A better understanding of the food-centric evolutionary foundations of human brain neuroplasticity is leading to the development of novel bioenergetic challenge-based patterns of eating and exercise aimed at improving cognitive health and resilience.

The cellular and molecular mechanisms by which intermittent food deprivation enhances cognition and overfeeding impairs cognition are being elucidated.

Epigenetic molecular DNA and chromatin protein modifications are impacted by energy intake and can propagate to future generations.

Continuous availability and consumption of energy-rich food in relatively sedentary modern-day humans negatively impacts the lifetime cognitive trajectories of parents and their children.

A major ecological factor that drove the evolution of cognition, namely food scarcity, has been largely eliminated from the day-to-day experiences of modern-day humans and domesticated animals.

Neuronal networks in brain regions critical for spatial navigation and decision-making evolved to enable success in competition for limited food availability in hazardous environments.

Brain structures and neuronal networks that mediate spatial navigation, decision-making, sociality, and creativity evolved, in part, to enable success in food acquisition. Here, I discuss evidence suggesting that the reason that overconsumption of energy-rich foods negatively impacts cognition is that signaling pathways that evolved to respond adaptively to food scarcity are relatively disengaged in the setting of continuous food availability. Obesity impairs cognition and increases the risk for some psychiatric disorders and dementias. Moreover, maternal and paternal obesity predispose offspring to poor cognitive outcomes by epigenetic molecular mechanisms. Neural signaling pathways that evolved to bolster cognition in settings of food insecurity can be stimulated by intermittent fasting and exercise to support the cognitive health of current and future generations.

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Cognitive effects of intentional weight loss in elderly obese individuals with mild cognitive impairment.

Caloric restriction in older adults-differential effects of weight loss and reduced weight on brain structure and function.

The relation of aerobic fitness to stroop task performance in preadolescent children.

Effect of environmental factors on intelligence quotient of children.

The effects of physical activity and physical fitness on children’s achievement and cognitive outcomes: a meta-analysis.

Mitochondrial SIRT3 mediates adaptive responses of neurons to exercise and metabolic and excitatory challenges.

Running-induced systemic cathepsin B secretion is associated with memory function.

Environmental enrichment increases transcriptional and epigenetic differentiation between mouse dorsal and ventral dentate gyrus.

Diet-induced paternal obesity impairs cognitive function in offspring by mediating epigenetic modifications in spermatozoa.

A review of the impact of maternal obesity on the cognitive function and mental health of the offspring.

Maternal obesity and neurodevelopmental and psychiatric disorders in offspring.

Maternal obesity and increased risk for autism and developmental delay among very preterm infants.

Maternal obesity and diabetes are linked to children’s autism and similar disorders.

Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders.

Maternal adiposity prior to pregnancy is associated with ADHD symptoms in offspring: evidence from three prospective pregnancy cohorts.

The impact of prepregnancy obesity on children’s cognitive test scores.

Maternal pre-pregnancy overweight and obesity, and child neuropsychological development: two southern european birth cohort studies.

Perinatal exposure to high-fat diet programs energy balance, metabolism and behavior in adulthood.

Enduring consequences of maternal obesity for brain inflammation and behavior of off-spring.

Maternal high-fat diet alters methylation and gene expression of dopamine and opioid-related genes.

Chronic consumption of a high-fat diet during pregnancy causes perturbations in the serotonergic system and increased anxiety–like behavior in non-human primate offspring.

Maternal overnutrition leads to cognitive and neurochemical abnormalities in C57BL/6 mice.

Physical exercise improves cognitive function by enhancing hippocampal neurogenesis and inhibiting apoptosis in male offspring born to obese mother.

Maternal obese-type gut microbiota differentially impact cognition, anxiety and compulsive behavior in male and female offspring in mice.

Caloric restriction increases neurotrophic factor levels and attenuates neurochemical and behavioral deficits in a primate model of Parkinson’s disease.

Dietary restriction normalizes glucose metabolism and BDNF levels, slows disease progression, and increases survival in huntingtin mutant mice.

Dietary restriction and 2-deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson’s disease.

Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer’s disease.

Food restriction reduces brain damage and improves behavioral outcome following excitotoxic and metabolic insults.

Chronic caloric restriction reduces tissue damage and improves spatial memory in a rat model of traumatic brain injury.

Age and energy intake interact to modify cell stress pathways and stroke outcome.

Dietary restriction and 2-deoxyglucose administration reduce focal ischemic brain damage and improve behavioral outcome: evidence for a preconditioning mechanism.

The effect of intermittent energy and carbohydrate restriction v. daily energy restriction on weight loss and metabolic disease risk markers in overweight women.

Alternate day calorie restriction improves clinical findings and reduces markers of oxidative stress and inflammation in overweight adults with moderate asthma.

Involvement of PGC-1α in the formation and maintenance of neuronal dendritic spines.

Glucose tolerance in adults after prenatal exposure to famine.

The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial.

Dietary restriction stimulates BDNF production in the brain and thereby protects neurons against excitotoxic injury.

Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate.

Evidence that brain-derived neurotrophic factor is required for basal neurogenesis and mediates, in part, the enhancement of neurogenesis by dietary restriction in the hippocampus of adult mice.

Running changes the brain: the long and the short of it.

Energy intake and exercise as determinants of brain health and vulnerability to injury and disease.

Metabolic and molecular framework for the enhancement of endurance by intermittent food deprivation.

Impact of intermittent fasting on health and disease processes.

Flipping the metabolic switch: understanding and applying the health benefits of fasting.

Physical activity interventions for neurocognitive and academic performance in overweight and obese youth: a systematic review.

Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons.

Voluntary exercise and caloric restriction enhance hippocampal dendritic spine density and BDNF levels in diabetic mice.

Roles of the lipid peroxidation product 4-hydroxynonenal in obesity, the metabolic syndrome, and associated vascular and neurodegenerative disorders.

The impacts of physical activity intervention on physical and cognitive outcomes in children with autism spectrum disorder.

The effects of aerobic exercise on academic engagement in young children with autism spectrum disorder.

Association of brain-derived neurotrophic factor (BDNF) haploinsufficiency with lower adaptive behaviour and reduced cognitive functioning in WAGR/11p13 deletion syndrome.

Hippocampal atrophy and altered brain responses to pleasant tastes among obese compared with healthy weight children.

Neurocognitive functions, particularly verbal abilities, were impaired in obese children with IR.

Higher adolescent body mass index is associated with lower regional gray and white matter volumes and lower levels of positive emotionality.

Neurocognitive correlates of obesity and obesity-related behaviors in children and adolescents.

The negative association of childhood obesity to cognitive control of action monitoring.

Association of obesity with cognitive function and brain structure in patients with major depressive disorder.

Hallmarks of brain aging: adaptive and pathological modification by metabolic states.

Associations between IQ, total and regional brain volumes and demography in a large normative sample of healthy children and adolescents.

Survival of the friendliest: Homo sapiens evolved via selection for prosociality.

Trends in cranial capacity and cranial index in Subsaharan Africa during the Holocene.

The postnatal development of the brain of poodles and wolves (author’s transl).

The evolution of the capacity for language: the ecological context and adaptive value of a process of cognitive hijacking.

The origins of animal domestication and husbandry: a major change in the history of humanity and the biosphere.

Flaked stones and old bones: biological and cultural evolution at the dawn of technology.

Why direct effects of predation complicate the social brain hypothesis: and how incorporation of explicit proximate behavioral mechanisms might help.

The Neurobiology of the Prefrontal Cortex.

Ways of thinking: from crows to children and back again.

Birds have primate-like numbers of neurons in the forebrain.

Interspecific allometry of the brain and brain regions in parrots (Psittaciformes): comparisons with other birds and primates.

Reverse replay of hippocampal place cells is uniquely modulated by changing reward.

Cellular mechanisms of spatial navigation in the medial entorhinal cortex.

Grid cells and place cells: an integrated view of their navigational and memory function.

Early-late life trade-offs and the evolution of ageing in the wild.

Glossary

a protein that is produced by neurons in response to bioenergetic challenges that has key roles in synaptic plasticity and learning and memory.

a species of bird in the crow family.

the ability to mentally manipulate information in ways that generate new ideas that can then be implemented to produce novel objects or plans of action.

molecular modifications of DNA, histones, and other chromatin-associated proteins that can result in changes in gene expression; examples include methylation, acetylation, and ubiquitination.

neurons in the entorhinal cortex with firing fields that form a regularly spaced hexagonal or triangular grid pattern.

the ability to acquire or infer, and retain information, and then apply it towards adaptive behaviors within an environment or occupation.

a feeding pattern that includes periods of time of sufficient length to deplete liver glycogen stores and elevate blood ketone levels.

a metabolic state that occurs during extended food deprivation or fasting in which liver glycogen stores have been depleted, and fatty acids mobilized from adipose cells are used to produce ketones (BHB and acetoacetate); the ketones are used by neurons to sustain their bioenergetic demands.

the ability to recount one’s past and plan for the future.

the process by which new neurons are generated from self-renewing stem cells.

neurons in the hippocampus that fire selectively when an animal is at one or only a few locations in its environment; place cells are prominent in the hippocampus.

the most anterior region of the frontal cortex, which has a major role in decision-making; it uses information about the current behavioral context to rapidly generate goals based on the current biological needs.

an evolutionary process that selects for individuals that cooperate with others to enhance group cohesiveness and the allocation of food and other vital resources.

the awareness and active interpretation of the ongoing and likely future behaviors of oneself and others.