Nutrients and behaviour: Research strategies for the investigation of taste characteristics,food preferences,hunger sensations and eating patterns in man

Although, as described elsewhere in this report, the consumption of particular nutrients can modify behaviors that are not directly related to eating, it seems highly likely that the main function of nutrient-induced changes in neurotransmitter synthesis is to provide the brain with information about what has been eaten, which the brain can then utilize in deciding what to eat next. This chapter summarizes research strategies and techniques which have been used to assess the effects of drugs and diseases on appetite and food consumption, and which might also be useful in exploring the effects of particular nutrients.Crude measures of total food intake and of global hunger ratings are probably too insensitive to reveal the subtle effects of many nutrients. Some alternative procedures allow the assessment of particular aspects of feeding behaviour, (e.g. food or nutrient choice), and of the relationships between such behaviour and the individual's metabolic and physiological state, sensory functions, taste hedonics, and affective response to foods.     

Long-term effects of environmentally relevant doses of 2,2',4,4',5,5' hexachlorobiphenyl (PCB153) on neurobehavioural development,health and spontaneous behaviour in maternally exposed mice

Background  

Polychlorinated biphenyls (PCBs) are widespread in the environment, human food and breast milk. Seafood is known to contain nutrients beneficial for the normal development and function of the brain, but also contaminants such as PCBs which are neurotoxic. Exposure to non-coplanar PCBs during brain development can disrupt spontaneous behaviour in mice and lead to hyperactive behaviour. Humans are chronically exposed to the highest relative levels of organochlorines in early childhood during brain development, though usually at doses which do not give clinical symptoms of toxicity. This study aimed to elucidate the developmental and behavioural effects of 2,2',4,4',5,5' hexachlorobiphenyl (PCB153) in mice, mimicking human exposure during gestation and lactation.     

Overview of modifiers of methylmercury neurotoxicity: chemicals, nutrients, and the social environment

It has been known for decades that methylmercury is a potent neurotoxicant, and that the developing brain is more susceptible to impairment as a result of methylmercury exposure than is the adult. Exposure to methylmercury is exclusively through consumption of fish and marine mammals. In recent years, the potential for protection against methylmercury toxicity by nutrients present in fish, particularly omega-3 fatty acids and selenium, has been explored in both epidemiological and experimental studies. There is evidence from several studies that fish consumption per se and methylmercury body burden act in opposition with regard to neuropsychological outcomes, whereas the evidence for a protective effect of specific nutrients is contradictory in both epidemiological and experimental studies published to date. The potential for methylmercury to interact with other chemicals present in marine food, particularly PCBs, has been explored in both animal models and human studies. Results may be both exposure- and endpoint-dependent. The Seychelles Islands study has explored the potential for the social environment to modify the effects of developmental methylmercury exposure. An understanding of the interactions of the multiple factors that determine the final behavioral outcome of exposure to methylmercury is crucial to risk assessment and risk management decisions.     

Assessing the Role of Sound in the Perception of Food and Drink

The consumption of food and drink are among the most multisensory of our perceptual experiences. In fact, the evaluation of foodstuffs is not only influenced by the unified oral sensation (or Gestalt) of taste and smell in the mouth but also by what the foods look, feel (i.e., oral texture, temperature, viscosity, etc.), and sound like (particularly for noisy foods such as crisps, celery, carrots, etc.) when we eat or drink them. The empirical literature reviewed here highlights the important role that auditory cues have on our perception of a variety of different food and drink items. In particular, changing the sounds that are made when we bite into a foodstuff, or the sounds that are made by carbonated drinks, have both been shown to have a dramatic effect on perception. Auditory stimuli that are not even directly food-related have also been shown to influence people’s behavior. The present article reviews the growing body of research, highlighting the significant effects that music and other auditory stimuli can have on people’s food choices. Taken together, the results of the studies reported here unequivocally show that what people hear (be it food-related or nonrelated sounds) can have a dramatic effect on their perceptions of food and drink. Finally, we report a number of explanations that have been put forward in order to account for these cross-modal effects.     

Intranasal Application of Vasopressin Fails to Elicit Changes in Brain Immediate Early Gene Expression,Neural Activity and Behavioural Performance of Rats

Intranasal administration has been widely used to investigate the effects of the neuropeptides vasopressin and oxytocin on human behaviour and neurological disorders, although exactly what happens when these neuropeptides are administered intranasally is far from clear. In particular, it is not clear whether a physiological significant amount of peptide enters the brain to account for the observed effects. In the present study, we investigated whether the intranasal administration of vasopressin and oxytocin to rats induces the expression of the immediate-early gene product Fos in brain areas that are sensitive to centrally-administered peptide, whether it alters neuronal activity in the way that centrally-administered peptide does, and whether it affects behaviour in the ways that are expected from studies of centrally-administered peptide. We found that, whereas i.c.v. injection of very low doses of vasopressin or oxytocin increased Fos expression in several distinct brain regions, intranasal administration of large doses of the peptides had no significant effect. By contrast to the effects of vasopressin applied topically to the main olfactory bulb, we saw no changes in the electrical activity of olfactory bulb mitral cells after intranasal vasopressin administration. In addition, vasopressin given intranasally had no significant effects on social recognition or short-term recognition memory. Finally, intranasal infusions of vasopressin had no significant effects on the parameters monitored on the elevated plus maze, a rodent model of anxiety. Our data obtained in rats suggest that, after intranasal administration, significant amounts of vasopressin and oxytocin do not reach areas in the brain at levels sufficient to change immediate early gene expression, neural activity or behaviour in the ways described for central administration of the peptides.     

Nutrition, brain function and behavior

Current food intake has been shown to directly affect neurotransmission, with resultant modification of behavior. The role of vitamin co-factors in brain function is discussed, with emphasis on changes in mood and neurological function with deficiency. The use of megadoses of vitamins for the treatment of psychiatric diseases has little scientific support at this time. Current research also does not substantiate the Feingold thesis of improvement in childhood hyperkinesis when an additive-free diet is consumed. The effects of medications used to moderate mood are related to changes in nutrient intake that in turn alters weight status. In addition, the effect of certain nutrients modifying the dose response to mood altering drugs has been discussed. Finally evidence for mood state directly affecting the capacity of the body to utilize nutrients is presented.     

Regulation and effects of hypothalamic galanin: relation to dietary fat, alcohol ingestion, circulating lipids and energy homeostasis

Galanin (GAL) is known to stimulate feeding behavior. This peptide has different properties and functions from other feeding stimulants, e.g., neuropeptide Y and agouti-related protein. Hypothalamic GAL is relatively unresponsive to food deprivation and to changes in corticosterone, glucose utilization, dietary carbohydrate and leptin. This indicates that this peptide is not essential under conditions when food is scarce or low-energy, high-carbohydrate diets are being consumed. In contrast, recent evidence suggests that GAL in the paraventricular nucleus (PVN) functions in close relation to dietary fat and alcohol. In particular, it mediates functions that allow animals to adapt to conditions of positive energy balance involving excess consumption of these nutrients. This peptide in the PVN is stimulated by a high-fat diet and also by alcohol. It is stimulated by an increase in circulating lipids caused by a fat-rich meal or alcohol consumption, and it rises during the middle of the active feeding cycle, when fat consumption and triglycerides naturally rise. When centrally injected, GAL in the PVN increases the consumption of food and alcohol. Moreover, it produces a significantly stronger feeding response in rats maintained on a fat-rich diet, which also promotes alcohol intake. This evidence supports the existence of non-homeostatic, positive feedback circuits between GAL and both dietary fat and alcohol. These circuits are believed to contribute to the large meal size, over-consumption of alcohol, and obesity which are generally associated with fat-rich foods.     

Qualitative analysis of feeding behaviour through dietary selection of nutrients

Studies of brain mechanisms controlling food intake and feeding behaviour have often neglected interactions between total food (energy) intake and qualitative aspects of the dietary intake. Generally, experimental animals are presented with a single diet of fixed nutritional composition. Thus, if as a result of a given treatment, an animal has an increased or decreased appetite for a specific nutrient, then this could manifest itself as an increase or decrease in intake from the sole diet offered. As selection of food is a characteristic behaviour of all animals, and their ability to monitor intake of specific nutrients is well known, then, giving experimental animals a choice of dietary constituents could result in a wider understanding of central mechanisms governing food intake. Exploiting the ability of rats to select dietary protein and carbohydrate has suggested that brain 5-hydroxytryptamine (5-HT) is involved in the regulation of protein/carbohydrate intake. Evidence from human studies suggests that appetite disturbances which occur in obese and mood-disturbed individuals may be linked to an impaired functioning of the brain 5-HT system.     

Gastrointestinal Regulation of Food Intake: General Aspects and Focus on Anandamide and Oleoylethanolamide

The gastrointestinal tract plays a pivotal role in the regulation of food intake and energy balance. Signals from the gastrointestinal tract generally function to limit ingestion in the interest of efficient digestion. These signals may be released into the bloodstream or may activate afferent neurones that carry information to the brain and its cognitive centres, which regulates food intake. The rate at which nutrients become systemically available is also influenced by gastrointestinal motility: a delay in gastric emptying may evoke a satiety effect. Recent evidence suggests that the endocannabinoid anandamide and the related acylethanolamide oleoylethanolamide are produced in the intestine and might regulate feeding behaviour by engaging sensory afferent neurones that converge information to specific areas of the brain. The intestinal levels of these acylethanolamides are inversely correlated to feeding, as food deprivation increases intestinal levels of anandamide (which acts in the gut as a 'hunger signal'), while it decreases the levels of oleoylethanolamide (which acts in the gut as a 'satiety signal'). Additionally, these acylethanolamides, whose gastric levels change in response to diet-induced obesity, alter gastrointestinal motility, which might contribute to their effect on food intake and nutrient absorption.     

Undernutrition of weanling and adult rats: Effects on operant responding

In the rat, brain growth is most vulnerable to undernutrition during the suckling period. Undernutrition at that stage also produces lasting effects on behaviour and it is often assumed that these are due to disturbances of brain growth. The proposal that this may not necessarily be so was explored by testing the behaviour of rats which had been undernourished at later stages of life and which, therefore, would be expected to show little or no deficit in brain growth. Rats were undernourished either immediately after weaning (25–67 days) or in adulthood (80–134 days) and were tested 3–4 months later on variable interval and variable ratio schedules of reinforcement with food as the reward. Their behaviour on these schedules was similar to that of rats undernourished during the suckling period: both groups responded or tended to respond at a higher rate than controls. Hence, it is possible that undernutrition at any stage in life may make animals more responsive to food when deprived subsequently. A cognitive mechanism for this change in behaviour is suggested.     

Development of structure and function in the infant brain: implications for cognition, language and social behaviour

Recent advances in cognitive neuroscience have allowed us to begin investigating the development of both structure and function in the infant brain. However, despite the rapid evolution of technology, surprisingly few studies have examined the intersection between brain and behaviour over the first years of life. Even fewer have done so in the context of a particular research question. This paper aims to provide an overview of four domains that have been studied using techniques amenable to elucidating the brain/behaviour interface: language, face processing, object permanence, and joint attention, with particular emphasis on studies focusing on early development. The importance of the unique role of development and the interplay between structure and function is stressed throughout. It is hoped that this review will serve as a catalyst for further thinking about the substantial gaps in our understanding of the relationship between brain and behaviour across development. Further, our aim is to provide ideas about candidate brain areas that are likely to be implicated in particular behaviours or cognitive domains.     

The role of corticotropin-releasing factor and urocortin in the modulation of ingestive behavior

Participation of the hypothalamo-pituitary-adrenocortical axis, and its primary brain trigger, corticotropin-releasing factor (CRF) in the control of ingestive behavior can be inferred from data suggesting that CRF and its homologue urocortin act in brain to limit appetite following administration in rodents. Moreover, levels of endogenous CRF, CRF(1)and CRF(2)receptors and CRF-binding protein, which sequesters CRF and urocortin, are altered by changes in nutritional status brought about by food restriction/repletion. Mediation of the anorexic effects of CRF and urocortin appear not to privilege CRF(1)receptors, unlike the anxiogenic effects of CRF which are primarily a consequence of CRF(1)receptor activation. Such fear-like consequences of CRF system activation constitute a non-specific mechanism whereby the emergence of behaviors incompatible with food intake may appear to suppress appetite without affecting hunger per se. However, enhanced appetite following administration of CRF receptor antagonists and the involvement of CRF systems in sexual appetite and drug-seeking behavior all suggest a role for CRF in ingestive behavior. In particular, available evidence suggests that physiologically relevant suppression of appetite may accompany CRF system activation occurring as a consequence of stressor exposure induced by nutrient imbalance, for example, or under conditions of excessive intake or consumption of unfamiliar foodstuffs.     

Opioid peptides and the control of human ingestive behaviour

A variety of evidence suggests that endogenous opioid peptides play a role in the short-term control of eating. More recently, opioid receptor antagonists like naltrexone have been approved as a treatment for alcohol dependence. Here we review the evidence for a role of opioid peptides in both normal and abnormal eating and drinking behaviours and in particular try to identify the nature of the role of opioids in these behaviours. Particular attention is paid to the idea that opioid reward processes may be involved both in the short-term control of eating and hedonic aspects of alcohol consumption, and parallels are drawn between the effects of opiate antagonists on food pleasantness and the experience of drinking alcohol. The review also explores the extent to which data from studies using opiate antagonists and agonists provide evidence for a direct role of endogenous opioids in the control of ingestive behaviour, or alternatively whether these data may be better explained through non-specific effects such as the nausea commonly reported following administration of opiate antagonists. The review concludes that the present data suggests a single opioid mechanism is unlikely to explain all aspects of ingestive behaviour, but also concludes that opioid-mediated reward mechanisms play an important control in hedonic aspects of ingestion. The review also highlights the need for further empirical work in order to elucidate further the role of opioid peptides in human ingestive behaviour.     

Origins of altered reinforcement effects in ADHD

Among dietary factors, learning and behavior are influenced not only by nutrients, but also by exposure to toxic food contaminants such as mercury that can disrupt metabolic processes and alter neuronal plasticity. Neurons lacking in plasticity are a factor in neurodevelopmental disorders such as autism and mental retardation. Essential nutrients help maintain normal neuronal plasticity. Nutritional deficiencies, including deficiencies in the long chain polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid, the amino acid methionine, and the trace minerals zinc and selenium, have been shown to influence neuronal function and produce defects in neuronal plasticity, as well as impact behavior in children with attention deficit hyperactivity disorder. Nutritional deficiencies and mercury exposure have been shown to alter neuronal function and increase oxidative stress among children with autism. These dietary factors may be directly related to the development of behavior disorders and learning disabilities. Mercury, either individually or in concert with other factors, may be harmful if ingested in above average amounts or by sensitive individuals. High fructose corn syrup has been shown to contain trace amounts of mercury as a result of some manufacturing processes, and its consumption can also lead to zinc loss. Consumption of certain artificial food color additives has also been shown to lead to zinc deficiency. Dietary zinc is essential for maintaining the metabolic processes required for mercury elimination. Since high fructose corn syrup and artificial food color additives are common ingredients in many foodstuffs, their consumption should be considered in those individuals with nutritional deficits such as zinc deficiency or who are allergic or sensitive to the effects of mercury or unable to effectively metabolize and eliminate it from the body.     

The role of oxytocin in regulation of appetitive behaviour,body weight and glucose homeostasis

Obesity and its associated complications have reached epidemic proportions in the USA and also worldwide, highlighting the need for new and more effective treatments. Although the neuropeptide oxytocin (OXT) is well recognised for its peripheral effects on reproductive behaviour, the release of OXT from somatodendrites and axonal terminals within the central nervous system (CNS) is also implicated in the control of energy balance. In this review, we summarise historical data highlighting the effects of exogenous OXT as a short‐term regulator of food intake in a context‐specific manner and the receptor populations that may mediate these effects. We also describe what is known about the physiological role of endogenous OXT in the control of energy balance and whether serum and brain levels of OXT relate to obesity on a consistent basis across animal models and humans with obesity. We describe recent data on the effectiveness of chronic CNS administration of OXT to decrease food intake and weight gain or to elicit weight loss in diet‐induced obese (DIO) and genetically obese mice and rats. Of clinical importance is the finding that chronic central and peripheral OXT treatments both evoke weight loss in obese animal models with impaired leptin signalling at doses that are not associated with visceral illness, tachyphylaxis or adverse cardiovascular effects. Moreover, these results have been largely recapitulated following chronic s.c. or intranasal treatment in DIO non‐human primates (rhesus monkeys) and obese humans, respectively. We also identify plausible mechanisms that contribute to the effects of OXT on body weight and glucose homeostasis in rodents, non‐human primates and humans. We conclude by describing the ongoing challenges that remain before OXT‐based therapeutics can be used as a long‐term strategy to treat obesity in humans.     

Neurofeedback: Principles,appraisal, and outstanding issues

Neurofeedback is a form of brain training in which subjects are fed back information about some measure of their brain activity which they are instructed to modify in a way thought to be functionally advantageous. Over the last 20 years, neurofeedback has been used to treat various neurological and psychiatric conditions, and to improve cognitive function in various contexts. However, in spite of a growing popularity, neurofeedback protocols typically make (often covert) assumptions on what aspects of brain activity to target, where in the brain to act and how, which have far‐reaching implications for the assessment of its potential and efficacy. Here we critically examine some conceptual and methodological issues associated with the way neurofeedback's general objectives and neural targets are defined. The neural mechanisms through which neurofeedback may act at various spatial and temporal scales, and the way its efficacy is appraised are reviewed, and the extent to which neurofeedback may be used to control functional brain activity discussed. Finally, it is proposed that gauging neurofeedback's potential, as well as assessing and improving its efficacy will require better understanding of various fundamental aspects of brain dynamics and a more precise definition of functional brain activity and brain‐behaviour relationships.     

Alcohol and violence and the possible role of serotonin

BACKGROUND: There is undisputed evidence linking alcohol consumption and violence and other forms of aggressive behaviour, and also linking aggression with dysfunction of the brain indolylamine serotonin (5-hydroxytryptamine or 5-HT). Alcohol consumption also causes major disturbances in the metabolism of brain serotonin. In particular, acute alcohol intake depletes brain serotonin levels in normal (non-alcohol-dependent) subjects. On the basis of the above statements, it is suggested that, at the biological level, alcohol may induce aggressive behaviour in susceptible individuals, at least in part, by inducing a strong depletion of brain serotonin levels. AIMS: In this article, evidence supporting these interrelationships and interactions will be summarized and discussed, the alcohol serotonin aggression hypothesis will be reiterated, and potential intervention strategies will be proposed.     

Aspartame,neurotoxicity, and seizures: A review

Physicians are asked to advise people with epilepsy whether consumption of aspartame (NutraSweet®) is safe and prudent. Aspartame is metabolized to l-phenylalanine, l-aspartate, and methanol. Each metabolite can produce toxic or excitatory effects in animal model systems but only at doses much higher than those feasible from human aspartame consumption. Secondary changes in brain levels of catecholamines and serotonin may occur because of competition precursor transport into brain; however, the clinical relevance of these changes is uncertain. In rodent models of epilepsy, aspartame may alter seizure thresholds when given in doses of 1,000 mg/kg, equivalent to consumption of about 400 diet soft drinks. Applicability of such animal data is questionable. Seizure thresholds in genetically photosensitive baboons are not altered by massive doses of aspartame. Scanty anecdotal clinical reports of overlaps between seizures and aspartame consumption have been published. Monitoring of consumer complaints by the Center for Disease Control and the Food and Drug Administration has failed to document an association of aspartame intake and epilepsy. No controlled clinical trials of aspartame in people with epilepsy have been published. Current evidence suggests that present consumption of aspartame does not induce brain damage, nor does it provoke seizures.     

The importance of alcohol misuse, malnutrition and genetic susceptibility on brain growth and plasticity

The "dyad: alcoholic mother and foetus" is a very complex entity in which several elements such as genes, metabolism, diet, drugs and social habits play a role at different stages in the development of the fetal brain damage. The literature on the effects of alcohol consumption on the developing brain is extensive but very few evidences have been reported regarding the combined neurotoxic effects of poor nutrition and alcohol consumption. The consequences of ethanol intake alone or combined with poor maternal nutrition appear to be severe and life-long. Alcohol exerts its neurotoxic effects on the developing brain directly by acting on fetal brain tissues, and indirectly either by interfering with placental physiology or by impairing the mother's physiology. Alcohol misuse in pregnancy is also frequently associated with other conditions that can potentially increase the brain damage such as poor nutrition and smoking. This article reviews the effects of poor nutrition and alcohol misuse during pregnancy on the development of the fetal brain and discusses the cumulative effects of these two environmental factors and their interaction with maternal and fetal genetic make-ups.     

Insulin,food intake,and reward

Over the past three decades, the hormone insulin has been acknowledged to have multiple effects in the brain, and its role has been validated by the identification of receptors and a transport system for insulin in the central nervous system. Much research has focused on the action of insulin to participate in a feedback loop for the regulation of energy balance. Additionally, more recent studies are demonstrating effects of insulin on brain reward pathways; insulin can interact directly with limbic circuitry to decrease the rewarding or reinforcing value of experimental and natural stimuli, including food. These studies are reviewed in the context of current knowledge of insulin action in the brain, and we offer speculation regarding the relevance of this expanded role of insulin in mental disorders.