Amygdala

The memory consolidation hypothesis proposed 100 years ago by Müller and Pilzecker continues to guide memory research. The hypothesis that new memories consolidate slowly over time has stimulated studies revealing the hormonal and neural influences regulating memory consolidation, as well as molecular and cellular mechanisms. This review examines the progress made over the century in understanding the timedependent processes that create our lasting memories.

Changing the strength of connections between neurons is widely assumed to be the mechanism by which memory traces are encoded and stored in the central nervous system. In its most general form, the synaptic plasticity and memory hypothesis states that "activity-dependent synaptic plasticity is induced at appropriate synapses during memory formation and is both necessary and sufficient for the information storage underlying the type of memory mediated by the brain area in which that plasticity is observed." We outline a set of criteria by which this hypothesis can be judged and describe a range of experimental strategies used to investigate it. We review both classical and newly discovered properties of synaptic plasticity and stress the importance of the neural architecture and synaptic learning rules of the network in which it is embedded. The greater part of the article focuses on types of memory mediated by the hippocampus, amygdala, and cortex. We conclude that a wealth of data supports the notion that synaptic plasticity is necessary for learning and memory, but that little data currently supports the notion of sufficiency. Annu. Rev. Neurosci. 2000.23:649-711. Downloaded from arjournals.annualreviews.org by Iowa State University on 02/10/05. For personal use only. Annu. Rev. Neurosci. 2000.23:649-711. Downloaded from arjournals.annualreviews.org by Iowa State University on 02/10/05. For personal use only.

Functional magnetic resonance imaging (fMRI) of the human brain was used to study whether the amygdala is activated in response to emotional stimuli, even in the absence of explicit knowledge that such stimuli were presented. Pictures of human faces bearing fearful or happy expressions were presented to 10 normal, healthy subjects by using a backward masking procedure that resulted in 8 of 10 subjects reporting that they had not seen these facial expressions. The backward masking procedure consisted of 33 msec presentations of fearful or happy facial expressions, their offset coincident with the onset of 167 msec presentations of neutral facial expressions. Although subjects reported seeing only neutral faces, blood oxygen level-dependent (BOLD) fMRI signal in the amygdala was significantly higher during viewing of masked fearful faces than during the viewing of masked happy faces. This difference was composed of significant signal increases in the amygdala to masked fearful faces as well as significant signal decreases to masked happy faces, consistent with the notion that the level of amygdala activation is affected differentially by the emotional valence of external stimuli. In addition, these facial expressions activated the sublenticular substantia innominata (SI), where signal increases were observed to both fearful and happy faces-suggesting a spatial dissociation of territories that respond to emotional valence versus salience or arousal value. This study, using fMRI in conjunction with masked stimulus presentations, represents an initial step toward determining the role of the amygdala in nonconscious processing.

We used positron emission tomography to study neural mechanisms underlying intensely pleasant emotional responses to music. Cerebral blood flow changes were measured in response to subject-selected music that elicited the highly pleasurable experience of ''shivers-down-the-spine'' or ''chills.'' Subjective reports of chills were accompanied by changes in heart rate, electromyogram, and respiration. As intensity of these chills increased, cerebral blood flow increases and decreases were observed in brain regions thought to be involved in reward͞motivation, emotion, and arousal, including ventral striatum, midbrain, amygdala, orbitofrontal cortex, and ventral medial prefrontal cortex. These brain structures are known to be active in response to other euphoriainducing stimuli, such as food, sex, and drugs of abuse. This finding links music with biologically relevant, survival-related stimuli via their common recruitment of brain circuitry involved in pleasure and reward.

Converging findings of animal and human studies provide compelling evidence that the amygdala is critically involved in enabling us to acquire and retain lasting memories of emotional experiences. This review focuses primarily on the findings of research investigating the role of the amygdala in modulating the consolidation of long-term memories. Considerable evidence from animal studies investigating the effects of posttraining systemic or intra-amygdala infusions of hormones and drugs, as well as selective lesions of specific amygdala nuclei, indicates that (a) the amygdala mediates the memory-modulating effects of adrenal stress hormones and several classes of neurotransmitters; (b) the effects are selectively mediated by the basolateral complex of the amygdala (BLA); (c) the influences involve interactions of several neuromodulatory systems within the BLA that converge in influencing noradrenergic and muscarinic cholinergic activation; (d) the BLA modulates memory consolidation via efferents to other brain regions, including the caudate nucleus, nucleus accumbens, and cortex; and (e) the BLA modulates the consolidation of memory of many different kinds of information. The findings of human brain imaging studies are consistent with those of animal studies in suggesting that activation of the amygdala influences the consolidation of long-term memory; the degree of activation of the amygdala by emotional arousal during encoding of emotionally arousing material (either pleasant or unpleasant) correlates highly with subsequent recall. The activation of neuromodulatory systems affecting the BLA and its projections to other brain regions involved in processing different kinds of information plays a key role in enabling emotionally significant experiences to be well remembered.

In this article we provide a unifying neural hypothesis on how individuals understand the actions and emotions of others. Our main claim is that the fundamental mechanism at the basis of the experiential understanding of others' actions is the activation of the mirror neuron system. A similar mechanism, but involving the activation of viscero-motor centers, underlies the experiential understanding of the emotions of others.

Carriers of the short allele of a functional 5¢ promoter polymorphism of the serotonin transporter gene have increased anxietyrelated temperamental traits, increased amygdala reactivity and elevated risk of depression. Here, we used multimodal neuroimaging in a large sample of healthy human subjects to elucidate neural mechanisms underlying this complex genetic association. Morphometrical analyses showed reduced gray matter volume in short-allele carriers in limbic regions critical for processing of negative emotion, particularly perigenual cingulate and amygdala. Functional analysis of those regions during perceptual processing of fearful stimuli demonstrated tight coupling as a feedback circuit implicated in the extinction of negative affect. Short-allele carriers showed relative uncoupling of this circuit. Furthermore, the magnitude of coupling inversely predicted almost 30% of variation in temperamental anxiety. These genotype-related alterations in anatomy and function of an amygdalacingulate feedback circuit critical for emotion regulation implicate a developmental, systems-level mechanism underlying normal emotional reactivity and genetic susceptibility for depression.

sites in each county, depending on the popularity of a given mixture with farmers. Plots ranged from 100 to 450 m 2 each, depending on ®eld size. Survey plots were assessed in late August for the severity of blast symptoms, expressed as the percentage of panicle branches that were necrotic due to the effects of M. grisea. Disease was assessed at ®ve sampling points in each plot, distributed in a uniform pattern. Twenty hills resulting from the transplanting process were evaluated at each sampling point, with each hill containing about 10 panicles per hill, to give a total of approximately 1,000 panicles evaluated per plot. Each sampled panicle was visually examined by experienced personnel to estimate the percentage of branches that were necrotic due to infection by M. grisea. Each panicle was given a rating 29 from 0 to 5, where 0 is no disease; 1 is less than 5% of panicle branches necrotic; 2 is 5±30% necrotic; 3 is 30±50% necrotic; 4 is greater than 50% necrotic; and 5 is 100% necrotic. Disease severity was summarized within each plot as {n , where n 0 ...n 5 is the number of culms in each of the respective disease categories. Thus, a disease severity of 0% would indicate no disease and 100% would indicate that 100% of panicle branches were necrotic. Plots were hand-harvested, threshed and weighed to determine grain yield. Individual varieties were evaluated separately in mixtures. Land equivalent ratios 22 were calculated as (yield ha -1 of variety A in mixture/yield ha -1 of variety A in monoculture) + (yield ha -1 of variety B in mixture/yield ha -1 of variety B in monoculture). Each survey plot was considered to be an experimental unit, and analyses were based on mean disease severities and grain yield for each plot. Statistical analyses were conducted separately by year and county owing to differences in disease level. One-tailed t-tests were used to determine if blast severity for each of the two varieties in each of the four mixtures differed signi®cantly from its corresponding monoculture control.

The progress made in understanding the insula in the decade following an earlier review (Augustine, Neurol. Res., 7 (1985) 2-10) is examined in this review. In these ten years, connections have been described between the insula and the orbital cortex, frontal operculum, lateral premotor cortex, ventral granular cortex, and medial area 6 in the frontal lobe. Insular connections between the second somatosensory area and retroinsular area of the parietal lobe have been documented. The insula was found to connect with the temporal pole and the superior temporal sulcus of the temporal lobe. It has an abundance of local intrainsular connections and projections to subdivisions of the cingulate gyms. The insula has connections with the lateral, lateral basal, central, cortical and medial amygdaloid nuclei. It also connects with nonamygdaloid areas such as the perirhinal cortex, entorhinal, and periamygdaloid cortex. The thalamic taste area, the parvicellular part of the ventral posteromedial nucleus, projects fibers to the ipsilateral insular-opercular cortex. In the past decade, confirmation has been given to the insula as a visceral sensory area, visceral motor area, motor association area, vestibular area, and language area. Recent studies have expanded the role of the insula as a somatosensory area, emphasizing its multifaceted, sensory role. The idea of the insula as limbic integration cortex has been affirmed and its role in Alzheimer's disease suggested.

extinction suggest that it is not a process of "unlearning" but rather is a process of new learning of fear inhibition. New York University New York, New York 10003 This view of extinction as an active learning process is supported by studies showing that after extinction the CR can return in a number of situations, such as the passage of time (spontaneous recovery), the presenta-Summary tion of the US alone (reinstatement), or if the animal is placed in the context of initial learning (renewal; see Understanding how fears are acquired is an important step in translating basic research to the treatment Bouton, 2002, for a review). Although animal models of the mechanisms of fear acquisition have been investi-of fear-related disorders. However, understanding how learned fears are diminished may be even more valuable.

Neuroscience is witnessing growing interest in understanding brain mechanisms of memory formation for emotionally arousing events, a development closely related to renewed interest in the concept of memory consolidation. Extensive research in animals implicates stress hormones and the amygdaloid complex as key,interacting modulators of memory consolidation for emotional events. Considerable evidence suggests that the amygdala is not a site of long-term explicit or declarative memory storage, but serves to influence memory-storage processes in other brain regions, such as the hippocampus, striatum and neocortex. Human-subject studies confirm the prediction of animal work that the amygdala is involved with the formation of enhanced declarative memory for emotionally arousing events.

One of the major limitations in the use of genetically modified mice for studying cognitive functions is the lack of regional and temporal control of gene function. To overcome these limitations, a forebrain-specific promoter was c o m b i n e d with the tetracycline transactivator system to achieve both regional and temporal control of transgene expression. Expression of an activated calcium-independent form of c a l c i u m -c a l m o d u l i n -d e p e ndent kinase II (CaMKII) resulted in a loss of h i p p o c a m p a l long-term potentiation in response to 10-hertz stimulation and a deficit in spatial memory, a form of explicit memory. Suppression of transgene expression reversed both the physiological and the memory deficit. When the transgene was expressed at high levels in the lateral amygdala and the striatum but not other forebrain structures, there was a deficit in fear conditioning, an implicit m e m o r y task, that also was reversible. Thus, the CaMKII signaling pathway is critical for both explicit and implicit m e m o r y storage, in a manner that is independent of its potential role in development.

| Emotionally significant experiences tend to be well remembered, and the amygdala has a pivotal role in this process. But the efficient encoding of emotional memories can become maladaptive -severe stress often turns them into a source of chronic anxiety.

This study takes advantage of continuing advances in the precision of magnetic resonance imaging (MRI) to quantify hippocampal volumes in a series of human subjects with a history of depression compared with controls. We sought to test the hypothesis that both age and duration of past depression would be inversely and independently correlated with hippocampal volume. A sample of 24 women ranging in age from 23 to 86 years with a history of recurrent major depression, but no medical comorbidity, and 24 case-matched controls underwent MRI scanning. Subjects with a history of depression (post-depressed) had smaller hippocampal volumes bilaterally than controls. Post-depressives also had smaller amygdala core nuclei volumes, and these volumes correlated with hippocampal volumes. In addition, post-depressives scored lower in verbal memory, a neuropsychological measure of hippocampal function, suggesting that the volume loss was related to an aspect of cognitive functioning. In contrast, there was no difference in overall brain size or general intellectual performance. Contrary to our initial hypothesis, there was no significant correlation between hippocampal volume and age in either post-depressive or control subjects, whereas there was a significant correlation with total lifetime duration of depression. This suggests that repeated stress during recurrent depressive episodes may result in cumulative hippocampal injury as reflected in volume loss.

Radiology ample, Mellers and coworkers have shown that the emo-2 MGH-NMR Center tional response to the outcome of a gamble depends on Department of Radiology the perceived value and likelihood of both the obtained 3 Department of Psychiatry outcome and its alternatives (Mellers et al., 1997). Thus, Massachusetts General Hospital and it feels better to receive $0 from a gamble when the Harvard Medical School unobtained alternative is a gain of $10 than when the Charlestown, Massachusetts 02129 alternative is a gain of $90; winning $50 feels better 4 Center for Studies in Behavioral Neurobiology when the odds of doing so are 10% than when the odds Concordia University are 90%. The influence of what might have been on the Montreal, Quebec H3G 1M8 response to an outcome is said to be "counterfactual." Canada Mellers et al. (1999) have shown that counterfactual in-5 Woodrow Wilson School of Public fluences also affect anticipated feelings. Their subjects and International Affairs expect to feel worse upon winning $0 when the alterna-Princeton University tive is $90 than when the alternative is only $10. Princeton, New Jersey 08544

Although prefrontal cortex has been implicated in the cognitive regulation of emotion, the cortical-subcortical interactions that mediate this ability remain poorly understood. To address this issue, we identified a right ventrolateral prefrontal region (vlPFC) whose activity correlated with reduced negative emotional experience during cognitive reappraisal of aversive images. We then applied a pathwaymapping analysis on subcortical regions to locate mediators of the association between vlPFC activity and reappraisal success (i.e., reductions in reported emotion). Results identified two separable pathways that together explained $50% of the reported variance in self-reported emotion: (1) a path through nucleus accumbens that predicted greater reappraisal success, and (2) a path through ventral amygdala that predicted reduced reappraisal success (i.e., more negative emotion). These results provide direct evidence that vlPFC is involved in both the generation and regulation of emotion through different subcortical pathways, suggesting a general role for this region in appraisal processes.

The mothers of infant rats show individual differences in the frequency of licking͞grooming and archedback nursing (LG-ABN) of pups that contribute to the development of individual differences in behavioral responses to stress. As adults, the offspring of mothers that exhibited high levels of LG-ABN showed substantially reduced behavioral fearfulness in response to novelty compared with the offspring of low LG-ABN mothers. In addition, the adult offspring of the high LG-ABN mothers showed significantly (i) increased central benzodiazepine receptor density in the central, lateral, and basolateral nuclei of the amygdala as well as in the locus ceruleus, (ii) increased ␣ 2 adrenoreceptor density in the locus ceruleus, and (iii) decreased corticotropin-releasing hormone (CRH) receptor density in the locus ceruleus. The expression of fear and anxiety is regulated by a neural circuitry that includes the activation of ascending noradrenergic projections from the locus ceruleus to the forebrain structures. Considering the importance of the amygdala, notably the anxiogenic influence of CRH projections from the amygdala to the locus ceruleus, as well as the anxiolytic actions of benzodiazepines, for the expression of behavioral responses to stress, these findings suggest that maternal care during infancy serves to ''program'' behavioral responses to stress in the offspring by altering the development of the neural systems that mediate fearfulness.

Using functional neuroimaging, we tested two hypotheses. First, we tested whether the amygdala has a neural response to sad and/or angry facial expressions. Secondly, we tested whether the orbitofrontal cortex has a specific neural response to angry facial expressions. Volunteer subjects were scanned, using PET, while they performed a sex discrimination task involving static grey-scale images Abbreviations: ANCOVA ϭ analysis of covariance; rCBF ϭ regional cerebral blood flow; SPM ϭ statistical parametric mapping by guest on July 23, 2016 http://brain.oxfordjournals.org/ Downloaded from Broks P, Young AW, Maratos EJ, Coffey PJ, Calder AJ, Isaac CL, et al. Face processing impairments after encephalitis: amygdala damage and recognition of fear.

Ten years ago, we reported that SM, a patient with rare bilateral amygdala damage, showed an intriguing impairment in her ability to recognize fear from facial expressions. Since then, the importance of the amygdala in processing information about facial emotions has been borne out by a number of lesion and functional imaging studies. Yet the mechanism by which amygdala damage compromises fear recognition has not been identified. Returning to patient SM, we now show that her impairment stems from an inability to make normal use of information from the eye region of faces when judging emotions, a defect we trace to a lack of spontaneous fixations on the eyes during free viewing of faces. Although SM fails to look normally at the eye region in all facial expressions, her selective impairment in recognizing fear is explained by the fact that the eyes are the most important feature for identifying this emotion. Notably, SM's recognition of fearful faces became entirely normal when she was instructed explicitly to look at the eyes. This finding provides a mechanism to explain the amygdala's role in fear recognition, and points to new approaches for the possible rehabilitation of patients with defective emotion perception.

Neuroimaging technology has provided unprecedented opportunities for elucidating the anatomical correlates of major depression. The knowledge gained from imaging research and from the postmortem studies that have been guided by imaging data is catalyzing a paradigm shift in which ...

We present in this paper a picture of the neural systems controlling defense that updates and simplifies Gray's "Neuropsychology of Anxiety". It is based on two behavioural dimensions: 'defensive distance' as defined by the Blanchards and 'defensive direction'. Defensive direction is a categorical dimension with avoidance of threat corresponding to fear and approach to threat corresponding to anxiety. These two psychological dimensions are mapped to underlying neural dimensions. Defensive distance is mapped to neural level, with the shortest defensive distances involving the lowest neural level (periaqueductal grey) and the largest defensive distances the highest neural level (prefrontal cortex). Defensive direction is mapped to separate parallel streams that run across these levels. A significant departure from prior models is the proposal that both fear and anxiety are represented at all levels. The theory is presented in a simplified form that does not incorporate the interactions that must occur between non-adjacent levels of the system. It also requires expansion to include the dimension of escapability of threat. Our current development and these proposed future extensions do not change the core concepts originally proposed by Gray and, we argue, demonstrate their enduring value. q

Recent data have emphasized the neurochemically distinct nature of subterritories in the accumbens part of the rat ventral striatum termed the core, shell, and rostral pole. In order to gain a more comprehensive understanding of how afferents are distributed relative to these subterritories, immunohistochemical detection of retrogradely transported Fluoro-Gold was carried out following iontophoretic injections intended to involve selectively one of the subterritories. The data revealed that a number of cortical d e r e n t s of the medial shell and core originate in separate areas, i.e., the dorsal peduncular, infralimbic, and posterior piriform cortices (to medial shell) and the dorsal prelimbic, anterior agranular insular, anterior cingulate, and perirhinal cortices (to core). The lateral shell and rostral pole are innervated by cortical structures that also project either to the medial shell or core. The orbital, posterior agranular insular, and entorhinal cortices, hippocampus, and basal amygdala were observed to innervate the accumbens in a topographic manner. Following core injections, strong bilateral cortical labeling was observed. Few labeled cortical cells were observed contralaterally following injections in the medial shell. Intermediate numbers of labeled neurons were observed in contralateral cortices following lateral shell injections.

Specialized neural systems have evolved for processing stimuli with particular emotional significance. Expedient detection of fear-related cues is critical for survival, and relies on dedicated circuits in which the amygdala has a key role 1 . In humans, the amygdala is consistently activated by fearful faces, even when those faces are not consciously perceived 2,3 . In some situations, the amygdala may also respond to fearful faces presented outside the focus of attention and not explicit ly identified, despite the fact that inattention is associated with decreased activation in face-selective areas in fusiform cortex 4 .

Brothers (Brothers L. Concepts in Neuroscience 1990;1:27-51) proposed a network of neural regions that comprise the "social brain", which includes the amygdala. Since the childhood psychiatric condition of autism involves deficits in "social intelligence", it is plausible that autism may be caused by an amygdala abnormality. In this paper we review the evidence for a social function of the amygdala. This includes reference to the Kluver-Bucy syndrome (which Hetzler and Griffin suggested may serve as an animal model of autism). We then review evidence for an amygdala deficit in people with autism, who are well known to have deficits in social behaviour. This includes a detailed summary of our recent functional magnetic resonance imaging (fMRI) study involving judging from the expressions of another person's eyes what that other person might be thinking or feeling. In this study, patients with autism or AS did not activate the amygdala when making mentalistic inferences from the eyes, whilst people without autism did show amygdala activity. The amygdala is therefore proposed to be one of several neural regions that are abnormal in autism. We conclude that the amygdala theory of autism contains promise and suggest some new lines of research. ᭧

This article reviews the modern literature on two key aspects of the central circuitry of emotion: the prefrontal cortex (PFC) and the amygdala. There are several different functional divisions of the PFC, including the dorsolateral, ventromedial, and orbital sectors. Each of these regions plays some role in affective processing that shares the feature of representing affect in the absence of immediate rewards and punishments as well as in different aspects of emotional regulation. The amygdala appears to be crucial for the learning of new stimulus-threat contingencies and also appears to be important in the expression of cue-specific fear. Individual differences in both tonic activation and phasic reactivity in this circuit play an important role in governing different aspects of anxiety. Emphasis is placed on affective chronometry, or the time course of emotional responding, as a key attribute of individual differences in propensity for anxiety that is regulated by this circuitry. Biol Psychiatry 2002;51: 68 -80

By homologous recombination of an internal ribosome entry site and Cre recombinase coding region into the 3'-untranslated region of the mouse Emx1 gene, we have generated a strain of mice, Emx1(IRES)cre, that expresses the Cre recombinase in a spatial and temporal pattern like that observed for Emx1. When mated to reporter strains, these mice are a sensitive means to fate-map the Emx1-expressing cells of the developing forebrain. Our results demonstrate that radial glia, Cajal-Retzius cells, glutamatergic neurons, astrocytes, and oligodendrocytes of most pallial structures originate from an Emx1-expressing lineage. On the other hand, most of the pallial GABAergic neurons arise outside the Emx1-expressing lineage. Structures that are located near the basal ganglia (e.g., the amygdala and endopiriform nuclei) are not uniformly derived from Emx1-expressing cells.

Magnetic resonance imaging (MRI)-based volumetric measurements of medial temporal lobe (MTL) structures can discriminate between normal elderly control subjects and patients with Alzheimer's disease (AD) of moderate to advanced severity. In terms of clinical utility, however, a more important issue concerns the ability of the technique to differentiate between normal elderly control subjects and AD patients with the very mildest form of the disease. We performed MRI-based volumetric measurements of the hippocampus, parahippocampal gyrus, and amygdala in 126 cognitively normal elderly control subjects and 94 patients with probable AD. The diagnosis of AD was made according to NINDS/ADRDA criteria, and disease severity was categorized by Clinical Dementia Rating (CDR) scores. Patients with CDR 0.5 were classified as very mild, CDR 1 as mild, and CDR 2 as moderate disease severity. Volumes of each structure declined with increasing age in control subjects and did so in parallel for...

Background: Converging lines of evidence have implicated the amygdala in the pathophysiology of posttraumatic stress disorder (PTSD). We previously developed a method for measuring automatic amygdala responses to general threat-related stimuli; in conjunction with functional magnetic resonance imaging, we used a passive viewing task involving masked presentations of human facial stimuli. Methods: We applied this method to study veterans with PTSD and a comparison cohort of combat-exposed veterans without PTSD.

Autism is a severe developmental disorder marked by a triad of deficits, including impairments in reciprocal social interaction, delays in early language and communication, and the presence of restrictive, repetitive and stereotyped behaviors. In this review, it is argued that the search for the neurobiological bases of the autism spectrum disorders should focus on the social deficits, as they alone are specific to autism and they are likely to be most informative with respect to modeling the pathophysiology of the disorder. Many recent studies have documented the difficulties persons with an autism spectrum disorder have accurately perceiving facial identity and facial expressions. This behavioral literature on face perception abnormalities in autism is reviewed and integrated with the functional magnetic resonance imaging (fMRI) literature in this area, and a heuristic model of the pathophysiology of autism is presented. This model posits an early developmental failure in autism i...

Among younger adults, the ability to willfully regulate negative affect, enabling effective responses to stressful experiences, engages regions of prefrontal cortex (PFC) and the amygdala. Because regions of PFC and the amygdala are known to influence the hypothalamicpituitary-adrenal axis, here we test whether PFC and amygdala responses during emotion regulation predict the diurnal pattern of salivary cortisol secretion. We also test whether PFC and amygdala regions are engaged during emotion regulation in older (62-to 64-year-old) rather than younger individuals. We measured brain activity using functional magnetic resonance imaging as participants regulated (increased or decreased) their affective responses or attended to negative picture stimuli. We also collected saliva samples for 1 week at home for cortisol assay. Consistent with previous work in younger samples, increasing negative affect resulted in ventral lateral, dorsolateral, and dorsomedial regions of PFC and amygdala activation. In contrast to previous work, decreasing negative affect did not produce the predicted robust pattern of higher PFC and lower amygdala activation. Individuals demonstrating the predicted effect (decrease Ͻ attend in the amygdala), however, exhibited higher signal in ventromedial prefrontal cortex (VMPFC) for the same contrast. Furthermore, participants displaying higher VMPFC and lower amygdala signal when decreasing compared with the attention control condition evidenced steeper, more normative declines in cortisol over the course of the day. Individual differences yielded the predicted link between brain function while reducing negative affect in the laboratory and diurnal regulation of endocrine activity in the home environment.

Positron emission tomography of cerebral glucose metabolism in adult human subjects was used to investigate amygdaloid complex (AC) activity associated with the storage of long-term memory for emotionally arousing events. Subjects viewed two videos (one in each of two separate positron emission tomography sessions, separated by 3-7

Effective mental functioning requires that cognition be protected from emotional conflict from interference by task-irrelevant emotionally salient stimuli. The neural mechanisms by which the brain detects and resolves emotional conflict are still largely unknown, however. Drawing on the classic Stroop conflict task, we developed a protocol that allowed us to dissociate the generation and monitoring of emotional conflict from its resolution. Using functional magnetic resonance imaging (fMRI), we find that activity in the amygdala and dorsomedial and dorsolateral prefrontal cortices reflects the amount of emotional conflict. By contrast, the resolution of emotional conflict is associated with activation of the rostral anterior cingulate cortex. Activation of the rostral cingulate is predicted by the amount of previous-trial conflict-related neural activity and is accompanied by a simultaneous and correlated reduction of amygdalar activity. These data suggest that emotional conflict is resolved through top-down inhibition of amygdalar activity by the rostral cingulate cortex.