The computational neurobiology of learning and reward

Following the suggestion that midbrain dopaminergic neurons encode a signal, known as a 'reward prediction error', used by artificial intelligence algorithms for learning to choose advantageous actions, the study of the neural substrates for reward-based learning has been strongly influenced by computational theories. In recent work, such theories have been increasingly integrated into experimental design and analysis. Such hybrid approaches have offered detailed new insights into the function of a number of brain areas, especially the cortex and basal ganglia. In part this is because these approaches enable the study of neural correlates of subjective factors (such as a participant's beliefs about the reward to be received for performing some action) that the computational theories purport to quantify.     

A common neurobiology for pain and pleasure

Pain and pleasure are powerful motivators of behaviour and have historically been considered opposites. Emerging evidence from the pain and reward research fields points to extensive similarities in the anatomical substrates of painful and pleasant sensations. Recent molecular-imaging and animal studies have demonstrated the important role of the opioid and dopamine systems in modulating both pain and pleasure. Understanding the mutually inhibitory effects that pain and reward processing have on each other, and the neural mechanisms that underpin such modulation, is important for alleviating unnecessary suffering and improving well-being.     

Drug addiction: the neurobiology of disrupted self-control

The nature of addiction is often debated along moral versus biological lines. However, recent advances in neuroscience offer insights that might help bridge the gap between these opposing views. Current evidence shows that most drugs of abuse exert their initial reinforcing effects by inducing dopamine surges in limbic regions, affecting other neurotransmitter systems and leading to characteristic plastic adaptations. Importantly, there seem to be intimate relationships between the circuits disrupted by abused drugs and those that underlie self-control. Significant changes can be detected in circuits implicated in reward, motivation and/or drive, salience attribution, inhibitory control and memory consolidation. Therefore, addiction treatments should attempt to reduce the rewarding properties of drugs while enhancing those of alternative reinforcers, inhibit conditioned memories and strengthen cognitive control. We posit that the time has come to recognize that the process of addiction erodes the same neural scaffolds that enable self-control and appropriate decision making.     

The neurobiology of zinc in health and disease

The use of zinc in medicinal skin cream was mentioned in Egyptian papyri from 2000 BC (for example, the Smith Papyrus), and zinc has apparently been used fairly steadily throughout Roman and modern times (for example, as the American lotion named for its zinc ore, 'Calamine'). It is, therefore, somewhat ironic that zinc is a relatively late addition to the pantheon of signal ions in biology and medicine. However, the number of biological functions, health implications and pharmacological targets that are emerging for zinc indicate that it might turn out to be 'the calcium of the twenty-first century'.     

Drug addiction: the neurobiology of behaviour gone awry

Drug addiction manifests as a compulsive drive to take a drug despite serious adverse consequences. This aberrant behaviour has traditionally been viewed as bad "choices" that are made voluntarily by the addict. However, recent studies have shown that repeated drug use leads to long-lasting changes in the brain that undermine voluntary control. This, combined with new knowledge of how environmental, genetic and developmental factors contribute to addiction, should bring about changes in our approach to the prevention and treatment of addiction.     

Timing in reward and decision processes

Sensitivity to time, including the time of reward, guides the behaviour of all organisms. Recent research suggests that all major reward structures of the brain process the time of reward occurrence, including midbrain dopamine neurons, striatum, frontal cortex and amygdala. Neuronal reward responses in dopamine neurons, striatum and frontal cortex show temporal discounting of reward value. The prediction error signal of dopamine neurons includes the predicted time of rewards. Neurons in the striatum, frontal cortex and amygdala show responses to reward delivery and activities anticipating rewards that are sensitive to the predicted time of reward and the instantaneous reward probability. Together these data suggest that internal timing processes have several well characterized effects on neuronal reward processing.     

Review. The neurobiology of pathological gambling and drug addiction: an overview and new findings

Gambling is a prevalent recreational behaviour. Approximately 5% of adults have been estimated to experience problems with gambling. The most severe form of gambling, pathological gambling (PG), is recognized as a mental health condition. Two alternate non-mutually exclusive conceptualizations of PG have considered it as an obsessive-compulsive spectrum disorder and a 'behavioural' addiction. The most appropriate conceptualization of PG has important theoretical and practical implications. Data suggest a closer relationship between PG and substance use disorders than exists between PG and obsessive-compulsive disorder. This paper will review data on the neurobiology of PG, consider its conceptualization as a behavioural addiction, discuss impulsivity as an underlying construct, and present new brain imaging findings investigating the neural correlates of craving states in PG as compared to those in cocaine dependence. Implications for prevention and treatment strategies will be discussed.     

Principles of pleasure prediction: specifying the neural dynamics of human reward learning

Accumulating evidence from nonhuman primates suggests that midbrain dopamine cells code reward prediction errors and that this signal subserves reward learning in dopamine-receiving brain structures. In this issue of Neuron, McClure et al. and O'Doherty et al. use event-related fMRI to provide some of the strongest evidence to date that the reward prediction error model of dopamine system activity applies equally well to human reward learning.     

Epigenetic effects of selenium and their implications for health

Alterations of epigenetic marks are linked to normal development and cellular differentiation as well as to the progression of common chronic diseases. The plasticity of these marks provides potential for disease therapies and prevention strategies. Macro- and micro-nutrients have been shown to modulate disease risk in part via effects on the epigenome. The essential micronutrient selenium affects human health outcomes, e.g., cancers, cardiovascular and autoimmune diseases, via selenoproteins and through a range of biologically active dietary selenocompounds and metabolism products thereof. This review provides an assessment of the current literature regarding epigenetic effects of dietary and synthetic selenocompounds, which include the modulation of marks and editors of epigenetic information and interference with one-carbon metabolism, which provides the methyl donor for DNA methylation. The relevance of a selenium-epigenome interaction for human health is discussed, and we also indicate where future studies will be helpful to gain a deeper understanding of epigenetic effects elicited by selenium.     

Mental health, attachment and breastfeeding: implications for adopted children and their mothers

ABSTRACT : Breastfeeding an adopted child has previously been discussed as something that is nice to do but without potential for significant benefit. This paper reviews the evidence in physiological and behavioural research, that breastfeeding can play a significant role in developing the attachment relationship between child and mother. As illustrated in the case studies presented, in instances of adoption and particularly where the child has experienced abuse or neglect, the impact of breastfeeding can be considerable. Breastfeeding may assist attachment development via the provision of regular intimate interaction between mother and child; the calming, relaxing and analgesic impact of breastfeeding on children; and the stress relieving and maternal sensitivity promoting influence of breastfeeding on mothers. The impact of breastfeeding as observed in cases of adoption has applicability to all breastfeeding situations, but may be especially relevant to other at risk dyads, such as those families with a history of intergenerational relationship trauma; this deserves further investigation.     

Contemporary approaches to neural circuit manipulation and mapping: focus on reward and addiction

Tying complex psychological processes to precisely defined neural circuits is a major goal of systems and behavioural neuroscience. This is critical for understanding adaptive behaviour, and also how neural systems are altered in states of psychopathology, such as addiction. Efforts to relate psychological processes relevant to addiction to activity within defined neural circuits have been complicated by neural heterogeneity. Recent advances in technology allow for manipulation and mapping of genetically and anatomically defined neurons, which when used in concert with sophisticated behavioural models, have the potential to provide great insight into neural circuit bases of behaviour. Here we discuss contemporary approaches for understanding reward and addiction, with a focus on midbrain dopamine and cortico-striato-pallidal circuits.