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

2025, Brain : a journal of neurology

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 (<200 ms), which-in turn-predicts intention attribution. The amygdala was the only site that systematically discriminated between critical conditions and predicted their classific...

2025, Brain : a journal of neurology

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 (<200 ms), which-in turn-predicts intention attribution. The amygdala was the only site that systematically discriminated between critical conditions and predicted their classific...

2025, Brain : a journal of neurology

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 (<200 ms), which-in turn-predicts intention attribution. The amygdala was the only site that systematically discriminated between critical conditions and predicted their classific...

2024, Journal of Neuroscience

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.

2024, ENeuro

The lateral amygdala (LA) plays a critical role in the formation of fear-conditioned associative memories. Previous studies have used c-fos regulated expression to identify a spatially restricted population of neurons within the LA that... more

The lateral amygdala (LA) plays a critical role in the formation of fear-conditioned associative memories. Previous studies have used c-fos regulated expression to identify a spatially restricted population of neurons within the LA that is specifically activated by fear learning. These neurons are likely to be a part of a memory engram, but, to date, functional evidence for this has been lacking. We show that neurons within a spatially restricted region of the LA had an increase in both the frequency and amplitude of spontaneous postsynaptic currents (sPSC) when compared to neurons recorded from home cage control mice. We then more specifically addressed if this increased synaptic activity was limited to learning-activated neurons. Using a fos-tau-LacZ (FTL) transgenic mouse line, we developed a fluorescence-based method of identifying and recording from neurons activated by fear learning (FTL ϩ) in acute brain slices. An increase in frequency and amplitude of sPSCs was observed in FTL ϩ neurons when compared to nonactivated FTL Ϫ neurons in fear-conditioned mice. No learning-induced changes were observed in the action potential (AP) input-output relationships. These findings support the idea that a discrete LA neuron population forms part of a memory engram through changes in synaptic connectivity.

2024, Frontiers in human neuroscience

Broca's area has been suggested as the area responsible for the domain-general hierarchical processing of language and music. Although meaningful action shares a common hierarchical structure with language and music, the role of... more

Broca's area has been suggested as the area responsible for the domain-general hierarchical processing of language and music. Although meaningful action shares a common hierarchical structure with language and music, the role of Broca's area in this domain remains controversial. To address the involvement of Broca's area in the processing action hierarchy, the activation of Broca's area was measured using near-infrared spectroscopy. Measurements were taken while participants watched silent movies that featured hand movements playing familiar and unfamiliar melodies. The unfamiliar melodies were reversed versions of the familiar melodies. Additionally, to investigate the effect of a motor experience on the activation of Broca's area, the participants were divided into well-trained and less-trained groups. The results showed that Broca's area in the well-trained participants demonstrated a significantly larger activation in response to the hand motion when an u...

2024, Journal of Neuroscience

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.

2023, Human Brain Mapping

The amygdala, a small deep brain structure involved in behavioral processing through interactions with other brain regions, has garnered increased attention in recent years in relation to pain processing. As pain is a multidimensional... more

The amygdala, a small deep brain structure involved in behavioral processing through interactions with other brain regions, has garnered increased attention in recent years in relation to pain processing. As pain is a multidimensional experience that encompasses physical sensation, affect, and cognition, the amygdala is well suited to play a part in this process. Multiple neuroimaging studies of pain in humans have reported activation in the amygdala. Here, we summarize these studies by performing a coordinate-based meta-analysis within experimentally induced and clinical pain studies using an activation likelihood estimate analysis. The results are presented in relation to locations of peak activation within and outside of amygdala subregions. The majority of studies identified coordinates consistent with human amygdala cytoarchitecture indicating reproducibility in neuroanatomical labeling across labs, analysis methods, and imaging modalities. Differences were noted between healthy and clinical pain studies: in clinical pain studies, peak activation was located in the laterobasal region, suggestive of the cognitive-affective overlay present among individuals suffering from chronic pain; while the less understood superficial region of the amygdala was prominent among experimental pain studies. Taken together, these findings suggest several important directions for further research exploring the amygdala's role in pain processing.

2023, NeuroImage: Clinical

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will... more

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2023, Neuroscience

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 ␤ 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].

2023, Brain : a journal of neurology

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 (<200 ms), which-in turn-predicts intention attribution. The amygdala was the only site that systematically discriminated between critical conditions and predicted their classific...

2023, Psychiatry Research: Neuroimaging

Anxiety disorders (AD) are the most prevalent group of psychiatric disorders in adolescents and young adults. Nevertheless, its pathophysiology of anxiety disorders is still poorly understood. This study investigated differences in the... more

Anxiety disorders (AD) are the most prevalent group of psychiatric disorders in adolescents and young adults. Nevertheless, its pathophysiology of anxiety disorders is still poorly understood. This study investigated differences in the functional connectivity of intrinsic amygdala-based networks of participants with and without AD. Resting state fMRI data were obtained from 18 participants with an AD and 19 healthy comparison individuals. Psychiatric diagnosis was assessed using standardized structured interviews. The comparison between groups was carried out using functional connectivity maps from six seed regions defined using probabilistic maps bilaterally within the amygdala (basolateral, superficial and centromedial amygdala). We found significant between-group differences in five clusters, which showed aberrant functional connectivity with the left basolateral amygdala: right precentral gyrus, right cingulate gyrus, bilateral precuneus, and right superior frontal gyrus in subjects with AD as compared with the comparison subjects. For the comparison subjects, the correlations between the amygdala and the five clusters were either non-significant, or negative. The present study suggests there is an intrinsic disruption in the communication between left basolateral amygdala and a network of brain regions involved with emotion regulation, and with the default mode network in adolescents and young adults with anxiety disorders.

2023, Cerebral Cortex

Uncertainty about potential negative future outcomes can cause stress and is a central feature of anxiety disorders. The stress and anxiety associated with uncertain situations may lead individuals to overestimate the frequency with which... more

Uncertainty about potential negative future outcomes can cause stress and is a central feature of anxiety disorders. The stress and anxiety associated with uncertain situations may lead individuals to overestimate the frequency with which uncertain cues are followed by negative outcomes, an example of covariation bias. Using functional magnetic resonance imaging, we found that uncertaintyrelated expectations modulated neural responses to aversion. Insula and amygdala responses to aversive pictures were larger after an uncertain cue (that preceded aversive or neutral pictures) than a certain cue (that always preceded aversive pictures). Anticipatory anterior cingulate cortex (ACC) activity elicited by the cues was inversely associated with the insula and amygdala responses to aversive pictures following the cues. Nearly 75% of subjects overestimated the frequency of aversive pictures following uncertain cues, and ACC and insula activity predicted this uncertainty-related covariation bias. Findings provide the first evidence of the brain mechanisms of covariation bias and highlight the temporal dynamics of ACC, insula, and amygdala recruitment for processing aversion in the context of uncertainty.

2023

Urbach–Wiethe (or lipoid proteinosis) disease (UWD) is a rare autosomal recessive disorder characterized by dermatological, psychiatric, and neurological symptoms. Presentation occurs during childhood, but can be observed from birth.... more

Urbach–Wiethe (or lipoid proteinosis) disease (UWD) is a rare autosomal recessive disorder characterized by dermatological, psychiatric, and neurological symptoms. Presentation occurs during childhood, but can be observed from birth. While benign, the disease is progressive and chronic with no known cure. Treatment modalities are palliative for symptoms. The extant literature consists mainly of anecdotal reports and case studies that are limited by small sample sizes and paucity of controlled studies. Incidence and prevalence rates are unknown. There are less than 500 documented cases reported worldwide, and of those, less than 50 cases demonstrate neurological and neuropsychiatric conditions. Worldwide occurrence of the disease is documented, with the largest cohort living in a remote area of South Africa. The affected individuals are mainly Caucasian, born to consanguineous parents, and from Dutch or German heritage. Patients affected have been reported in China, Pakistan and Iran...

2023, Clinical and experimental neurology

Urbach–Wiethe (or lipoid proteinosis) disease (UWD) is a rare autosomal recessive disorder characterized by dermatological, psychiatric, and neurological symptoms. Presentation occurs during childhood, but can be observed from birth.... more

Urbach–Wiethe (or lipoid proteinosis) disease (UWD) is a rare autosomal recessive disorder characterized by dermatological, psychiatric, and neurological symptoms. Presentation occurs during childhood, but can be observed from birth. While benign, the disease is progressive and chronic with no known cure. Treatment modalities are palliative for symptoms. The extant literature consists mainly of anecdotal reports and case studies that are limited by small sample sizes and paucity of controlled studies. Incidence and prevalence rates are unknown. There are less than 500 documented cases reported worldwide, and of those, less than 50 cases demonstrate neurological and neuropsychiatric conditions. Worldwide occurrence of the disease is documented, with the largest cohort living in a remote area of South Africa. The affected individuals are mainly Caucasian, born to consanguineous parents, and from Dutch or German heritage. Patients affected have been reported in China, Pakistan and Iran...

2023, Brain : a journal of neurology

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 (<200 ms), which-in turn-predicts intention attribution. The amygdala was the only site that systematically discriminated between critical conditions and predicted their classific...

2023, NeuroImage: Clinical

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will... more

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2023, Brain : a journal of neurology

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 (<200 ms), which-in turn-predicts intention attribution. The amygdala was the only site that systematically discriminated between critical conditions and predicted their classific...

2023, Psychiatry Research: Neuroimaging

Anxiety disorders (AD) are the most prevalent group of psychiatric disorders in adolescents and young adults. Nevertheless, its pathophysiology of anxiety disorders is still poorly understood. This study investigated differences in the... more

Anxiety disorders (AD) are the most prevalent group of psychiatric disorders in adolescents and young adults. Nevertheless, its pathophysiology of anxiety disorders is still poorly understood. This study investigated differences in the functional connectivity of intrinsic amygdala-based networks of participants with and without AD. Resting state fMRI data were obtained from 18 participants with an AD and 19 healthy comparison individuals. Psychiatric diagnosis was assessed using standardized structured interviews. The comparison between groups was carried out using functional connectivity maps from six seed regions defined using probabilistic maps bilaterally within the amygdala (basolateral, superficial and centromedial amygdala). We found significant between-group differences in five clusters, which showed aberrant functional connectivity with the left basolateral amygdala: right precentral gyrus, right cingulate gyrus, bilateral precuneus, and right superior frontal gyrus in subjects with AD as compared with the comparison subjects. For the comparison subjects, the correlations between the amygdala and the five clusters were either non-significant, or negative. The present study suggests there is an intrinsic disruption in the communication between left basolateral amygdala and a network of brain regions involved with emotion regulation, and with the default mode network in adolescents and young adults with anxiety disorders.

2023, Journal of research on adolescence : the official journal of the Society for Research on Adolescence

We examined whether cognitive control moderates the effects of emotion on adolescent internalizing and externalizing symptomatology in a longitudinal study of 138 adolescents. Self-reported positive affect (PA) and negative affect and... more

We examined whether cognitive control moderates the effects of emotion on adolescent internalizing and externalizing symptomatology in a longitudinal study of 138 adolescents. Self-reported positive affect (PA) and negative affect and behavioral and neural indicators of cognitive control, indexed by performance and prefrontal hemodynamic response during a cognitive interference task, were collected at Time 1. Self-reported internalizing and externalizing symptomatology were collected at Time 1 and Time 2 (1 year later). Results indicated that higher PA predicted decreases in externalizing symptomatology, but only for adolescents with poor neural cognitive control. No moderation effects were found for behavioral cognitive control. Findings imply the beneficial effects of PA on the development of externalizing problems among adolescents with poor prefrontal functioning.

2023, International Journal of Environmental Research and Public Health

This study investigates age and cultural differences in the negative effects of senders’ wearing masks on receivers’ readabilities of senders’ facially expressed emotions in interpersonal interactions. An online experiment was thus... more

This study investigates age and cultural differences in the negative effects of senders’ wearing masks on receivers’ readabilities of senders’ facially expressed emotions in interpersonal interactions. An online experiment was thus conducted with Koreans and Americans aged over 20 years. Based on sampling quotas by nationality, age group and gender, Korean (n = 240) and American (n = 273) participants were recruited from panel members of a Korean research company and Amazon’s Mechanical Turk via email and the website, respectively. The participants played receiver roles to infer senders’ facially expressed emotions presented in photos in the experiment. They judged emotions facially expressed by the senders without masks and with masks are shown in photos. The results revealed that the senders’ wearing masks reduced the readabilities of the senders’ facially expressed anger among participants aged 30–49 years more than among participants aged 20–29 years. The senders’ wearing masks ...

2023, Brain : a journal of neurology

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 (<200 ms), which-in turn-predicts intention attribution. The amygdala was the only site that systematically discriminated between critical conditions and predicted their classific...

2022, Diagnostic Pathology

Lipoid proteinosis is a rare autosomal recessive disease characterized by cutaneous and mucosal lesions and hoarseness appearing in early childhood that is caused by homozygous or compound heterozygous mutations in the ECM1 gene located... more

Lipoid proteinosis is a rare autosomal recessive disease characterized by cutaneous and mucosal lesions and hoarseness appearing in early childhood that is caused by homozygous or compound heterozygous mutations in the ECM1 gene located on chromosome 1q21. The aim of the study was to investigate the molecular genetic defect underlying lipoid proteinosis in a consanguineous Pakistani family. Methods Genotyping of seven members of the family was performed by amplifying microsatellite markers, tightly linked to the ECM1 gene. To screen for mutations in the ECM1 gene, all of its exons and splice junctions were PCR amplified from genomic DNA and analyzed by SSCP and sequenced directly in an ABI 3130 genetic analyzer. Results The results revealed linkage of the LP family to the ECM1 locus. Sequence analysis of the coding exons and splice junctions of the ECM1 gene revealed a novel homozygous mutation (c.616C > T) in exon 6, predicted to replace glutamine with stop codon (p.Q206X) at am...

2022, Journal of Neuroscience

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.

2022, Journal of Neuroscience

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.

2022, Neuroscience

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 ␤ 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].

2022, Nature Neuroscience

2022, Nature Neuroscience

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.

2022, NeuroImage: Clinical

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will... more

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2022, NeuroImage: Clinical

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will... more

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2022, Cerebral Cortex

Uncertainty about potential negative future outcomes can cause stress and is a central feature of anxiety disorders. The stress and anxiety associated with uncertain situations may lead individuals to overestimate the frequency with which... more

Uncertainty about potential negative future outcomes can cause stress and is a central feature of anxiety disorders. The stress and anxiety associated with uncertain situations may lead individuals to overestimate the frequency with which uncertain cues are followed by negative outcomes, an example of covariation bias. Using functional magnetic resonance imaging, we found that uncertaintyrelated expectations modulated neural responses to aversion. Insula and amygdala responses to aversive pictures were larger after an uncertain cue (that preceded aversive or neutral pictures) than a certain cue (that always preceded aversive pictures). Anticipatory anterior cingulate cortex (ACC) activity elicited by the cues was inversely associated with the insula and amygdala responses to aversive pictures following the cues. Nearly 75% of subjects overestimated the frequency of aversive pictures following uncertain cues, and ACC and insula activity predicted this uncertainty-related covariation bias. Findings provide the first evidence of the brain mechanisms of covariation bias and highlight the temporal dynamics of ACC, insula, and amygdala recruitment for processing aversion in the context of uncertainty.

2022, Cerebral Cortex

Uncertainty about potential negative future outcomes can cause stress and is a central feature of anxiety disorders. The stress and anxiety associated with uncertain situations may lead individuals to overestimate the frequency with which... more

Uncertainty about potential negative future outcomes can cause stress and is a central feature of anxiety disorders. The stress and anxiety associated with uncertain situations may lead individuals to overestimate the frequency with which uncertain cues are followed by negative outcomes, an example of covariation bias. Using functional magnetic resonance imaging, we found that uncertaintyrelated expectations modulated neural responses to aversion. Insula and amygdala responses to aversive pictures were larger after an uncertain cue (that preceded aversive or neutral pictures) than a certain cue (that always preceded aversive pictures). Anticipatory anterior cingulate cortex (ACC) activity elicited by the cues was inversely associated with the insula and amygdala responses to aversive pictures following the cues. Nearly 75% of subjects overestimated the frequency of aversive pictures following uncertain cues, and ACC and insula activity predicted this uncertainty-related covariation bias. Findings provide the first evidence of the brain mechanisms of covariation bias and highlight the temporal dynamics of ACC, insula, and amygdala recruitment for processing aversion in the context of uncertainty.

2022, NeuroImage: Clinical

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will... more

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2022, NeuroImage: Clinical

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will... more

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

2022, Behavioral Neuroscience

The role of the basolateral amygdala (BLA) in the acquisition and expression of Pavlovian fear conditioning was examined in 80 rats. Excitotoxic lesions were made in the BLA using N-methyl-o-aspartate 7 days before or 1, 14, or 28 days... more

The role of the basolateral amygdala (BLA) in the acquisition and expression of Pavlovian fear conditioning was examined in 80 rats. Excitotoxic lesions were made in the BLA using N-methyl-o-aspartate 7 days before or 1, 14, or 28 days after Pavlovian fear conditioning. Conditioning consisted of three pairings of a tone with an aversive footshock in a novel chamber, and freezing behavior served as an index of conditional fear. BLA lesions abolished conditional freezing to both the contextual and acoustic conditional stimuli at all training-to-lesion intervals, and the magnitude of the impairment did not vary as a function of the training-to-lesion interval. Reacquisition training elevated levels of freezing in rats with BLA lesions but did not reduce the magnitude of their deficit in relation to that of controls. These results reveal that neurons in the BLA have an enduring role in the expression of conditional fear.

2022, Molecular Psychiatry

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2022, Brain : a journal of neurology

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 (<200 ms), which-in turn-predicts intention attribution. The amygdala was the only site that systematically discriminated between critical conditions and predicted their classific...

2022, PLOS ONE

Background Theory and research suggest that social dominance is important for multiple forms of psychopathology, and yet few studies have considered multiple dimensions of psychopathology simultaneously, and relatively few have used... more

Background Theory and research suggest that social dominance is important for multiple forms of psychopathology, and yet few studies have considered multiple dimensions of psychopathology simultaneously, and relatively few have used well-validated behavioral indices. Method Among 81 undergraduates, we used a well-validated experimental approach of assigning participants to a leadership or subordinate position, and we examined how self-rated severity of depression, social anxiety, manic tendencies, and psychopathy relate to psychophysiological and affective reactivity to this role. Results Consistent with hypotheses, manic symptoms related to more discomfort in the subordinate role compared to the leadership role, as evidenced by more decline in positive affect, more discomfort, and a larger RSA decline, while depression symptoms related to a more positive response to the subordinate role than the leadership role, including more positive affect and more comfort in the assigned role. ...

2022, The Journal of neuroscience : the official journal of the Society for Neuroscience

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...

2022, Brain : a journal of neurology

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 (<200 ms), which-in turn-predicts intention attribution. The amygdala was the only site that systematically discriminated between critical conditions and predicted their classific...

2022, Journal of Pragmatics

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.

2022, Social Cognitive and Affective Neuroscience

In this study, we compared the effects of using neutral face masks vs non-face pattern masks on amygdala activity to masked fearful faces. Twenty-seven subjects viewed 18 s blocks of either fearful or happy faces masked with either... more

In this study, we compared the effects of using neutral face masks vs non-face pattern masks on amygdala activity to masked fearful faces. Twenty-seven subjects viewed 18 s blocks of either fearful or happy faces masked with either neutral faces or patterns, while their brain activity was measured using functional magnetic resonance imaging. Results replicated increased amygdala activation to face-masked fearful vs happy faces. In the pattern mask condition, the amygdala discriminated between masked fearful and happy faces, but this effect manifested as a decrease in activation to fearful faces compared to happy faces. This interactive effect between facial expression and mask stimulus shows that amygdala responses to masked fearful faces are influenced by the fearful stimuli per se as well as their interaction with the mask stimulus.

2022, Proceedings of the Royal Society B: Biological Sciences

It is presently unknown whether our response to affective vocalizations is specific to those generated by humans or more universal, triggered by emotionally matched vocalizations generated by other species. Here, we used functional... more

It is presently unknown whether our response to affective vocalizations is specific to those generated by humans or more universal, triggered by emotionally matched vocalizations generated by other species. Here, we used functional magnetic resonance imaging in normal participants to measure cerebral activity during auditory stimulation with affectively valenced animal vocalizations, some familiar (cats) and others not (rhesus monkeys). Positively versus negatively valenced vocalizations from cats and monkeys elicited different cerebral responses despite the participants' inability to differentiate the valence of these animal vocalizations by overt behavioural responses. Moreover, the comparison with human non-speech affective vocalizations revealed a common response to the valence in orbitofrontal cortex, a key component on the limbic system. These findings suggest that the neural mechanisms involved in processing human affective vocalizations may be recruited by heterospecific...

2022, Brain, Behavior, and Immunity

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.

2022, Molecular Syndromology

Lipoid proteinosis (LP) is an autosomal recessive genodermatosis known to be caused by mutations in ECM1. Nonsense and missense mutations are the most common variations in LP. Up to date, only 6 splice site mutations have been observed.... more

Lipoid proteinosis (LP) is an autosomal recessive genodermatosis known to be caused by mutations in ECM1. Nonsense and missense mutations are the most common variations in LP. Up to date, only 6 splice site mutations have been observed. We report on a 26-year-old female LP patient from a Turkish consanguineous family carrying a novel homozygous splice site mutation in intron 8 of the ECM1 gene and summarize the current knowledge on ECM1 mutations and possible genotype-phenotype correlations.

2021

A number of mutations in extracellular matrix protein 1 (ECM1) that is a glycoprotein and expressed in skin and other tissues are reported to cause a rare, autosomal recessive disorder called lipoid proteinosis (LP). The peculiar... more

A number of mutations in extracellular matrix protein 1 (ECM1) that is a glycoprotein and expressed in skin and other tissues are reported to cause a rare, autosomal recessive disorder called lipoid proteinosis (LP). The peculiar manifestation of LP is hoarseness of voice caused by laryngeal infiltration in infancy. Skin and mucous membrane changes clinically become apparent, and the disease typically follows a slowly progressive, yet often benign, course. About 300 cases of LP have been reported, but occurrence in siblings is rare. In this study, two siblings (18 and 24-year-old) of a Pakistani family were reported to have LP. This study presents two brothers with scaly itchy lesions on whole body, hoarse voice and macroglossia. Their deceased father had similar clinical manifestations but mother, younger brother and sister were unaffected. Blood from affected and clinically unaffected family members were collected with informed consent. The ECM1 gene containing 10 exons were amplified and sequenced. Both patients showed non-pathogenic missense and silent mutations in exon 6 and 8. In exon 6, a nucleotide C was substituted to T (C→ → → →T) at codon 2, in patient 1. This nonpathogenic missense mutation causes appearance of amino acid cysteine instead of arginine that is part of normal ECM1 protein. In patient 2, polymorphism of nucleotide C to T (C/T) was observed observed in exion 6 that may lead to the appearance of cysteine and/or arginine in the resulting gene product. In exon 8, a nucleotide G was substituted to A (G→ → → →A) at codon 53, in patient 1. This substitution leads to a silent mutation as serine is coded by both forms of codon. In patient 2, polymorphism of nucleotide G to A (G/A) was observed in exion 8 that do not cause any change in the coded amino acid. These findings represent a set of missense and silent mutations supporting an unusual function of ECM1 protein, broadening the spectrum of disease-linked mutations in rare cases of LP.

2021, Neurology research international

We used functional magnetic resonance imaging to investigate the neural basis of the mere exposure effect in music listening, which links previous exposure to liking. Prior to scanning, participants underwent a learning phase, where... more

We used functional magnetic resonance imaging to investigate the neural basis of the mere exposure effect in music listening, which links previous exposure to liking. Prior to scanning, participants underwent a learning phase, where exposure to melodies was systematically varied. During scanning, participants rated liking for each melody and, later, their recognition of them. Participants showed learning effects, better recognising melodies heard more often. Melodies heard most often were most liked, consistent with the mere exposure effect. We found neural activations as a function of previous exposure in bilateral dorsolateral prefrontal and inferior parietal cortex, probably reflecting retrieval and working memory-related processes. This was despite the fact that the task during scanning was to judge liking, not recognition, thus suggesting that appreciation of music relies strongly on memory processes. Subjective liking per se caused differential activation in the left hemispher...

2021, Neurology Research International

We used functional magnetic resonance imaging to investigate the neural basis of the mere exposure effect in music listening, which links previous exposure to liking. Prior to scanning, participants underwent a learning phase, where... more

We used functional magnetic resonance imaging to investigate the neural basis of the mere exposure effect in music listening, which links previous exposure to liking. Prior to scanning, participants underwent a learning phase, where exposure to melodies was systematically varied. During scanning, participants rated liking for each melody and, later, their recognition of them. Participants showed learning effects, better recognising melodies heard more often. Melodies heard most often were most liked, consistent with the mere exposure effect. We ...

2021, NeuroImage

The blood oxygen level-dependent (BOLD) signal time course in the auditory cortex is characterized by two components, an initial transient peak and a subsequent sustained plateau with smaller amplitude. Because the T 2 * signal detected... more

The blood oxygen level-dependent (BOLD) signal time course in the auditory cortex is characterized by two components, an initial transient peak and a subsequent sustained plateau with smaller amplitude. Because the T 2 * signal detected by functional magnetic resonance imaging (fMRI) depends on at least two counteracting factors, blood oxygenation and volume, we examined whether the reduction in the sustained BOLD signal results from decreased levels of oxygenation or from increased levels of blood volume. We used conventional fMRI to quantify the BOLD signal and fMRI in combination with superparamagnetic contrast agent to quantify blood volume and employed repetition rate-modulated sounds in a silent background to manipulate the response amplitude in the auditory cortex. In the BOLD signal, the initial peak reached 3.3% with pulsed sound and 1.9% with continuous sound, whereas the sustained BOLD signal fell to 2.2% with pulsed sound and to 0.5% with continuous sound, respectively. The repetition rate-dependent reduction in the sustained BOLD amplitude was accompanied by concordant changes in sustained blood volume levels, which, compared to silence, increased by ϳ30% with pulsed and by ϳ10% with continuous sound. Thus, our data suggest that the reduced amplitude of the sustained BOLD signal reflects stimulus-dependent modulation of blood oxygenation rather than blood volume-related effects.