Amygdala structure and function Research Papers (original) (raw)

But in a tentative and schematic way, may collegues and I (Mishkin) can begin to describe how the brain remembers. Ultimately, to be sure, memory is a series of molecular events. What we chart is the territory within which those events... more

But in a tentative and schematic way, may collegues and I (Mishkin) can begin to describe how the brain remembers. Ultimately, to be sure, memory is a series of molecular events. What we chart is the territory within which those events take place. Measurements of the electrical activity of neurons or their uptake of radioactive glucose have distinguished parts of the brain that are active during tasks related to learning. With the increase in (brain) size has come greater complexity. The structures we study in the macaque all have counterparts in the human brain, but their functions may well have diverged in the course of evolution. A study of the neural pathway responsible for visual perception was in fact the starting point for our inquiry into memory. These results and others led us to postulate that visual information is processed sequentially along the path. The cells respond to progressively more of an object's physical properties including its size, shape, color and texture-until, in the final stations of the interferior temporal cortex, they synthesize a complete representation of the object.

Consolidation is a process through which labile memories are made persistent [Science 287 (2000) 248]; [Annu Rev Psychol 55 (2004) 51]. When retrieved, a consolidated memory is rendered labile again and undergoes reconsolidation [Learn... more

Consolidation is a process through which labile memories are made persistent [Science 287 (2000) 248]; [Annu Rev Psychol 55 (2004) 51]. When retrieved, a consolidated memory is rendered labile again and undergoes reconsolidation [Learn Mem 7 (2000) 73]; [Trends Neurosci 26 (2003) 65]). Reconsolidation thus offers the opportunity to manipulate memory after it is formed, and may therefore provide a means of treating intrusive memories associated with post-traumatic stress disorder (PTSD). Reconsolidation is most usually studied using protein synthesis inhibitors, which is not practical in humans. However, the beta adrenergic receptor antagonist propranolol impairs consolidation of declarative memory in humans [Science 287 (2000) 248]; [Nature 371 (1994) 702] and consolidation and reconsolidation of inhibitory avoidance learning in rats [Brain Res 368 (1986) 125]; [J Neurosci 19 (1999) 6623]. Here, we show that systemic or intra-amygdala infused propranolol blocks reconsolidation but not consolidation. If the effects on reconsolidation are verified in humans, the results would suggest the possibility that propranolol after memory retrieval might be an effective way of treatment of intrusive memories in PTSD. That the systemic effects of propranolol on reconsolidation are achieved via an action in the amygdala is especially important in light of the fact that PTSD involves alterations in the amygdala [Arch Gen Psychiatry 53 (1996) 380].

Neuropeptides vasopressin and oxytocin regulate a variety of behaviors ranging from maternal and pair bonding to aggression and fear. Their role in modulating fear responses has been widely recognized, but not yet well understood. Animal... more

Neuropeptides vasopressin and oxytocin regulate a variety of behaviors ranging from maternal and pair bonding to aggression and fear. Their role in modulating fear responses has been widely recognized, but not yet well understood. Animal and human studies indicate the major role of the amygdala in controlling fear and anxiety. The amygdala is involved in detecting threat stimuli and linking them to defensive behaviors. This is accomplished by projections connecting the central nucleus of the amygdala (CeA) to the brain stem and to hypothalamic structures, which organize fear responses. A recent study by Huber et al (Science 2005) demonstrates that vasopressin and oxytocin modulate the excitatory inputs into the CeA in opposite manners. Therefore this finding elucidates the mechanisms through which these neuropeptides may control the expression of fear.

It is axiomatic in the study of pragmatics that speakers must make choices from a myriad of variants in phonology, morphology and syntax ''on the fly'' during the course of interaction. However, the specific psychological and... more

It is axiomatic in the study of pragmatics that speakers must make choices from a myriad of variants in phonology, morphology and syntax ''on the fly'' during the course of interaction. However, the specific psychological and neurophysiological mechanisms that both prompt these choices have largely been taken for granted. Theoretical approaches to this problem in the past have focused on linguistic mechanisms such as ''metapragmatics'' or cultural approaches such as the analysis of ''habitus.'' While acknowledging the importance of these approaches, in this paper I extend this view by suggesting that these instantaneous choices are largely governed by the same cognitive mechanisms that govern emotional response. Drawing on the work of contemporary neurophysiology, pragmatic philosophy and phenomenology, I draw on examples from Japanese, Persian and Javanese.

The amygdaloid body is a limbic nuclear complex characterized by connections with the thalamus, the brainstem and the neocortex. The recent advances in functional neurosurgery regarding the treatment of refractory epilepsy and several... more

The amygdaloid body is a limbic nuclear complex characterized by connections with the thalamus, the brainstem and the neocortex. The recent advances in functional neurosurgery regarding the treatment of refractory epilepsy and several neuropsychiatric disorders renewed the interest in the study of its functional Neuroanatomy. In this scenario, we felt that a morphological study focused on the amygdaloid body and its connections could improve the understanding of the possible implications in functional neurosurgery. With this purpose we performed a morfological study using nine formalin-fixed human hemispheres dissected under microscopic magnification by using the fiber dissection technique originally described by Klingler. In our results the amygdaloid body presents two divergent projection systems named dorsal and ventral amyg-dalofugal pathways connecting the nuclear complex with the septum and the hypothalamus. Furthermore, the amygdaloid body is connected with the hippocampus through the amygdalo-hippocampal bundle, with the anterolateral temporal cortex through the amygdalo-temporalis fascicle, the anterior commissure and the temporo-pulvinar bundle of Arnold, with the insular cortex through the lateral olfactory stria, with the ambiens gyrus, the para-hippocampal gyrus and the basal forebrain through the cingulum, and with the frontal cortex through the uncinate fascicle. Finally, the amygdaloid body is connected with the brainstem through the medial forebrain bundle. Our description of the topographic anatomy of the amygdaloid body and its connections, hopefully represents a useful tool for clinicians and scientists, both in the scope of application and speculation.

Love is one of the most desired experiences. The quest for understanding human bonds, especially love, was traditionally a domain of the humanities. Recent developments in biological sciences yield new insights into the mechanisms... more

Love is one of the most desired experiences. The quest
for understanding human bonds, especially love, was traditionally a domain of the humanities. Recent developments in biological sciences yield new insights into the mechanisms underlying the formation and maintenance of human relationships. Animal models of reproductive behaviors, mother–infant attachment and pair bonding complemented by human studies reveal neuroendocrine foundations of prosocial behaviors and emotions. Amongst various identified neurotransmitters and modulators, which control affiliative behaviors, the particular role of nanopeptides has been indicated. New studies suggest that these chemicals are not only involved in regulating bonding processes in animals but also contribute to generating positive social attitudes
and feelings in humans.

Non-invasive neuroimaging is increasingly used for investigating the human amygdala. Accurate functional localization in the amygdala region is, however, challenging and quantitative data on the anatomical specificity of functional... more

Non-invasive neuroimaging is increasingly used for investigating the human amygdala. Accurate functional localization in the amygdala region is, however, challenging and quantitative data on the anatomical specificity of functional amygdala imaging is lacking. We have therefore retrospectively investigated 114 recently published human functional imaging studies concerned with the amygdala. We determined the anatomical assignment probabilities of a total of 339 reported activation sites to the amygdala defined using a cytoarchitectonically verified probabilistic atlas system. We find that approximately 50% of reported responses were located in the region with high probability (≥80%) of belonging to the amygdala. This group included responses related both to stimuli of positive and negative emotional valence. Approximately 10% of reported response sites were assigned to the hippocampus, with up to 100% assignment probability. The remaining peaks were either located in the border regions of the amygdala and/or hippocampus or outside of both of these structures. Within the amygdala, the majority of peaks (96.3%) were found in the laterobasal (LB) and superficial (SF) subregions. Only 3.7% of peaks were found in the centromedial group (CM), possibly because anatomically delineating the CM region of the amygdala is particularly difficult and hence its extent might have been underestimated. Moreover, these results show that a core region of the amygdala is responsive to stimuli both of positive and negative emotional valence. The current findings highlight the usefulness of probabilistic amygdala maps and also point to a need for the development of accurate in vivo delineation and parcellation of the amygdala.

To explore the extent to which functional systems within the human posterior parietal cortex and the superior temporal sulcus are involved in the perception of action, we measured cerebral metabolic activity in human subjects by positron... more

To explore the extent to which functional systems within the human posterior parietal cortex and the superior temporal sulcus are involved in the perception of action, we measured cerebral metabolic activity in human subjects by positron emission tomography during the perception of simulations of biological motion with point-light displays. The experimental design involved comparisons of activity during the perception of goal-directed hand action, whole body motion, object motion, and random motion. The results demonstrated that the perception of scripts of goal-directed hand action implicates the cortex in the intraparietal sulcus and the caudal part of the superior temporal sulcus, both in the left hemisphere. By contrast, the rostrocaudal part of the right superior temporal sulcus and adjacent temporal cortex, and limbic structures such as the amygdala, are involved in the perception of signs conveyed by expressive body movements.

Understanding the heritability of neural systems linked to psychopathology is not sufficient to implicate them as intergenerational neural mediators. By closely examining how individual differences in neural phenotypes and psychopathology... more

Understanding the heritability of neural systems linked to psychopathology is not sufficient to implicate them as intergenerational neural mediators. By closely examining how individual differences in neural phenotypes and psychopathology cosegregate as they fall through the family tree, we can identify the brain systems that underlie the parent-to-child transmission of psychopathology. Although research has identified genes and neural circuits that contribute to the risk of developing anxiety and depression, the specific neural systems that mediate the inborn risk for these debilitating disorders remain unknown. In a sample of 592 young rhesus monkeys that are part of an extended multigenerational pedigree, we demonstrate that metabolism within a tripartite prefrontal-limbic-midbrain circuit mediates some of the inborn risk for developing anxiety and depression. Importantly, although brain volume is highly heritable early in life, it is brain metabolism—not brain structure—that is the critical intermediary between genetics and the childhood risk to develop stress-related psychopathology.

Habituation is a fundamental form of learning manifested by a decrement of neuronal responses to repeated sensory stimulation. In addition, habituation is also known to occur on the behavioral level, manifested by reduced emotional... more

Habituation is a fundamental form of learning manifested by a decrement of neuronal responses to repeated sensory stimulation. In addition, habituation is also known to occur on the behavioral level, manifested by reduced emotional reactions to repeatedly presented affective stimuli. It is, however, not clear which brain areas show a decline in activity during repeated sensory stimulation on the same time scale as reduced valence and arousal experience and whether these areas can be delineated from other brain areas with habituation effects on faster or slower time scales. These questions were addressed using functional magnetic resonance imaging acquired during repeated stimulation with piano melodies. The magnitude of functional responses in the laterobasal amygdala and in related cortical areas and that of valence and arousal ratings, given after each music presentation, declined in parallel over the experiment. In contrast to this longterm habituation (43 min), short-term decreases occurring within seconds were found in the primary auditory cortex. Sustained responses that remained throughout the whole investigated time period were detected in the ventrolateral prefrontal cortex extending to the dorsal part of the anterior insular cortex. These findings identify an amygdalocortical network that forms the potential basis of affective habituation in humans.

Habituation is a fundamental form of learning manifested by a decrement of neuronal responses to repeated sensory stimulation. In addition, habituation is also known to occur on the behavioral level, manifested by reduced emotional... more

Habituation is a fundamental form of learning manifested by a decrement of neuronal responses to repeated sensory stimulation. In addition, habituation is also known to occur on the behavioral level, manifested by reduced emotional reactions to repeatedly presented affective stimuli. It is, however, not clear which brain areas show a decline in activity during repeated sensory stimulation on the same time scale as reduced valence and arousal experience and whether these areas can be delineated from other brain areas with habituation effects on faster or slower time scales. These questions were addressed using functional magnetic resonance imaging acquired during repeated stimulation with piano melodies. The magnitude of functional responses in the laterobasal amygdala and in related cortical areas and that of valence and arousal ratings, given after each music presentation, declined in parallel over the experiment. In contrast to this longterm habituation (43 min), short-term decreases occurring within seconds were found in the primary auditory cortex. Sustained responses that remained throughout the whole investigated time period were detected in the ventrolateral prefrontal cortex extending to the dorsal part of the anterior insular cortex. These findings identify an amygdalocortical network that forms the potential basis of affective habituation in humans.

In the present study, we examined the role of the auditory thalamus [medial division of the medial geniculate nucleus and the adjacent posterior intralaminar nucleus (MGm/PIN)] in auditory pavlovian fear conditioning using pharmacological... more

In the present study, we examined the role of the auditory thalamus [medial division of the medial geniculate nucleus and the adjacent posterior intralaminar nucleus (MGm/PIN)] in auditory pavlovian fear conditioning using pharmacological manipulation of intracellular signaling pathways. ...

Reversal learning has been extensively studied across species as a task that indexes the ability to flexibly make and reverse deterministic stimulus-reward associations. Although various brain lesions have been found to affect performance... more

Reversal learning has been extensively studied across species as a task that indexes the ability to flexibly make and reverse deterministic stimulus-reward associations. Although various brain lesions have been found to affect performance on this task, the behavioral processes affected by these lesions have not yet been determined. This task includes at least two kinds of learning. First, subjects have to learn and reverse stimulus-reward associations in each block of trials. Second, subjects become more proficient at reversing choice preferences as they experience more reversals. We have developed a Bayesian approach to separately characterize these two learning processes. Reversal of choice behavior within each block is driven by a combination of evidence that a reversal has occurred, and a prior belief in reversals that evolves with experience across blocks. We applied the approach to behavior obtained from 89 macaques, comprising 12 lesion groups and a control group. We found th...

Non-invasive neuroimaging is increasingly used for investigating the human amygdala. Accurate functional localization in the amygdala region is, however, challenging and quantitative data on the anatomical specificity of functional... more

Non-invasive neuroimaging is increasingly used for investigating the human amygdala. Accurate functional localization in the amygdala region is, however, challenging and quantitative data on the anatomical specificity of functional amygdala imaging is lacking. We have therefore retrospectively investigated 114 recently published human functional imaging studies concerned with the amygdala. We determined the anatomical assignment probabilities of a total of 339 reported activation sites to the amygdala defined using a cytoarchitectonically verified probabilistic atlas system. We find that approximately 50% of reported responses were located in the region with high probability (≥80%) of belonging to the amygdala. This group included responses related both to stimuli of positive and negative emotional valence. Approximately 10% of reported response sites were assigned to the hippocampus, with up to 100% assignment probability. The remaining peaks were either located in the border regions of the amygdala and/or hippocampus or outside of both of these structures. Within the amygdala, the majority of peaks (96.3%) were found in the laterobasal (LB) and superficial (SF) subregions. Only 3.7% of peaks were found in the centromedial group (CM), possibly because anatomically delineating the CM region of the amygdala is particularly difficult and hence its extent might have been underestimated. Moreover, these results show that a core region of the amygdala is responsive to stimuli both of positive and negative emotional valence. The current findings highlight the usefulness of probabilistic amygdala maps and also point to a need for the development of accurate in vivo delineation and parcellation of the amygdala.

Understanding the physical encoding of a memory (the engram) is a fundamental question in neuroscience. Although it has been established that the lateral amygdala is a key site for encoding associative fear memory, it is currently unclear... more

Understanding the physical encoding of a memory (the engram) is a fundamental question in neuroscience. Although it has been established that the lateral amygdala is a key site for encoding associative fear memory, it is currently unclear whether the spatial distribution of neurons encoding a given memory is random or stable. Here we used spatial principal components analysis to quantify the topography of activated neurons, in a select region of the lateral amygdala, from rat brains encoding a Pavlovian conditioned fear memory. Our results demonstrate a stable, spatially patterned organization of amygdala neurons are activated during the formation of a Pavlovian conditioned fear memory. We suggest that this stable neuronal assembly constitutes a spatial dimension of the engram.

Studies of reconsolidation, in which retrieved memories are altered and restored, offer an approach for exploring the associative structure of fear memory. We found that exposure to the unconditioned stimulus initiates an unconditioned... more

Studies of reconsolidation, in which retrieved memories are altered and restored, offer an approach for exploring the associative structure of fear memory. We found that exposure to the unconditioned stimulus initiates an unconditioned stimulus−specific reconsolidation of learned fear in rats that depended on the amygdala. Thus, specific features of the unconditioned stimulus appear to be encoded in the
amygdala as part of fear memories stored there.

Consolidated long-term fear memories become labile and can be disrupted after being reactivated by the presentation of the unconditioned stimulus (US). Whether this is due to an alteration of the conditioned stimulus (CS) representation... more

Consolidated long-term fear memories become labile and can be disrupted after being reactivated by the presentation of the unconditioned stimulus (US). Whether this is due to an alteration of the conditioned stimulus (CS) representation in the lateral amygdala (LA) is not known. Here, we show in rats that fear memory reactivation through presentation of the aversive US, like CS presentation, triggers a process which,when disrupted, results in a selective depotentiation of CS-evoked neural responses in the LA in correlation with a selective suppression of CS-elicited fear memory. Thus, an aversive US triggers the reconsolidation of its associated predictor representation in LA. This new finding suggests that sensory-specific associations are stored in the lateral amygdala, allowing for their selective alteration by
either element of the association.

Some individuals are endowed with a biology that renders them more reactive to novelty and potential threat. When extreme, this anxious temperament (AT) confers elevated risk for the development of anxiety, depression and substance... more

Some individuals are endowed with a biology that renders them more reactive to novelty and potential threat. When extreme, this
anxious temperament (AT) confers elevated risk for the development of anxiety, depression and substance abuse. These disorders
are highly prevalent, debilitating and can be challenging to treat. The high-risk AT phenotype is expressed similarly in children and
young monkeys and mechanistic work demonstrates that the central (Ce) nucleus of the amygdala is an important substrate.
Although it is widely believed that the flow of information across the structural network connecting the Ce nucleus to other brain
regions underlies primates’ capacity for flexibly regulating anxiety, the functional architecture of this network has remained poorly
understood. Here we used functional magnetic resonance imaging (fMRI) in anesthetized young monkeys and quietly resting
children with anxiety disorders to identify an evolutionarily conserved pattern of functional connectivity relevant to early-life
anxiety. Across primate species and levels of awareness, reduced functional connectivity between the dorsolateral prefrontal cortex,
a region thought to play a central role in the control of cognition and emotion, and the Ce nucleus was associated with increased
anxiety assessed outside the scanner. Importantly, high-resolution 18-fluorodeoxyglucose positron emission tomography imaging
provided evidence that elevated Ce nucleus metabolism statistically mediates the association between prefrontal-amygdalar
connectivity and elevated anxiety. These results provide new clues about the brain network underlying extreme early-life anxiety
and set the stage for mechanistic work aimed at developing improved interventions for pediatric anxiety.

BACKGROUND: The human amygdala plays a crucial role in processing social signals, such as face expressions, particularly fearful ones, and facilitates responses to them in face-sensitive cortical regions. This contributes to social... more

BACKGROUND:
The human amygdala plays a crucial role in processing social signals, such as face expressions, particularly fearful ones, and facilitates responses to them in face-sensitive cortical regions. This contributes to social competence and individual amygdala size correlates with that of social networks. While rare patients with focal bilateral amygdala lesion typically show impaired recognition of fearful faces, this deficit is variable, and an intriguing possibility is that other brain regions can compensate to support fear and social signal processing.
METHODS:
To investigate the brain's functional compensation of selective bilateral amygdala damage, we performed a series of behavioral, psychophysiological, and functional magnetic resonance imaging experiments in two adult female monozygotic twins (patient 1 and patient 2) with equivalent, extensive bilateral amygdala pathology as a sequela of lipoid proteinosis due to Urbach-Wiethe disease.
RESULTS:
Patient 1, but not patient 2, showed preserved recognition of fearful faces, intact modulation of acoustic startle responses by fear-eliciting scenes, and a normal-sized social network. Functional magnetic resonance imaging revealed that patient 1 showed potentiated responses to fearful faces in her left premotor cortex face area and bilaterally in the inferior parietal lobule.
CONCLUSIONS:
The premotor cortex face area and inferior parietal lobule are both implicated in the cortical mirror-neuron system, which mediates learning of observed actions and may thereby promote both imitation and empathy. Taken together, our findings suggest that despite the pre-eminent role of the amygdala in processing social information, the cortical mirror-neuron system may sometimes adaptively compensate for its pathology.
Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

The experience of aversion is shaped by multiple physiological and psychological factors including one's expectations. Recent work has shown that expectancy manipulation can alter perceptions of aversive events and concomitant brain... more

The experience of aversion is shaped by multiple physiological and psychological factors including one's expectations. Recent work has shown that expectancy manipulation can alter perceptions of aversive events and concomitant brain activation. Accruing evidence indicates a primary role of altered expectancies in the placebo eVect. Here, we probed the mechanism by which expectation attenuates sensory taste transmission by examining how brain areas activated by misleading information during an expectancy period modulate insula and amygdala activation to a highly aversive bitter taste. In a rapid event-related fMRI design, we showed that activations in the rostral anterior cingulate cortex (rACC), orbitofrontal cortex (OFC), and dorsolateral prefrontal cortex to a misleading cue that the taste would be mildly aversive predicted decreases in insula and amygdala activation to the highly aversive taste. OFC and rACC activation to the misleading cue were also associated with less aversive ratings of that taste. Additional analyses revealed consistent results demonstrating functional connectivity among the OFC, rACC, and insula. Altering expectancies of upcoming aversive events are shown here to depend on robust functional associations among brain regions implicated in prior work on the placebo eVect.

Studies of reconsolidation, in which retrieved memories are altered and restored, offer a novel approach for exploring the associative structure of fear memory. Here we show in rats that exposure to the unconditioned stimulus initiates an... more

Studies of reconsolidation, in which retrieved memories are altered and restored, offer a novel approach for exploring the associative structure of fear memory. Here we show in rats that exposure to the unconditioned stimulus initiates an unconditioned stimulus-specific reconsolidation of learned fear that depends on the amygdala. Thus, specific features of the unconditioned stimulus appear to be encoded in the amygdala as part of fear memories stored there. Protein synthesis-dependent memory reconsolidation has attracted much attention because of its possible application in treatment of mental disorders, such as anxiety or addictive disorders (1-3). Studies of reconsolidation also provide a novel way to explore the structure of memory traces. Many studies of reconsolidation have involved auditory fear conditioning, in which an acoustic conditioned stimulus is paired with an unconditioned stimulus, typically a mild electric shock to the feet or to the eyelids. Subsequent exposure to the conditioned stimulus alone then triggers fear responses, such as freezing (4). Considerable evidence suggests that the lateral amygdala is a key site required for fear memory Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms Author Contributions J.D. designed the experiments, conducted experiments, analyzed the data, interpreted the results, wrote the initial manuscript and was involved in the revision process. L.D-M. was involved in conducting experiments, analyzing the data, interpreting the results, writing and revising the manuscript. D.E.A.B. conducted all the statistical data analysis and was involved in designing the experiments, interpreting the results, writing and revising the manuscript. V.D. was involved in designing and conducting the experiments, interpreting the results, as well as writing and revising the manuscript. J.E.L. was involved in the design of the studies, the interpretation of the results and the preparation and revision of the manuscript.

Mild Cognitive Impairment (MCI) patients experience problems in financial abilities that affect everyday functioning. To date, the neural correlates of decline in this domain are unclear. This study aims at examining the correlation... more

Mild Cognitive Impairment (MCI) patients experience problems in financial abilities that affect everyday functioning. To date, the neural correlates of decline in this domain are unclear. This study aims at examining the correlation between the pattern of brain atrophy of MCI patients and performance on financial abilities. Forty-four MCI patients and thirty-seven healthy controls underwent structural magnetic resonance imaging, and assessment of financial abilities by means of the Numerical Activities of Daily Living Financial battery (NADL-F). As compared to healthy controls, MCI patients showed impaired performance in three out of the seven domains assessed by NADL-F: Item purchase, percentage, and financial concepts. The patients' performance in the NADL-F correlated with memory, language, visuo-spatial, and abstract reasoning composite scores. The analysis also revealed that volumetric differences in the limbic structures significantly correlated with financial abilities in MCI. Specifically, the patients' performance in the NADL-F was correlated with atrophy in the left medial and lateral amygdala and the right anterior thalamic radiation. These findings suggest that completing daily financial tasks involves sub-cortical regions in MCI and presumably also the motivational and emotional processes associated to them. Involvement of altered limbic structures in MCI patients suggests that impairment in financial abilities may be related to emotional and reflexive processing deficits.

A decisive element of moral cognition is the detection of harm and its assessment as intentional or unintentional. Moral cognition engages brain networks supporting mentalizing, intentionality, empathic concern and evaluation. These... more

A decisive element of moral cognition is the detection of harm and its assessment as intentional or unintentional. Moral cognition engages brain networks supporting mentalizing, intentionality, empathic concern and evaluation. These networks rely on the amygdala as a critical hub, likely through frontotemporal connections indexing stimulus salience. We assessed inferences about perceived harm using a paradigm validated through functional magnetic resonance imaging, eye-tracking and electroencephalogram recordings. During
the task, we measured local field potentials in three patients with depth electrodes (n = 115) placed in the amygdala and in several
frontal, temporal, and parietal locations. Direct electrophysiological recordings demonstrate that intentional harm induces early activity in the amygdala (<200ms), which—in turn—predicts intention attribution. The amygdala was the only site that systematically discriminated between critical conditions and predicted their classification of events as intentional. Moreover, connectivity analysis showed that intentional harm induced stronger frontotemporal information sharing at early stages. Results support the ‘many roads’ view of the amygdala and highlight its role in the rapid encoding of intention and salience—critical components of mentalizing and moral evaluation.

When reactivated, memories enter a labile, protein synthesis– dependent state, a process referred to as reconsolidation. Here, we show in rats that fear memory retrieval produces a synaptic potentiation in the lateral amygdala that is... more

When reactivated, memories enter a labile, protein synthesis–
dependent state, a process referred to as reconsolidation. Here,
we show in rats that fear memory retrieval produces a synaptic
potentiation in the lateral amygdala that is selective to the
reactivated memory, and that disruption of reconsolidation is
correlated with a reduction of synaptic potentiation in the lateral amygdala. Thus, both retrieval and reconsolidation alter
memories via synaptic plasticity at selectively targeted synapses.

Stress, in its many forms, is long associated with the etiology and course of schizophrenia. The mechanisms mediating the impacts of stress are not fully elucidated. Here it is proposed that stress induced cortisol alters kynurenic acid... more

Stress, in its many forms, is long associated with the etiology and course of schizophrenia. The mechanisms mediating the impacts of stress are not fully elucidated. Here it is proposed that stress induced cortisol alters kynurenic acid (KA) and quinolinic acid (QA) in the cortex and amygdala/striatum, respectively. These effects are significantly modulated by BAG-1 (bcl-2 associated anthanogene) and involve ROS, IL-18, and the induction of IDO (indoleamine 2,3-dioxygenase). The kynurenine pathway (KP) products response to stress seems to mediate both prenatal etiology and symptom course in adulthood.
It is suggested that the effects of cortisol and quinolinic acid in the amygdala, coupled to an increase in dopamine efflux, mediate amygdala driven developmental changes in the cortex and VTA/N.Accumbens junction. This change in patterned brain activity co-ordinates alterations in motivated behaviour and thought outputs. Such developmental alterations determine changes in sensory–amygdala interactions, readily allowing developmental links to changes in lateral inhibition and pre-pulse inhibition.
Decreases in vitamin D3 and melatonin further potentiate such stress induced changes. The likely involvement of glia in mediating increases in the KP products suggests that adaptation to stress is driven
by neuronal activity as a form of glia to glia communication.

When reactivated, memories enter a labile, protein synthesisdependent state, a process referred to as reconsolidation. Here, we show in rats that fear memory retrieval produces a synaptic potentiation in the lateral amygdala that is... more

When reactivated, memories enter a labile, protein synthesisdependent state, a process referred to as reconsolidation. Here, we show in rats that fear memory retrieval produces a synaptic potentiation in the lateral amygdala that is selective to the reactivated memory, and that disruption of reconsolidation is correlated with a reduction of synaptic potentiation in the lateral amygdala. Thus, both retrieval and reconsolidation alter memories via synaptic plasticity at selectively targeted synapses.

Non-invasive neuroimaging is increasingly used for investigating the human amygdala. Accurate functional localization in the amygdala region is, however, challenging and quantitative data on the anatomical specificity of functional... more

Non-invasive neuroimaging is increasingly used for investigating the human amygdala. Accurate functional localization in the amygdala region is, however, challenging and quantitative data on the anatomical specificity of functional amygdala imaging is lacking. We have therefore retrospectively investigated 114 recently published human functional imaging studies concerned with the amygdala. We determined the anatomical assignment probabilities of a total of 339 reported activation sites to the amygdala defined using a cytoarchitectonically verified probabilistic atlas system. We find that approximately 50% of reported responses were located in the region with high probability (≥80%) of belonging to the amygdala. This group included responses related both to stimuli of positive and negative emotional valence. Approximately 10% of reported response sites were assigned to the hippocampus, with up to 100% assignment probability. The remaining peaks were either located in the border regions of the amygdala and/or hippocampus or outside of both of these structures. Within the amygdala, the majority of peaks (96.3%) were found in the laterobasal (LB) and superficial (SF) subregions. Only 3.7% of peaks were found in the centromedial group (CM), possibly because anatomically delineating the CM region of the amygdala is particularly difficult and hence its extent might have been underestimated. Moreover, these results show that a core region of the amygdala is responsive to stimuli both of positive and negative emotional valence. The current findings highlight the usefulness of probabilistic amygdala maps and also point to a need for the development of accurate in vivo delineation and parcellation of the amygdala.

Understanding the physical encoding of a memory (the engram) is a fundamental question in neuroscience. Although it has been established that the lateral amygdala is a key site for encoding associative fear memory, it is currently unclear... more

Understanding the physical encoding of a memory (the engram) is a fundamental question in neuroscience. Although it has been established that the lateral amygdala is a key site for encoding associative fear memory, it is currently unclear whether the spatial distribution of neurons encoding a given memory is random or stable. Here we used spatial principal components analysis to quantify the topography of activated neurons, in a select region of the lateral amygdala, from rat brains encoding a Pavlovian conditioned fear memory. Our results demonstrate a stable, spatially patterned organization of amygdala neurons are activated during the formation of a Pavlovian conditioned fear memory. We suggest that this stable neuronal assembly constitutes a spatial dimension of the engram.

Adolescent alcohol use is common and evidence suggests that early use may lead to an increased risk of later dependence. Persisting neuroadaptions in the amygdala as a result of chronic alcohol use have been associated with negative... more

Adolescent alcohol use is common and evidence suggests that early use may lead to an increased risk of later dependence. Persisting neuroadaptions in the amygdala as a result of chronic alcohol use have been associated with negative emotional states that may lead to increased alcohol intake. This study assessed the long-term impact of ethanol consumption on levels of several basolateral amygdala mRNAs in rats that consumed ethanol in adolescence or adulthood. Male Long-Evans rats were allowed restricted access to ethanol or water during adolescence (P28, n = 11, controls = 11) or adulthood (P80, n = 8, controls = 10) for 18 days. After a sixty day abstinent period, the brain was removed and sections containing the basolateral amygdala were taken. In situ hybridization was performed for GABA A α 1 , glutamic acid decarboxylase (GAD 67 ), corticotropin releasing factor (CRF), and N-methyl-D-aspartate (NMDA) NR2A mRNAs. A significant decrease was observed in GABA A α 1 , GAD 67 , and CRF, but not NR2A, mRNAs in adult rats that consumed ethanol in comparison to controls. No significant changes were seen in adolescent consumers of ethanol for any of the probes tested. A separate analysis for each probe in the piriform cortex ascertained that the changes after ethanol consumption were specific to the basolateral amygdala. These results indicate that chronic ethanol consumption induces age-dependent alterations in basolateral amygdala neurochemistry.

Dysfunction in the prefrontal cortex, amygdala, and hippocampus is believed to underlie the development of much psychopathology. However, to date only limited longitudinal data relate early behavior with neural structure later in life.... more

Dysfunction in the prefrontal cortex, amygdala, and hippocampus is believed to underlie the development of much psychopathology. However, to date only limited longitudinal data relate early behavior with neural structure later in life. Our objective was to examine the relationship of early life externalizing behavior with adolescent brain structure. We report here the first longitudinal study linking externalizing behavior during preschool to brain structure during adolescence. We examined the relationship of preschool externalizing behavior with amygdala, hippocampus, and prefrontal cortex volumes at age 15 years in a community sample of 76 adolescents followed longitudinally since their mothers' pregnancy. A significant gender by externalizing behavior interaction revealed that males-but not females-with greater early childhood externalizing behavior had smaller amygdala volumes at adolescence (t = 2.33, p = .023). No significant results were found for the hippocampus or the prefrontal cortex.

Dysfunction in the prefrontal cortex, amygdala, and hippocampus is believed to underlie the development of much psychopathology. However, to date only limited longitudinal data relate early behavior with neural structure later in life.... more

Dysfunction in the prefrontal cortex, amygdala, and hippocampus is believed to underlie the development of much psychopathology. However, to date only limited longitudinal data relate early behavior with neural structure later in life. Our objective was to examine the relationship of early life externalizing behavior with adolescent brain structure. We report here the first longitudinal study linking externalizing behavior during preschool to brain structure during adolescence. We examined the relationship of preschool externalizing behavior with amygdala, hippocampus, and prefrontal cortex volumes at age 15 years in a community sample of 76 adolescents followed longitudinally since their mothers' pregnancy. A significant gender by externalizing behavior interaction revealed that males-but not females-with greater early childhood externalizing behavior had smaller amygdala volumes at adolescence (t = 2.33, p = .023). No significant results were found for the hippocampus or the prefrontal cortex.

In the present study, we examined the role of the auditory thalamus [medial division of the medial geniculate nucleus and the adjacent posterior intralaminar nucleus (MGm/PIN)] in auditory pavlovian fear conditioning using pharmacological... more

In the present study, we examined the role of the auditory thalamus [medial division of the medial geniculate nucleus and the adjacent posterior intralaminar nucleus (MGm/PIN)] in auditory pavlovian fear conditioning using pharmacological manipulation of intracellular signaling pathways. In the first experiment, rats were given intrathalamic infusions of the MEK (mitogen-activated protein kinase kinase) inhibitor 1,4-diamino-2,3-dicyano-1,4-bis(o-aminophenylmercapto) butadiene (U0126) before fear conditioning. Findings revealed that long-term memory (assessed at 24 h) was impaired, whereas short-term memory (assessed at 1–3 h) of fear conditioning was
intact. In the second experiment, rats received immediate posttraining intrathalamic infusion of U0126, the mRNA synthesis inhibitor 5,6-dichloro-1--D-ribofuranosylbenzimidazole (DRB), or infusion of the protein synthesis inhibitor anisomycin. Posttraining infusion
of either U0126 or DRB significantly impaired long-term retention of fear conditioning, whereas infusion of anisomycin had no effect. In the final experiment, rats received intrathalamic infusion of U0126 before long-term potentiation (LTP)-inducing stimulation of thalamic inputs to the lateral nucleus of the amygdala (LA). Findings revealed that thalamic infusion of U0126 impaired LTP in the LA. Together, these results suggest the possibility that MGm/PIN cells that project to the LA contribute to memory formation via ERK
(extracellular signal-regulated kinase)-mediated transcription, but that they do so by promoting protein synthesis-dependent
plasticity locally in the LA.

The amygdala is known to play an important role in the response to facial expressions that convey fear. However, it remains unclear whether the amygdalas response to fear reflects its role in the interpretation of danger and threat, or... more

The amygdala is known to play an important role in the response to facial expressions that convey fear. However, it remains unclear whether the amygdalas response to fear reflects its role in the interpretation of danger and threat, or whether it is to some extent activated by all facial expressions of emotion. Previous attempts to address this issue using neuroimaging have been confounded by differences in the use of control stimuli across studies. Here, we address this issue using a block design functional magnetic resonance imaging paradigm, in which we compared the response to face images posing expressions of fear, anger, happiness, disgust and sadness with a range of control conditions. The responses in the amygdala to different facial expressions were compared with the responses to a non-face condition (buildings), to mildly happy faces and to neutral faces. Results showed that only fear and anger elicited significantly greater responses compared with the control conditions involving faces. Overall, these findings are consistent with the role of the amygdala in processing threat, rather than in the processing of all facial expressions of emotion, and demonstrate the critical importance of the choice of comparison condition to the pattern of results.