrition. We hope this review can facilitate the collaborative march toward precision nutrition during pregnancy and the first year of life.

Despite the reported benefits of diet on cognition in older adults, randomized controlled trials (RCT) testing the impact of dietary interventions on cognitive scores have yielded less promising results when cognition was assessed via neuropsychological tests. More recently, neuroimaging has been used to identify more subtle brain-related changes associated to cognition. Hence, employing a combination of neuroimaging techniques with neuropsychological tests could clarify this controversy. To determine the effect of diet on cognitive performance, we conducted a systematic review of PubMed and Scopus databases for all studies, on middle-aged and older adults, combining neuroimaging, neuropsychological tests, and data on dietary patterns. The inclusion criteria were met by 14 observational studies and no RCTs. The range of brain measures assessed varied from volumes to white matter integrity, functional connectivity, brain glucose metabolism and beta-amyloid deposition. Given the variability of methods used in assessing cognitive performance, diet and brain correlates, conducting a meta-analysis was not possible. Here the evidence suggests that, in observational studies, dietary patterns may be associated with brain correlates that have been shown to precede cognitive decline. As such, neuroimaging should be included in future RCTs to identify any benefits of diet on brain measures linked with cognitive health.

Dietary habits are known to affect health, including the rate of brain ageing and susceptibility to diseases. This study examines the longitudinal relationship between dietary diversity and hippocampal volume, which is a key structure of memory processing and is known to be impaired in dementia.

Subjects were aged 40-89 years (n = 1683, men: 50.6%) and participated in a 2-year follow-up study of the National Institute for Longevity Sciences-Longitudinal Study of Aging. Dietary intake was calculated from 3-day dietary records, and dietary diversity was determined using the Quantitative Index for Dietary Diversity at baseline. Longitudinal changes in hippocampal and total grey matter volumes were estimated by T1-weighted brain magnetic resonance imaging and FreeSurfer software. Estimated mean brain volume change in relation to dietary diversity score quintiles was assessed by the general linear model, adjusted for age, sex, education, smoking status, alcohol intake, physical activity, and comorbidities.

The mean (± standard deviation) % decreases in hippocampal and total grey matter volume during the 2-year follow-up were 1.00% (±2.27%) and 0.78% (±1.83%), respectively. Multivariate-adjusted decreases in total grey matter volume were associated with dietary diversity score (p = 0.065, p for trend = 0.017), and the % decrease in hippocampal volume was more strongly associated with the dietary diversity score: the estimated mean (± standard error) values were 1.31% (±0.12%), 1.07% (±0.12%), 0.98% (±0.12%), 0.81% (±0.12%), and 0.85% (±0.12%), according to dietary diversity quintiles in ascending order (p = 0.030, p for trend = 0.003).

Among community dwellers, increased dietary diversity may be a new nutritional strategy to prevent hippocampal atrophy.

Deficiency of vitamin B-12 is common in pregnant Indian women. Assessment of neurophysiological measures using event-related potentials (ERPs) may yield additional information on the effects of maternal B-12 supplementation on child brain function.

The objective of the study was to evaluate the effects of vitamin B-12 supplementation (50 μg daily orally) during pregnancy on the childhood ERP measures of positive waveform ∼300 ms after stimulus (P300) and mismatch negativity.

This study was a follow-up of children born to pregnant women who received oral vitamin B-12 supplements (n = 62) compared with children of pregnant women who received placebo (n = 70) from a randomized controlled trial. The mean ± SD child age was 72 ± 1 mo. We used the Enobio system to assess the ERP measures P300 and mismatch negativity.

There were no significant differences in the primary outcomes, amplitudes, and latencies of the P300 results and the mismatch negativity between children in the supplementation and placebo groups. We combined the intervention and placebo groups for secondary analyses. On multiple variable regression analysis after adjusting for treatment group, intrauterine growth restriction, and home environment, P300 amplitude in children was significantly higher in the lowest tertile of third-trimester maternal methylmalonic acid (MMA) concentrations (β = 3034.04; 95% CI: 923.24, 5144.83) compared with the highest MMA tertile (β = 1612.12; 95% CI: -258.86, 3483.10, P = 0.005).

While no significant effects of maternal vitamin B-12 supplementation on children's ERP measures were seen at 72 mo, elevated maternal MMA concentrations in the third trimester were negatively associated with P300 amplitude in children. It may be worthwhile to study the impact of maternal and infant vitamin B-12 supplementation on childhood brain structure and function in longer and larger trials. The parent trial was registered at clinicaltrials.gov as NCT00641862.

Maternal nutrition is an important factor for infant neurodevelopment. However, prior magnetic resonance imaging (MRI) studies on maternal nutrients and infant brain have focused mostly on preterm infants or on few specific nutrients and few specific brain regions. We present a first study in term-born infants, comprehensively correlating 73 maternal nutrients with infant brain morphometry at the regional (61 regions) and voxel (over 300 000 voxel) levels. Both maternal nutrition intake diaries and infant MRI were collected at 1 month of life (0.9 ± 0.5 months) for 92 term-born infants (among them, 54 infants were purely breastfed and 19 were breastfed most of the time). Intake of nutrients was assessed via standardized food frequency questionnaire. No nutrient was significantly correlated with any of the volumes of the 61 autosegmented brain regions. However, increased volumes within subregions of the frontal cortex and corpus callosum at the voxel level were positively correlated with maternal intake of omega-3 fatty acids, retinol (vitamin A) and vitamin B12, both with and without correction for postmenstrual age and sex (P < 0.05, q < 0.05 after false discovery rate correction). Omega-3 fatty acids remained significantly correlated with infant brain volumes after subsetting to the 54 infants who were exclusively breastfed, but retinol and vitamin B12 did not. This provides an impetus for future larger studies to better characterize the effect size of dietary variation and correlation with neurodevelopmental outcomes, which can lead to improved nutritional guidance during pregnancy and lactation.

Magnetoencephalography (MEG) is a relatively modern neuroimaging technique able to study normal and pathological brain functioning with temporal resolution in the order of milliseconds and adequate spatial resolution. Although its clinical applications are still relatively limited, great advances have been made in recent years in the field of dementia and Alzheimer's disease (AD) in particular. In this chapter, we briefly describe the physiological phenomena underlying MEG brain signals and the different metrics that can be computed from these data in order to study the alterations disrupting brain activity not only in demented patients, but also in the preclinical and prodromal stages of the disease. Changes in non-linear brain dynamics, power spectral properties, functional connectivity and network topological changes observed in AD are narratively summarized in the context of the pathophysiology of the disease. Furthermore, the potential of MEG as a potential biomarker to identify AD pathology before dementia onset is discussed in the light of current knowledge and the relationship between potential MEG biomarkers and current established hallmarks of the disease is also reviewed. To this aim, findings from different approaches such as resting state or during the performance of different cognitive paradigms are discussed.Lastly, there is an increasing interest in current scientific literature in promoting interventions aimed at modifying certain lifestyles, such as nutrition or physical activity among others, thought to reduce or delay AD risk. We discuss the utility of MEG as a potential marker of the success of such interventions from the available literature.

Assessing outcomes and the impact from behavioral nutrition interventions has remained challenging because of the lack of methods available beyond traditional nutrition assessment tools and techniques. With the current high global obesity and related chronic disease rates, novel methods to evaluate the impact of behavioral nutrition-based interventions are much needed. The objective of this narrative review is to describe and review the current status of knowledge as it relates to 4 different innovative methods or tools to assess behavioral nutrition interventions. Methods reviewed include 1) the assessment of stress and stress responsiveness to enhance the evaluation of nutrition interventions, 2) eye-tracking technology in nutritional interventions, 3) smartphone biosensors to assess nutrition and health-related outcomes, and 4) skin carotenoid measurements to assess fruit and vegetable intake. Specifically, the novel use of functional magnetic resonance imaging, by characterizing the brain's responsiveness to an intervention, can help researchers develop programs with greater efficacy. Similarly, if eye-tracking technology can enable researchers to get a better sense as to how participants view materials, the materials may be better tailored to create an optimal impact. The latter 2 techniques reviewed, smartphone biosensors and methods to detect skin carotenoids, can provide the research community with portable, effective, nonbiased ways to assess dietary intake and quality and more in the field. The information gained from using these types of methodologies can improve the efficacy and assessment of behavior-based nutrition interventions.

We investigated cross-sectional associations between circulating homocysteine, folate, biomarkers of vitamin B₁₂ status and brain volumes. We furthermore compared brain volumes of participants who received daily folic acid and vitamin B₁₂ supplementation with participants who did not.

Participants of the B-PROOF study (n = 2919) were assigned to 400 µg folic acid and 500 µg vitamin B₁₂, or a placebo. After two years of intervention, T₁-weighted magnetic resonance imaging (MRI) scans were made in a random subsample (n = 218) to obtain grey and white matter volume, and total brain volume (TBV). Plasma homocysteine, serum folate, vitamin B₁₂, holotranscobalamin, and methylmalonic acid concentrations were measured.

Multiple linear regression analyses showed inverse associations between plasma homocysteine with TBV (β = -0.91, 95% CI -1.85-0.03; p = 0.06) and between serum folate and TBV (β = -0.20, 95% CI -0.38, -0.02; p = 0.03). No significant associations were observed for serum vitamin B₁₂ and holotranscobalamin. Fully adjusted ANCOVA models showed that the group that received B-vitamins had a lower TBV (adjusted mean 1064, 95% CI 1058-1069 mL) than the non-supplemented group (1072, 95% CI 1067-1078 mL, p = 0.03).

Results were contradictory, with higher Hcy levels associated with lower TBV, but also with higher folate levels associated with lower TBV. In addition, the lack of a baseline measurement withholds us from giving recommendations on whether folic acid and vitamin B₁₂ supplementation will be beneficial above and beyond normal dietary intake for brain health.

DNA methylation provides an attractive possible means for propagating the effects of environmental inputs during fetal life and impacting subsequent adult mental health, which is leading to increasing collaboration between molecular biologists, nutritionists and psychiatrists. An area of interest is the potential role of folate, not just in neural tube closure in early pregnancy, but in later major neurodevelopmental events, with consequences for later sociocognitive maturation. Here, we set the scene for recent discoveries by reviewing the major events of neural development during fetal life, with an emphasis on tissues and structures where dynamic methylation changes are known to occur. Following this, we give an indication of some of the major classes of genes targeted by methylation and important for neurological and behavioral development. Finally, we highlight some cognitive disorders where methylation changes are implicated as playing an important role.

Very low birth weight (VLBW, birth weight<1500 g) children have increased risk of behavioral problems. Diffusion tensor imaging (DTI) of the brain shows reduced white matter maturation. Long-chain polyunsaturated fatty acids are hypothesized to improve both myelination and behavioral outcome.

To test the hypothesis that postnatal supplementation with docosahexaenoic acid (DHA) and arachidonic acid (AA) to very low birth weight infants would influence cerebral white matter measured by DTI and improve behavioral outcome at 8 years of age.

Eight-year follow-up of a randomized, double-blinded, placebo-controlled study of postnatal supplementation with DHA and AA to 129 VLBW infants fed human milk.

Ninety-eight children (76%) met for follow-up at 8 years.

Cerebral white matter measured by DTI. Behavioral outcome measured by Strengths and Difficulties questionnaire and selected scales from the Child Behavior Checklist.

No significant differences between the intervention group and the control group were found on white matter microstructure or behavioral data. A non-significant finding of higher fractional anisotropy (FA) in a cluster in the corpus callosum of the intervention group is discussed.

The present study is the first long-term follow-up of a randomized controlled trial with DHA and AA to human milk fed VLBW infants exploring cerebral white matter microstructure measured by DTI and parent-reported behavioral problems. No effects on white matter microstructure or behavioral outcome were observed at 8 years of age.

To test the hypothesis that supplementation with the long chain polyunsaturated fatty acids docosahexaenoic acid (DHA) and arachidonic acid (AA) to very low birth weight (VLBW) infants would improve long-term cognitive functions and influence neuroanatomical volumes and cerebral cortex measured by MRI.

The current study is a follow-up of a randomized, double-blinded, placebo-controlled study of supplementation with high-dose DHA (0.86%) and AA (0.91%) to 129 VLBW infants fed human milk. Ninety-eight children participated at 8 years follow-up and completed a broad battery of cognitive tests. Eighty-one children had cerebral MRI scans of acceptable quality.

There were no significant differences between the intervention group and the control group on any of the cognitive measures. Equally, MRI data on segmental brain volumes and cerebral cortex volume, area, and thickness suggested no overall group effect.

This study is the first long-term follow-up of a randomized controlled trial with supplementation of DHA and AA to human milk fed VLBW infants investigating both cognitive functions and brain macrostructure measured by MRI. No cognitive or neuroanatomical effects of the supplementation were detected at 8 years of age.

Functional, molecular and genetic neuroimaging has highlighted the existence of brain anomalies and neural vulnerability factors related to obesity and eating disorders such as binge eating or anorexia nervosa. In particular, decreased basal metabolism in the prefrontal cortex and striatum as well as dopaminergic alterations have been described in obese subjects, in parallel with increased activation of reward brain areas in response to palatable food cues. Elevated reward region responsivity may trigger food craving and predict future weight gain. This opens the way to prevention studies using functional and molecular neuroimaging to perform early diagnostics and to phenotype subjects at risk by exploring different neurobehavioral dimensions of the food choices and motivation processes. In the first part of this review, advantages and limitations of neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), positron emission tomography (PET), single photon emission computed tomography (SPECT), pharmacogenetic fMRI and functional near-infrared spectroscopy (fNIRS) will be discussed in the context of recent work dealing with eating behavior, with a particular focus on obesity. In the second part of the review, non-invasive strategies to modulate food-related brain processes and functions will be presented. At the leading edge of non-invasive brain-based technologies is real-time fMRI (rtfMRI) neurofeedback, which is a powerful tool to better understand the complexity of human brain-behavior relationships. rtfMRI, alone or when combined with other techniques and tools such as EEG and cognitive therapy, could be used to alter neural plasticity and learned behavior to optimize and/or restore healthy cognition and eating behavior. Other promising non-invasive neuromodulation approaches being explored are repetitive transcranial magnetic stimulation (rTMS) and transcranial direct-current stimulation (tDCS). Converging evidence points at the value of these non-invasive neuromodulation strategies to study basic mechanisms underlying eating behavior and to treat its disorders. Both of these approaches will be compared in light of recent work in this field, while addressing technical and practical questions. The third part of this review will be dedicated to invasive neuromodulation strategies, such as vagus nerve stimulation (VNS) and deep brain stimulation (DBS). In combination with neuroimaging approaches, these techniques are promising experimental tools to unravel the intricate relationships between homeostatic and hedonic brain circuits. Their potential as additional therapeutic tools to combat pharmacorefractory morbid obesity or acute eating disorders will be discussed, in terms of technical challenges, applicability and ethics. In a general discussion, we will put the brain at the core of fundamental research, prevention and therapy in the context of obesity and eating disorders. First, we will discuss the possibility to identify new biological markers of brain functions. Second, we will highlight the potential of neuroimaging and neuromodulation in individualized medicine. Third, we will introduce the ethical questions that are concomitant to the emergence of new neuromodulation therapies.

Throughout the life span, the brain is a metabolically highly active organ that uses a large proportion of total nutrient and energy intake. Furthermore, the development and repair of neural tissue depend on the proper intake of essential structural nutrients, minerals, and vitamins. Therefore, what we eat, or refrain from eating, may have an important impact on our cognitive ability and mental performance. Two of the key areas in which diet is thought to play an important role are in optimizing neurodevelopment in children and in preventing neurodegeneration and cognitive decline during aging. From early development to aging, brain imaging can detect structural, functional, and metabolic changes in humans and modifications due to altered nutrition or to additional nutritional supplementation. Inclusion of imaging measures in clinical studies can increase understanding with regard to the modification of brain structure, metabolism, and functional endpoints and may provide early sensitive measures of long-term effects. In this symposium, the utility of existing brain imaging technologies to assess the effects of nutritional intervention in humans is described. Examples of current research showing the utility of these markers are reviewed.