Excessive consumption of low-nutrient, high-calorie foods is the leading cause of obesity, preventable chronic disease, 1 and premature death in adults. Unhealthy dietary choices and obesity have adverse effects on all major organ systems of the body, including the brain, with new evidence suggesting, for example, that excessive adiposity increases the risk of neurodegenerative diseases such as Alzheimer’s disease. 2 But what is the effect of poor diet and obesity on the developing brains and minds of youth?
Emerging evidence suggests that the adolescent brain may be particularly susceptible to the effect of obesity and excessive consumption of nutrient-poor, high-calorie foods.3 Adolescence is the period of development that begins with the onset of puberty and ends with the beginning of adulthood.
According to the WHO, adolescence is the period spanning the ages of 10 to 19 years, although others maintain that this period is somewhat longer due to continued physical and neurobiological development in the early 20s.4 Regardless of the precise definition, Adolescence is recognized as a period of susceptibility to health risks due to the rapid growth and increased psychological plasticity that marks this period.
Compared to all other neurological processes, this susceptibility seems most evident in the regulatory processes that govern dietary behavior and decision making. Regulatory processes are crucial to practicing a healthy diet as they help inhibit the urge to consume foods that are highly palatable and calorie-dense. However, regulatory processes are underdeveloped in adolescence due to the continued development of the prefrontal cortex, an area of the brain constantly linked to self-regulation.
Less appreciated but equally important is the finding that adolescence is also a period in which the adverse neurological effects of obesogenic diets could be potentiated precisely because the brain is plastic during this period. Together, these factors contribute to what could be described as a dual vulnerability of the adolescent brain to the health risks associated with excessive consumption of calorie-dense foods.
In this Review, the authors describe how the developmental state of the prefrontal cortex during adolescence increases the risk of overconsuming palatable, high-calorie foods.
Additionally, they describe preclinical animal research demonstrating that these unhealthy eating habits negatively affect central aspects of neurochemical signaling, reward processing, and inhibitory neurotransmission, which are essential for adaptive cognition, and that these biological and behavioral effects can be more pronounced in adolescence than in adulthood.
| The young mind under construction |
Because adolescence is a period of marked psychological development and ongoing neuroplasticity, experience has a greater effect on brain structure and function than it does in adulthood.5 During adolescence, the brain undergoes extensive functioning. neurobiological and functional remodeling, particularly in brain regions responsible for behavioral control and reward seeking, especially in the prefrontal cortex and dopaminergic reward pathways.6–9
Key maturational developments include dendritic pruning to refine synaptic connections and increased axonal myelination.7,8,10
The observed increase in myelination, and, by extension, white matter connectivity, increases the speed of impulse conduction in specific regions of the neurocircuit, facilitating greater integration of brain activity essential for higher-order cognitive function.11 Brain development in adolescence facilitates the emergence of cognitive flexibility, reasoning, planning and impulse control with the transition to adulthood.12,13
The maturing adolescent brain is uniquely susceptible to environmental influences and experiences that can shape neurocircuitry development by local remodeling. This process is known as experience-dependent neuroplasticity, 14 a general term that describes dynamic reorganization of brain structures and functions in response to environmental inputs. Environmental experiences or stimuli can strengthen connections between presynaptic and postsynaptic neurons in a process called long-term potentiation.15
With repeated exposure to the same experience or environmental stimuli, these connections stabilize and the distribution of stabilized connections influences patterns of axonal and dendritic growth.15 Neurotransmitters including dopamine play key roles in modulating neuroplasticity and variability. interindividual in functional activation patterns and cognitive abilities.15
Dopaminergic and cholinergic neurotransmitter systems, in particular, are thought to be important for the development of cognitive control and skills across the lifespan; The activity and responsiveness of these systems follows an inverted U-shaped pattern, peaking during early adolescence. 16 The development of balance in these neurotransmitter systems during adolescence is therefore crucial for optimal brain function in adulthood.
| Diet quality as a dictator of brain health: a neurodevelopmental perspective |
Brain development can be influenced by multiple environmental factors, of which diet quality is an important factor.17 In 2019, the authors outlined a neurocognitive model describing how individual differences in stimuli in the lateral prefrontal cortex can lead to excessive consumption of tasty, calorie-dense foods.18
Over time, persistent and excessive consumption of calorie-dense foods can lead to lasting changes in the structure and function of the prefrontal cortex, 19 including alteration of dopamine signaling20,21 and inhibitory neurotransmitter systems within this area of the brain. .22,23 This alteration leads to impaired cognitive control, further driving persistent and excessive intake of palatable, calorie-dense foods.18
As the prefrontal cortex is still undergoing major processes of development and maturation during adolescence, 24 sustained and excessive consumption of high-fat and high-sugar foods during adolescence could have a greater influence on neurodevelopmental trajectories than any other period of life. development.
Furthermore, research in rodents has indicated that excess consumption of palatable high-calorie foods during the rodent’s equivalent of adolescence could have a pervasive functional effect on the brain, leading to long-lasting deficits in learning and memory. 25
| Adolescence as a period of increased sensitivity to reward |
Adolescence is a period of heightened emotionality, 26 during which adolescents show increased reward drive and reduced cognitive control.27 The prefrontal cortex continues to develop during adolescence, while limbic regions reach maturity much earlier in development. This difference in the timing of maturation creates an imbalance between reward-driven behaviors (limbic system) and top-down cognitive regulation (prefrontal cortex), manifesting as increased sensitivity to rewards and decreased regulation of the brain. behavior.28,29
Behavioral underregulation has been linked to underdeveloped connectivity between the amygdala (a key node of the limbic system) and the prefrontal cortex during adolescence,30 which is observed across species, including humans31 and rodents.32
This imbalance between top-down regulatory regions and subcortical regions can lead to excessive eating behaviors, motivated by food rewards, 18 emotional eating, 33 and binge eating, 34 which are key risk factors for obesity.
More specifically, the enhanced sensitivity to rewards observed during adolescence has been attributed to age-dependent changes in frontostriatal circuit maturation.8,26
The development of the prefrontal cortex lags behind the development of subcortical reward regions, resulting in a propensity for impulsivity and sensation-seeking behaviors in adolescents.12,26
Indeed, several lines of evidence consistently demonstrated that, compared to adulthood, striatal responses to reward are exaggerated during adolescence 29 and that this pattern of activation is associated with trait impulsivity and the likelihood of engaging in behaviors. risk.35
Collectively, neurochemical, structural, and electrophysiological evidence shows that dopaminergic reward innervation originating from the ventral tegmental area to the prefrontal cortex and nucleus accumbens matures during adolescence.36 This process explains why rewarding behaviors, including consumption of tasty foods are frequent in young people.37
| Why do young people have a hard time saying no to high-calorie, appetizing foods? |
Adolescents have a higher dietary intake of refined sugar and fat than any other age group.38 This association has been attributed to increased food consumption during this developmental period, changes in the independence of food choice, and increased sensitivity natural to the reward. In the modern obesogenic food environment, dietary self-regulation skills are essential to control the consumption of calorie-dense foods.
The effective heart of dietary self-regulation is the ability to inhibit (or suppress) appetitive impulses elicited by appetitive and stimulating food cues, and to appropriately evaluate the nutritional value of available food options. Such self-regulation skills were linked to the cognitive control network, particularly the lateral prefrontal cortex.
Recruitment of the lateral prefrontal cortex is essential for modulating cortical activity in the reward region, enabling neurocognitive mechanisms necessary to buffer food-evoked cravings and motivation to eat, capabilities that are still developing in adolescence.
Adolescents have increased levels of food consumption, in part due to the elevated metabolic activity that drives the rapid physical growth and development that comes with puberty, including the gain of muscle mass in adolescent males and fat mass in adolescent females.39 ,40 Rapid growth is observed in all species, so adolescent rats have the highest caloric intake during this period relative to their body weight.41
In mice, accelerated adolescent growth can partially accommodate the excess caloric load of high-fat diets without the considerable weight gain typically seen in adult animals consuming similar diets.42 Therefore, adolescence could provide partial protection against the development of obesity.
However, in the absence of negative consequences (e.g., excess weight), behavioral habits acquired during adolescence could enhance excessive consumption of high-calorie foods in adulthood, and the consequences may not be evident in later life. immediate. This premise highlights a growing need to consider diet quality, rather than weight alone, as a key factor that may influence adolescent brain health.
Reward circuits in the brain are activated by consumption of palatable foods.43,44 The developmental change in caloric need that occurs alongside an increased drive to engage in reward-driven behaviors may promote the consumption of palatable, high-calorie foods during adolescence.45,46
In the absence of mature top-down regulatory processes, striatal dopamine release in response to a rewarding event is exaggerated in adolescents compared to adults, making adolescents more sensitive to reward value than adults.12
Furthermore, increased striatal dopamine release in response to stimuli associated with rewarding foods could make it difficult for adolescents to control their consumption.
Increased neural response to rewarding events in conjunction with continued maturation of the prefrontal cortex could enhance adolescent susceptibility to overconsumption of foods that are nutritionally deprived and calorie-dense.
Many neuroimaging studies signify the importance of prefrontal cortex regions in regulating cravings and consuming palatable foods. Areas in the prefrontal cortex, such as the dorsolateral prefrontal cortex, play a crucial role in regulating appetitive rewards in the short term, allowing individuals to select more beneficial, but less palatable, rewards in the long term.18
Indeed, motivation to consume palatable high-calorie foods is negatively associated with brain activity (measured by blood oxygen level-dependent hemodynamic response using functional magnetic resonance imaging) in the dorsolateral prefrontal cortex and medial prefrontal cortex in individuals. reporting strong urges to consume these foods.47
Furthermore, reduced activation of the superior and middle frontal gyrus, ventrolateral prefrontal cortex, and medial prefrontal cortex in response to food rewards is associated with increased body mass index in adolescents.48 Correspondingly, evidence of prospective imaging studies suggests that elevated striatal activity in response to palatable food cues is associated with increased body weight and fat mass in adolescents.49
In contrast, successful weight loss in adolescents was associated with increased brain activity in the dorsolateral prefrontal cortex in response to images of appetizing calorie-dense foods, supporting the argument that increased activity in the prefrontal cortex in response to food cues which could play a crucial role in modulating food choices.50
Together, these data indicate that food seeking and consumption behaviors may be especially pronounced in young people, and that this association is related to a reduction in prefrontal regulation of food reward cues.
The industrialization of food production has led to the massive development of cheap, appetizing foods that are heavily marketed in a way that exploits pleasure responses, leading to excessive purchasing and consumption. More than 84% of media advertisements seen by children and adolescents are for high-calorie foods and drinks.51
These ads are present on television, social media websites, and apps.5 In Canada alone, teens are exposed to more than 14.4 million food ads a year on their favorite websites.53 This widespread marketing of tasty foods in calories in combination with its ubiquitous presence in the modern environment can promote excessive consumption. In fact, there is growing evidence that these advertisements can influence children’s and adolescents’ preferences and attitudes toward high-calorie foods, increasing the risk of consumption and unhealthy diets in general.54
| food for thought |
As described above, the brain adapts to the environment and experiences through the processes of neuroplasticity. The foods consumed as part of the modern diet are considered a powerful environmental influence on adolescent neurodevelopment.
Rodent studies, in which rodents were fed diets that replicate human diets high in saturated fats and refined sugars, indicate that excessive consumption of these foods underpins alterations in a variety of neurotransmitter systems in cortical brain regions responsible for control. behavioral.
Chronic stimulation of the maturing mesocorticolimbic dopamine reward system during adolescence by excessive consumption of palatable foods may lead to long-lasting neurobiological changes in neurotransmitters and endocrine systems.9,55 Adaptive changes in neurotransmission could recalibrate the brain system. reward to promote greater food reward preference and evoke cognitive dysregulation.56
In rodent studies, excessive consumption of palatable foods leads to adaptive changes in dopamine signaling pathways within brain regions that control reward processing and decision making, including the prefrontal cortex, 57 nucleus accumbens. ,58,59 and the hippocampus.60,61
Although this review focuses on the prefrontal cortex as a driver of food choice, the hippocampus plays an integral role in regulating dietary choices and the consumption of high-calorie foods (see Hargrave and colleagues62 for an overview).
The consumption of highly palatable foods evokes the release of dopamine in the mesocorticolimbic system, so frequent consumption of these foods can lead to overstimulation of this pathway.63
Adaptive changes that occur in receptor expression to compensate for this overstimulation, including downregulation of dopamine D2 receptors in the striatum, result in a neurochemical blunting of reward responses to typically rewarding stimuli.63
It has been proposed that adaptive changes to reward systems may lead to impaired reward responses and further drive foraging behaviors to compensate for reduced reward experience.64 Additionally, studies in rodents indicate that effects on dopaminergic reward signaling neurocircuitry may be persistent.65
As dopamine is a modulator of cortical plasticity, these adaptive responses to diet quality can potentially influence plasticity processes during this malleable period, leading to the observed structural and functional changes observed in people with obesity ( panel).
The susceptibility of the adolescent brain to alterations evoked by a diet of palatable foods could emerge as altered motivated behaviors. Experimentally, motivation in rodents is measured through progressive ratio tasks that require an increasing number of responses, such as lever presses, to obtain a reward.
Male rats that consumed a high-sugar diet during adolescence, but not in adulthood, were less motivated to press a lever for tasty food reward as adults than rats that had not consumed a high-sugar diet during adolescence. adolescence.77
In contrast, adolescent female rats that consumed high-sugar diets showed increased motivation for rewards, which is indicative of craving.77 These studies showed that high-sugar diets can alter the reward-processing neurocircuitry in a way dependent on sex and age, with greater susceptibility in adolescent males.
| Development of balance in the brain |
During brain development, dopamine plays a key role in controlling excitatory and inhibitory neurotransmission in the prefrontal cortex.78 In the postnatal brain, γ-aminobutyric acid (GABA) is the major inhibitory neurotransmitter and glutamate is the major neurotransmitter. exciter The balance between excitation and inhibition is essential for brain network function and cognitive control.
The disrupted balance between excitation and inhibition is linked to neuropsychiatric conditions, including autism and schizophrenia.79,80 Neurochemical data indicate that inhibitory GABAergic neurotransmission, particularly within the prefrontal cortex, is still developing during adolescence,80 and could promote impulsive and risky behaviors characteristic of adolescence.29
Late maturation of inhibitory GABAergic signaling in the brain also results in a prolonged period of susceptibility within the highly plastic adolescent brain. Consumption of low-quality, high-calorie foods during adolescence is proposed to trigger functional changes in dopaminergic signaling,59 which in turn could alter the development of inhibitory GABAergic signaling in the prefrontal cortex.77,81
As the balance of excitatory and inhibitory neurotransmission in the mature prefrontal cortex is important for higher-order cognition and behavioral control, 82 these changes in dopaminergic, and subsequently GABAergic, signaling activated by junk food consumption may produce profound effects on behavior.
Adult rats exposed to a high-fat diet, for example, have altered GABAergic signaling in the hippocampus and prefrontal cortex.83 The authors’ research demonstrated that consumption of a high-sucrose diet during adolescence is associated with a reduction of GABAergic neurons in cortical regions essential for cognition, and manifests as cognitive deficits and dysregulated behavioral control.22,81
Additionally, research in rodents points to obesity-induced changes in extracellular matrix structures surrounding brain neurons called perineuronal networks.84 These structures regulate the activation of cortical neurons involved in cognition, often co-located with parvalbumin interneurons, thus acting to restrict plasticity and control synapse formation.84
As perineuronal cortical networks have a long developmental trajectory, showing maturation in juvenile and adolescent periods in a regionally dependent manner, disruption of these structures could lead to alterations in the plasticity and remodeling of connectivity between cortical regions.
However, a better understanding of the neurochemical systems altered by the consumption of highly palatable foods is crucial for the development of potential treatments and therapeutic interventions that could protect the brain and restore aspects of function when the young brain is in a highly malleable state. and responsive.
| Clinical significance |
Childhood and adolescent obesity is among the most important global health problems.
Statistics indicate that 18.5% of children and adolescents in the United States were living with obesity in 2015–16.85
Similar trends are seen around the world, with rates rising rapidly in low- and middle-income countries; 86 However, in developed nations (e.g., Canada, USA), obesity rates began to reach a state of little or no change.87
Childhood and adolescent obesity are of concern, as children and adolescents with obesity are more likely to maintain their weight status into and throughout adulthood, and are at greater risk of developing diabetes and cardiovascular disease at a younger age. than the average.88
As highlighted in this review, the impact of diet quality on the developing brain has long-lasting implications that could further facilitate obesogenic dietary behaviors.
Sustained and excessive consumption of foods high in saturated fats and refined sugars may influence the development of brain circuits necessary to facilitate self-regulatory behaviors that are key to limiting excessive consumption.18 Therefore, there is a crucial need to develop interventions effective in improving diet quality and reducing obesity in young people, to reduce the negative physiological impact of obesity throughout life.
As adolescence offers partial protection against the development of excessive adiposity, there is an increased need to focus on dietary quality within this age range, rather than on obesity as the primary focus. These therapeutic interventions could protect the brain and restore aspects of function, and could be most effective while the young brain is in a highly malleable state.
Specific behavioral interventions that are effective for adolescent populations need to be considered. Interventions in this age group often fail when they do not consider adolescents’ need to feel respected and the importance of social status (see Yeager and colleagues89 for an overview). For example, implicit attitudes and purchasing behaviors for calorie-dense foods are significantly reduced when adolescents are taught about the manipulative marketing practices used by the food industry.90
The success of this intervention was linked to focusing on values that adolescents felt were important (e.g., social justice, asserting individual autonomy, and rejecting adult control), highlighting the need to consider interventions aligned with the value in this population.
Furthermore, interventions are often aimed at preventing obesity rather than improving diet quality per se. As highlighted above, this focus on obesity may not be the most appropriate approach, just as physical indices of diet quality (e.g., excess weight and adiposity) may not emerge until late in life.
Exercise interventions, to date, are among the most promising means of improving brain health and cognitive control. Across the lifespan, exercise interventions improve cognitive performance; 91 This improvement was attributed to exercise-induced changes in the structural and functional integrity of the prefrontal cortex and hippocampus, 92,93 which are cortical regions shown to be susceptible to obesity.
Furthermore, evidence highlighted that aerobic exercise can decrease the neural response to appetizing food cues and modulate hunger circuits to improve dietary choices.94,95 However, there is little research on the effect of exercise interventions on the adolescent brain, with current research focused on older adults91 or pre-adolescent children.96
Considering the tangible benefits of exercise interventions, there is a need to expand this line of work to adolescent populations, especially young populations prone to dysregulation of eating behaviors (e.g., people with obesity or binge eating disorders).
| Translational challenges and outstanding questions |
While animal models allow exquisite control over diet quality and food intake, food choice in humans is complex and can be framed as a socio-environmental behavior influenced by environmental cues, cultural preferences, social attitudes, and genetics. .
Due to the fluidity of human dietary choices, most diets consist of a combination of healthy and unhealthy high-calorie items, in contrast to controlled laboratory models, which may only represent the extreme diets consumed by few people.
Therefore, there is an essential need for large-scale prospective studies in humans, particularly in adolescents. Such research is especially pertinent given the growth of the body of behavioral and imaging studies in humans highlighting the short-term97 and long-term effect of obesity and obesogenic diets on cognitive processes and brain structures in humans.98,99
It is only through large-scale collaborative approaches that the scientific community will be able to model the development of dietary self-regulation, the effect of poor diets on the developing brain, and the dose-response relationship between the consumption of calorie-dense foods and poor adaptation of neural developmental trajectories. With the emergence of large-scale open source multisite projects, such as the Adolescent Brain and Cognitive Development study, 100 such projects are logistically feasible.
Finally, in this review we focus on prefrontal cortex regulation of subcortical reward regions as the main factor driving dietary decisions.
This approach was specific to the developmental approach the authors applied, in which these subcortical regions often fully develop before the prefrontal cortex. This difference in developmental trajectories is thought to contribute to the observed increase in reward sensitivity seen in adolescence, making adolescents more receptive to the rewarding aspects of high-calorie, appetitive foods.
However, consumption behaviors are modulated by an extensive network of brain regions, including the hippocampus, hypothalamus, and amygdala.101 Additionally, a growing field of research is elucidating how the microbiota-gut-brain axis may affect neurodevelopment; One potential pathway could be the role of the axis in maintaining metabolic homeostasis (see Borre and colleagues76 for an overview). As such, future work needs to examine how diet and gut microbiota influence neurodevelopmental trajectories.
| Conclusion |
In this review, the authors propose that adolescence is a period of dual susceptibility, during which regulatory processes govern dietary behavior and decision making is still underdeveloped due to the continued development of the lateral prefrontal cortex. As such, emerging self-regulation and increased independence over food choices may make adolescents prone to choosing unhealthy food options.
However, the inherent plasticity of the young brain could potentiate the adverse neurological effects of obesogenic diets. These diet-induced changes (described above) may manifest as poor cognitive control and increased impulsivity toward and throughout adulthood, further enhancing the cycle of dysregulated eating behaviors in adulthood.
In conclusion, the available evidence highlights that clinicians and researchers need to shift the focus from body size and obesity to the quality of the diet itself.
The physical growth observed during adolescence can partially accommodate excessive caloric load without the considerable weight gain typically seen in adults. As such, the negative impact of a poor diet may not be overtly evident.
However, as highlighted above, diet quality can have a severe and detrimental impact on the developing brain, and attention should be focused on understanding and intervening during this period of susceptibility.
