As experiences of pleasure & displeasure, hedonics are omnipresent in daily life; as core processes, they accompany emotions, motivation, bodily states, &c; optimal hedonic functioning seems the basis of well-being & aesthetic experiences

The Role of Hedonics in the Human Affectome. Susanne Becker et al. Neuroscience & Biobehavioral Reviews, May 6 2019. https://doi.org/10.1016/j.neubiorev.2019.05.003

Highlights
•    As experiences of pleasure and displeasure, hedonics are omnipresent in daily life.
•    As core processes, hedonics accompany emotions, motivation, bodily states, etc.
•    Orbitofrontal cortex and nucleus accumbens appear to be hedonic brain hubs.
•    Several mental illnesses are characterized by altered hedonic experiences.
•    Optimal hedonic functioning seems the basis of well-being and aesthetic experiences.

Abstract: Experiencing pleasure and displeasure is a fundamental part of life. Hedonics guide behavior, affect decision-making, induce learning, and much more. As the positive and negative valence of feelings, hedonics are core processes that accompany emotion, motivation, and bodily states. Here, the affective neuroscience of pleasure and displeasure that has largely focused on the investigation of reward and pain processing, is reviewed. We describe the neurobiological systems of hedonics and factors that modulate hedonic experiences (e.g., cognition, learning, sensory input). Further, we review maladaptive and adaptive pleasure and displeasure functions in mental disorders and well-being, as well as the experience of aesthetics. As a centerpiece of the Human Affectome Project, language used to express pleasure and displeasure was also analyzed, and showed that most of these analyzed words overlap with expressions of emotions, actions, and bodily states. Our review shows that hedonics are typically investigated as processes that accompany other functions, but the mechanisms of hedonics (as core processes) have not been fully elucidated.

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2.2.1.1 Animal work
Early investigations of the functional neuroanatomy of pleasure and reward in mammals stemmed from the seminal work by Olds and Milner (Olds & Milner, 1954). A series of pioneering experiments showed that rodents tend to increase instrumental lever-pressing to deliver brief, direct intracranial electrical stimulation of septal nuclei. Interestingly, rodents and other non human animals would maintain this type of self-stimulation for hours, working until reaching complete physical exhaustion (Olds, 1958). This work led to the popular description of the neurotransmitter dopamine as the ‘happy hormone’.

However, subsequent electrophysiological and voltammetric assessments as well as microdialysis clearly show that dopamine does not drive the hedonic experience of reward (liking), but rather the motivation to obtain such reward (wanting), that is the instrumental behavior of reward-driven actions (Berridge & Kringelbach, 2015; Wise, 1978). Strong causal evidence for this idea has emerged from rodent studies, including pharmacologically blocking of dopamine receptors or using genetic knockdown mutations in rodents. When dopamine is depleted or dopamine neurons destroyed, reward related instrumental behavior significantly decreases with animals becoming oblivious to previously rewarding stimuli (Baik, 2013; Schultz, 1998). In contrast, hyperdopaminergic mice with dopamine transporter knockdown mutations exhibit largely enhanced acquisition and greater incentive performance for rewards (Pecina et al., 2003). These studies show that phasic release of dopamine specifically acts as a signal of incentive salience, which underlies reinforcement learning (Salamone & Correa, 2012; Schultz, 2013).  Such dopaminergic functions have been related to the mesocorticolimbic circuitry: Microinjections to pharmacologically stimulate dopaminergic neurons in specific sub-regions of the nucleus accumbens (NA) selectively enhance wanting with no effects on liking. However, microinjections to stimulate opioidergic neurons increase the hedonic impact of sucrose reward and wanting responses, likely caused by opioid-induced dopamine release (Johnson & North, 1992). Importantly, different populations of neurons in the ventral pallidum (as part of the mesocorticolimbic circuitry) track specifically the pharmacologically induced enhancements of hedonic and motivational signals (Smith et al., 2011).

The double dissociation of the neural systems underlying wanting and liking has been confirmed many times (Laurent et al., 2012), leading to the concept that positive hedonic responses (liking) are specifically mediated in the brain by endogenous opioids in ‘hedonic hot-spots’ (Pecina et al., 2006). The existence of such hedonic hot-spots has been confirmed in the NA, ventral pallidum, and parabrachial nucleus of the pons (Berridge & Kringelbach, 2015).  In addition, some evidence suggests further hot-spots in the insula and orbitofrontal cortex (OFC; Castro & Berridge, 2017).

Hedonic hot-spots in the brain might be important not only to generate the feeling of pleasure, but also to maintain a certain level of pleasure. In line with this assumption, damage to hedonic hot-spots in the ventral pallidum can transform pleasure into displeasure, illustrating that there is no clear-cut border between neurobiological mechanisms of pleasure and displeasure but rather many intersections. For example sweet sucrose taste, normally inducing strong liking responses, elicits negative and disgust reactions in rats after the damage of a hedonic hot-spot in the ventral pallidum (Ho & Berridge, 2014). In addition to hot-spots that might be essential in maintaining a certain pleasure level, ‘cold spots’ have been found in the NA, ventral pallidum, OFC, and insula. In such cold-spots, opioidergic stimulation suppresses liking responses, which in hot spots causes a stark increase in liking responses (Castro & Berridge, 2014, 2017). A balanced interplay between cold- and hot-spots within the same brain regions such as the NA, ventral pallidum, OFC, and insula may allow for a sophisticated control of positive and negative hedonic responses (see ‘affective keyboard’ in Section 2.2.3). In line with such an assumed sophisticated control, it has to be noted that hedonic hot- and cold-spots are not to be hardwired in the brain. Depending, for example, on external factors creating stressful or pleasant, relaxed environments, the coding of valence can change in such hot-spots from positive to negative and vice versa (Berridge, 2019). Such phenomena have been observed in the NA (Richard & Berridge, 2011) and amygdala (Flandreau et al., 2012; Warlow et al., 2017), likely contributing to a fine-tuned control of hedonic responses dependent on environmental factors.

2.2.1.2. Human work

Confirming results from animal research, a brain network termed the ‘reward circuit’ has been described in human research, which includes the cortico-ventral basal ganglia system, including the ventral striatum (VS) and midbrain (i.e., the ventral tegmental area; Gottfried, 2011; Richards et al., 2013).  Within the reward circuit, reward-linked information is processed across a circuit that involves glutamatergic projections from the OFC and anterior cingulate cortex (ACC), as well as dopaminergic projections from the midbrain into the VS (Richards et al., 2013).

However, as previously described, reward cannot be equated with pleasure, given that reward processing comprises wanting and liking (Berridge et al., 2009; Reynolds & Berridge, 2008). Further, reward processing is modulated by subjective value and utility, which is formed by individual needs, desires, homeostatic states, and situational influences (Rangel et al., 2008). As such, pleasure as a core process is most closely related to ‘liking’ expressed during reward consumption. During such reward consumption, human neuroimaging studies have consistently noted a central role of the VS (including the NA) corresponding to results from animal research. The VS is consistently activated during the anticipation and consumption of reward (Liu et al., 2011).  Interestingly, the VS is also activated during the imagery of pleasant experiences, including drug use in substance abusers, pleasant sexual encounters, and athletic success (Costa et al., 2010). Despite a vast literature emphasizing that the VS is implicated in the processing of hedonic aspects of reward in humans, this brain area has not been well parcellated into functional sub-regions (primarily because of limited resolution in human neuroimaging).  Nevertheless, using an anatomical definition of the core and shell of the NA, one study successfully described differential encoding of the valence of reward and pain in separable structural and functional brain networks with sources in the core and shell of the NA (Baliki et al., 2013). This finding again highlights the overlaps of pleasure and displeasure systems, rendering the separated investigation of pleasure and displeasure functions somewhat artificial.

In addition to the VS, the OFC has received much attention in human research on reward and hedonic experiences (Berridge & Kringelbach, 2015).  Much of the current knowledge on the functions of the OFC in hedonic experiences is based on human neuroimaging, because the translation from animal work has proven to be challenging because of differences in the prefrontal cortex (PFC; Wallis, 2011). The OFC has been described in numerous human functional magnetic resonance imaging (fMRI) studies to represent the subjective value of rewarding stimuli (Grabenhorst & Rolls, 2011). More specifically, the OFC has been described as the first stage of cortical processing, in which the value and pleasure of reward are explicitly represented. With its many reciprocal anatomical connections to other brain regions important in reward processing, the OFC is in an optimal position to distribute information on subjective value and pleasure in order to optimize different behavioral strategies. For example, the OFC is well connected to the ACC, insular cortex, somatosensory areas, amygdala, and striatum (Carmichael & Price, 1995; Cavada et al., 2000; Mufson & Mesulam, 1982).

Besides the VS and the OFC, multiple other brain regions are involved in reward processing, including the caudate, putamen, thalamus, amygdala, anterior insula, ACC, posterior cingulate cortex, inferior parietal lobule, and sub-regions of the PFC other than the OFC (Liu et al., 2011). Reward involves processing of complex stimuli that involve many more components beyond wanting and liking, such as attention, arousal, evaluation, memory, learning, decision-making, etc.

In addition to higher-level cortical representations, pleasure also appears to be coded at very low levels of peripheral sensory processing. As an illustration, hedonic representations of smells are already present in peripheral sensory cells. There are differences in electrical activity of the human olfactory epithelium in response to pleasant vs. unpleasant odors (Lapid et al., 2011).  Further, responses to the hedonic valence of odors involve differential activation of the autonomic nervous system (e.g., fluctuations in heart rate and skin conductance; Joussain et al., 2017). Together with the above-described results on central processing of pleasure, these findings highlight that extensive neurobiological systems are implicated in the processing of positive hedonic feelings including peripheral and autonomic components. In line with findings from the animal work, it can be assumed that environmental factors such as perceived stress affect these neurobiological systems leading to plastic changes (Juarez & Han, 2016; Li, 2013) and thus a sophisticated control of hedonic feelings adapted to situational factors.

2.2.2 Displeasure and pain—from animal models to human models