Emotion Review

http://emr.sagepub.com/ Current Emotion Research in Behavioral Neuroscience: The Role(s) of the Amygdala
Jorge L. Armony Emotion Review 2013 5: 104 originally published online 4 October 2012 DOI: 10.1177/1754073912457208 The online version of this article can be found at: http://emr.sagepub.com/content/5/1/104

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EMR5110.1177/1754073912457208Emotion ReviewArmony / Current Emotion Research

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Emotion Review Vol. 5, No. 1 (January 2013) 104115 The Author(s) 2012 ISSN 1754-0739 DOI: 10.1177/1754073912457208 er.sagepub.com

Current Emotion Research in Behavioral Neuroscience: The Role(s) of the Amygdala

Jorge L. Armony

Department of Psychiatry, McGill University, Canada Douglas Mental Health University Institute, Canada International Laboratory for Brain, Music, and Sound Research (BRAMS), Canada

Abstract
Substantial advances in our understanding of the neural bases of emotional processing have been made over the past decades. Overall, studies in humans and other animals highlight the key role of the amygdala in the detection and evaluation of stimuli with affective value. Nonetheless, contradictory findings have been reported, especially in terms of the exact role of this structure in the processing of different emotions, giving rise to different neural models of emotion. For instance, although the amygdala has traditionally been considered as exclusively involved in fear (and possibly anger), more recent work suggests that it may be important for processing other types of emotions, and even nonemotional information. A review of the main findings in this field is presented here, together with some of the hypotheses that have been put forward to interpret this literature and explain its inconsistencies.

Keywords
amygdala, anatomy, emotion, facial expressions, fear conditioning, functional magnetic resonance imaging, music, neuroimaging, vocalizations

In the late 1800s Brown and Schafer (1888) reported that large bilateral temporal lesions transformed fierce monkeys into tame animals, albeit only temporarily. A few decades later, Heinrich Kluver and Paul Bucy (1939) found that removal of both temporal lobes in rhesus monkeys resulted in a dramatic behavioral changes. In particular, these animals exhibited a loss of emotional reactivity. For instance, they showed a decrease in fear and were generally calm and approached objects, animals, or humans that they would usually consider as threatening. Kluver and Bucy called this pattern of behavior psychic blindness (now known as the KluverBucy syndrome), to highlight the fact that although the animals did not exhibit any significant sensory deficits, they appeared to be unable to fully grasp the emotional meaning of stimuli. Importantly, Weiskrantz (1956) demonstrated that lesions restricted to the amygdala complex resulted in a similar pattern of behavior as the one observed by Kluver and Bucy. Furthermore, he showed that the amygdala was also necessary for aversive classical conditioning. Following these landmark studies, a large body of evidence emerged confirming

and further delineating the key role of the amygdala in emotional processing, first mainly through the use of the fear conditioning model in rodents and, more recently, with the use of neuroimaging techniques in humans. This article provides a review of this literature. The emphasis on the amygdala is in no way meant to imply that other brain regions are not also important, or even crucial, for emotional processing. Yet I chose to focus on this structure because of its established role in emotion, the vast amount of data collected using different stimuli, paradigms, and species and, critically, because of the numerous inconsistencies and controversies in terms of its specific function.

The Amygdala
Anatomy
The amygdala is a relatively small structure located in the medial temporal lobe, anterior to the hippocampus (Figure 1).

Author note: Parts of this article were adapted from a book chapter prepared for The Oxford Handbook of Auditory Science: The Auditory Brain (Palmer & Rees, 2010). The author is supported by the Canada Research Chairs Program. I am grateful to Joe LeDoux and Isabelle Peretz for helpful discussions related to some of the topics covered here. Corresponding author: Jorge L. Armony, Douglas Institute Research, 6875 LaSalle Boulevard, F.B.C. Pavilion, Verdun, QC H4H 1R3, Canada. Email: jorge.armony@mcgill.ca

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either complete (Machado, Kazama, & Bachevalier, 2009) or restricted to the central nucleus (Kalin, Shelton, & Davidson, 2004), cause significant reductions in fear responses to snakes and/or human intruders, as well as decreases in stress hormone concentrations. The effects of amygdala lesions on social interactions with other monkeys, on the other hand, seem to be quite complex, as they depend on the context (e.g., number of the individuals; Machado & Bachevalier, 2006) and the age of lesion (Bauman, Lavenex, Mason, Capitanio, & Amaral, 2004). Amygdala lesions also interfere with innate fear responses in rats. For instance, operated animals exhibit significantly reduced freezing and avoidance behavior in the presence of a cat (Blanchard & Blanchard, 1972) and diminished immobility when placed in an open field (Coover, Ursin, & Levine, 1973).
Figure 1. Sagittal view of a three-dimensional reconstruction of the amygdala and hippocampus in the left hemisphere.

Connectivity
Most of what we know about the connections to, within, and from the amygdala has been learned from anatomy and auditory physiology studies in rats. Nonetheless, most of what is described here appears to generally apply to other species and sensory modalities. An acoustic stimulus is transmitted from cochlear receptors through the brain stem to the auditory thalamus, the medial geniculate body (MGB). Information then reaches the amygdala by way of two parallel pathways: a direct projection originating mainly in the medial division of the MGB (MGm) and the associated posterior intralaminar nucleus (PIN), and an indirect one, from all areas of the MGB, which reaches the amygdala via the cerebral cortex. Both pathways terminate primarily in the lateral nucleus (LA), the main sensory input of the amygdala, often converging onto the same cells (Li, Stutzmann, & LeDoux, 1996). Importantly, a substantial proportion of cells in the PIN contribute to both pathways; that is, they project both to the LA and to the auditory cortex (Doron & LeDoux, 2000). Therefore, some of the information transmitted from the thalamus to the amygdala via the direct and indirect routes originates and terminates in the same neurons, although with different latencies: Monosynaptic transmission from the MGm/PIN to LA neurons is fast (<10 ms; Li, Phillips, & LeDoux, 1995), whereas information traveling through the indirect cortical pathway requires longer time to reach the amygdala (>20 ms; Quirk, Armony, & LeDoux, 1997). In contrast, this latter pathway has higher information-processing capacity. These anatomical and physiological differences suggest possible complementary roles of these two routes in the processing of emotional stimuli. That is, the direct thalamic pathway could provide rapid, but not very precise, emotional information, whereas the cortical inputs to the amygdala would convey a slower but more detailed representation of the stimulus (LeDoux, 1996). According to this model, the initial fast information conveyed by the subcortical pathway would prepare the amygdala for triggering defensive responses to a potential threat. These responses, however, would not be fully engaged until the more detailed information about the threat stimulus arriving from the cortical pathway confirmed that the perceived stimulus does indeed indicate the

The term amygdalar nucleus was first used by Burdach in the early 19th century to describe an almond-shaped cell mass of gray matter deep within the anterior portion of the human medial temporal lobe (Swanson, 2003). Later, Johnston (1923) described the amygdalar region in numerous mammalian species, nonmammalian vertebrates, and human embryos. He identified, on the basis of their relative locations within the amygdaloid complex, six main nuclei: the central and medial nuclei, which formed the old part of the amygdala, and the newly added cortical, basal, accessory basal, and lateral nuclei. The region that Burdach called amygdala referred to the three latter nuclei, which are now collectively termed the basolateral amygdala complex. Although there is no complete agreement yet on its exact borders or the nomenclature of its nuclei, it is generally accepted that the amygdala is composed of about a dozen nuclei, each of them in turn subdivided into several subregions with unique architectonic, histochemical, and physiological characteristics. Interestingly, the amygdala seems to have been highly conserved throughout evolution, so that its basic structure and function are very similar across mammals, from rodents to monkeys and humans (Figure 2). In fact, it has been argued that some nonmammalian species, including birds (Lowndes & Davies, 1994) and fish (Portavella, Torres, & Salas, 2004), also possess an amygdala-like structure, important for the acquisition and expression of emotional responses.

Lesion Studies
The findings from the early lesion experiments were largely confirmed in subsequent studies. Total bilateral amygdala damage in monkeys was shown to result in reduced emotional responses, consumption of previously rejected items (e.g., meat or feces), and excessive exploration of inanimate objects, while partial amygdala damage produced some of these symptoms, but typically in a less pronounced fashion (Aggleton & Passingham, 1981). Furthermore, neurotoxic amygdala lesionswhich kill cell bodies but spare fibers of passage

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Figure 2. (A) Nissl-stained coronal sections of the rat (top), monkey (middle), and human (bottom) brains, showing the location of the left amygdala. (B) Schematic representation of the location of some of the main divisions of the amygdala for each of the species. L = lateral nucleus; Ldl = dorsolateral; Lvl = ventrolateral; Lm = medial; Ld = dorsal; Ldi = dorsal intermediate; Lv = ventral; Lvi = ventral intermediate; Ll = lateral; Lm = medial; B = basal nucleus; Bi = intermediate; Bpc = parvicellular; Bmc = magnocellular; AB = accessory basal nucleus; ABmc = magnocellular; ABpc = parvicellular; AB vm = ventromedial; M = medial nucleus; Mc = caudal; Mcd = central, dorsal part; Mcv = central, ventral part; CE = central nucleus; CEl = lateral; CEm = medial; CEi = intermediate; CEc = capsular; PAC = periamygdaloid cortex; COa = anterior cortical nucleus; I = intercalated nuclei; PL = paralaminar nucleus. Adapted with permission from Pitkanen & Kemppainen (2002).

presence of immediate danger. Furthermore, the thalamic pathway may be less susceptible to topdown attentional modulation and could therefore be important for detecting the presence of danger when the signal originates outside the current focus of attention. Feedback projections from the amygdala to cortical areas would in turn provide an interrupt signal to redirect attentional resources to the origin of the potential threat (Armony & Dolan, 2002). Within the amygdala, information flows from the LA to the central nucleus (CE) through direct projections as well as

other indirect intra-amygdala circuits. The central nucleus constitutes the main effector system of the amygdala, providing the interface with the systems involved in controlling the various emotional, particularly defensive, responses. That is, whereas lesions of the CE abolish the expression of fear responses of all types, lesions of areas to which the CE projects interfere with specific responses (LeDoux, Iwata, Cicchetti, & Reis, 1988). For example, lesions of the lateral hypothalamus interfere with sympathetic nervous system mediated responses (such as changes in blood pressure),

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whereas lesions of the central gray eliminate behavioral conditioned responses (e.g., freezing). The amygdala is also connected to other cortical and subcortical structures (see Freese & Amaral, 2009; Pitkanen, 2000). The unidirectional projections from the basal nucleus to the striatum are thought to mediate instrumental behavior, that is, emotionrelated actions (e.g., escaping from a predator), in contrast to the emotional reactions (e.g., freezing) mediated by the outputs of the central nucleus. There are also important bilateral connections between the amygdala and the hippocampus: The hippocampus provides the amygdala with contextual information during emotional events (R. G. Phillips & LeDoux, 1992), while the denser amygdala inputs to the hippocampus are important for the emotional modulation of memory (LaBar & Cabeza, 2006). The amygdala is also heavily interconnected with the prefrontal cortex (PFC), particularly the orbital and medial regions. Some of these projections could underlie the proposed amygdala-dependent capture of attention by emotional stimuli (Armony & Dolan, 2002). In addition, there are light projections from the lateral PFC and premotor cortex to the basal nucleus. The projections that connect the ventromedial PFC (infralimbic cortex in rats) with inhibitory cells in the amygdalasuch as the lateral division of the central nucleus (CeL) and intercalated neuronsare of particular importance, as they are involved in emotion regulation and extinction of previously acquired fear responses (Quirk, Garcia, & Gonzalez-Lima, 2006).

Physiology
Cells in the LA tend to have very low spontaneous activity (less than 1 Hz) and relatively high thresholds (about 3050 dB above the primary auditory system). Studies in rats show that LA neurons, particularly those in the dorsal division, can respond to simple auditory stimuli with very short latencies, between 10 and 20 ms. These early bursts, which most likely correspond to direct inputs from the thalamus, are often followed by longer latency responses (typically 60100 ms; Bordi & LeDoux, 1992). Amygdala neurons usually habituate quickly to repeated presentations of the same neutral stimulus, but they respond strongly if the stimulus is changed, becomes less predictable, or if it acquires affective value (e.g., through conditioning). Thus, amygdala cells behave as emotional novelty detectors: They respond quickly and strongly to new stimuli in the environment, but learn to ignore them if these have no biologically relevant consequences. Their low baseline rate and high threshold may serve as a safety mechanism to minimize the probability of false alarms. Most LA neurons in the rat display broad frequency receptive fields, with a preference to high frequencies (above 10 kHz). Interestingly, this range corresponds to that of the warning calls emitted by these animals when they are threatened (in the 22 kHz range) and during positive situations (in the range of 50 kHz). These observations suggest that amygdala cells may be tuned to preferentially respond to species-specific stimuli, particularly those with emotional content. Furthermore, responses to

these two types of calls can be differentiated by amygdala neurons. Specifically, 22 kHz (negative) and 50 kHz (positive) calls tend to elicit tonic increases and decreases in firing rates, respectively (Parsana, Li, & Brown, 2012). This preference of amygdala cells for species-specific stimuli, especially those with affective value, can also be observed in other species. For instance, conspecifics meows are the most effective auditory stimuli to drive amygdala cells in a cat (Sawa & Delgado, 1963). Likewise, a large proportion of monkey amygdala neurons preferentially respond to monkey faces (Leonard, Rolls, Wilson, & Baylis, 1985), often showing selectivity for a particular identity and/or facial expression. In the latter case, threatening expressions typically elicit significant increases in firing rates (Gothard, Battaglia, Erickson, Spitler, & Amaral, 2007) and functional magnetic resonance imaging (fMRI) activity (Hoffman, Gothard, Schmid, & Logothetis, 2007), whereas neutral or appeasing faces tend to be associated with decreased firing rates (Gothard et al., 2007), but can also elicit increased responses, compared to meaningless stimuli such as scrambled faces (Hoffman et al., 2007). Amygdala cells in the monkey also respond more strongly to same-species vocalizations, especially those associated with distress (e.g., isolation peeps and snake calls) (Kling, Lloyd, & Perryman, 1987). Furthermore, as in rats, most auditory neurons in the lateral and basal nuclei of the monkey amygdala have a preference for unfamiliar stimuli, to which they habituate quickly (within two or three repetitions) when they have no meaningful consequences (Nishijo, Ono, & Nishino, 1988). Although most neurons in the monkey amygdala respond preferentially to visual stimuli, a large proportion of them, especially in the central nucleus, can be modulated by auditory information. For instance, responses to dynamic facial expressions can be enhanced by the simultaneous presentation of the corresponding vocalization (Kuraoka & Nakamura, 2007), especially in the case of fear-related stimuli (i.e., scream). These findings support the hypothesis that the amygdala integrates information from different sensory modalities to produce a supramodal representation of emotional information.

Fear conditioning
Significant advances in our understanding of how the brain processes emotional information have been made mainly through the use of a simple yet powerful experimental paradigm: classical or Pavlovian conditioning. In its simplest form, aversive or fear conditioning involves the pairing of an emotionally neutral conditioned stimulus (CS), such as a tone or a light, with an intrinsically powerful aversive unconditioned stimulus (US), such as a loud sound or a mild electric shock. After a few pairings, sometimes even just one, the CS acquires aversive properties and therefore, when presented alone, it will elicit a variety of species-specific behavioral, physiological, and hormonal defensive reactions. That is, through conditioning, a previously meaningless stimulus becomes a warning signal that informs the organism about the presence of an impending threat in the environment, allowing it to respond to, and possibly avoid, the

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dangerous situation. One of the key advantages of the fear conditioning paradigm, therefore, is that responses to the exact same stimulus can be measured, and compared, before and after it acquires affective value. Often, another neutral stimulus (CS-), which has not been explicitly paired with the US, can be used to identify any general nonspecific effects that result from the overall aversive experience of fear conditioning (e.g., increased arousal, sensitization, etc.). Conditioned fear responses that are typically measured in rats include freezing (i.e., absence of any movement except those associated with breathing), vocalizations, increase of heart rate, blood pressure, defecation, and the potentiation of reflexes such as the acoustic startle response. In humans, the conditioned responses that are usually recorded include muscle tension, pupil dilation, changes in heart rate, blood pressure, respiration, and, most often, electrodermal or skin conductance responses (SCR), which are mediated by the sympathetic nervous system.

transiently plastic cells appear to act as an error detector between the predicted and experienced outcomes associated with the CS presentation (Quirk et al., 1997). In contrast to these transiently plastic neurons, a group of cells in the ventral portion of LAd exhibit a distinct, complementary behavior, as they have longer latency responses to the CS (3040 ms after onset). These long-term plastic cells, likely receiving intra-amygdala and/or cortico-amygdala inputs, take a larger number of trials to reach their maximal response but maintain increased CS-elicited activity throughout conditioning and even extinction (Repa et al., 2001). Critically, plasticity in both types of neurons tends to precede the development of behavioral fear responses, demonstrating that plasticity in LAd is not simply a reflection of behavioral responses. In fact, it can be shown that behavioral fear is neither necessary nor sufficient for the expression of conditioning-induced changes in CS-elicited activity in LA neurons (Goosens, Hobin, & Maren, 2003).

Neural Mechanisms
As described earlier, auditory information reaches the lateral nucleus of the amygdala from the auditory thalamus by way of two parallel pathways: one directly connecting both structures and a second, indirect one, which passes through cortical areas. Lesion studies have shown that either pathway alone can support conditioning to a simple CS, such as a tone of a single frequency (Romanski & LeDoux, 1992). Moreover, animals with complete ablation of the auditory cortex show intact frequency generalization behavioral gradients (i.e., conditioned responses to other stimuli with frequencies similar to that of the CS), suggesting that the direct subcortical pathway is sufficient for some aspects of stimulus discrimination (Armony, Servan-Schreiber, Romanski, Cohen, & LeDoux, 1997). There are, however, limits to the capacity of the thalamoamygdala pathway, and cortical inputs are likely to become necessary for successful discrimination of more complex sounds, such as rising and falling frequency-modulated (FM) tones (Rybalko, Suta, Nwabueze-Ogbo, & Syka, 2006). Cells across the amygdala develop conditioning-induced plasticity after a few CSUS pairings. In particular, neurons in the dorsal aspect of the LA (LAd), the main target of the direct thalamic projections and a site of convergence of CS and US information (Romanski, LeDoux, Clugnet, & Bordi, 1993), exhibit short-latency increases to the auditory CS as a result of conditioning. The earliest plasticity occurs 1020 ms after CS onset, most likely corresponding to direct inputs from the thalamus. These cells, which are mainly located in the dorsal tip of the LAd, usually show a maximal response to the CS after a few CSUS pairings (i.e., the beginning of the conditioning phase) and again at the beginning of extinction, when the CS is presented alone, in the absence of the US. That is, these neurons respond strongly when the value of the CS as predictor of the US is changing (early conditioning and extinction), but return to their baseline levels when the CSUS relation remains constant (late conditioning and extinction phases). In other words, these

Human studies
Studies in human subjects have largely confirmed the critical role of the amygdala in emotional processing and replicated many of the findings obtained with experimental animals. Lesion studies have mainly focused on neurological patients with damage to the amygdala (and usually surrounding cortical areas and the hippocampus) following unilateral temporal lobe resection performed to treat refractory temporal lobe epilepsy (TLE). In addition, a few studies have examined individuals who suffer from a rare disorder named UrbachWiethe syndrome, as in about 30% of the cases patients present with bilateral calcification of the amygdala, sparing, in most cases, surrounding structures. In addition, our knowledge about the specific involvement of the amygdala in emotional perception and learning, and its interactions with other brain regions, has grown dramatically over the past decade through the use of functional neuroimaging techniques, in particular positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) (Armony & Han, in press). Knowledge about the neural bases of emotion, particularly fear, obtained from studies in experimental animals and humans, has also contributed to a better understanding of certain psychiatric disorders. For instance, fear conditioning has been proposed as a useful model to explain, at least in part, some aspects of post-traumatic stress disorder (PTSD), which has been found to be often associated with a hypersensitive amygdala and a hyporesponsive ventromedial prefrontal cortex (vmPFC) (Rauch, Shin, & Phelps, 2006).

Fear Conditioning
A seminal study (Bechara et al., 1995) showed that patient SM, who has focal bilateral amygdala damage as a result of Urbach Wiethe syndrome, was impaired in the acquisition of conditioned autonomic responses to a visual or auditory CS, as

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measured by electrodermal activity, even though she exhibited intact declarative memory of the conditioning procedure (e.g., which stimulus was paired with the US). Notably, the opposite pattern was found in a patient with hippocampal damage but intact amygdala; namely, he developed normal conditioned physiological responses to the CS but showed no episodic memory of the CSUS pairing. Studies in patients with unilateral temporal lobectomy have produced similar findings (LaBar, LeDoux, Spencer, & Phelps, 1995; Peper, Karcher, Wohlfarth, Reinshagen, & LeDoux, 2001). However, other studies have reported the development of conditioninginduced skin conductance responses in these patients, but only when they were explicitly aware of the CSUS contingency (Coppens, Spruyt, Vandenbulcke, van Paesschen, & Vansteenwegen, 2009). Complementing the findings obtained in neurological patients, the critical role of the amygdala in human fear conditioning has also been demonstrated in the healthy brain through the use of neuroimaging techniques. These studies have consistently shown amygdala activation during fear conditioning across different modalities (Phelps & LeDoux, 2005). In contrast to electrophysiological techniques, however, fMRI and PET cannot be used to investigate the latencies of these conditioned responses, due to their limited temporal resolution. Nonetheless, the use of so-called event-related paradigms in fMRI has enabled researchers to investigate the time course of amygdala responses across conditioning trials. Some of these studies (Buchel, Morris, Dolan, & Friston, 1998; LaBar, Gatenby, Gore, LeDoux, & Phelps, 1998) reported an enhanced amygdala response to the CS only at the beginning of the conditioning session, with its activity returning to baseline levels in the later stages of the procedure. This temporal pattern of amygdala activation appears to be consistent with the behavior of the transiently plastic cells in LAd described in single-unit recordings in rats. Unfortunately, the source of these activations cannot be localized to particular amygdala subnuclei, given the spatial resolution that is currently available with these neuroimaging methods (on the order of a few millimeters). Critically, amygdala activity seems to be specific to conditioning, as orienting or unconditioned SCRs are not associated with significant activity in this region (Knight, Nguyen, & Bandettini, 2005). In apparent contrast to animal studies, which showed that conditioning-induced responses in the amygdala are not necessarily related to explicit fear behavior (Goosens et al., 2003), a trial-by-trial analysis of fMRI responses revealed amygdala activation only for the trials in which a conditioned SCR was produced (Cheng, Knight, Smith, & Helmstetter, 2006). Conditioned fear responses to a CS can develop even without a direct experience of the US (Olsson & Phelps, 2007). Observational or vicarious fear conditioning has been reported in mice and monkeys when they watch a conspecific undergo an aversive experience, especially when the individuals are related. Similar findings have been reported in humans and shown to engage the amygdala. Moreover, conditioned responses, and amygdala activation, particularly in the left hemisphere, can be

generated through instructional fear conditioning, that is, by simply telling the individual about the CSUS contingency.

Perception of Emotional Expressions

In contrast to studies in experimental animals, particularly rodents, where fear conditioning has typically been the paradigm of choice to study emotional processing, humans studies have largely focused on the perception of stimuli with affective value and, in particular, emotional expressions. These are not only crucial for survival, as they serve to signal others the presence of danger or food, but they also are essential for social interactions. Importantly, several psychiatric disorders are associated with deficits in the recognition or expression of emotional expressions. Faces. In a highly influential study, Adolphs, Tranel, Damasio, and Damasio (1994) showed that patient SM, who has focal bilateral amygdala damage, was profoundly impaired in the recognition of fearful facial expressions, but was able to recognize other expressions such as anger, sadness, and happiness. Results from subsequent studies in other patients with bilateral or unilateral amygdala damage seem to support, at least in general terms, this initial finding, although they also point towards a large variability in the specific effects, possibly due in part to individual (Adolphs et al., 1999) and task-related (Siebert, Markowitsch, & Bartel, 2003) differences. Hundreds of neuroimaging studies have explored amygdala responses to emotional facial expressions. While the vast majority focused on fearful faces, a growing number has also investigated responses to other basic emotions, namely anger, happiness, disgust, and sadness, as well as some more subtle emotional expressions, such as contempt (Sambataro et al., 2006). Data from a recent quantitative meta-analysis of neuroimaging studies of visual emotional stimuli (Sergerie, Chochol, & Armony, 2008) confirmed that the amygdala responds not only to fearful faces, but to all the other basic emotions, without significant differences in magnitude among them (but see Fusar-Poli et al., 2009). These results contribute to a growing notion that, at least in humans, the amygdala may not be exclusively tuned to detect threat-related information. Furthermore, a few studies have reported that amygdala responses to emotionally neutral faces are modulated by their perceived level of trustworthiness. Specifically, amygdala activation increases linearly as a function of untrustworthiness (Winston, Strange, ODoherty, & Dolan, 2002). These imaging findings are consistent with a study showing that patients with bilateral amygdala damage tend to judge unfamiliar individuals as more approachable and trustworthy compared to healthy controls (Adolphs, Tranel, & Damasio, 1998), and in line with the notion that untrustworthy individuals could represent potential threat. However, a recent study suggests that amygdala response to face trustworthiness is in fact nonlinear; that is, not only does it respond to untrustworthy faces, but also to highly trustworthy ones (Said, Baron, & Todorov, 2009). In other words, the amygdala would respond to individuals who may warrant an action from the observereither approach, because they seem very trustworthy, or withdraw, in the opposite case.

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One question that has interested researchers is to what extent amygdala responses to facial expressions, particularly those of fear, are processed in an automatic fashion. Based on fear conditioning studies in rats (see above), it had been hypothesized that the amygdala should respond to threat-related stimuli regardless of whether or not they arise within the current focus of attention, or even when they are not consciously perceived. Some neuroimaging studies supported this hypothesis, as they showed amygdala activation in response to fearful stimuli presented without subjects awareness in healthy controls, using backward masking (Whalen et al., 1998), and in patients with blindsight (Morris, DeGelder, Weiskrantz, & Dolan, 2001) and hemispatial neglect (Vuilleumier et al., 2002). Similarly, amygdala responses to unattended fearful faces were reported in studies which manipulated spatial or object-based attention (Vuilleumier, 2009). However, other studies have challenged the view of an attention-independent response of the amygdala to threat stimuli (Pessoa, 2005). The putative attention-independent response of the amygdala has been shown to be modulated by individual differences such as anxiety and sex (Bishop, Duncan, & Lawrence, 2004; Dickie & Armony, 2008), an effect that could potentially help explain some of the conflicting findings. Furthermore, intracranial amygdala recordings in a patient with epilepsy revealed an enhanced, attention-independent response to fearful faces about 200 ms after stimulus onset, followed by a sustained response (~750 ms latency) which was modulated by attention (Pourtois, Spinelli, Seeck, & Vuilleumier, 2010). As the fMRI signal integrates neural information across a relatively large time window, it is possible that different contributions of these two components to the overall hemodynamic response could lead to differences in the observed modulatory effects of attention on emotion. Bodies. Several fMRI studies have shown that the amygdala also responds to body expressions of emotion. De Gelder (2006) reported amygdala responses to static body postures of fear, especially in the right hemisphere, whereas Grezes and coworkers showed amygdala activation associated with the presentation of dynamic body expressions of anger and fear (Pichon, de Gelder, & Grezes, 2009). Similar to faces, amygdala response to threat-related body expressions does not seem to be significantly modulated by selective attention (Pichon, de Gelder, & Grezes, 2012). However, in contrast to the case of faces, where activity is modulated by gaze direction (stronger for fearful faces with averted gaze and angry faces with direct gaze; NDiaye, Sander, & Vuilleumier, 2009; but see Adams, Gordon, Baird, Ambady, & Kleck, 2003), the magnitude of amygdala responses appears to be similar for dynamic body expressions of anger directed towards the perceiver or to someone else (Grezes, Adenis, Pouga, & Armony, in press). Vocalizations. As is the case with other animals, humans can also express emotions using their voice. Laughing, crying, and screaming are very efficient ways of conveying information about ones emotional state, as well as of informing others about relevant events that arise in the environment (Scherer, 1995).

They complement information relayed through other modalities, such as facial expressions and, in fact, they may be more efficient than the latter, as they do not require a direct line of view to be accurately decoded. However, despite their importance, they have been much less studied than human facial expressions and, to date, results have been mixed in terms of the involvement of the amygdala in their processing. For instance, studies in neurological patients have found both impaired (Dellacherie, Hasboun, Baulac, Belin, & Samson, 2011; Scott et al., 1997) and intact (Adolphs & Tranel, 1999; Anderson & Phelps, 1998) recognition of vocal expressions of fear in patients with amygdala lesions. Likewise, early neuroimaging studies of nonlinguistic emotional vocalizations yielded inconsistent findings in terms of amygdala activation, with both positive and negative results (for a review, see Armony & LeDoux, 2010). Given that emotional vocal expressions are as meaningful and biologically important as facial expressions, this inconsistency is puzzling, especially when contrasted with the findings from studies using facial expressions. Nonetheless, it is important to consider that previous vocalization studies used very different stimuli and paradigms, especially in terms of the control condition against which emotional vocalizations were compared. For example, activations associated with vocal expressions of emotion have been obtained by comparing them to mildly happy vocalizations (M. L. Phillips et al., 1998), voiced nasal sounds (Morris, Scott, & Dolan, 1999), silence (K. Sander & Scheich, 2001), and speech or nonvocal sounds (Meyer, Zysset, von Cramon, & Alter, 2005). This stands in contrast to the case of facial expressions, where hundreds of studies have been conducted using a fairly similar (or, in many cases, identical) stimulus set across studies (e.g., the Ekman set) and neutral faces as the control condition. The choice of control condition is particularly relevant, as the magnitude of the effects, and therefore whether it reaches the threshold of statistical significance, strongly depends on its choice (Sergerie et al., 2008). Furthermore, in most cases, the vocal stimuli used were quite long (~20 s) which may have had an influence on amygdala responses, given its rapid habituation rate. Indeed, an fMRI study comparing short emotional vocalizations to neutral ones, each produced by a different speaker, in a paradigm very similar to those used with visual stimuli, revealed bilateral amygdala activation to both positive (pleasure and laughter) and negative (fear and sadness) vocalizations (Fecteau, Belin, Joanette, & Armony, 2007). Interestingly, post hoc analyses revealed that the amygdala activation was equally driven by negative and positive vocalizations. In fact, responses in the right amygdala were stronger to positive than to negative vocalizations. Thus, as with facial expressions, there is growing evidence that the amygdala responds not only to auditory expressions of fear, but also to other emotions, including positive ones. Prosody. Humans can also convey auditory emotional information through language. Critically, speech can carry emotional information not only in the semantic content of the utterances (i.e., what is being said), but also in the modulation of intonation (i.e., how it is being said). Affective prosody refers to our ability to detect emotion in speech based on

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variations in pitch, loudness, and rhythm, regardless of the actual words being spoken. There is relatively little support for a specific involvement of the amygdala in decoding emotional prosody (Adolphs & Tranel, 1999; Anderson & Phelps, 1998; but see Scott et al., 1997). Likewise, the majority of neuroimaging studies have failed to report significant amygdala activity associated with emotional prosody recognition (Imaizumi, Mori, Kiritani, & Yumoto, 1997; Pourtois, de Gelder, Bol, & Crommelinck, 2005; Royet et al., 2000). Instead, studies in patients with focal brain lesions (Adolphs, Damasio, & Tranel, 2002) and neuroimaging experiments (Bruck, Kreifelts, & Wildgruber, 2011) suggest that recognition of emotional prosody depends on a distributed network of areas, mainly located within the (right) frontal and parietal lobes, as well as in the superior temporal gyrus and sulcus. However, amygdala activation, especially in response to angry prosody, has been recently reported (Fruhholz, Ceravolo, & Grandjean, 2012; D. Sander et al., 2005). However, some studies seem to suggest that, rather than responding to prosody per se, the amygdala responds to specific features of the stimuli, mainly related to frequency and energy (Fruhholz et al., 2012; Leitman et al., 2010), which differ across emotions and are important predictors of emotion recognition and categorization (Banse & Scherer, 1996; Juslin & Laukka, 2001). Music. Music constitutes another type of auditory emotional stimuli, one that is arguably uniquely human. It has been long recognized that music is a very effective way to express and induce emotional states. Whether emotional music constitutes an innate, biologically prepared stimulus class or instead is a result of culture and learning is still under debate. Nonetheless, there is strong evidence that emotions expressed by music are, at least to some degree, recognized across cultures (Peretz, Aub, & Armony, in press) and that they follow some specific rules, some of which may follow the patterns present in emotional prosody (Bowling, Sundararajan, Han, & Purves, 2012). For instance musical pieces in major modes typically express joy and excitement, whereas those in minor keys convey a feeling of gloom, despair, sorrow, grief (Heinlein, 1928, p. 102). Moreover, babies as young as 9 months of age can discriminate happy and sad music (Flom, Gentile, & Pick, 2008), further supporting the notion that emotional music recognition is innate, although learning cannot be ruled out (Saffran, Johnson, Aslin, & Newport, 1999). Initial, albeit indirect, evidence for a role of the amygdala in processing emotional music comes from a study by Blood and Zatorre (2001). They observed amygdala deactivation associated with the experience of chills (shivers down the spine) evoked by highly pleasant music. Other neuroimaging studies have also reported amygdala activation in response to unpleasant (dissonant) music compared to pleasant musical excerpts (Koelsch, Fritz, von Cramon, Muller, & Friederici, 2006), unpleasant and pleasant music compared to silence (Ball et al., 2007), and syntactically irregular, compared to regular, chord sequences (Koelsch, Fritz, & Schlaug, 2008). Amygdala activation has also been reported for sad, compared

to happy, music (Mitterschiffthaler, Fu, Dalton, Andrew, & Williams, 2007). Yet not all neuroimaging studies have reported significant amygdala activation to emotional music (for a review, see Peretz et al., in press). Given the variability in stimuli, tasks, and contrasts between studies (similar to the case of vocalizations discussed earlier), it is difficult to explain the discrepancy in the literature. One possible interpretation has been put forward by Koelsch (2010), namely that processing of emotion in music relies more on the (anterior) hippocampus than on the amygdala. The involvement of the medial temporal lobes (including the amygdala and/or hippocampus) in the processing of emotional music has also received some support from lesion studies, particularly in patients with temporal lobe resection due to epilepsy (Gosselin, Peretz, Hasboun, Baulac, & Samson, 2011; Khalfa, Roy, Rainville, Dalla Bella, & Peretz, 2008), although the findings here are also inconsistent (Dellacherie, Bigand, Molin, Baulac, & Samson, 2011). Intriguingly, although SM was able to recognize emotional vocalizations normally, she did show deficits in the recognition of fearful and sad music (Gosselin, Peretz, Johnsen, & Adolphs, 2007). In summary, while there is some evidence that the amygdala is involved in the processing of emotional music, results from lesion and neuroimaging studies are thus far inconclusive. In particular, it remains to be determined whether the amygdala responds to the actual emotional information carried by music or, as may also be the case with prosody, it detects certain acoustic parameters that are associated with specific musical emotions (e.g., frequency).

Novelty Detection
In addition to demonstrating the involvement of the amygdala in the processing of emotional stimuli, recent neuroimaging studies have highlighted its role in the detection of neutral novel stimuli, in particular those that have behavioral relevance. For instance, the amygdala was shown to respond to infrequent, emotionally neutral task-relevant visual (Ousdal et al., 2008) and auditory (Kiehl et al., 2005) stimuli more than to similar, but task-irrelevant, ones. However, in the latter study significant amygdala activation was also observed for the presentation of novel, behaviorally irrelevant, auditory stimuli, although the magnitude of this response was smaller than that corresponding to novel task-relevant stimuli (Kiehl et al., 2005). The involvement of the amygdala in the detection of novel stimuli, even when these have no explicit relevance, was further confirmed by Blackford, Buckholtz, Avery, and Zald (2010), who showed that both novel common and uncommon stimuli elicited significant activation in the amygdala and hippocampus, compared to familiar ones, but only the amygdala responded more strongly to unusual than common novel pictures. Finally, Herry et al. (2007) observed that unpredictability in the timing of neutral, behaviorally irrelevant, auditory temporal sequences increased activity in the amygdala in mice (measured by the expression of the immediate-early gene c-fos) and humans (using fMRI), which was associated with anxiety-like behavior. Importantly,

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although the authors in these last two studies attempted to statistically control for the nonspecific effects of arousal (the unusual or unpredictable stimuli were perceived as more arousing), it is not possible to completely rule out an influence of this variable in the observed amygdala activity.

conclusion
There is very strong experimental support for a crucial involvement of the amygdala in detecting and processing emotional information, both innate and learned. Whereas most studies confirm the importance of this structure in fear processing, they also showespecially through the use of neuroimaging techniques in humansthat the amygdala plays a role in processing other, including positive, emotions as well as stimuli that may not have an obvious survival value (e.g., music). These findings have led to several models regarding the specific function of the amygdala, beyond threat detection. Most of these posit a role of the amygdala in processing stimuli that have biological significance or are goal-relevant (e.g., D. Sander, Grafman, & Zalla, 2003). However, as described in the previous section, several studies have demonstrated a significant amygdala response to novel or uncommon stimuli even when these have no intrinsic or acquired emotional value and they are not task-relevant. Thus, the amygdala appears to respond to novel, unexpected stimuli, to which it rapidly habituates when these have no biologically or behaviorally relevant consequences. Thus, it would act as a novelty detector for stimuli with potential biological significance, responding more strongly and consistently to those with actual relevance.

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