Role of the amygdala in processing visual social stimuli

Anders, Ende, Jungho¨fer, Kissler & Wildgruber (Eds.) Progress in Brain Research, Vol. 156 ISSN 0079-6123 Copyright r 2006 Elsevier B.V. All rights reserved

CHAPTER 20

Role of the amygdala in processing visual social stimuli Ralph Adolphs and Michael Spezio Division of the Humanities and Social Sciences, HSS 228-77, California Institute of Technology, Pasadena, CA 91125, USA

Abstract: We review the evidence implicating the amygdala as a critical component of a neural network of social cognition, drawing especially on research involving the processing of faces and other visual social stimuli. We argue that, although it is clear that social behavioral representations are not stored in the amygdala, the most parsimonious interpretation of the data is that the amygdala plays a role in guiding social behaviors on the basis of socioenvironmental context. Thus, it appears to be required for normal social cognition. We propose that the amygdala plays this role by attentionally modulating several areas of visual and somatosensory cortex that have been implicated in social cognition, and in helping to direct overt visuospatial attention in face gaze. We also hypothesize that the amygdala exerts attentional modulation of simulation in somatosensory cortices such as supramarginal gyrus and insula. Finally, we argue that the term emotion be broadened to include increased attention to bodily responses and their representation in cortex. Keywords: amygdala; face processing; simulation; lesion studies; social cognition; emotion severely limit a primate’s range of social responses, perhaps going so far as to eliminate some part or all of the social repertoire altogether. More recent findings challenge the view that the amygdala is required for basic social behaviors. Yet the question remains open whether the amygdala is a required component for normal social cognition. For example, is the amygdala necessary for the normal information processing associated with an organism’s evaluation of a visual social stimulus, such as a facial expression (on which subsequent behaviors could then be based)? We will see that an answer to this question depends on a new consideration of evidence for the amygdala’s role. The view we will present takes into consideration evidence regarding the amygdala’s role in modulating autonomic arousal, new evidence regarding the amygdala’s potential to affect visuospatial and visual objectbased attention, and recent accounts that explain

Introduction The amygdala has long been implicated in primate social cognition and behavior, due primarily to the well-known work by Kluver and Bucy (1939) and the studies by Kling and colleagues (Dicks et al., 1968; Kling, 1968, 1974; Kling et al., 1970, 1979; Brothers et al., 1990). An influential view of the amygdala emerging from early studies of its function was that it acts as a generative locus of social cognition and behavior, required to link the perception of any stimuli to information about their value to an organism (Weiskrantz, 1956). One interpretation of this view is that the amygdala is a primary source of social behavior, and the lack of a functioning amygdala would be expected to Corresponding author. Tel.: +1-626-395-4486; Fax: +1-626-793-8580; E-mail: [email protected] DOI: 10.1016/S0079-6123(06)56020-0

363

364

social cognition in terms of simulation theory. These newer developments have posed something of a puzzle for older theories of the amygdala. We will review some older findings first, and the framework that was based on them. Then we will introduce the new findings and framework, and end by proposing a framework describing the amygdala’s function in recognizing the social value of stimuli.

Shifting views of the amygdala in social cognition Studies of the primate amygdala began in the 1930s with Kluver and Bucy’s well-known experiments in monkeys (Kluver and Bucy, 1937, 1997). Following large bitemporal lesions that encompassed the amygdala, the animals came to exhibit a constellation of impairments in recognizing the emotional and social meaning of stimuli—the so-called ‘‘psychic blindness’’ of Kluver–Bucy syndrome. Notably, the monkeys became exceptionally tame and placid, a behavioral abnormality that has been replicated to some degree in later studies (Emery et al., 2001; Kalin et al., 2001, 2004; Izquierdo et al., 2005). The animals also exhibited a variety of other unusual behaviors, including hypermetamorphosis and hypersexuality that have not been so reliably replicated. Modern-day studies using selective neurotoxins to lesion the amygdala, sparing surrounding tissues, not surprisingly provide a much more muted and selective picture. Such selective lesions, like the earlier lesions, do result in the lack of a normal ‘‘brake’’ on behavior, and the animals tend to approach objects and situations that normal monkeys would avoid—they are also seldom regarded as dominant by other monkeys (Meunier et al., 1999; Emery et al., 2001). Yet the selective amygdala lesions do not produce monkeys that exhibit the array of unusual behavior as Kluver and Bucy described. The recent lesion studies in monkeys have also begun to highlight how complex the role of the amygdala in regulating social behavior is likely to be. The consequences of amygdala lesions are quite different depending on the age at which they are made, and infant monkeys with amygdala lesions actually show exaggerated social fear responses

rather than the placidity that tends to be seen in adults (Prather et al., 2001; Bauman et al., 2004b). Furthermore, there are notable differences between (the relatively small number of) different studies of how amygdala lesions in monkeys affect basic social behaviors such as canonical facial expressions, bodily postures (e.g., ‘‘present groom’’), and attachment behaviors. These differences between studies likely reflect effects of additional factors such as lesion methodology and extent, lab- vs. wild rearing, or the exact species used (Bachevalier and Loveland, 2006). For example, there is evidence suggesting that amygdala lesions profoundly impair even basic social behaviors in monkeys (Bachevalier et al., 1999; Meunier et al., 1999; Meunier and Bachevalier, 2002). Amaral and colleagues, however, found no impairment in basic social behaviors following selective neurotoxic amygdala lesions, though they did find impairments in the appropriate deployment of these social behaviors (Bauman et al., 2004a, b). Given this heterogeneity, it has been argued that the amygdala is not required for monkeys to show the full repertoire of social behaviors, because under some circumstances animals with complete bilateral amygdala lesions, nevertheless, can show all the components of emotional and social behaviors that normal monkeys would show (Amaral et al., 2003a), even if they are deployed abnormally (Bauman et al., 2004a). The most parsimonious interpretation of the data thus far is rather that the amygdala plays a role in guiding social behaviors on the basis of the socioenvironmental context with which an animal is faced. It is important to keep in mind that the socioenvironmental context is likely to include not only what is available to the monkey in the immediate circumstance, but also information that has been neurally encoded throughout development as the monkey has learned and adapted to the surrounding world. Here we see a shift in viewpoint from the amygdala as a structure that itself stores and activates patterns of basic social behaviors to one in which the amygdala plays an influential role in the deployment of these behaviors. This view predicts that primates lacking a functional amygdala retain the ability to display the full range of basic social behaviors while being impaired in the appropriate context-dependent

365

deployment of these behaviors and of more complex social behaviors. The idea is similar to the difference between a novice chess player who knows how each piece moves and even several useful openings and a grand master who can rapidly choose the appropriate move among a myriad of options. This shift in understanding of the amygdala’s role in social cognition to some extent parallels debates regarding the amygdala’s role in certain forms of memory. As with social behavior, declarative memory is not stored in the amygdala as such, but is influenced by the amygdala’s processing and projection into other structures, such as the hippocampus in the case of memory (McGaugh, 2004). As we will see below, this new framework of the amygdala’s role in social cognition is supported by a number of studies showing that the amygdala influences the evaluation of stimuli in contributing to the perception, recognition, and judgment of socially relevant stimuli.

Impaired social cognition in humans following amygdala damage While the amygdala has been implicated in monkey social behavior for some time, it is only very recently that such a role has been established in humans, and that detailed hypotheses have been investigated regarding the underlying mechanisms. Here, we review evidence that the amygdala has a role in the recognition of emotion from faces, in interpreting eye gaze, and in more complex social judgments in humans. Two early studies showed that bilateral damage confined mainly to the amygdala resulted in a disproportionately severe impairment in the ability to recognize fear from facial expressions (Adolphs et al., 1994; Young et al., 1995). One patient in particular, SM, had damage that was relatively restricted to the amygdala (Fig. 1A–C), and an impairment that was very specific to the recognition of fear (Adolphs et al., 2000). SM’s lesion encompassed the entire amygdala bilaterally and extended also into anterior portions of the entorhinal cortex; there was no damage evident to any other structures. When shown standardized emotional facial expressions that depicted the six ‘‘basic’’ emotions

(happiness, surprise, fear, anger, disgust, and sadness), SM was insensitive to the intensity of the emotion shown in fear, but not in other expressions (Fig. 1D) (Adolphs et al., 1994). The specificity to fear was confirmed using morphs (linear blends) between the different emotions: the closer to the fear prototype the emotional expressions were, the more impaired SM’s recognition became. The impairment was all the more striking because she was able to recognize other kinds of information from fearful faces normally (such as judging their gender, age, or identity), and because she was able to discriminate the faces normally when presented pairwise (on same/different judgments). When shown an expression of fear and asked in an unconstrained task simply to name the emotion, she typically replied that she did not know what the emotion was. If forced, she would often mistake fear for surprise, anger, or sadness (but never happiness). SM’s impaired recognition of fear was followed up in a series of studies that showed that SM does have at least some components of the concept of fear, because she can use the word relatively appropriately in conversation, she believes she knows what fear is, and she can in fact retrieve many facts about fear (such that being confronted with a bear would make one afraid, etc.) (Adolphs et al., 1995). While the amygdala’s role in recognizing fear in other sensory modalities remains unclear, in SM’s case she was even able to recognize fear from tone of voice (prosody) normally (Adolphs and Tranel, 1999). But she could not recognize it from the face, nor could she generate an image of the facial expression when given the name (e.g., when asked to draw it) (Adolphs et al., 1995). The impaired recognition of fear thus seemed to be relatively specific to the facial expression—the use of other visual information, such as context and body posture, was less compromised. In fact, adding facial expressions to scenes initially devoid of faces decreased the accuracy of emotion recognition in subjects with bilateral amygdala damage, whereas it increased it in healthy subjects (Adolphs and Tranel, 2003). Several studies have followed up these initial findings. Other lesion studies have found impaired recognition of fear from facial expressions following bilateral amygdala damage (Calder et al., 1996;

366

Fig. 1. Bilateral amygdala lesions impair recognition of emotion from faces. There are two structural MRI slices (A) showing intact hippocampus (B) and bilateral amygdala lesion (C) for SM. SM’s ratings of the degree to which a face expressed a particular emotion are shown in (D) (SM: closed triangles; controls: open circles) and the correlation between SM’s ratings and normal ratings is shown in (E) for each facial expression. From Adolphs et al. (1994).

367

Broks et al., 1998; Adolphs et al., 1999b), and functional imaging studies have found activation of the amygdala when subjects view fearful faces (Breiter et al., 1996; Morris et al., 1996; Whalen et al., 2001). However, the findings are not as specific as in the case of SM. Several lesion subjects with complete bilateral amygdala damage were impaired also on emotions other than fear (always negatively valenced emotions) (Adolphs et al., 1999b), and in several cases their impairment in recognizing anger, disgust, or sadness was more severe than their impairment in recognizing fear. Similarly, functional imaging studies found activation of the amygdala to expressions other than fear, such as happiness (Canli et al., 2002; Williams et al., 2005), surprise (Kim et al., 2004), sadness (Wang et al., 2005), and anger (Whalen et al., 2001). A further function of the amygdala in processing aspects of faces comes from studies of its role in processing the eyes in a face. The eyes and their direction of gaze are key social signals in many species (Emery, 2000), especially apes and humans, whose white sclera makes the pupil more easily visible and permits better discrimination of gaze. Eyes signal important information about emotional states, and there is evidence from functional imaging studies that at least some of this processing recruits the amygdala (Baron-Cohen et al., 1999; Kawashima et al., 1999; Wicker et al., 2003b). The amygdala’s involvement in processing gaze direction in emotional faces has been explored recently. It was found that direct gaze facilitated amygdala activation in response to approach-oriented emotions such as anger, whereas averted gaze facilitated amygdala activation to avoidance-oriented emotions such as fear (Adams and Kleck, 2003). Further, the amygdala has been found to be active during monitoring for direct gaze (Hooker et al., 2003). The amygdala’s role is not limited to making judgments about basic emotions, but includes a role in making social judgments, as well. This function was already suggested by earlier studies in nonhuman primates (Kluver and Bucy, 1937; Rosvold et al., 1954; Brothers et al., 1990; Kling and Brothers, 1992), which demonstrated impaired social behavior following amygdala damage and amygdala responses to complex social stimuli. They have been corroborated in recent times by studies in monkeys

with more selective amygdala lesions, and by using more sophisticated ways of assessing social behavior (Emery and Amaral, 1999; Emery et al., 2001), and consistent findings have been shown now also in humans. We have found that the amygdala is important for judging complex mental states and social emotions from faces (Adolphs et al., 2002), and for judging the trustworthiness of people from viewing their face (Adolphs et al., 1998; Winston et al., 2002). Relatedly, the amygdala shows differential habituation of activation to faces of people of another race (Hart et al., 2000), and amygdala activation has been found to correlate with race stereotypes of which the viewer may be unaware (Phelps et al., 2000). On the basis of these findings, some recent studies suggest a general role for the amygdala in so-called ‘‘theory of mind’’ abilities: the collection of abilities whereby we attribute internal mental states, intentions, desires, and emotions to other people (Baron-Cohen et al., 2000; Fine et al., 2001). Various theories have been put forth to account for some of these findings, some proposing that the amygdala is specialized for recognition of emotions that are high in arousal (Adolphs et al., 1999a), or that relate to withdrawal (Anderson et al., 2000), or that require disambiguation (Whalen, 1999). It is fair to say that, at present, there is no single accepted scheme to explain which emotion categories are affected by amygdala damage. These differences notwithstanding, we can identify a general framework for understanding the mechanisms by which the amygdala normally contributes to emotion judgment and social cognition. The framework is built upon (1) recent work showing (a) the amygdala’s ability to influence visual processing at early stages, and (b) the amygdala’s role in influencing overt attention to the eyes in a face; (2) the amygdala’s role in autonomic arousal; and (3) work implicating the pulvinar and Brodmann area 40 (SII) in the processing of affectively aversive visual stimuli. Each of these elements is supported by evidence from neuroanatomical studies of the internal and external connectivity of the amygdala. Our current neuroanatomical understanding of the amygdala, which consists of a number of separate nuclei in primates (Price, 2003), supports a scheme whereby faces are associated

368

with their emotional meaning in the lateral and basolateral nuclei, in interaction with additional brain structures such as orbitofrontal and medial prefrontal cortices (Ghashghaei and Barbas, 2002). This evaluation is conveyed to central and basomedial amygdala nuclei whose projections then influence processing in visual cortex, processing that elicits autonomic and motor responses in the body (Price, 2003), and/or processing that involves somatosensory areas putatively involved in simulation-based transformations of the visual percept to an internal bodily representation (Gallese et al., 2004; Rizzolatti and Craighero, 2004; see also Keysers and Gazzola, this volume). We will consider each of these aspects of the amygdala’s function in social cognition.

The amygdala influences early visual processing of faces and affective stimuli There is abundant data regarding the cortical processing of faces, and such cortical processing presumably can serve to provide highly processed input to the amygdala. To briefly review this, functional magnetic resonance imaging (fMRI) studies have revealed an array of higher order visual cortical regions that are engaged in face processing, including the fusiform face area (FFA) in the fusiform gyrus, the face-sensitive area in the superior temporal sulcus (STS), and superior and middle temporal gyrus (Kanwisher et al., 1997; McCarthy, 1999; Haxby et al., 2000). The STS in particular has been implicated in the detection of gaze direction in humans and nonhuman primates (Campbell et al., 1990; Puce et al., 1998; Wicker et al., 1998, 2003b; Calder et al., 2002; Hooker et al., 2003; Pourtois et al., 2004). A distributed array of visually responsive regions in the temporal lobe appears to encode classes of biologically salient objects, notably faces and bodies, in humans (Downing et al., 2001; Haxby et al., 2001; Spiridon and Kanwisher, 2002) as in monkeys (Pinsk et al., 2005). Regions in the superior temporal lobe appear specialized to process biological motion stimuli, such as point-light displays of people (Haxby et al., 2000; Grossman and Blake, 2002). It has been generally supposed that

higher order cortices in temporal lobe first encode the visual properties of socially relevant stimuli, and that this information is then subsequently passed to neurons within the ventromedial prefrontal cortex and the amygdala that associate the visual percept with its emotional meaning. This standard view of a strong feedforward input to the amygdala, one in which visual cortices in the temporal lobe comprise a series of visual processing stages the later components of which feed into the amygdala, is now being modified. Accumulating evidence strongly supports the notion that the amygdala can directly influence visual processing, even at very early stages. Recent anatomical studies show that the amygdala projects topographically to the ventral visual stream, from rostral temporal cortical area TE to caudal primary visual cortex (V1) (Amaral et al., 2003b). A majority of projections from the basal nucleus to V1 and TE colocalize with synaptophysin, suggesting that the amygdala can exert direct influence on synaptic associations at multiple stages of primary and object-based visual processing (Freese and Amaral, 2005). Such direct influence on cortical visual processing may be a later evolutionary adaptation, as these anatomical projections have not been reported in rats and cats (Price, 2003). Through this architecture in primates, the amygdala can link the perception of stimuli to an emotional response, and then subsequently modulate cognition on the basis of the value of the perceived stimulus (Amaral and Insausti, 1992; Adolphs, 2002). Thus, perception and evaluation of faces are closely intertwined. Functional neuroimaging in humans indicates that these structural pathways from the amygdala to visual areas are put to use in social cognition, specifically in the modulation of attention. Activation in the amygdala has been shown to predict extrastriate cortex activation specific to fearful facial expressions (Morris et al., 1998a). Lesions of the amygdala eliminate facial expression-specific activations in occipital and fusiform cortices (Vuilleumier et al., 2004). Such findings are consistent with the dependence of visual processing on prior amygdala processing of visual information, in a manner specific to the information’s associated value for the organism. Even more striking is evidence from single unit studies of face-selective neurons in TE and

369

STS of macaque monkeys (Sugase et al., 1999). These neurons discriminate between faces and objects about 50 ms faster than they discriminate between facial expressions, which is enough time for the action of projections from the amygdala. Expression-dependent activity in these neurons occurs within 150 ms following stimulus onset, consistent with the notion that input from the amygdala occurs early in visual processing. Clearly, rapid input of visual information to the amygdala is required for the amygdala to exert an expression-dependent influence on the ventral visual system prior to the observed expression-dependent activity in the latter system. The medial nucleus of the pulvinar complex provides such a pathway, as it forms a strong projection to the lateral and basolateral nuclei of the amygdala in macaque monkeys (Jones and Burton, 1976; Aggleton et al., 1980; Romanski et al., 1997). There is now evidence that these connections exist and are functionally active in humans. In healthy controls, masked facial stimuli activate the amygdala in the absence of awareness (Ohman, 2005), together with activation of the superior colliculus and the pulvinar (Liddell et al., 2005). Functional connectivity of the right amygdala with the right pulvinar and superior colliculus increases, and connectivity with fusiform and orbitofrontal cortices decreases, during subliminal presentation of fear-conditioned faces (Morris et al., 1998b, 1999). The left amygdala shows no masking-dependent changes in connectivity. A patient with blindsight (i.e., residual visual capacity without perceptual awareness) in the right cortical field nevertheless showed preserved ability to guess correctly the identity of facial expressions presented to his blind hemifield (de Gelder et al., 1999). Both fearful and fear-conditioned faces presented to the blind hemifield increased the functional connectivity between the right amygdala, superior colliculus, and posterior thalamus (i.e., the pulvinar) (Morris et al., 2001). A recent study of a patient with total cortical blindness (i.e., destruction of bilateral visual cortices) found that the patient could correctly guess the facial expression of a displayed face, but could not guess the identity of other stimuli, i.e., emotional or not (Pegna et al., 2005). The right but not the left amygdala in this patient showed expression-dependent activation,

consistent with evidence from neuroimaging of subliminal processing of faces in healthy controls (Morris et al., 1998b). Further evidence supporting the involvement of a pulvinar–amygdala–inferotemporal pathway in the rapid visual processing of emotional stimuli comes from a patient who sustained a complete and focal loss of the left pulvinar (Ward et al., 2005). In a paradigm designed to measure how threatening images interfere with a goal-directed task, the patient’s behavior indicated that the threatening images interfered with subsequent color identification of a single letter (‘‘O’’) when the images were presented to the ipsilesional field, but no interference was observed when the threatening images were presented to the contralesional field. Interference by images in the contralesional field returned if they were displayed for a relatively long time (600 ms vs. 300 ms). In light of the evidence presented here, it appears that the pulvinar–amygdala pathway is required for the extremely rapid processing of threat, and is capable of using the results of this processing to influence visual perception in primary and higher visual cortices.

The amygdala influences face gaze In addition to influencing visual processing even at very early stages, recent evidence suggests that the amygdala affects face gaze in a surprisingly direct manner (Adolphs et al., 2005). This is consistent with the amygdala’s influence on visual processing and with previous work showing that the amygdala affects visual and visuospatial attention. Lesions of the amygdala, particularly of the left amygdala, seriously impair the attentional benefit in the perception of aversive words during an attentional blink paradigm involving rapid stimulus presentation and target detection (Anderson and Phelps, 2001). Emotional facial expressions and aversive nonfacial stimuli overcome attentional deficits in patients showing neglect due to right parietal lesions (Vuilleumier and Schwartz, 2001a, b). It is likely that the latter finding is the result of exogenous attentional modulation by the amygdala in visual cortex and perhaps in visually responsive prefrontal cortex. Recall that the amygdala is required for facial expression-specific activation of early visual cortex (Vuilleumier et al.,

370

2004), evidence that fits well within an understanding of the amygdala as part of an attentional network responsive to visual stimuli having value for an organism. We have seen that the amygdala influences information processing in visual cortices and that it is strongly implicated in attention to evaluatively salient stimuli. It is possible, then, that the amygdala plays a role, via its projections to visual cortex particularly, in directing overt attention during the exploration of a face in social judgment. Face gaze, that is, might be dependent on evaluative processing within the amygdala. More specifically, in light of the evidence that the amygdala is sensitive to gaze direction in a face, it is likely that an attentional role for the amygdala would include directing gaze to the eyes in a face. Indeed, a recent study of face gaze in a patient with bilateral amygdala damage supports this view (Adolphs et al., 2005). The study tested a patient (SM) with complete and focal bilateral amygdala lesions during emotion judgment, measuring both face gaze and the use of facial information. To understand SM’s use of facial information during a simple emotion judgment, the study used the Bubbles technique and compared the result with those obtained from typical, agematched controls. SM displayed a marked reduction impairment of the ability to use the eyes in a face, compared to controls (Fig. 2A–D). Subsequent investigation of SM’s face gaze using eyetracking revealed a near absence of gaze to the eyes during visual exploration of faces (Fig. 2E–G). When SM was instructed to look only at the eyes while making emotion judgments from faces (Fig. 2H), performance in recognizing fear returned to normal (Fig. 2I). Yet this remarkable recovery in emotion judgment was not sustained once SM went back to nondirected, free viewing of faces. These results provide the first evidence showing a requirement for the amygdala in direct eye gaze, extending our understanding of the amygdala’s influential role in visuospatial attention to faces during social judgment. In keeping with the new view of the amygdala described in the section ‘‘Shifting views of the amygdala in social cognition,’’ these findings support the notion that the amygdala is a crucial component of normal social cognition, while not

being required for basic social behaviors. SM clearly displayed direct eye gaze after being instructed to do so, and was even able to use the information that direct eye gaze provided to fully recover her recognition of fear faces. An absence of a functioning amygdala thus does not result in a loss of the ability to engage in the social behavior of direct eye gaze. However, the amygdala is required for the appropriate deployment of this social behavior via its processing of socioenvironmental context and its influence on visual attentional systems involved in social cognition. We will see this theme reappear in relation to the amygdala’s role in autonomic arousal to facial expressions and in visuosomatosensoric processing of facial expressions of emotion.

The amygdala mediates autonomic arousal elicited by faces The human amygdala was originally thought to have a key role in the generation of normal autonomic responses associated with orienting and arousal due to studies of amygdalectomized monkeys (Bagshaw and Benzies, 1968; Bagshaw and Coppock, 1968; Pribram et al., 1979). Monkeys with bilateral amygdalectomies fail to produce the expected changes in skin conductance response (SCR), heart rate, and respiratory rate in response to irregularly repeated sounds, while ear movements to the sounds are normal (Bagshaw and Benzies, 1968). Further, these animals show no Pavlovian conditioning of SCR when a conditioned stimulus is paired with electrical stimulation to the skin (Bagshaw and Coppock, 1968; Pribram et al., 1979), although they do show normal SCR in response to the unconditioned stimulus (Bagshaw and Coppock, 1968). However, in humans, amygdala lesions appear not to affect orienting SCRs (Tranel and Damasio, 1989), while severely impairing Pavlovian conditioning of SCRs (Bechara et al., 1995). It is therefore the linking of a conditioned stimulus with an unconditioned stimulus and its associated autonomic response that requires the amygdala, and not the generation of the autonomic response, associated with orienting or otherwise.

371

Fig. 2. Bilateral amygdala lesions impair the use of the eyes and gaze to the eyes during emotion judgment. Using the Bubbles method (see Adolphs et al., 2005) to identify face areas used during emotion judgment, SM (B) differed from controls (A), such that controls exhibited much greater use of the eyes (C) than SM, while SM did not rely more on any area of the face than did controls (D). While looking at whole faces, SM exhibited abnormal face gaze (E), making far fewer fixations to the eyes than did controls. This was observed across emotions (F) and across tasks (G; free viewing, emotion judgment, gender discrimination). When SM was instructed to look at the eyes (I, ‘‘SM eyes’’) in a whole face, she could do this (H), resulting in a remarkable recovery in ability to recognize the facial expression of fear (I).

Neuroimaging studies of classical conditioning are consistent with the work using the lesion method. In an analysis contrasting SCR+ trials with SCR- trials in an orienting paradigm, activations occurred in the hippocampus, anterior cingulate, and ventromedial prefrontal cortex, but not

in the amygdala, while they found increased activation in the amygdala only with conditioned SCR (Williams et al., 2000; Knight et al., 2005). A study of SCR in several different cognitive/behavioral tasks found that SCR covaries with activation in ventromedial prefrontal cortex (Brodmann 10/32),

372

supramarginal gyrus (Brodmann 40), cingulomotor cortex (Brodmann 6/24), posterior cingulate cortex (Brodmann 23/30), right cerebellum, and thalamus (Patterson et al., 2002). More recently, in a study of the neural systems underlying arousal and SCR elicited by static images, the brain area that most closely associated with SCR variability was the ventromedial prefrontal cortex (Anders et al., 2004). These findings are consistent with what was seen using the lesion method and support the notion that the amygdala is not required for SCR. Facial images are conditioned with an aversive unconditioned stimulus; however, fMRI reveals CS+ specific activations in the anterior cingulate, anterior insula, and bilateral amygdala (Buchel et al., 1998), suggesting a role for the amygdala in evaluative associations. Such influence of the amygdala in evaluative assessment is supported by evidence implicating the right amygdala in the generation of SCR in response to emotionally arousing visual stimuli (Glascher and Adolphs, 2003). Lesions of the right temporal lobe and bilateral temporal area, including lesions to the amygdala, impaired normal SCRs to nonfacial stimuli that were emotionally arousing. Further, when SCR is used to partition recorded amygdala activation in a fearful vs. neutral face contrast, no expression-dependent difference in amygdala activation is seen unless an associated SCR is observed (Williams et al., 2001). Again, this is consistent with an evaluative function of the amygdala, this time directly in relation to facial expressions of emotion. Here is another example of how a function that was once held to be dependent directly on the amygdala, namely SCR, is actually influenced by the action of the amygdala without actually requiring the amygdala. Rather, the amygdala evaluates the socioenvironmental context and influences the deployment of SCR in an appropriate manner, either for learning in a classical conditioning paradigm or for normal evaluation of visual stimuli such as faces. It is likely that this action is dependent on the central nucleus of the amygdala (Price and Amaral, 1981; Price, 2003), though it is also possible that projections from the basal nucleus of the amygdala to the ventromedial prefrontal cortex and cingulate cortex and from

the basomedial nucleus to the insula influence these nuclei that appear crucial to the generating of SCR (Amaral and Price, 1984).

The amygdala and simulation: somatosensory attention as a component of emotional response to faces in social judgment So far, we have seen that the amygdala acts to influence key components of object-based visual processing, visuospatial attention, and autonomic responses during the processing of facial expressions in social judgment. One important component of emotion judgment not yet addressed in this scheme is systems that have been implicated by simulation theoretic approaches to social cognition (Gallese et al., 2004; Rizzolatti and Craighero, 2004, see also Keysers and Gazzola, this volume). We will briefly outline a proposal for the amygdala’s action on this system, which we view as primarily being one of somatosensory attention. Attentional modulation of the somatosensory cortices by the amygdala, we propose, involves several aspects analogous to attentional modulation in other contexts. First, the amygdala’s action could increase the sensitivity of somatosensory cortices to the signals received from the body. Second, amygdala inputs could enhance selectivity of inputs to, activity within, and outputs from somatosensory cortices. Finally, past associations established within these cortices may be reactivated so as to facilitate neural traces having resulted from previous learning. In sum, we are extending the amygdala’s role in emotional response from its important and well-established role as facilitating bodily responses to emotional stimuli (Damasio, 1996) to a role in modulating the cortical processing of those responses via somatosensory attentional mechanisms. This move implies that emotion may be understood as being both increased autonomic responses (i.e., the ‘‘body’’ loop) and stored cortical representations of those responses (the ‘‘as-if’’ loop), as well as increased attention to those responses and their representation in cortex. On this view, emotion, at least in part, is attentional modulation of those neural systems dedicated to processing somatosensory signals, serving to

373

establish the value of a particular socioenvironmental context for an organism. Several lines of evidence now point to the involvement of somatosensory cortices in the judgment of emotion from faces. Bilateral lesions of the insula completely abolish the ability to judge the emotion of disgust from static and dynamic facial displays (Calder et al., 2000; Adolphs et al., 2003). Such lesions also appear to abolish the ability to be disgusted by nonfood items that are widely recognized as disgusting. Consistent with the lesion data, neuroimaging reveals activation of the insula when observing dynamic displays of facial disgust (Wicker et al., 2003a). Lesions of the right somatosensory areas, particularly including the supramarginal gyrus (SMG; Brodmann 40), seriously impair judging emotion from faces (Adolphs et al., 1996, 2000) and from bodily motion conveyed in point-light displays (Heberlein et al., 2004). Again, neuroimaging data are consistent with the idea that SII is important for judging emotion from faces (Winston et al., 2003). Looking at dynamic displays of smiling activates areas such as SII in the right hemisphere, including regions within the supramarginal gyrus and left anterior insula, and these areas are also activated when smiling (Hennenlotter et al., 2005). The ventral amygdala is found to be activated only during observation, however. The pivotal role in judging facial emotion suspected to be played by the supramarginal gyrus is intriguing in light of its evolutionary homology to area 7b in macaque monkeys (Rizzolatti and Craighero, 2004). Area 7b is a cortical region with facial haptic neurons whose haptic spatial receptive fields and preferred directions of haptic stimulation overlap considerably with their visuospatial receptive fields and preferred directions of movement in the visual field (Duhamel et al., 1998). Most importantly, neurons in 7b exhibit mirror neuron-like qualities in single unit recordings (Rizzolatti and Craighero, 2004). In the monkey, there are several neuroanatomical pathways that could permit the amygdala to act on somatosensory cortices such as SMG and insula in a way similar to that described at the beginning of this section. The basal and basomedial nuclei of the amygdala project lightly and directly to area 7 of the

monkey parietal cortex (Amaral and Price, 1984). Moreover, the medial division of the pulvinar projects strongly to area 7b along with other areas in the parietal cortex (Mesulam et al., 1977; Romanski et al., 1997), and it is known that the central nucleus of the amygdala projects back to the medial pulvinar, the same nucleus that conveys rapid visual input to the amygdala (Price and Amaral, 1981). It is plausible, then, that the amygdala acts on SMG via the pulvinar, as well as by its direct projections. The amygdala also projects heavily into the insula region (Amaral and Price, 1984), an area strongly implicated in simulation-based processing of facial emotion and in the representation of emotion (Adolphs et al., 2003; Wicker et al., 2003a). It is thus more likely in the case of the insula than in the case of the SMG that the amygdala acts directly via its many projections from basal and basomedial nuclei into this cortical region. The proposal here regarding the amygdala’s possible role in attentionally modulating somatosensory cortices is consistent with what is established by the evidence reviewed in the previous two sections. It is not likely, in other words, that the amygdala itself is a locus of simulation. Rather, it is much more plausible that it interprets the socioenvironmental context and then affects simulation networks such as may inhabit the somatosensory cortices detailed here. Two brief points might be made before moving on to a summary of the current view of the amygdala’s function in judging emotions from faces and other visual social stimuli. One is that evidence from neuroimaging experiments and single unit studies is required in order to test the framework detailed here. Use of dynamic causal modeling or Granger causality, for example, in the analysis of fMRI data would help discern whether amygdala activation precedes and predicts activation in SMG and insula. The second point is a more general one regarding the relation of amygdala activation to emotional experience and pathology. It is simply this: the amygdala likely is not itself a generator of such experience, either in healthy persons or in emotional disturbance, a view consistent with data from some amygdala lesion patients (Anderson and Phelps, 2002). Instead, the amygdala helps to control attention

374

inward, i.e., toward the body and encoded emotional associations. Malfunction in these inward attention networks could very likely yield the kind of negatively valent ideation and sensations often accompanying mental illness. The new model for how the amygdala contributes to the recognition of emotion from visual social stimuli We are now able to articulate a coherent view of the amygdala’s action in judging emotion from a face. The story proceeds like this (Fig. 3): visual input to the amygdala, which can occur very rapidly via the pulvinar, results in initial modulation of subsequent visual inputs from visual cortex. Attentional modulation of somatosensory (i.e., putative simulation) cortex occurs so as to increase sensitivity to and selectivity for bodily responses and encoded emotional associations. Modulation of temporal visual cortex by the amygdala may, via coarse visuospatial coding in these neurons, influence the dorsal ‘‘where’’ stream so as to direct visuospatial attention to emotionally salient features (e.g., the eyes in a face). Richer visual input

from object-selective visual cortex soon follows; and this, together with input from other areas, leads to the generation of autonomic responses via action by the central nucleus. Each of these steps casts the amygdala as an important (attentional) modulator of neural systems, and a key aspect of the proposal here is the amygdala’s influence on simulation systems. Importantly, each element in this new framework of the amygdala’s function is supported with empirical data. Moreover, the connection between amygdala processing and simulation networks is supported by anatomical detail, though the functional relevance of this connectivity has yet to be clearly established. A more complete functional understanding of this relationship is sure to come given the evident energy and productivity of research into these networks of social cognition. Acknowledgments The authors thank Fred Gosselin and Dirk Neumann for helpful discussions. This work was supported by grants from the National Institute of

Fig. 3. Schematic of the proposed action of the amygdala in attentionally modulating visual and somatosensory cortical areas either directly or via projections to the pulvinar.

375

Mental Health, the Cure Autism New Foundation, and the Pfeiffer Research Foundation.

References Adams Jr., R.B., Gordon, H.L., Baird, A.A., Ambady, N. and Kleck, R.E. (2003) Effects of gaze on amygdala sensitivity to anger and fear faces. Science, 300: 1536. Adams Jr., R.B. and Kleck, R.E. (2003) Perceived gaze direction and the processing of facial displays of emotion. Psychol. Sci., 14: 644–647. Adolphs, R. (2002) Recognizing emotion from facial expressions: psychological and neurological mechanisms. Behav. Cogn. Neurosci. Rev., 1: 21–61. Adolphs, R., Baron-Cohen, S. and Tranel, D. (2002) Impaired recognition of social emotions following amygdala damage. J. Cogn. Neurosci., 14: 1264–1274. Adolphs, R., Damasio, H., Tranel, D., Cooper, G. and Damasio, A.R. (2000) A role for somatosensory cortices in the visual recognition of emotion as revealed by three-dimensional lesion mapping. J. Neurosci., 20: 2683–2690. Adolphs, R., Damasio, H., Tranel, D. and Damasio, A.R. (1996) Cortical systems for the recognition of emotion in facial expressions. J. Neurosci., 16: 7678–7687. Adolphs, R., Gosselin, F., Buchanan, T.W., Tranel, D., Schyns, P. and Damasio, A.R. (2005) A mechanism for impaired fear recognition after amygdala damage. Nature, 433: 68–72. Adolphs, R., Russell, J.A. and Tranel, D. (1999a) A role for the human amygdala in recognizing emotional arousal from unpleasant stimuli. Psychol. Sci., 10: 167–171. Adolphs, R. and Tranel, D. (1999) Intact recognition of emotional prosody following amygdala damage. Neuropsychologia, 37: 1285–1292. Adolphs, R. and Tranel, D. (2003) Amygdala damage impairs emotion recognition from scenes only when they contain facial expressions. Neuropsychologia, 41: 1281–1289. Adolphs, R., Tranel, D. and Damasio, A.R. (1998) The human amygdala in social judgment. Nature, 393: 470–474. Adolphs, R., Tranel, D. and Damasio, A.R. (2003) Dissociable neural systems for recognizing emotions. Brain Cogn., 52: 61–69. Adolphs, R., Tranel, D., Damasio, H. and Damasio, A. (1994) Impaired recognition of emotion in facial expressions following bilateral damage to the human amygdala. Nature, 372: 669–672. Adolphs, R., Tranel, D., Damasio, H. and Damasio, A.R. (1995) Fear and the human amygdala. J. Neurosci., 15: 5879–5891. Adolphs, R., Tranel, D., Hamann, S., Young, A.W., Calder, A.J., Phelps, E.A., Anderson, A., Lee, G.P. and Damasio, A.R. (1999b) Recognition of facial emotion in nine individuals with bilateral amygdala damage. Neuropsychologia, 37: 1111–1117. Aggleton, A., Burton, M. and Passingham, R. (1980) Cortical and subcortical afferents to the amygdala of the rhesus monkey (Macaca mulatta). Brain Res., 190: 347–368.

Amaral, D.G., Bauman, M.D., Capitanio, J.P., Lavenex, P., Mason, W.A., Mauldin-Jourdain, M.L. and Mendoza, S.P. (2003a) The amygdala: is it an essential component of the neural network for social cognition? Neuropsychologia, 41: 517–522. Amaral, D.G., Behniea, H. and Kelly, J.L. (2003b) Topographic organization of projections from the amygdala to the visual cortex in the macaque monkey. Neuroscience, 118: 1099–10120. Amaral, D.G. and Insausti, R. (1992) Retrograde transport of D-[3 H]-aspartate injected into the monkey amygdaloid complex. Exp. Brain Res., 88: 375–388. Amaral, D.G. and Price, J.L. (1984) Amygdalo-cortical projections in the monkey (Macaca fascicularis). J. Comp. Neurol., 230: 465–496. Anders, S., Lotze, M., Erb, M., Grodd, W. and Birbaumer, N. (2004) Brain activity underlying emotional valence and arousal: a response-related fMRI study. Hum. Brain Mapp., 23: 200–209. Anderson, A.K. and Phelps, E.A. (2001) Lesions of the human amygdala impair enhanced perception of emotionally salient events. Nature, 411: 305–309. Anderson, A.K. and Phelps, E.A. (2002) Is the human amygdala critical for the subjective experience of emotion? Evidence of intact dispositional affect in patients with amygdala lesions. J. Cogn. Neurosci., 14: 709–720. Anderson, A.K., Spencer, D.D., Fulbright, R.K. and Phelps, E.A. (2000) Contribution of the anteromedial temporal lobes to the evaluation of facial emotion. Neuropsychology, 14: 526–536. Bachevalier, J., Beauregard, M. and Alvarado, M.C. (1999) Long-term effects of neonatal damage to the hippocampal formation and amygdaloid complex on object discrimination and object recognition in rhesus monkeys (Macaca mulatta). Behav. Neurosci., 113: 1127–1151. Bachevalier, J. and Loveland, K.A. (2006) The orbitofrontalamygdala circuit and self-regulation of social-emotional behavior in autism. Neurosci. Biobehav. Rev., 30: 97–117. Bagshaw, M.H. and Benzies, S. (1968) Multiple measures of the orienting reaction and their dissociation after amygdalectomy in monkeys. Exp. Neurol., 20: 175–187. Bagshaw, M.H. and Coppock, H.W. (1968) Galvanic skin response conditioning deficit in amygdalectomized monkeys. Exp. Neurol., 20: 188–196. Baron-Cohen, S., Ring, H.A., Bullmore, E.T., Wheelwright, S., Ashwin, C. and Williams, S.C. (2000) The amygdala theory of autism. Neurosci. Biobehav. Rev., 24: 355–364. Baron-Cohen, S., Ring, H.A., Wheelwright, S., Bullmore, E.T., Brammer, M.J., Simmons, A. and Williams, S.C. (1999) Social intelligence in the normal and autistic brain: an fMRI study. Eur. J. Neurosci., 11: 1891–1898. Bauman, M.D., Lavenex, P., Mason, W.A., Capitanio, J.P. and Amaral, D.G. (2004a) The development of mother-infant interactions after neonatal amygdala lesions in rhesus monkeys. J. Neurosci., 24: 711–721. Bauman, M.D., Lavenex, P., Mason, W.A., Capitanio, J.P. and Amaral, D.G. (2004b) The development of social behavior

376 following neonatal amygdala lesions in rhesus monkeys. J. Cogn. Neurosci., 16: 1388–1411. Bechara, A., Tranel, D., Damasio, H., Adolphs, R., Rockland, C. and Damasio, A.R. (1995) Double dissociation of conditioning and declarative knowledge relative to the amygdala and hippocampus in humans. Science, 269: 1115–1118. Breiter, H.C., Etcoff, N.L., Whalen, P.J., Kennedy, W.A., Rauch, S.L., Buckner, R.L., Strauss, M.M., Hyman, S.E. and Rosen, B.R. (1996) Response and habituation of the human amygdala during visual processing of facial expression. Neuron, 17: 875–887. Broks, P., Young, A.W., Maratos, E.J., Coffey, P.J., Calder, A.J., Isaac, C.L., Mayes, A.R., Hodges, J.R., Montaldi, D., Cezayirli, E., Roberts, N. and Hadley, D. (1998) Face processing impairments after encephalitis: amygdala damage and recognition of fear. Neuropsychologia, 36: 59–70. Brothers, L., Ring, B. and Kling, A. (1990) Response of neurons in the macaque amygdala to complex social stimuli. Behav. Brain Res., 41: 199–213. Buchel, C., Morris, J., Dolan, R.J. and Friston, K.J. (1998) Brain systems mediating aversive conditioning: an event-related fMRI study. Neuron, 20: 947–957. Calder, A.J., Keane, J., Manes, F., Antoun, N. and Young, A.W. (2000) Impaired recognition and experience of disgust following brain injury. Nat. Neurosci., 3: 1077–1078. Calder, A.J., Lawrence, A.D., Keane, J., Scott, S.K., Owen, A.M., Christoffels, I. and Young, A.W. (2002) Reading the mind from eye gaze. Neuropsychologia, 40: 1129–1138. Calder, A.J., Young, A.W., Rowland, D., Perrett, D.I., Hodges, J.R. and Etcoff, N.L. (1996) Facial emotion recognition after bilateral amygdala damage: differentially severe impairment of fear. Cogn. Neuropsychol., 13: 699–745. Campbell, R., Heywood, C.A., Cowey, A., Regard, M. and Landis, T. (1990) Sensitivity to eye gaze in prosopagnosic patients and monkeys with superior temporal sulcus ablation. Neuropsychologia, 28: 1123–1142. Canli, T., Sivers, H., Whitfield, S.L., Gotlib, I.H. and Gabrieli, J.D. (2002) Amygdala response to happy faces as a function of extraversion. Science, 296: 2191. Damasio, A.R. (1996) The somatic marker hypothesis and the possible functions of the prefrontal cortex. Philos. Trans. R. Soc. Lond. B Biol. Sci., 351: 1413–1420. de Gelder, B., Vroomen, J., Pourtois, G. and Weiskrantz, L. (1999) Non-conscious recognition of affect in the absence of striate cortex. Neuroreport., 10: 3759–3763. Dicks, D., Myers, R.E. and Kling, A. (1968) Uncus and amygdala lesions: effects on social behavior in the free-ranging rhesus monkey. Science, 165: 69–71. Downing, P.E., Jiang, Y., Shuman, M. and Kanwisher, N. (2001) A cortical area selective for visual processing of the human body. Science, 293: 2470–2473. Duhamel, J.R., Colby, C.L. and Goldberg, M.E. (1998) Ventral intraparietal area of the macaque: congruent visual and somatic response properties. J. Neurophysiol., 79: 126–136. Emery, N.J. (2000) The eyes have it: the neuroethology, function and evolution of social gaze. Neurosci. Biobehav. Rev., 24: 581–604.

Emery, N.J. and Amaral, D.G. (1999) The role of the amygdala in primate social cognition. In: Lane R.D., NadelL. (Ed.), Cognitive Neuroscience of Emotion. Oxford University Press, Oxford. Emery, N.J., Capitanio, J.P., Mason, W.A., Machado, C.J., Mendoza, S.P. and Amaral, D.G. (2001) The effects of bilateral lesions of the amygdala on dyadic social interactions in rhesus monkeys (Macaca mulatta). Behav. Neurosci., 115: 515–544. Fine, C., Lumsden, J. and Blair, R.J. (2001) Dissociation between ‘theory of mind’ and executive functions in a patient with early left amygdala damage. Brain, 124: 287–298. Freese, J.L. and Amaral, D.G. (2005) The organization of projections from the amygdala to visual cortical areas TE and V1 in the macaque monkey. J. Comp. Neurol., 486: 295–317. Gallese, V., Keysers, C. and Rizzolatti, G. (2004) A unifying view of the basis of social cognition. Trends Cogn. Sci., 8: 396–403. Ghashghaei, H.T. and Barbas, H. (2002) Pathways for emotion: interactions of prefrontal and anterior temporal pathways in the amygdala of the rhesus monkey. Neuroscience, 115: 1261–1279. Glascher, J. and Adolphs, R. (2003) Processing of the arousal of subliminal and supraliminal emotional stimuli by the human amygdala. J. Neurosci., 23: 10274–10282. Grossman, E.D. and Blake, R. (2002) Brain areas active during visual perception of biological motion. Neuron, 35: 1167–1175. Hart, A.J., Whalen, P.J., Shin, L.M., McInerney, S.C., Fischer, H. and Rauch, S.L. (2000) Differential response in the human amygdala to racial outgroup vs ingroup face stimuli. Neuroreport, 11: 2351–2355. Haxby, J.V., Gobbini, M.I., Furey, M.L., Ishai, A., Schouten, J.L. and Pietrini, P. (2001) Distributed and overlapping representations of faces and objects in ventral temporal cortex. Science, 293: 2425–2430. Haxby, J.V., Hoffman, E.A. and Gobbini, M.I. (2000) The distributed human neural system for face perception. Trends Cogn. Sci., 4: 223–233. Heberlein, A.S., Adolphs, R., Tranel, D. and Damasio, H. (2004) Cortical regions for judgments of emotions and personality traits from point-light walkers. J. Cogn. Neurosci., 16: 1143–1158. Hennenlotter, A., Schroeder, U., Erhard, P., Castrop, F., Haslinger, B., Stoecker, D., Lange, K.W. and Ceballos-Baumann, A.O. (2005) A common neural basis for receptive and expressive communication of pleasant facial affect. Neuroimage, 26: 581–591. Hooker, C.I., Paller, K.A., Gitelman, D.R., Parrish, T.B., Mesulam, M.M. and Reber, P.J. (2003) Brain networks for analyzing eye gaze. Brain Res. Cogn. Brain Res., 17: 406–418. Izquierdo, A., Suda, R.K. and Murray, E.A. (2005) Comparison of the effects of bilateral orbital prefrontal cortex lesions and amygdala lesions on emotional responses in rhesus monkeys. J. Neurosci., 25: 8534–8542. Jones, E.G. and Burton, H. (1976) A projection from the medial pulvinar to the amygdala in primates. Brain Res., 104: 142–147.

377 Kalin, N.H., Shelton, S.E. and Davidson, R.J. (2004) The role of the central nucleus of the amygdala in mediating fear and anxiety in the primate. J. Neurosci., 24: 5506–5515. Kalin, N.H., Shelton, S.E., Davidson, R.J. and Kelley, A.E. (2001) The primate amygdala mediates acute fear but not the behavioral and physiological components of anxious temperament. J. Neurosci., 21: 2067–2074. Kanwisher, N., McDermott, J. and Chun, M.M. (1997) The fusiform face area: a module in human extrastriate cortex specialized for face perception. J. Neurosci., 17: 4302–4311. Kawashima, R., Sugiura, M., Kato, T., Nakamura, A., Hatano, K., Ito, K., Fukuda, H., Kojima, S. and Nakamura, K. (1999) The human amygdala plays an important role in gaze monitoring. A PET study. Brain, 122(Pt 4): 779–783. Kim, H., Somerville, L.H., Johnstone, T., Polis, S., Alexander, A.L., Shin, L.M. and Whalen, P.J. (2004) Contextual modulation of amygdala responsivity to surprised faces. J. Cogn. Neurosci., 16: 1730–1745. Kling, A. (1968) Effects of amygdalectomy and testosterone on sexual behavior of male juvenile macaques. J. Comp. Physiol. Psychol., 65: 466–471. Kling, A. (1974) Differential effects of amygdalectomy in male and female nonhuman primates. Arch. Sex Behav., 3: 129–134. Kling, A.S. and Brothers, L.A. (1992) The amygdala and social behavior. In: Aggleton, A.P. (Ed.), The Amygdala: Neurobiological Aspects of Emotion, Memory, and Mental Dysfunction. Wiley-Liss, New York. Kling, A., Lancaster, J. and Benitone, J. (1970) Amygdalectomy in the free-ranging vervet (Cercopithecus aethiops). J. Psychiatr. Res., 7: 191–199. Kling, A., Steklis, H.D. and Deutsch, S. (1979) Radiotelemetered activity from the amygdala during social interactions in the monkey. Exp. Neurol., 66: 88–96. Kluver, H. and Bucy, P.C. (1937) Psychic blindness and other symptoms following bilateral temporal amygdalectomy in Rhesus monkeys. Am. J. Physiol., 119: 352–353. Kluver, H. and Bucy, P.C. (1939) Preliminary analysis of functions of the temporal lobes in monkeys. Arch. Neurol. Psychiat., 2: 979–1000. Kluver, H. and Bucy, P.C. (1997) Preliminary analysis of functions of the temporal lobes in monkeys. 1939. J. Neuropsych. Clin. Neurosci., 9: 606–620. Knight, D.C., Nguyen, H.T. and Bandettini, P.A. (2005) The role of the human amygdala in the production of conditioned fear responses. Neuroimage, 26: 1193–1200. Liddell, B.J., Brown, K.J., Kemp, A.H., Barton, M.J., Das, P., Peduto, A., Gordon, E. and Williams, L.M. (2005) A direct brainstem-amygdala-cortical ‘alarm’ system for subliminal signals of fear. Neuroimage, 24: 235–243. McCarthy, G. (1999) Physiological studies of face processing in humans. In: Gazzaniga, M.S. (Ed.), The New Cognitive Neurosciences. MIT Press, Cambridge, MA, pp. 393–410. McGaugh, J.L. (2004) The amygdala modulates the consolidation of memories of emotionally arousing experiences. Annu. Rev. Neurosci., 27: 1–28.

Mesulam, M.M., Van Hoesen, G.W., Pandya, D.N. and Geschwind, N. (1977) Limbic and sensory connections of the inferior parietal lobule (area PG) in the rhesus monkey: a study with a new method for horseradish peroxidase histochemistry. Brain Res., 136: 393–414. Meunier, M. and Bachevalier, J. (2002) Comparison of emotional responses in monkeys with rhinal cortex or amygdala lesions. Emotion, 2: 147–161. Meunier, M., Bachevalier, J., Murray, E.A., Malkova, L. and Mishkin, M. (1999) Effects of aspiration versus neurotoxic lesions of the amygdala on emotional responses in monkeys. Eur. J. Neurosci., 11: 4403–4418. Morris, J.S., DeGelder, B., Weiskrantz, L. and Dolan, R.J. (2001) Differential extrageniculostriate and amygdala responses to presentation of emotional faces in a cortically blind field. Brain, 124: 1241–1252. Morris, J.S., Friston, K.J., Buchel, C., Frith, C.D., Young, A.W., Calder, A.J. and Dolan, R.J. (1998a) A neuromodulatory role for the human amygdala in processing emotional facial expressions. Brain, 121(Pt 1): 47–57. Morris, J.S., Frith, C.D., Perrett, D.I., Rowland, D., Young, A.W., Calder, A.J. and Dolan, R.J. (1996) A differential neural response in the human amygdala to fearful and happy facial expressions. Nature, 383: 812–815. Morris, J.S., Ohman, A. and Dolan, R.J. (1998b) Conscious and unconscious emotional learning in the human amygdala. Nature, 393: 467–470. Morris, J.S., Ohman, A. and Dolan, R.J. (1999) A subcortical pathway to the right amygdala mediating ‘‘unseen’’ fear. Proc. Natl. Acad. Sci. USA, 96: 1680–1685. Ohman, A. (2005) The role of the amygdala in human fear: automatic detection of threat. Psychoneuroendocrinology, 30: 953–958. Patterson II, J.C., Ungerleider, L.G. and Bandettini, P.A. (2002) Task-independent functional brain activity correlation with skin conductance changes: an fMRI study. Neuroimage, 17: 1797–1806. Pegna, A.J., Khateb, A., Lazeyras, F. and Seghier, M.L. (2005) Discriminating emotional faces without primary visual cortices involves the right amygdala. Nat. Neurosci., 8: 24–25. Phelps, E.A., O’Connor, K.J., Cunningham, W.A., Funayama, E.S., Gatenby, J.C., Gore, J.C. and Banaji, M.R. (2000) Performance on indirect measures of race evaluation predicts amygdala activation. J. Cogn. Neurosci., 12: 729–738. Pinsk, M.A., DeSimone, K., Moore, T., Gross, C.G. and Kastner, S. (2005) Representations of faces and body parts in macaque temporal cortex: a functional MRI study. Proc. Natl. Acad. Sci. USA, 102: 6996–7001. Pourtois, G., Sander, D., Andres, M., Grandjean, D., Reveret, L., Olivier, E. and Vuilleumier, P. (2004) Dissociable roles of the human somatosensory and superior temporal cortices for processing social face signals. Eur. J. Neurosci., 20: 3507–3515. Prather, M.D., Lavenex, P., Mauldin-Jourdain, M.L., Mason, W.A., Capitanio, J.P., Mendoza, S.P. and Amaral, D.G. (2001) Increased social fear and decreased fear of objects in monkeys with neonatal amygdala lesions. Neuroscience, 106: 653–658.

378 Pribram, K.H., Reitz, S., McNeil, M. and Spevack, A.A. (1979) The effect of amygdalectomy on orienting and classical conditioning in monkeys. Pavlov J. Biol. Sci., 14: 203–217. Price, J.L. (2003) Comparative aspects of amygdala connectivity. Ann. NY Acad. Sci., 985: 50–58. Price, J.L. and Amaral, D.G. (1981) An autoradiographic study of the projections of the central nucleus of the monkey amygdala. J. Neurosci., 1: 1242–1259. Puce, A., Allison, T., Bentin, S., Gore, J.C. and McCarthy, G. (1998) Temporal cortex activation in humans viewing eye and mouth movements. J. Neurosci., 18: 2188–2199. Rizzolatti, G. and Craighero, L. (2004) The mirror–neuron system. Annu. Rev. Neurosci., 27: 169–192. Romanski, L.M., Giguere, M., Bates, J.F. and Goldman-Rakic, P.S. (1997) Topographic organization of medial pulvinar connections with the prefrontal cortex in the rhesus monkey. J. Comp. Neurol., 379: 313–332. Rosvold, H.E., Mirsky, A.F. and Pribram, K.H. (1954) Influence of amygdalectomy on social behavior in monkeys. J. Comp. Physiol. Psychol., 47: 173–178. Spiridon, M. and Kanwisher, N. (2002) How distributed is visual category information in human occipito-temporal cortex? An fMRI study. Neuron, 35: 1157–1165. Sugase, Y., Yamane, S., Ueno, S. and Kawano, K. (1999) Global and fine information coded by single neurons in the temporal visual cortex. Nature, 400: 869–873. Tranel, D. and Damasio, H. (1989) Intact electrodermal skin conductance responses after bilateral amygdala damage. Neuropsychologia, 27: 381–390. Vuilleumier, P., Richardson, M.P., Armony, J.L., Driver, J. and Dolan, R.J. (2004) Distant influences of amygdala lesion on visual cortical activa during emotional face processing. Nat. Neurosci., 7: 1271–1278. Vuilleumier, P. and Schwartz, S. (2001a) Beware and be aware: capture of spatial attention by fear-related stimuli in neglect. Neuroreport, 12: 1119–1122. Vuilleumier, P. and Schwartz, S. (2001b) Emotional facial expressions capture attention. Neurology, 56: 153–158. Wang, L., McCarthy, G., Song, A.W. and Labar, K.S. (2005) Amygdala activation to sad pictures during high-field (4 tesla) functional magnetic resonance imaging. Emotion, 5: 12–22. Ward, R., Danziger, S. and Bamford, S. (2005) Response to visual threat following damage to the pulvinar. Curr. Biol., 15: 571–573.

Weiskrantz, L. (1956) Behavioral changes associated with ablation of the amygdaloid complex in monkeys. J. Comp. Physiol. Psychol., 49: 381–391. Whalen, P.J. (1999) Fear, vigilance, and ambiguity: initial neuroimaging studies of the human amygdala. Curr. Dir. Psychol. Sci., 7: 177–187. Whalen, P.J., Shin, L.M., McInerney, S.C., Fischer, H., Wright, C.I. and Rauch, S.L. (2001) A functional MRI study of human amygdala responses to facial expressions of fear versus anger. Emotion, 1: 70–83. Wicker, B., Keysers, C., Plailly, J., Royet, J.P., Gallese, V. and Rizzolatti, G. (2003a) Both of us disgusted in My insula: the common neural basis of seeing and feeling disgust. Neuron, 40: 655–664. Wicker, B., Michel, F., Henaff, M.A. and Decety, J. (1998) Brain regions involved in the perception of gaze: a PET study. Neuroimage, 8: 221–227. Wicker, B., Perrett, D.I., Baron-Cohen, S. and Decety, J. (2003b) Being the target of another’s emotion: a PET study. Neuropsychologia, 41: 139–146. Williams, LM., Brammer, M.J., Skerrett, D., Lagopolous, J., Rennie, C., Kozek, K., Olivieri, G., Peduto, T. and Gordon, E. (2000) The neural correlates of orienting: an integration of fMRI and skin conductance orienting. Neuroreport, 11: 3011–3015. Williams, M.A., McGlone, F., Abbott, D.F. and Mattingley, J.B. (2005) Differential amygdala responses to happy and fearful facial expressions depend on selective attention. Neuroimage, 24: 417–425. Williams, L.M., Phillips, M.L., Brammer, M.J., Skerrett, D., Lagopoulos, J., Rennie, C., Bahramali, H., Olivieri, G., David, A.S., Peduto, A. and Gordon, E. (2001) Arousal dissociates amygdala and hippocampal fear responses: evidence from simultaneous fMRI and skin conductance recording. Neuroimage, 14: 1070–1079. Winston, J.S., O’Doherty, J. and Dolan, R.J. (2003) Common and distinct neural responses during direct and incidental processing of multiple facial emotions. Neuroimage, 20: 84–97. Winston, J.S., Strange, B.A., O’Doherty, J. and Dolan, R.J. (2002) Automatic and intentional brain responses during evaluation of trustworthiness of faces. Nat. Neurosci., 5: 277–283. Young, A.W., Aggleton, J.P., Hellawell, D.J., Johnson, M., Broks, P. and Hanley, J.R. (1995) processing impairments after amygdalotomy. Brain, 118(Pt 1): 15–24.