Re-valuing the amygdala

Recent advances indicate that the amygdala represents valence: a general appetitive/aversive affective characteristic that bears similarity to the neuroeconomic concept of value. Neurophysiological studies show that individual amygdala neurons respond differentially to a range of stimuli with positive or negative affective significance. Meanwhile, increasingly specific lesion/inactivation studies reveal that the amygdala is necessary for processes — for example, fear extinction and reinforcer devaluation — that involve updating representations of value. Furthermore, recent neuroimaging studies suggest that the human amygdala mediates performance on many reward-based decision-making tasks. The encoding of affective significance by the amygdala might be best described as a representation of state value — a representation that is useful for coordinating physiological, behavioral, and cognitive responses in an affective/emotional context.

Introduction

For many years, the amygdala was thought of primarily as a center for fear in the brain. This perception was fueled by a wealth of experimental data, mainly from rodents, that emerged from the fear conditioning paradigm (summarized in [1, 2]). Classic lesion and inactivation studies established that the amygdala is essential for the perception of fear, the expression of fearful behavior, and the acquisition of fear in response to stimuli that had been paired with aversive outcomes (Pavlovian fear conditioning) (e.g. [3], reviewed in [4]). Neurophysiological studies, which also were mainly limited to rodents, showed that cells in the basolateral amygdala (BLA) had firing rates that were highly sensitive to stimuli that were associated with fear-inducing events, and also to the aversive events themselves [4, 5].

While new light continues to be shed on the detailed functioning of the amygdala with regard to fear learning and fearful behavior, in recent years, a surge of work in humans and non-human primates has led to an expanded conception of the amygdala's role. The anatomical connections of the amygdala in primates hint at a reason for this: especially compared to rodents, humans and non-human primates have a hugely elaborated prefrontal cortex (PFC) [6], many parts of which — especially medial and orbital areas — have extensive bidirectional connections with the amygdala [7, 8, 9, 10]. The amygdala receives input from a full range of higher sensory and poly-sensory areas, and projects back to them in turn, even to primary sensory targets (connections that may be unique to primates) [11, 12, 13]. Other targets of amygdala output include the hippocampus, basal ganglia, perirhinal and entorhinal cortices, the basal forebrain, and subcortical structures such as the hypothalamus [14]. In sum, the anatomical situation of the amygdala seems to imply the potential for a far more wide-ranging role than ‘danger alarm.’

Using a combination of new techniques and innovative extensions of old ones, neuroscientists have uncovered a role for the amygdala in a wide variety of tasks with an emotional component, whether appetitive or aversive [15]. Emotional responses frequently occur in reaction to stimuli that predict impending rewarding or aversive reinforcement, and they are often described within a framework that uses two axes to characterize emotions: arousal (from calm to excited) and valence (from extremely negative to extremely positive) [16]. As we discuss below, recent data implicate the amygdala in processing information related to both arousal and valence; we will focus mainly, but not exclusively, on processing related to valence.

The concept of positive and negative valence is related to recent work by neuroscientists seeking to understand the neural basis of economic choice. According to neuroeconomic theory, a ‘universal currency’ of value should be encoded in the brain in order to effectively compare different economic options [17, 18, 19]; moreover, the values of stimuli, the values of actions, and ‘state value’ — the value of the overall situation of an organism at a given moment — are essential variables in theoretical accounts of learning [20, 21]. Using decision-making tasks, scientists have characterized neural signals correlated with value, where value is defined within an economic framework (reviewed in [18, 19]). In contrast, most studies focused on the amygdala have not used decision-making tasks; rather, they used classical or instrumental conditioning tasks, in which subjects learn the association between conditioned stimuli (CSs) and appetitive or aversive unconditioned stimuli (USs). Many types of associations between a CS and US may be formed during conditioning [22] — such as those between the CS and the motor response elicited by the US, or the sensory properties of the US — but, as we will discuss, considerable evidence now indicates that amygdala neurons encode information about the overall affective or motivational significance of USs associated with CSs. Therefore, we would argue that information about ‘valence’ encoded by the amygdala probably corresponds to ‘value’ as it is studied in decision-making tasks; we will use the terms ‘value’ and ‘valence’ interchangeably.

This review will examine recent progress in our understanding of whether and how value — in all its multifaceted senses — is encoded by the amygdala in rodents, humans, and non-human primates. We will consider the small but growing body of neurophysiological evidence concerning how the activity of individual amygdala neurons encodes the value of stimuli, and perhaps more general quantities, such as state value; and we will examine how this view of amygdala function may be supported by recent evidence from lesions and inactivation of the amygdala, and from observation of amygdala activity using functional imaging. Along the way, we will consider emerging ideas about how a representation of value might be ‘read out’ and used by other brain areas such as the orbitofrontal cortex (OFC). Overall, recent work paints a compelling picture of the amygdala as a key brain area for the processing and propagation of signals pertaining to value, and therefore as an essential part of the neural foundation of motivated behavior and emotion.