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Sample records for left amygdala involvement

  1. Spider phobia is associated with decreased left amygdala volume: a cross-sectional study

    Science.gov (United States)

    2013-01-01

    Background Evidence from animal and human studies imply the amygdala as the most critical structure involved in processing of fear-relevant stimuli. In phobias, the amygdala seems to play a crucial role in the pathogenesis and maintenance of the disorder. However, the neuropathology of specific phobias remains poorly understood. In the present study, we investigated whether patients with spider phobia show altered amygdala volumes as compared to healthy control subjects. Methods Twenty female patients with spider phobia and twenty age-matched healthy female controls underwent magnetic resonance imaging to investigate amygdala volumes. The amygdalae were segmented using an automatic, model-based segmentation tool (FSL FIRST). Differences in amygdala volume were investigated by multivariate analysis of covariance with group as between-subject factor and left and right amygdala as dependent factors. The relation between amygdala volume and clinical features such as symptom severity, disgust sensitivity, trait anxiety and duration of illness was investigated by Spearman correlation analysis. Results Spider phobic patients showed significantly smaller left amygdala volume than healthy controls. No significant difference in right amygdala volume was detected. Furthermore, the diminished amygdala size in patients was related to higher symptom severity, but not to higher disgust sensitivity or trait anxiety and was independent of age. Conclusions In summary, the results reveal a relation between higher symptom severity and smaller left amygdala volume in patients with spider phobia. This relation was independent of other potential confounders such as the disgust sensitivity or trait anxiety. The findings suggest that greater spider phobic fear is associated with smaller left amygdala. However, the smaller left amygdala volume may either stand for a higher vulnerability to develop a phobic disorder or emerge as a consequence of the disorder. PMID:23442196

  2. Differential Contribution of Right and Left Amygdala to Affective Information Processing

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    Hans J. Markowitsch

    1999-01-01

    Full Text Available Evidence for a differential involvement of the human left and right amygdala in emotional and cognitive behaviour is reviewed, with a particular emphasis on functional imaging results and case reports on patients with amygdalar damage. The available evidence allows one to conclude that there is definitely a hemisphere specific processing difference between the left and right amygdala. However, between studies the direction of the asymmetry is partly incongruent. In spite of this, the following tentative proposals are made: the left amygdala is more closely related to affective information encoding with a higher affinity to language and to detailed feature extraction, and the right amygdala to affective information retrieval with a higher affinity to pictorial or image-related material. Furthermore, the right amygdala may be more strongly engaged than the left one in a fast, shallow or gross analysis of affect-related information.

  3. The left amygdala: A shared substrate of alexithymia and empathy.

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    Goerlich-Dobre, Katharina Sophia; Lamm, Claus; Pripfl, Juergen; Habel, Ute; Votinov, Mikhail

    2015-11-15

    Alexithymia, a deficit in emotional self-awareness, and deficits in empathy, which encompasses the awareness of other's emotions, are related constructs that are both associated with a range of psychopathological disorders. Neuroimaging studies suggest that there is overlap between the neural bases of alexithymia and empathy, but no systematic comparison has been conducted so far. The aim of this structural magnetic resonance imaging study was to disentangle the overlap and differences between the morphological profiles of the cognitive and affective dimensions of alexithymia and empathy, and to find out to what extent these differ between women and men. High-resolution T1 anatomical images were obtained from 125 healthy right-handers (18-42 years), 70 women and 55 men. By means of voxel-based morphometry, region of interest (ROI) analyses were performed on gray matter volumes of several anatomically defined a-priori regions previously linked to alexithymia and empathy. Partial correlations were conducted within the female and male group using ROI parameter estimates as dependent variables and the cognitive and affective dimensions of alexithymia and empathy, respectively, as predictors, controlling for age. Results were considered significant if they survived Holm-Bonferroni correction for multiple comparisons. The left amygdala was identified as a key substrate of both alexithymia and empathy. This association was characterized by an opposite pattern: The cognitive alexithymia dimension was linked to smaller, the two empathy dimensions to larger left amygdala volume. While sex-specific effects were not observed for empathy, they were evident for the affective alexithymia dimension: Men-but not women-with difficulty fantasizing had smaller gray matter volume in the middle cingulate cortex. Moreover, structural covariance patterns between the left amygdala and other emotion-related brain regions differed markedly between alexithymia and empathy. These differences

  4. Selective involvement of the amygdala in systemic lupus erythematosus.

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    Bart J Emmer

    2006-12-01

    Full Text Available BACKGROUND: Antibodies specifically affect the amygdala in a mouse model of systemic lupus erythematosus (SLE. The aim of our study was to investigate whether there is also specific involvement of the amygdala in human SLE. METHODS AND FINDINGS: We analyzed a group of 37 patients with neuropsychiatric SLE (NP-SLE, 21 patients with SLE, and a group of 12 healthy control participants with diffusion weighted imaging (DWI. In addition, in a subset of eight patients, plasma was available to determine their anti-NMDAR antibody status. From the structural magnetic resonance imaging data, the amygdala and the hippocampus were segmented, as well as the white and gray matter, and the apparent diffusion coefficient (ADC was retrieved. ADC values between controls, patients with SLE, and patients with NP-SLE were tested using analysis of variance with post-hoc Bonferroni correction. No differences were found in the gray or white matter segments. The average ADC in the amygdala of patients with NP-SLE and SLE (940 x 10(-6 mm2/s; p = 0.006 and 949 x 10(-6 mm2/s; p = 0.019, respectively was lower than in healthy control participants (1152 x 10(-6 mm2/s. Mann-Whitney analysis revealed that the average ADC in the amygdala of patients with anti-NMDAR antibodies (n = 4; 802 x 10(-6 mm2/s was lower (p = 0.029 than the average ADC of patients without anti-NMDAR antibodies (n = 4; 979 x 10(-6 mm2/s and also lower (p = 0.001 than in healthy control participants. CONCLUSIONS: This is the first study to our knowledge to observe damage in the amygdala in patients with SLE. Patients with SLE with anti-NMDAR antibodies had more severe damage in the amygdala compared to SLE patients without anti-NMDAR antibodies.

  5. Divergent functions of the left and right central amygdala in visceral nociception.

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    Sadler, Katelyn E; McQuaid, Neal A; Cox, Abigail C; Behun, Marissa N; Trouten, Allison M; Kolber, Benedict J

    2017-04-01

    The left and right central amygdalae (CeA) are limbic regions involved in somatic and visceral pain processing. These 2 nuclei are asymmetrically involved in somatic pain modulation; pain-like responses on both sides of the body are preferentially driven by the right CeA, and in a reciprocal fashion, nociceptive somatic stimuli on both sides of the body predominantly alter molecular and physiological activities in the right CeA. Unknown, however, is whether this lateralization also exists in visceral pain processing and furthermore what function the left CeA has in modulating nociceptive information. Using urinary bladder distension (UBD) and excitatory optogenetics, a pronociceptive function of the right CeA was demonstrated in mice. Channelrhodopsin-2-mediated activation of the right CeA increased visceromotor responses (VMRs), while activation of the left CeA had no effect. Similarly, UBD-evoked VMRs increased after unilateral infusion of pituitary adenylate cyclase-activating polypeptide in the right CeA. To determine intrinsic left CeA involvement in bladder pain modulation, this region was optogenetically silenced during noxious UBD. Halorhodopsin (NpHR)-mediated inhibition of the left CeA increased VMRs, suggesting an ongoing antinociceptive function for this region. Finally, divergent left and right CeA functions were evaluated during abdominal mechanosensory testing. In naive animals, channelrhodopsin-2-mediated activation of the right CeA induced mechanical allodynia, and after cyclophosphamide-induced bladder sensitization, activation of the left CeA reversed referred bladder pain-like behaviors. Overall, these data provide evidence for functional brain lateralization in the absence of peripheral anatomical asymmetries.

  6. Neuromyelitis optica spectrum disorder presenting with repeated hypersomnia due to involvement of the hypothalamus and hypothalamus-amygdala linkage.

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    Kume, Kodai; Deguchi, Kazushi; Ikeda, Kazuyo; Takata, Tadayuki; Kokudo, Yohei; Kamada, Masaki; Touge, Tetsuo; Takahashi, Toshiyuki; Kanbayashi, Takashi; Masaki, Tsutomu

    2015-06-01

    We report the case of a 46-year-old Japanese woman with neuromyelitis optica spectrum disorder presenting with repeated hypersomnia accompanied by decreased CSF orexin level. First episode associated with hypothalamic-pituitary dysfunction showed bilateral hypothalamic lesions that can cause secondary damage to the orexin neurons. The second episode associated with impaired memory showed a left temporal lesion involving the amygdala. The mechanism remains unknown, but the reduced blood flow in the hypothalamus ipsilateral to the amygdala lesion suggested trans-synaptic hypothalamic dysfunction secondary to the impaired amygdala. A temporal lesion involving the amygdala and hypothalamus could be responsible for hypersomnia due to neuromyelitis optica spectrum disorder. © The Author(s), 2015.

  7. Involvement of the amygdala in memory storage: Interaction with other brain systems

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    McGaugh, James L.; Cahill, Larry; Roozendaal, Benno

    1996-01-01

    There is extensive evidence that the amygdala is involved in affectively influenced memory. The central hypothesis guiding the research reviewed in this paper is that emotional arousal activates the amygdala and that such activation results in the modulation of memory storage occurring in other brain regions. Several lines of evidence support this view. First, the effects of stress-related hormones (epinephrine and glucocorticoids) are mediated by influences involving the amygdala. In rats, lesions of the amygdala and the stria terminalis block the effects of posttraining administration of epinephrine and glucocorticoids on memory. Furthermore, memory is enhanced by posttraining intra-amygdala infusions of drugs that activate β-adrenergic and glucocorticoid receptors. Additionally, infusion of β-adrenergic blockers into the amygdala blocks the memory-modulating effects of epinephrine and glucocorticoids, as well as those of drugs affecting opiate and GABAergic systems. Second, an intact amygdala is not required for expression of retention. Inactivation of the amygdala prior to retention testing (by posttraining lesions or drug infusions) does not block retention performance. Third, findings of studies using human subjects are consistent with those of animal experiments. β-Blockers and amygdala lesions attenuate the effects of emotional arousal on memory. Additionally, 3-week recall of emotional material is highly correlated with positron-emission tomography activation (cerebral glucose metabolism) of the right amygdala during encoding. These findings provide strong evidence supporting the hypothesis that the amygdala is involved in modulating long-term memory storage. PMID:8942964

  8. Amygdala's involvement in facilitating associative learning-induced plasticity: a promiscuous role for the amygdala in memory acquisition.

    Science.gov (United States)

    Chau, Lily S; Galvez, Roberto

    2012-01-01

    It is widely accepted that the amygdala plays a critical role in acquisition and consolidation of fear-related memories. Some of the more widely employed behavioral paradigms that have assisted in solidifying the amygdala's role in fear-related memories are associative learning paradigms. With most associative learning tasks, a neutral conditioned stimulus (CS) is paired with a salient unconditioned stimulus (US) that elicits an unconditioned response (UR). After multiple CS-US pairings, the subject learns that the CS predicts the onset or delivery of the US, and thus elicits a learned conditioned response (CR). Most fear-related associative paradigms have suggested that an aspect of the fear association is stored in the amygdala; however, some fear-motivated associative paradigms suggest that the amygdala is not a site of storage, but rather facilitates consolidation in other brain regions. Based upon various learning theories, one of the most likely sites for storage of long-term memories is the neocortex. In support of these theories, findings from our laboratory, and others, have demonstrated that trace-conditioning, an associative paradigm where there is a separation in time between the CS and US, induces learning-specific neocortical plasticity. The following review will discuss the amygdala's involvement, either as a site of storage or facilitating storage in other brain regions such as the neocortex, in fear- and non-fear-motivated associative paradigms. In this review, we will discuss recent findings suggesting a broader role for the amygdala in increasing the saliency of behaviorally relevant information, thus facilitating acquisition for all forms of memory, both fear- and non-fear-related. This proposed promiscuous role of the amygdala in facilitating acquisition for all memories further suggests a potential role of the amygdala in general learning disabilities.

  9. Right and left amygdalae activation in patients with major depression receiving antidepressant treatment, as revealed by fMRI.

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    Chen, Yen-Ting; Huang, Min-Wei; Hung, I-Chung; Lane, Hsien-Yuan; Hou, Chun-Ju

    2014-10-08

    A differential contribution of the right and left amygdalae to affective information processing has been proposed. However, the direction of this lateralization has not been confirmed. In this study, we used a pre- and post-treatment (escitalopram) design to analyze the relative differences between neural activity in the right and left amygdalae during exposure to emotional stimuli in currently depressed patients. To the best of our knowledge, this study is to compare neural activity between the left and right amygdalae in people with depression. Our findings could lead to the development of parameters or biomarkers for depressive symptoms and treatment response. We used a pre-post-test design without a control group. Twenty currently depressed participants underwent an emotion processing task during fMRI. These participants were then treated with an antidepressant for 6 weeks. We used amygdala region-of-interest analysis to evaluate the hemodynamic response during exposure to colored emotional pictures. In total, thirteen of the 20 participants were placed into a separate group based on degree of response to antidepressants. The partial response group had an averaged HDRS score of 10.75 ± 2.25 and an averaged DBOLDLR signal of 189.18 ± 140.23 (m1 = 8), and the remitted group had an averaged HDRS score of 4.80 ± 1.64 and an averaged DBOLDLR signal of 421.26 ± 109.19 (m2 = 5). Each individual had lateralized amygdala activity, and the direction of asymmetry persisted following treatment. Amygdala responses to four types of emotional stimuli did not significantly change (p > 0.05) with treatment in either the right or the left amygdala. However, the difference in neural activity between the right and left amygdalae was greater after treatment, and the variation in neural activity was larger in the left amygdala. We found that the response between the right and left amygdala did not differ in terms of time series, although activity increased after pharmaceutical

  10. Involvement of the amygdala in memory storage: Interaction with other brain systems

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    McGaugh, James L.; Cahill, Larry; Roozendaal, Benno

    1996-01-01

    There is extensive evidence that the amygdala is involved in affectively influenced memory. The central hypothesis guiding the research reviewed in this paper is that emotional arousal activates the amygdala and that such activation results in the modulation of memory storage occurring in other brain regions. Several lines of evidence support this view. First, the effects of stress-related hormones (epinephrine and glucocorticoids) are mediated by influences involving ...

  11. Abnormal left and right amygdala-orbitofrontal cortical functional connectivity to emotional faces: state versus trait vulnerability markers of depression in bipolar disorder.

    Science.gov (United States)

    Versace, Amelia; Thompson, Wesley K; Zhou, Donli; Almeida, Jorge R C; Hassel, Stefanie; Klein, Crystal R; Kupfer, David J; Phillips, Mary L

    2010-03-01

    Amygdala-orbitofrontal cortical (OFC) functional connectivity (FC) to emotional stimuli and relationships with white matter remain little examined in bipolar disorder individuals (BD). Thirty-one BD (type I; n = 17 remitted; n = 14 depressed) and 24 age- and gender-ratio-matched healthy individuals (HC) viewed neutral, mild, and intense happy or sad emotional faces in two experiments. The FC was computed as linear and nonlinear dependence measures between amygdala and OFC time series. Effects of group, laterality, and emotion intensity upon amygdala-OFC FC and amygdala-OFC FC white matter fractional anisotropy (FA) relationships were examined. The BD versus HC showed significantly greater right amygdala-OFC FC (p relationship (p = .001) between left amygdala-OFC FC to sad faces and FA in HC. In BD, antidepressants were associated with significantly reduced left amygdala-OFC FC to mild sad faces (p = .001). In BD, abnormally elevated right amygdala-OFC FC to sad stimuli might represent a trait vulnerability for depression, whereas abnormally elevated left amygdala-OFC FC to sad stimuli and abnormally reduced amygdala-OFC FC to intense happy stimuli might represent a depression state marker. Abnormal FC measures might normalize with antidepressant medications in BD. Nonlinear amygdala-OFC FC-FA relationships in BD and HC require further study. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  12. Differential Involvement of Amygdala and Cortical NMDA Receptors Activation upon Encoding in Odor Fear Memory

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    Hegoburu, Chloé; Parrot, Sandrine; Ferreira, Guilaume; Mouly, Anne-Marie

    2014-01-01

    Although the basolateral amygdala (BLA) plays a crucial role for the acquisition of fear memories, sensory cortices are involved in their long-term storage in rats. However, the time course of their respective involvement has received little investigation. Here we assessed the role of the glutamatergic N-methyl-D-aspartate (NMDA) receptors in the…

  13. The Amygdala Is Involved in Affective Priming Effect for Fearful Faces

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    Yang, J.; Cao, Z.; Xu, X.; Chen, G.

    2012-01-01

    The object of this study was to investigate whether the amygdala is involved in affective priming effect after stimuli are encoded unconsciously and consciously. During the encoding phase, each masked face (fearful or neutral) was presented to participants six times for 17 ms each, using a backward masking paradigm. During the retrieval phase,…

  14. Occupancy of serotonin transporters in the amygdala by paroxetine in association with attenuation of left amygdala activation by negative faces in major depressive disorder

    NARCIS (Netherlands)

    Ruhe, Henricus G.; Koster, Michiel; Booij, Jan; van Herk, Marcel; Veltman, Dick J.; Schene, Aart H.

    2014-01-01

    Amygdala hyperactivation in major depressive disorder (MDD) might be attenuated by selective serotonin reuptake inhibitors (SSRls), but the working mechanism remains unclear. We hypothesized that higher amygdala serotonin transporter (SERT) occupancy by paroxetine results in greater attenuation of

  15. Occupancy of serotonin transporters in the amygdala by paroxetine in association with attenuation of left amygdala activation by negative faces in major depressive disorder

    NARCIS (Netherlands)

    Ruhé, Henricus G.; Koster, Michiel; Booij, Jan; van Herk, Marcel; Veltman, Dick J.; Schene, Aart H.

    2014-01-01

    Amygdala hyperactivation in major depressive disorder (MDD) might be attenuated by selective serotonin reuptake inhibitors (SSRIs), but the working mechanism remains unclear. We hypothesized that higher amygdala serotonin transporter (SERT) occupancy by paroxetine results in greater attenuation of

  16. Monitoring and control of amygdala neurofeedback involves distributed information processing in the human brain.

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    Paret, Christian; Zähringer, Jenny; Ruf, Matthias; Gerchen, Martin Fungisai; Mall, Stephanie; Hendler, Talma; Schmahl, Christian; Ende, Gabriele

    2018-03-30

    Brain-computer interfaces provide conscious access to neural activity by means of brain-derived feedback ("neurofeedback"). An individual's abilities to monitor and control feedback are two necessary processes for effective neurofeedback therapy, yet their underlying functional neuroanatomy is still being debated. In this study, healthy subjects received visual feedback from their amygdala response to negative pictures. Activation and functional connectivity were analyzed to disentangle the role of brain regions in different processes. Feedback monitoring was mapped to the thalamus, ventromedial prefrontal cortex (vmPFC), ventral striatum (VS), and rostral PFC. The VS responded to feedback corresponding to instructions while rPFC activity differentiated between conditions and predicted amygdala regulation. Control involved the lateral PFC, anterior cingulate, and insula. Monitoring and control activity overlapped in the VS and thalamus. Extending current neural models of neurofeedback, this study introduces monitoring and control of feedback as anatomically dissociated processes, and suggests their important role in voluntary neuromodulation. © 2018 Wiley Periodicals, Inc.

  17. Left or right? Lateralizing temporal lobe epilepsy by dynamic amygdala fMRI.

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    Ives-Deliperi, Victoria; Butler, James Thomas; Jokeit, Hennric

    2017-05-01

    In this case series, the findings of 85 functional MRI studies employing a dynamic fearful face paradigm are reported. Previous findings have shown the paradigm to generate bilateral amygdala activations in healthy subjects and unilateral activations in patients with MTLE, in the contralateral hemisphere to seizure origin. Such findings suggest ipsilateral limbic pathology and offer collateral evidence in lateralizing MTLE. The series includes 60 patients with TLE, 12 patients with extra-temporal lobe epilepsy, and 13 healthy controls. Functional MRI studies using a 1.5T scanner were conducted over a three-year period at a single epilepsy center and individual results were compared with EEG findings. In the cohort of unilateral TLE patients, lateralized activations of the amygdala were concordant with EEG findings in 76% of patients (77% lTLE, 74% rTLE). The differences in the mean lateralized indices of the lTLE, rTLE, and healthy control groups were all statistically significant. Lateralized amygdala activations were concordant with EEG findings in only 31% of the 12 patients with extra-temporal lobe epilepsy and bilateral amygdala activations were generated in all but one of the healthy control subjects. This case series further endorses the utility of the dynamic fearful face functional MRI paradigm using the widely available 1.5T as an adjunctive investigation to lateralize TLE. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Limbic justice--amygdala involvement in immediate rejection in the Ultimatum Game.

    Directory of Open Access Journals (Sweden)

    Katarina Gospic

    2011-05-01

    Full Text Available Imaging studies have revealed a putative neural account of emotional bias in decision making. However, it has been difficult in previous studies to identify the causal role of the different sub-regions involved in decision making. The Ultimatum Game (UG is a game to study the punishment of norm-violating behavior. In a previous influential paper on UG it was suggested that frontal insular cortex has a pivotal role in the rejection response. This view has not been reconciled with a vast literature that attributes a crucial role in emotional decision making to a subcortical structure (i.e., amygdala. In this study we propose an anatomy-informed model that may join these views. We also present a design that detects the functional anatomical response to unfair proposals in a subcortical network that mediates rapid reactive responses. We used a functional MRI paradigm to study the early components of decision making and challenged our paradigm with the introduction of a pharmacological intervention to perturb the elicited behavioral and neural response. Benzodiazepine treatment decreased the rejection rate (from 37.6% to 19.0% concomitantly with a diminished amygdala response to unfair proposals, and this in spite of an unchanged feeling of unfairness and unchanged insular response. In the control group, rejection was directly linked to an increase in amygdala activity. These results allow a functional anatomical detection of the early neural components of rejection associated with the initial reactive emotional response. Thus, the act of immediate rejection seems to be mediated by the limbic system and is not solely driven by cortical processes, as previously suggested. Our results also prompt an ethical discussion as we demonstrated that a commonly used drug influences core functions in the human brain that underlie individual autonomy and economic decision making.

  19. The magical activation of left amygdala when reading Harry Potter: an fMRI study on how descriptions of supra-natural events entertain and enchant.

    Science.gov (United States)

    Hsu, Chun-Ting; Jacobs, Arthur M; Altmann, Ulrike; Conrad, Markus

    2015-01-01

    Literature containing supra-natural, or magical events has enchanted generations of readers. When reading narratives describing such events, readers mentally simulate a text world different from the real one. The corresponding violation of world-knowledge during this simulation likely increases cognitive processing demands for ongoing discourse integration, catches readers' attention, and might thus contribute to the pleasure and deep emotional experience associated with ludic immersive reading. In the present study, we presented participants in an MR scanner with passages selected from the Harry Potter book series, half of which described magical events, while the other half served as control condition. Passages in both conditions were closely matched for relevant psycholinguistic variables including, e.g., emotional valence and arousal, passage-wise mean word imageability and frequency, and syntactic complexity. Post-hoc ratings showed that readers considered supra-natural contents more surprising and more strongly associated with reading pleasure than control passages. In the fMRI data, we found stronger neural activation for the supra-natural than the control condition in bilateral inferior frontal gyri, bilateral inferior parietal lobules, left fusiform gyrus, and left amygdala. The increased activation in the amygdala (part of the salience and emotion processing network) appears to be associated with feelings of surprise and the reading pleasure, which supra-natural events, full of novelty and unexpectedness, brought about. The involvement of bilateral inferior frontal gyri likely reflects higher cognitive processing demand due to world knowledge violations, whereas increased attention to supra-natural events is reflected in inferior frontal gyri and inferior parietal lobules that are part of the fronto-parietal attention network.

  20. The magical activation of left amygdala when reading Harry Potter: an fMRI study on how descriptions of supra-natural events entertain and enchant.

    Directory of Open Access Journals (Sweden)

    Chun-Ting Hsu

    Full Text Available Literature containing supra-natural, or magical events has enchanted generations of readers. When reading narratives describing such events, readers mentally simulate a text world different from the real one. The corresponding violation of world-knowledge during this simulation likely increases cognitive processing demands for ongoing discourse integration, catches readers' attention, and might thus contribute to the pleasure and deep emotional experience associated with ludic immersive reading. In the present study, we presented participants in an MR scanner with passages selected from the Harry Potter book series, half of which described magical events, while the other half served as control condition. Passages in both conditions were closely matched for relevant psycholinguistic variables including, e.g., emotional valence and arousal, passage-wise mean word imageability and frequency, and syntactic complexity. Post-hoc ratings showed that readers considered supra-natural contents more surprising and more strongly associated with reading pleasure than control passages. In the fMRI data, we found stronger neural activation for the supra-natural than the control condition in bilateral inferior frontal gyri, bilateral inferior parietal lobules, left fusiform gyrus, and left amygdala. The increased activation in the amygdala (part of the salience and emotion processing network appears to be associated with feelings of surprise and the reading pleasure, which supra-natural events, full of novelty and unexpectedness, brought about. The involvement of bilateral inferior frontal gyri likely reflects higher cognitive processing demand due to world knowledge violations, whereas increased attention to supra-natural events is reflected in inferior frontal gyri and inferior parietal lobules that are part of the fronto-parietal attention network.

  1. Sex-related differences in amygdala functional connectivity during resting conditions.

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    Kilpatrick, L A; Zald, D H; Pardo, J V; Cahill, L F

    2006-04-01

    Recent neuroimaging studies have established a sex-related hemispheric lateralization of amygdala involvement in memory for emotionally arousing material. Here, we examine the possibility that sex-related differences in amygdala involvement in memory for emotional material develop from differential patterns of amygdala functional connectivity evident in the resting brain. Seed voxel partial least square analyses of regional cerebral blood flow data revealed significant sex-related differences in amygdala functional connectivity during resting conditions. The right amygdala was associated with greater functional connectivity in men than in women. In contrast, the left amygdala was associated with greater functional connectivity in women than in men. Furthermore, the regions displaying stronger functional connectivity with the right amygdala in males (sensorimotor cortex, striatum, pulvinar) differed from those displaying stronger functional connectivity with the left amygdala in females (subgenual cortex, hypothalamus). These differences in functional connectivity at rest may link to sex-related differences in medical and psychiatric disorders.

  2. Post-Acquisition Release of Glutamate and Norepinephrine in the Amygdala Is Involved in Taste-Aversion Memory Consolidation

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    Guzman-Ramos, Kioko; Osorio-Gomez, Daniel; Moreno-Castilla, Perla; Bermudez-Rattoni, Federico

    2012-01-01

    Amygdala activity mediates the acquisition and consolidation of emotional experiences; we have recently shown that post-acquisition reactivation of this structure is necessary for the long-term storage of conditioned taste aversion (CTA). However, the specific neurotransmitters involved in such reactivation are not known. The aim of the present…

  3. Amygdala’s involvement in facilitating associative learning-induced plasticity: a promiscuous role for the amygdala in memory acquisition

    Directory of Open Access Journals (Sweden)

    Lily S Chau

    2012-10-01

    Full Text Available It is widely accepted that the amygdala plays a critical role in acquisition and consolidation of fear-related memories. Some of the more widely employed behavioral paradigms that have assisted in solidifying the amygdala’s role in fear-related memories are associative learning paradigms. With most associative learning tasks, a neutral conditioned stimulus (CS is paired with a salient unconditioned stimulus (US that elicits an unconditioned response (UR. After multiple CS-US pairings, the subject learns that the CS predicts the onset or delivery of the US, and thus elicits a learned conditioned response (CR. Most fear-related associative paradigms have suggested that an aspect of the fear association is stored in the amygdala; however, some fear-motivated associative paradigms suggest that the amygdala is not a site of storage, but rather facilitates consolidation in other brain regions. Based upon various learning theories, one of the most likely sites for storage of long-term memories is the neocortex. In support of these theories, findings from our laboratory, and others, have demonstrated that trace-conditioning, an associative paradigm where there is a separation in time between the CS and US, induces learning-specific neocortical plasticity. The following review will discuss the amygdala’s involvement, either as a site of storage or facilitating storage in other brain regions such as the neocortex, in fear- and non-fear-motivated associative paradigms. In this review, we will discuss recent findings suggesting a broader role for the amygdala in increasing the saliency of behaviorally relevant information, thus facilitating acquisition for all forms of memory, both fear- and non-fear-related. This proposed promiscuous role of the amygdala in facilitating acquisition for all memories further suggests a potential role of the amygdala in general learning disabilities.

  4. The amygdala and decision-making.

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    Gupta, Rupa; Koscik, Timothy R; Bechara, Antoine; Tranel, Daniel

    2011-03-01

    Decision-making is a complex process that requires the orchestration of multiple neural systems. For example, decision-making is believed to involve areas of the brain involved in emotion (e.g., amygdala, ventromedial prefrontal cortex) and memory (e.g., hippocampus, dorsolateral prefrontal cortex). In this article, we will present findings related to the amygdala's role in decision-making, and differentiate the contributions of the amygdala from those of other structurally and functionally connected neural regions. Decades of research have shown that the amygdala is involved in associating a stimulus with its emotional value. This tradition has been extended in newer work, which has shown that the amygdala is especially important for decision-making, by triggering autonomic responses to emotional stimuli, including monetary reward and punishment. Patients with amygdala damage lack these autonomic responses to reward and punishment, and consequently, cannot utilize "somatic marker" type cues to guide future decision-making. Studies using laboratory decision-making tests have found deficient decision-making in patients with bilateral amygdala damage, which resembles their real-world difficulties with decision-making. Additionally, we have found evidence for an interaction between sex and laterality of amygdala functioning, such that unilateral damage to the right amygdala results in greater deficits in decision-making and social behavior in men, while left amygdala damage seems to be more detrimental for women. We have posited that the amygdala is part of an "impulsive," habit type system that triggers emotional responses to immediate outcomes. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. Involvement of CRFR1 in the Basolateral Amygdala in the Immediate Fear Extinction Deficit.

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    Hollis, Fiona; Sevelinges, Yannick; Grosse, Jocelyn; Zanoletti, Olivia; Sandi, Carmen

    2016-01-01

    Several animal and clinical studies have highlighted the ineffectiveness of fear extinction sessions delivered shortly after trauma exposure. This phenomenon, termed the immediate extinction deficit, refers to situations in which extinction programs applied shortly after fear conditioning may result in the reduction of fear behaviors (in rodents, frequently measured as freezing responses to the conditioned cue) during extinction training, but failure to consolidate this reduction in the long term. The molecular mechanisms driving this immediate extinction resistance remain unclear. Here we present evidence for the involvement of the corticotropin releasing factor (CRF) system in the basolateral amygdala (BLA) in male Wistar rats. Intra-BLA microinfusion of the CRFR 1 antagonist NBI30775 enhances extinction recall, whereas administration of the CRF agonist CRF 6-33 before delayed extinction disrupts recall of extinction. We link the immediate fear extinction deficit with dephosphorylation of GluA1 glutamate receptors at Ser 845 and enhanced activity of the protein phosphatase calcineurin in the BLA. Their reversal after treatment with the CRFR 1 antagonist indicates their dependence on CRFR 1 actions. These findings can have important implications for the improvement of therapeutic approaches to trauma, as well as furthering our understanding of the neurobiological mechanisms underlying fear-related disorders.

  6. Positive Facial Affect – An fMRI Study on the Involvement of Insula and Amygdala

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    Pohl, Anna; Anders, Silke; Schulte-Rüther, Martin; Mathiak, Klaus; Kircher, Tilo

    2013-01-01

    Imitation of facial expressions engages the putative human mirror neuron system as well as the insula and the amygdala as part of the limbic system. The specific function of the latter two regions during emotional actions is still under debate. The current study investigated brain responses during imitation of positive in comparison to non-emotional facial expressions. Differences in brain activation of the amygdala and insula were additionally examined during observation and execution of facial expressions. Participants imitated, executed and observed happy and non-emotional facial expressions, as well as neutral faces. During imitation, higher right hemispheric activation emerged in the happy compared to the non-emotional condition in the right anterior insula and the right amygdala, in addition to the pre-supplementary motor area, middle temporal gyrus and the inferior frontal gyrus. Region-of-interest analyses revealed that the right insula was more strongly recruited by (i) imitation and execution than by observation of facial expressions, that (ii) the insula was significantly stronger activated by happy than by non-emotional facial expressions during observation and imitation and that (iii) the activation differences in the right amygdala between happy and non-emotional facial expressions were increased during imitation and execution, in comparison to sole observation. We suggest that the insula and the amygdala contribute specifically to the happy emotional connotation of the facial expressions depending on the task. The pattern of the insula activity might reflect increased bodily awareness during active execution compared to passive observation and during visual processing of the happy compared to non-emotional facial expressions. The activation specific for the happy facial expression of the amygdala during motor tasks, but not in the observation condition, might reflect increased autonomic activity or feedback from facial muscles to the amygdala. PMID

  7. Positive facial affect - an fMRI study on the involvement of insula and amygdala.

    Directory of Open Access Journals (Sweden)

    Anna Pohl

    Full Text Available Imitation of facial expressions engages the putative human mirror neuron system as well as the insula and the amygdala as part of the limbic system. The specific function of the latter two regions during emotional actions is still under debate. The current study investigated brain responses during imitation of positive in comparison to non-emotional facial expressions. Differences in brain activation of the amygdala and insula were additionally examined during observation and execution of facial expressions. Participants imitated, executed and observed happy and non-emotional facial expressions, as well as neutral faces. During imitation, higher right hemispheric activation emerged in the happy compared to the non-emotional condition in the right anterior insula and the right amygdala, in addition to the pre-supplementary motor area, middle temporal gyrus and the inferior frontal gyrus. Region-of-interest analyses revealed that the right insula was more strongly recruited by (i imitation and execution than by observation of facial expressions, that (ii the insula was significantly stronger activated by happy than by non-emotional facial expressions during observation and imitation and that (iii the activation differences in the right amygdala between happy and non-emotional facial expressions were increased during imitation and execution, in comparison to sole observation. We suggest that the insula and the amygdala contribute specifically to the happy emotional connotation of the facial expressions depending on the task. The pattern of the insula activity might reflect increased bodily awareness during active execution compared to passive observation and during visual processing of the happy compared to non-emotional facial expressions. The activation specific for the happy facial expression of the amygdala during motor tasks, but not in the observation condition, might reflect increased autonomic activity or feedback from facial muscles to the

  8. Asymmetric Engagement of Amygdala and Its Gamma Connectivity in Early Emotional Face Processing

    Science.gov (United States)

    Liu, Tai-Ying; Chen, Yong-Sheng; Hsieh, Jen-Chuen; Chen, Li-Fen

    2015-01-01

    The amygdala has been regarded as a key substrate for emotion processing. However, the engagement of the left and right amygdala during the early perceptual processing of different emotional faces remains unclear. We investigated the temporal profiles of oscillatory gamma activity in the amygdala and effective connectivity of the amygdala with the thalamus and cortical areas during implicit emotion-perceptual tasks using event-related magnetoencephalography (MEG). We found that within 100 ms after stimulus onset the right amygdala habituated to emotional faces rapidly (with duration around 20–30 ms), whereas activity in the left amygdala (with duration around 50–60 ms) sustained longer than that in the right. Our data suggest that the right amygdala could be linked to autonomic arousal generated by facial emotions and the left amygdala might be involved in decoding or evaluating expressive faces in the early perceptual emotion processing. The results of effective connectivity provide evidence that only negative emotional processing engages both cortical and subcortical pathways connected to the right amygdala, representing its evolutional significance (survival). These findings demonstrate the asymmetric engagement of bilateral amygdala in emotional face processing as well as the capability of MEG for assessing thalamo-cortico-limbic circuitry. PMID:25629899

  9. Involvement of serotonin 2A receptor activation in modulating medial prefrontal cortex and amygdala neuronal activation during novelty-exposure.

    Science.gov (United States)

    Hervig, Mona El-Sayed; Jensen, Nadja Cecilie Hvid; Rasmussen, Nadja Bredo; Rydbirk, Rasmus; Olesen, Mikkel Vestergaard; Hay-Schmidt, Anders; Pakkenberg, Bente; Aznar, Susana

    2017-05-30

    The medial prefrontal cortex (PFC) plays a major role in executive function by exerting a top-down control onto subcortical areas. Novelty-induced frontal cortex activation is 5-HT 2A receptor (5-HT 2A R) dependent. Here, we further investigated how blockade of 5-HT 2A Rs in mice exposed to a novel open-field arena affects medial PFC activation and basolateral amygdala (BLA) reactivity. We used c-Fos immunoreactivity (IR) as a marker of neuronal activation and stereological quantification for obtaining the total number of c-Fos-IR neurons as a measure of regional activation. We further examined the impact of 5-HT 2A R blockade on the striatal-projecting BLA neurons. Systemic administration of ketanserin (0.5mg/kg) prior to novel open-field exposure resulted in reduced total numbers of c-Fos-IR cells in dorsomedial PFC areas and the BLA. Moreover, there was a positive correlation between the relative time spent in the centre of the open-field and BLA c-Fos-IR in the ketanserin-treated animals. Unilateral medial PFC lesions blocked this effect, ascertaining an involvement of this frontal cortex area. On the other hand, medial PFC lesioning exacerbated the more anxiogenic-like behaviour of the ketanserin-treated animals, upholding its involvement in modulating averseness. Ketanserin did not affect the number of activated striatal-projecting BLA neurons (measured by number of Cholera Toxin b (CTb) retrograde labelled neurons also being c-Fos-IR) following CTb injection in the ventral striatum. These results support a role of 5-HT 2A R activation in modulating mPFC and BLA activation during exposure to a novel environment, which may be interrelated. Conversely, 5-HT 2A R blockade does not seem to affect the amygdala-striatal projection. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Stress Sensitive Healthy Females Show Less Left Amygdala Activation in Response to Withdrawal-Related Visual Stimuli under Passive Viewing Conditions

    Science.gov (United States)

    Baeken, Chris; Van Schuerbeek, Peter; De Raedt, Rudi; Vanderhasselt, Marie-Anne; De Mey, Johan; Bossuyt, Axel; Luypaert, Robert

    2012-01-01

    The amygdalae are key players in the processing of a variety of emotional stimuli. Especially aversive visual stimuli have been reported to attract attention and activate the amygdalae. However, as it has been argued that passively viewing withdrawal-related images could attenuate instead of activate amygdalae neuronal responses, its role under…

  11. Sex differences in the functional connectivity of the amygdalae in association with cortisol.

    Science.gov (United States)

    Kogler, Lydia; Müller, Veronika I; Seidel, Eva-Maria; Boubela, Roland; Kalcher, Klaudius; Moser, Ewald; Habel, Ute; Gur, Ruben C; Eickhoff, Simon B; Derntl, Birgit

    2016-07-01

    Human amygdalae are involved in various behavioral functions such as affective and stress processing. For these behavioral functions, as well as for psychophysiological arousal including cortisol release, sex differences are reported. Here, we assessed cortisol levels and resting-state functional connectivity (rsFC) of left and right amygdalae in 81 healthy participants (42 women) to investigate potential modulation of amygdala rsFC by sex and cortisol concentration. Our analyses revealed that rsFC of the left amygdala significantly differed between women and men: Women showed stronger rsFC than men between the left amygdala and left middle temporal gyrus, inferior frontal gyrus, postcentral gyrus and hippocampus, regions involved in face processing, inner-speech, fear and pain processing. No stronger connections were detected for men and no sex difference emerged for right amygdala rsFC. Also, an interaction of sex and cortisol appeared: In women, cortisol was negatively associated with rsFC of the amygdalae with striatal regions, mid-orbital frontal gyrus, anterior cingulate gyrus, middle and superior frontal gyri, supplementary motor area and the parietal-occipital sulcus. Contrarily in men, positive associations of cortisol with rsFC of the left amygdala and these structures were observed. Functional decoding analyses revealed an association of the amygdalae and these regions with emotion, reward and memory processing, as well as action execution. Our results suggest that functional connectivity of the amygdalae as well as the regulatory effect of cortisol on brain networks differs between women and men. These sex-differences and the mediating and sex-dependent effect of cortisol on brain communication systems should be taken into account in affective and stress-related neuroimaging research. Thus, more studies including both sexes are required. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  12. Dynamic Amygdala Influences on the Fronto-Striatal Brain Mechanisms Involved in Self-Control of Impulsive Desires.

    Science.gov (United States)

    Krämer, Bernd; Gruber, Oliver

    2015-01-01

    Human decisions are guided by a variety of motivational factors, such as immediate rewards, long-term goals, and emotions. We used functional magnetic resonance imaging to investigate the dynamic functional interactions between the amygdala, the nucleus accumbens, and the prefrontal cortex that underlie the influences of emotions, desires, and rationality on human decisions. We found that increased functional connectivity between the amygdala and the nucleus accumbens facilitated the approach of an immediate reward in the presence of emotional information. Further, increased functional interactions of the anteroventral prefrontal cortex with the amygdala and the nucleus accumbens were associated with rational decisions in dilemma situations. These findings support previous animal studies by demonstrating that emotional signals from the amygdala and goal-oriented information from prefrontal cortices interface in the nucleus accumbens to guide human decisions and reward-directed actions. © 2015 S. Karger AG, Basel.

  13. No change in N-acetyl aspartate in first episode of moderate depression after antidepressant treatment: 1H magnetic spectroscopy study of left amygdala and left dorsolateral prefrontal cortex

    Directory of Open Access Journals (Sweden)

    Bajs Janović M

    2014-09-01

    Full Text Available Maja Bajs Janović,1,3 Petra Kalember,2 Špiro Janović,1,3 Pero Hrabač,2 Petra Folnegović Grošić,1 Vladimir Grošić,4 Marko Radoš,5 Neven Henigsberg2,61University Department of Psychiatry, Clinical Hospital Center Zagreb, Zagreb, 2Polyclinic Neuron, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Zagreb, 3University North, Varaždin, 4Psychiatric Hospital Sveti Ivan, Zagreb, 5University Department of Radiology, Clinical Hospital Center Zagreb, Zagreb, 6Psychiatric Clinic Vrapče, Zagreb, CroatiaBackground: The role of brain metabolites as biological correlates of the intensity, symptoms, and course of major depression has not been determined. It has also been inconclusive whether the change in brain metabolites, measured with proton magnetic spectroscopy, could be correlated with the treatment outcome. Methods: Proton magnetic spectroscopy was performed in 29 participants with a first episode of moderate depression occurring in the left dorsolateral prefrontal cortex and left amygdala at baseline and after 8 weeks of antidepressant treatment with escitalopram. The Montgomery-Asberg Depression Rating Scale, the Hamilton Rating Scale for Depression, and the Beck Depression Inventory were used to assess the intensity of depression at baseline and at the endpoint of the study. At endpoint, the participants were identified as responders (n=17 or nonresponders (n=12 to the antidepressant therapy. Results: There was no significant change in the N-acetyl aspartate/creatine ratio (NAA/Cr after treatment with antidepressant medication. The baseline and endpoint NAA/Cr ratios were not significantly different between the responder and nonresponder groups. The correlation between NAA/Cr and changes in the scores of clinical scales were not significant in either group. Conclusion: This study could not confirm any significant changes in NAA after antidepressant treatment in the first episode of moderate depression, or in

  14. Altered task-based and resting-state amygdala functional connectivity following real-time fMRI amygdala neurofeedback training in major depressive disorder.

    Science.gov (United States)

    Young, Kymberly D; Siegle, Greg J; Misaki, Masaya; Zotev, Vadim; Phillips, Raquel; Drevets, Wayne C; Bodurka, Jerzy

    2018-01-01

    We have previously shown that in participants with major depressive disorder (MDD) trained to upregulate their amygdala hemodynamic response during positive autobiographical memory (AM) recall with real-time fMRI neurofeedback (rtfMRI-nf) training, depressive symptoms diminish. Here, we assessed the effect of rtfMRI-nf on amygdala functional connectivity during both positive AM recall and rest. The current manuscript consists of a secondary analysis on data from our published clinical trial of neurofeedback. Patients with MDD completed two rtfMRI-nf sessions (18 received amygdala rtfMRI-nf, 16 received control parietal rtfMRI-nf). One-week prior-to and following training participants also completed a resting-state fMRI scan. A GLM-based functional connectivity analysis was applied using a seed ROI in the left amygdala. We compared amygdala functional connectivity changes while recalling positive AMs from the baseline run to the final transfer run during rtfMRI-nf training, as well during rest from the baseline to the one-week follow-up visit. Finally, we assessed the correlation between change in depression scores and change in amygdala connectivity, as well as correlations between amygdala regulation success and connectivity changes. Following training, amygdala connectivity during positive AM recall increased with widespread regions in the frontal and limbic network. During rest, amygdala connectivity increased following training within the fronto-temporal-limbic network. During both task and resting-state analyses, amygdala-temporal pole connectivity decreased. We identified increased amygdala-precuneus and amygdala-inferior frontal gyrus connectivity during positive memory recall and increased amygdala-precuneus and amygdala-thalamus connectivity during rest as functional connectivity changes that explained significant variance in symptom improvement. Amygdala-precuneus connectivity changes also explain a significant amount of variance in neurofeedback

  15. Stress-induced resistance to the fear memory labilization/reconsolidation process. Involvement of the basolateral amygdala complex.

    Science.gov (United States)

    Espejo, Pablo Javier; Ortiz, Vanesa; Martijena, Irene Delia; Molina, Victor Alejandro

    2016-10-01

    Consolidated memories can enter into a labile state after reactivation followed by a restabilization process defined as reconsolidation. This process can be interfered with Midazolam (MDZ), a positive allosteric modulator of the GABA-A receptor. The present study has evaluated the influence of prior stress on MDZ's interfering effect. We also assessed the influence of both systemic and intra-basolateral amygdala (BLA) infusion of d-cycloserine (DCS), a partial agonist of the NMDA receptors, on the MDZ effect in previously stressed rats. Furthermore, we analyzed the effect of stress on the expression of Zif-268 and the GluN2B sites, two molecular markers of the labilization/reconsolidation process, following reactivation. The results revealed that prior stress resulted into a memory trace that was insensitive to the MDZ impairing effect. Both systemic and intra-BLA DCS administration previous to reactivation restored MDZ's disruptive effect on memory reconsolidation in stressed animals. Further, reactivation enhanced Zif-268 expression in the BLA in control unstressed rats, whereas no elevation was observed in stressed animals. In agreement with the behavioral findings, DCS restored the increased level of Zif-268 expression in the BLA in stressed animals. Moreover, memory reactivation in unstressed animals elevated GluN2B expression in the BLA, thus suggesting that this effect is involved in memory destabilization, whereas stressed animals did not reveal any changes. These findings are consistent with resistance to the MDZ effect in these rats, indicating that stress exposure prevents the onset of destabilization following reactivation. In summary, prior stress limited both the occurrence of the reactivation-induced destabilization and restabilization. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. The Responsive Amygdala: Treatment-induced Alterations in Functional Connectivity in Pediatric Complex Regional Pain Syndrome

    Science.gov (United States)

    Simons, LE; Pielech, M; Erpelding, N; Linnman, C; Moulton, E; Sava, S; Lebel, A; Serrano, P; Sethna, N; Berde, C; Becerra, L; Borsook, D

    2014-01-01

    The amygdala is a key brain region with efferent and afferent neural connections that involve complex behaviors such as pain, reward, fear and anxiety. This study evaluated resting state functional connectivity of the amygdala with cortical and subcortical regions in a group of chronic pain patients (pediatric complex regional pain syndrome) with age-gender matched controls before and after intensive physical-biobehavioral pain treatment. Our main findings include (1) enhanced functional connectivity from the amygdala to multiple cortical, subcortical, and cerebellar regions in patients compared to controls, with differences predominantly in the left amygdala in the pre-treated condition (disease state); (2) dampened hyperconnectivity from the left amygdala to the motor cortex, parietal lobe, and cingulate cortex after intensive pain rehabilitation treatment within patients with nominal differences observed among healthy controls from Time 1 to Time 2 (treatment effects); (3) functional connectivity to several regions key to fear circuitry (prefrontal cortex, bilateral middle temporal lobe, bilateral cingulate, hippocampus) correlated with higher pain-related fear scores and (4) decreases in pain-related fear associated with decreased connectivity between the amygdala and the motor and somatosensory cortex, cingulate, and frontal areas. Our data suggest that there are rapid changes in amygdala connectivity following an aggressive treatment program in children with chronic pain and intrinsic amygdala functional connectivity activity serving as a potential indicator of treatment response. PMID:24861582

  17. H1-histamine receptors in the amygdala are involved in emotional memory but do not mediate anxiety-related behaviors in mice submitted to EPM testing.

    Science.gov (United States)

    Serafim, K R; Gianlorenço, A C L; Daher, F P; Mattioli, R

    2012-10-01

    This study investigated the role of amygdala H(1) receptors in state-dependent memory deficits induced by l-histidine (LH). Tests using an elevated plus-maze (EPM) were performed on two consecutive days: Trial 1 (T1) and Trial 2 (T2). Before each trial, mice were intraperitoneally (IP) injected with LH (500mg/kg). Two hours later, they were microinjected with the H(1) receptor antagonist, chlorpheniramine (CPA 0.016, 0.052, or 0.16 nmol/0.1μl), or saline (SAL) into the amygdala and submitted to the EPM. LH-CPA did not affect trial 1 performances in the EPM, which indicated that these drugs did not affect anxiety. Emotional memory, as revealed by a reduction in open arm exploration between both trials, was present in the SAL-SAL groups as well as in the SAL-CPA groups for the lower doses of CPA (0.016 and 0.052nmol). On the contrary, neither the LH-SAL group nor the LH-CPA groups exhibited this decrease in open arm activity between both trials, which reveals that LH impaired emotional memory. While intra-amygdalar CPA did not interact with LH effect, it impaired per se the emotional memory performances at the highest dose (0.16nmol). No significant changes were observed in the number of enclosed arm entries (EAE), an EPM index of general exploratory activity. These results may be attributed to a combined effect in the different nucleus of the amygdala. Taken together, these results suggest that the H(1) receptors in the amygdala are not implicated in anxiety-like behaviors but are involved in emotional states induced by the T1/T2 EPM protocol in mice. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Manual morphometry of hippocampus and amygdala in adults with attention-deficit hyperactivity disorder.

    Science.gov (United States)

    Nickel, Kathrin; Tebartz van Elst, Ludger; Perlov, Evgeniy; Jitten-Schachenmeier, Renate; Beier, Daniel; Endres, Dominique; Goll, Peter; Philipsen, Alexandra; Maier, Simon

    2017-09-30

    Previous studies have pointed to the involvement of limbic structures in the genesis of attention deficit hyperactivity disorder (ADHD). The present researchers manually segmented magnetic resonance images of 30 individuals with ADHD and 30 individually matched controls, focusing on amygdala and hippocampus volumes. Neither hippocampus nor amygdala volume differed significantly between individuals with and without ADHD. However, ADHD patients with higher hyperactivity scores had significantly smaller left amygdala volumes. This finding suggests that limbic alterations are significant in hyperactive symptoms in the pathophysiology of ADHD. Copyright © 2017. Published by Elsevier B.V.

  19. Involvement of the Left Supramarginal Gyrus in Manipulation Judgment Tasks: Contributions to Theories of Tool Use.

    Science.gov (United States)

    Lesourd, Mathieu; Osiurak, François; Navarro, Jordan; Reynaud, Emanuelle

    2017-09-01

    Two theories of tool use, namely the gesture engram and the technical reasoning theories, make distinct predictions about the involvement of the left inferior parietal lobe (IPL) in manipulation judgement tasks. The objective here is to test these alternative predictions based on previous studies on manipulation judgment tasks using transcranial magnetic stimulations (TMS) targeting the left supramarginal gyrus (SMG). We review recent TMS studies on manipulation judgement tasks and confront these data with predictions made by both tool use theories. The left SMG is a highly intertwined region, organized following several functionally distinct areas and TMS may have disrupted a cortical network involved in the ability to use tools rather than only one functional area supporting manipulation knowledge. Moreover, manipulation judgement tasks may be impaired following virtual lesions outside the IPL. These data are more in line with the technical reasoning hypothesis, which assumes that the left IPL does not store manipulation knowledge per se. (JINS, 2017, 23, 685-691).

  20. Instrumental learning and relearning in individuals with psychopathy and in patients with lesions involving the amygdala or orbitofrontal cortex.

    Science.gov (United States)

    Mitchell, D G V; Fine, C; Richell, R A; Newman, C; Lumsden, J; Blair, K S; Blair, R J R

    2006-05-01

    Previous work has shown that individuals with psychopathy are impaired on some forms of associative learning, particularly stimulus-reinforcement learning (Blair et al., 2004; Newman & Kosson, 1986). Animal work suggests that the acquisition of stimulus-reinforcement associations requires the amygdala (Baxter & Murray, 2002). Individuals with psychopathy also show impoverished reversal learning (Mitchell, Colledge, Leonard, & Blair, 2002). Reversal learning is supported by the ventrolateral and orbitofrontal cortex (Rolls, 2004). In this paper we present experiments investigating stimulus-reinforcement learning and relearning in patients with lesions of the orbitofrontal cortex or amygdala, and individuals with developmental psychopathy without known trauma. The results are interpreted with reference to current neurocognitive models of stimulus-reinforcement learning, relearning, and developmental psychopathy. Copyright (c) 2006 APA, all rights reserved.

  1. A causal involvement of the left supramarginal gyrus during the retention of musical pitches.

    Science.gov (United States)

    Schaal, Nora K; Williamson, Victoria J; Kelly, Maria; Muggleton, Neil G; Pollok, Bettina; Krause, Vanessa; Banissy, Michael J

    2015-03-01

    Brain stimulation studies have previously demonstrated a causal link between general pitch memory processes and activity within the left supramarginal gyrus (SMG). Building on this evidence, the present study tested the impact of left SMG stimulation on two distinct pitch memory phases, retention and encoding. Repetitive transcranial magnetic stimulation (rTMS) was employed during the retention stage (Experiment 1) and the encoding phase (Experiment 2) of a pitch recognition task. Stimulation was applied on a trial-by-trial basis over the left SMG (target site) or the vertex (control site). A block without TMS was also completed. In Experiment 1, rTMS over the left SMG during pitch retention led to significantly increased reaction times compared to control conditions. In Experiment 2 no rTMS modulation effects were found during encoding. Experiment 3 was conducted as a control for non-specific stimulation effects; no effects were found when rTMS was applied over the left SMG at the two different time points during a perceptual task. Taken together, these findings highlight a phase-specific involvement of the left SMG in the retention phase of pitch memory, thereby indicating that the left SMG is involved in the maintenance of pitch information. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Morphology of congenital portosystemic shunts involving the left colic vein in dogs and cats.

    Science.gov (United States)

    White, R N; Parry, A T

    2016-05-01

    To describe the anatomy of congenital portosystemic shunts involving the left colic vein in dogs and cats. Retrospective review of a consecutive series of dogs and cats managed for congenital portosystemic shunts. For inclusion a shunt involving the left colic vein with recorded intraoperative mesenteric portovenography or computed tomography angiography along with direct gross surgical observations at the time of surgery was required. Six dogs and three cats met the inclusion criteria. All cases had a shunt which involved a distended left colic vein. The final communication with a systemic vein was variable; in seven cases (five dogs, two cats) it was via the caudal vena cava, in one cat it was via the common iliac vein and in the remaining dog it was via the internal iliac vein. In addition, two cats showed caudal vena cava duplication. The morphology of this shunt type appeared to be a result of an abnormal communication between either the left colic vein or the cranial rectal vein and a pelvic systemic vein (caudal vena cava, common iliac vein or internal iliac vein). This information may help with surgical planning in cases undergoing shunt closure surgery. © 2016 British Small Animal Veterinary Association.

  3. Differential involvement of left prefrontal cortex in inductive and deductive reasoning.

    Science.gov (United States)

    Goel, Vinod; Dolan, Raymond J

    2004-10-01

    While inductive and deductive reasoning are considered distinct logical and psychological processes, little is known about their respective neural basis. To address this issue we scanned 16 subjects with fMRI, using an event-related design, while they engaged in inductive and deductive reasoning tasks. Both types of reasoning were characterized by activation of left lateral prefrontal and bilateral dorsal frontal, parietal, and occipital cortices. Neural responses unique to each type of reasoning determined from the Reasoning Type (deduction and induction) by Task (reasoning and baseline) interaction indicated greater involvement of left inferior frontal gyrus (BA 44) in deduction than induction, while left dorsolateral (BA 8/9) prefrontal gyrus showed greater activity during induction than deduction. This pattern suggests a dissociation within prefrontal cortex for deductive and inductive reasoning.

  4. Physiopathological approach to infective endocarditis in chronic hemodialysis patients: left heart versus right heart involvement.

    Science.gov (United States)

    Bentata, Yassamine

    2017-11-01

    Infectious endocarditis (IE), a complication that is both cardiac and infectious, occurs frequently and is associated with a heavy burden of morbidity and mortality in chronic hemodialysis patients (CHD). About 2-6% of chronic hemodialysis patients develop IE and the incidence is 50-60 times higher among CHD patients than in the general population. The left heart is the most frequent location of IE in CHD and the different published series report a prevalence of left valve involvement varying from 80% to 100%. Valvular and perivalvular abnormalities, alteration of the immune system, and bacteremia associated with repeated manipulation of the vascular access, particularly central venous catheters, comprise the main factors explaining the left heart IE in CHD patients. While left-sided IE develops in altered valves in a high-pressure system, right-sided IE on the contrary, generally develops in healthy valves in a low-pressure system. Right-sided IE is rare, with its incidence varying from 0% to 26% depending on the study, and the tricuspid valve is the main location. Might the massive influx of pathogenic and virulent germs via the central venous catheter to the right heart, with the tricuspid being the first contact valve, have a role in the physiopathology of IE in CHD, thus facilitating bacterial adhesion? While the physiopathology of left-sided IE entails multiple and convincing mechanisms, it is not the case for right-sided IE, for which the physiopathological mechanism is only partially understood and remains shrouded in mystery.

  5. Impaired Emotional Declarative Memory Following Unilateral Amygdala Damage

    OpenAIRE

    Adolphs, Ralph; Tranel, Daniel; Denburg, Natalie

    2000-01-01

    Case studies of patients with bilateral amygdala damage and functional imaging studies of normal individuals have demonstrated that the amygdala plays a critical role in encoding emotionally arousing stimuli into long-term declarative memory. However, several issues remain poorly understood: the separate roles of left and right amygdala, the time course over which the amygdala participates in memory consolidation, and the type of knowledge structures it helps consolidate. We investigated thes...

  6. Prior stress promotes the generalization of contextual fear memories: Involvement of the gabaergic signaling within the basolateral amygdala complex.

    Science.gov (United States)

    Bender, C L; Otamendi, A; Calfa, G D; Molina, V A

    2018-04-20

    Fear generalization occurs when a response, previously acquired with a threatening stimulus, is transferred to a similar one. However, it could be maladaptive when stimuli that do not represent a real threat are appraised as dangerous, which is a hallmark of several anxiety disorders. Stress exposure is a major risk factor for the occurrence of anxiety disorders and it is well established that it influences different phases of fear memory; nevertheless, its impact on the generalization of contextual fear memories has been less studied. In the present work, we have characterized the impact of acute restraint stress prior to contextual fear conditioning on the generalization of this fear memory, and the role of the GABAergic signaling within the basolateral amygdala complex (BLA) on the stress modulatory effects. We have found that a single stress exposure promoted the generalization of this memory trace to a different context that was well discriminated in unstressed conditioned animals. Moreover, this effect was dependent on the formation of a contextual associative memory and on the testing order (i.e., conditioning context first vs generalization context first). Furthermore, we observed that increasing GABA-A signaling by intra-BLA midazolam administration prior to the stressful session exposure prevented the generalization of fear memory, whereas intra-BLA administration of the GABA-A antagonist (Bicuculline), prior to fear conditioning, induced the generalization of fear memory in unstressed rats. We concluded that stress exposure, prior to contextual fear conditioning, promotes the generalization of fear memory and that the GABAergic transmission within the BLA has a critical role in this phenomenon. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. A Transient Upregulation of Glutamine Synthetase in the Dentate Gyrus Is Involved in Epileptogenesis Induced by Amygdala Kindling in the Rat.

    Directory of Open Access Journals (Sweden)

    Hong-Liu Sun

    Full Text Available Reduction of glutamine synthetase (GS function is closely related to established epilepsy, but little is known regarding its role in epileptogenesis. The present study aimed to elucidate the functional changes of GS in the brain and its involvement in epileptogenesis using the amygdala kindling model of epilepsy induced by daily electrical stimulation of basolateral amygdala in rats. Both expression and activity of GS in the ipsilateral dentate gyrus (DG were upregulated when kindled seizures progressed to stage 4. A single dose of L-methionine sulfoximine (MSO, in 2 µl, a selective GS inhibitor, was administered into the ipsilateral DG on the third day following the first stage 3 seizure (just before GS was upregulated. It was found that low doses of MSO (5 or 10 µg significantly and dose-dependently reduced the severity of and susceptibility to evoked seizures, whereas MSO at a high dose (20 µg aggravated kindled seizures. In animals that seizure acquisition had been successfully suppressed with 10 µg MSO, GS upregulation reoccurred when seizures re-progressed to stage 4 and re-administration of 10 µg MSO consistently reduced the seizures. GLN at a dose of 1.5 µg abolished the alleviative effect of 10 µg MSO and deleterious effect of 20 µg MSO on kindled seizures. Moreover, appropriate artificial microRNA interference (1 and 1.5×10(6 TU/2 µl of GS expression in the ipsilateral DG also inhibited seizure progression. In addition, a transient increase of GS expression and activity in the cortex was also observed during epileptogenesis evoked by pentylenetetrazole kindling. These results strongly suggest that a transient and region-specific upregulation of GS function occurs when epilepsy develops into a certain stage and eventually promotes the process of epileptogenesis. Inhibition of GS to an adequate degree and at an appropriate timing may be a potential therapeutic approach to interrupting epileptogenesis.

  8. Distinct contributions of reactive oxygen species in amygdala to bee venom-induced spontaneous pain-related behaviors.

    Science.gov (United States)

    Lu, Yun-Fei; Neugebauer, Volker; Chen, Jun; Li, Zhen

    2016-04-21

    Reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, play essential roles in physiological plasticity and are also involved in the pathogenesis of persistent pain. Roles of peripheral and spinal ROS in pain have been well established, but much less is known about ROS in the amygdala, a brain region that plays an important role in pain modulation. The present study explored the contribution of ROS in the amygdala to bee venom (BV)-induced pain behaviors. Our data show that the amygdala is activated following subcutaneous BV injection into the left hindpaw, which is reflected in the increased number of c-Fos positive cells in the central and basolateral amygdala nuclei in the right hemisphere. Stereotaxic administration of a ROS scavenger (tempol, 10mM), NADPH oxidase inhibitor (baicalein, 5mM) or lipoxygenase inhibitor (apocynin, 10mM) into the right amygdala attenuated the BV-induced spontaneous licking and lifting behaviors, but had no effect on BV-induced paw flinch reflexes. Our study provides further evidence for the involvement of the amygdala in nociceptive processing and pain behaviors, and that ROS in amygdala may be a potential target for treatment strategies to inhibit pain. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. The Dissociative Subtype of Posttraumatic Stress Disorder: Unique Resting-State Functional Connectivity of Basolateral and Centromedial Amygdala Complexes.

    Science.gov (United States)

    Nicholson, Andrew A; Densmore, Maria; Frewen, Paul A; Théberge, Jean; Neufeld, Richard Wj; McKinnon, Margaret C; Lanius, Ruth A

    2015-09-01

    Previous studies point towards differential connectivity patterns among basolateral (BLA) and centromedial (CMA) amygdala regions in patients with posttraumatic stress disorder (PTSD) as compared with controls. Here we describe the first study to compare directly connectivity patterns of the BLA and CMA complexes between PTSD patients with and without the dissociative subtype (PTSD+DS and PTSD-DS, respectively). Amygdala connectivity to regulatory prefrontal regions and parietal regions involved in consciousness and proprioception were expected to differ between these two groups based on differential limbic regulation and behavioral symptoms. PTSD patients (n=49) with (n=13) and without (n=36) the dissociative subtype and age-matched healthy controls (n=40) underwent resting-state fMRI. Bilateral BLA and CMA connectivity patterns were compared using a seed-based approach via SPM Anatomy Toolbox. Among patients with PTSD, the PTSD+DS group exhibited greater amygdala functional connectivity to prefrontal regions involved in emotion regulation (bilateral BLA and left CMA to the middle frontal gyrus and bilateral CMA to the medial frontal gyrus) as compared with the PTSD-DS group. In addition, the PTSD+DS group showed greater amygdala connectivity to regions involved in consciousness, awareness, and proprioception-implicated in depersonalization and derealization (left BLA to superior parietal lobe and cerebellar culmen; left CMA to dorsal posterior cingulate and precuneus). Differences in amygdala complex connectivity to specific brain regions parallel the unique symptom profiles of the PTSD subgroups and point towards unique biological markers of the dissociative subtype of PTSD.

  10. The effect of anticipation and the specificity of sex differences for amygdala and hippocampus function in emotional memory.

    Science.gov (United States)

    Mackiewicz, Kristen L; Sarinopoulos, Issidoros; Cleven, Krystal L; Nitschke, Jack B

    2006-09-19

    Prior research has shown memory is enhanced for emotional events. Key brain areas involved in emotional memory are the amygdala and hippocampus, which are also recruited during aversion and its anticipation. This study investigated whether anticipatory processes signaling an upcoming aversive event contribute to emotional memory. In an event-related functional MRI paradigm, 40 healthy participants viewed aversive and neutral pictures preceded by predictive warning cues. Participants completed a surprise recognition task directly after functional MRI scanning or 2 weeks later. In anticipation of aversive pictures, bilateral dorsal amygdala and anterior hippocampus activations were associated with better immediate recognition memory. Similar associations with memory were observed for activation of those areas in response to aversive pictures. Anticipatory activation predicted immediate memory over and above these associations for picture viewing. Bilateral ventral amygdala activations in response to aversive pictures predicted delayed memory only. We found that previously reported sex differences of memory associations with left amygdala for women and with right amygdala for men were confined to the ventral amygdala during picture viewing and delayed memory. Results support an established animal model elucidating the functional neuroanatomy of the amygdala and hippocampus in emotional memory, highlight the importance of anticipatory processes in such memory for aversive events, and extend neuroanatomical evidence of sex differences for emotional memory.

  11. Left auditory cortex is involved in pairwise comparisons of the direction of frequency modulated tones

    Directory of Open Access Journals (Sweden)

    Nicole eAngenstein

    2013-07-01

    Full Text Available Evaluating series of complex sounds like those in speech and music requires sequential comparisons to extract task-relevant relations between subsequent sounds. With the present functional magnetic resonance imaging (fMRI study, we investigated whether sequential comparison of a specific acoustic feature within pairs of tones leads to a change in lateralized processing in the auditory cortex of humans. For this we used the active categorization of the direction (up versus down of slow frequency modulated (FM tones. Several studies suggest that this task is mainly processed in the right auditory cortex. These studies, however, tested only the categorization of the FM direction of each individual tone. In the present study we ask the question whether the right lateralized processing changes when, in addition, the FM direction is compared within pairs of successive tones. For this we use an experimental approach involving contralateral noise presentation in order to explore the contributions made by the left and right auditory cortex in the completion of the auditory task. This method has already been applied to confirm the right-lateralized processing of the FM direction of individual tones. In the present study, the subjects were required to perform, in addition, a sequential comparison of the FM-direction in pairs of tones. The results suggest a division of labor between the two hemispheres such that the FM direction of each individual tone is mainly processed in the right auditory cortex whereas the sequential comparison of this feature between tones in a pair is probably performed in the left auditory cortex.

  12. Involvement of serotonin 2A receptor activation in modulating medial prefrontal cortex and amygdala neuronal activation during novelty-exposure

    DEFF Research Database (Denmark)

    Hervig, Mona El-Sayed; Jensen, Nadja Cecilie Hvid; Rasmussen, Nadja Bredo

    2017-01-01

    The medial prefrontal cortex (PFC) plays a major role in executive function by exerting a top-down control onto subcortical areas. Novelty-induced frontal cortex activation is 5-HT2A receptor (5-HT2AR) dependent. Here, we further investigated how blockade of 5-HT2ARs in mice exposed to a novel open-field...... of 5-HT2AR blockade on the striatal-projecting BLA neurons. Systemic administration of ketanserin (0.5 mg/kg) prior to novel open-field exposure resulted in reduced total numbers of c-Fos-IR cells in dorsomedial PFC areas and the BLA. Moreover, there was a positive correlation between the relative time...... spent in the centre of the open-field and BLA c-Fos-IR in the ketanserin-treated animals. Unilateral medial PFC lesions blocked this effect, ascertaining an involvement of this frontal cortex area. On the other hand, medial PFC lesioning exacerbated the more anxiogenic-like behaviour of the ketanserin...

  13. FKBP5 and specific microRNAs via glucocorticoid receptor in the basolateral amygdala involved in the susceptibility to depressive disorder in early adolescent stressed rats.

    Science.gov (United States)

    Xu, Jingjing; Wang, Rui; Liu, Yuan; Liu, Dexiang; Jiang, Hong; Pan, Fang

    2017-12-01

    Exposure to stressful events induces depressive-like symptoms and increases susceptibility to depression. However, the molecular mechanisms are not fully understood. Studies reported that FK506 binding protein51 (FKBP5), the co-chaperone protein of glucocorticoid receptors (GR), plays a crucial role. Further, miR-124a and miR-18a are involved in the regulation of FKBP5/GR function. However, few studies have referred to effects of early life stress on depressive-like behaviours, GR and FKBP5, as well as miR-124a and miR-18a in the basolateral amygdala (BLA) from adolescence to adulthood. This study aimed to examine the dynamic alternations of depressive-like behaviours, GR and FKBP5, as well as miR-124a and miR-18a expressions in the BLA of chronic unpredictable mild stress (CUMS) rats and dexamethasone administration rats during the adolescent period. Meanwhile, the GR antagonist, RU486, was used as a means of intervention. We found that CUMS and dexamethasone administration in the adolescent period induced permanent depressive-like behaviours and memory impairment, decreased GR expression, and increased FKBP5 and miR-124a expression in the BLA of both adolescent and adult rats. However, increased miR-18a expression in the BLA was found only in adolescent rats. Depressive-like behaviours were positively correlated with the level of miR-124a, whereas GR levels were negatively correlated with those in both adolescent and adult rats. Our results suggested FKBP5/GR and miR-124a in the BLA were associated with susceptibility to depressive disorder in the presence of stressful experiences in early life. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Altered task-based and resting-state amygdala functional connectivity following real-time fMRI amygdala neurofeedback training in major depressive disorder

    Directory of Open Access Journals (Sweden)

    Kymberly D. Young

    2018-01-01

    Conclusions: Neurofeedback training to increase amygdala hemodynamic activity during positive AM recall increased amygdala connectivity with regions involved in self-referential, salience, and reward processing. Results suggest future targets for neurofeedback interventions, particularly interventions involving the precuneus.

  15. Structural Variation within the Amygdala and Ventromedial Prefrontal Cortex Predict Memory for Impressions in Older Adults

    Directory of Open Access Journals (Sweden)

    Brittany Shane Cassidy

    2012-08-01

    Full Text Available Research has shown that lesions to regions involved in social and emotional cognition disrupt socioemotional processing and memory. We investigated how structural variation of regions involved in socioemotional memory (ventromedial prefrontal cortex [vmPFC], amygdala, as opposed to a region implicated in explicit memory (hippocampus, affected memory for impressions in young and older adults. Anatomical MRI scans for fifteen young and fifteen older adults were obtained and reconstructed to gather information about cortical thickness and subcortical volume. Young adults had greater amygdala and hippocampus volumes than old, and thicker left vmPFC than old, although right vmPFC thickness did not differ across the age groups. Participants formed behavior-based impressions and responded to interpersonally meaningful, social but interpersonally irrelevant, or non-social prompts, and completed a memory test. Results showed that greater left amygdala volume predicted enhanced overall memory for impressions in older but not younger adults. Increased right vmPFC thickness in older, but not younger, adults correlated with enhanced memory for impressions formed in the interpersonally meaningful context. Hippocampal volume was not predictive of social memory in young or older adults. These findings demonstrate the importance of structural variation in regions linked to socioemotional processing in the retention of impressions with age, and suggest that the amygdala and vmPFC play an integral role when encoding and retrieving social information.

  16. The involvement of CRF1 receptor within the basolateral amygdala and dentate gyrus in the naloxone-induced conditioned place aversion in morphine-dependent mice.

    Science.gov (United States)

    Valero, E; Gómez-Milanés, I; Almela, P; Ribeiro Do Couto, B; Laorden, M L; Milanés, M V; Núñez, C

    2018-06-08

    Drug withdrawal-associated aversive memories trigger relapse to drug-seeking behavior. Corticotrophin-releasing factor (CRF) is an important mediator of the reinforcing properties of drugs of abuse. However, the involvement of CRF1 receptor (CRF1R) in aversive memory induced by opiate withdrawal has yet to be elucidated. We used the conditioned-place aversion (CPA) paradigm to evaluate the role of CRF1R on opiate withdrawal memory acquisition, along with plasticity-related processes that occur after CPA within the basolateral amygdala (BLA) and dentate gyrus (DG). Male mice were rendered dependent on morphine and injected acutely with naloxone before paired to confinement in a naloxone-associated compartment. The CPA scores as well as the number of TH-positive neurons (in the NTS-A2 noradrenergic cell group), and the expression of the transcription factors Arc and pCREB (in the BLA and DG) were measured with and without CRF1R blockade. Mice subjected to conditioned naloxone-induced morphine withdrawal robustly expressed CPA. Pre-treatment with the selective CRF1R antagonist CP-154,526 before naloxone conditioning session impaired morphine withdrawal-induced aversive memory acquisition. CP-154,526 also antagonized the enhanced number of TH-positive neurons in the NTS-A2 that was seen after CPA. Increased Arc expression and Arc-pCREB co-localization were seen in the BLA after CPA, which was not modified by CP-154,526. In the DG, CPA was accompanied by a decrease of Arc expression and no changes in Arc-pCREB co-localization, whereas pre-treatment with CP-154,526 induced an increase in both parameters. These results indicate that CRF-CRF1R pathway could be a critical factor governing opiate withdrawal memory storage and retrieval and might suggest a role for TH-NA pathway in the effects of withdrawal on memory. Our results might indicate that the blockade of CRF1R could represent a promising pharmacological treatment strategy approach for the attenuation of the relapse

  17. Disorganized Attachment in Infancy Predicts Greater Amygdala Volume in Adulthood

    Science.gov (United States)

    Lyons-Ruth, K.; Pechtel, P.; Yoon, S.A.; Anderson, C.M.; Teicher, M.H.

    2016-01-01

    Early life stress in rodents is associated with increased amygdala volume in adulthood. In humans, the amygdala develops rapidly during the first two years of life. Thus, disturbed care during this period may be particularly important to amygdala development. In the context of a 30-year longitudinal study of impoverished, highly stressed families, we assessed whether disorganization of the attachment relationship in infancy was related to amygdala volume in adulthood. Amygdala volumes were assessed among 18 low-income young adults (8M/10F, 29.33±0.49 years) first observed in infancy (8.5±5.6 months) and followed longitudinally to age 29. In infancy (18.58±1.02 mos), both disorganized infant attachment behavior and disrupted maternal communication were assessed in the standard Strange Situation Procedure (SSP). Increased left amygdala volume in adulthood was associated with both maternal and infant components of disorganized attachment interactions at 18 months of age (overall r = .679, p attachment disturbance in adolescence, were not significantly related to left amygdala volume. Left amygdala volume was further associated with dissociation and limbic irritability in adulthood. Finally, left amygdala volume mediated the prediction from attachment disturbance in infancy to limbic irritability in adulthood. Results point to the likely importance of quality of early care for amygdala development in human children as well as in rodents. The long-term prediction found here suggests that the first two years of life may be an early sensitive period for amygdala development during which clinical intervention could have particularly important consequences for later child outcomes. PMID:27060720

  18. Human amygdala response to dynamic facial expressions of positive and negative surprise.

    Science.gov (United States)

    Vrticka, Pascal; Lordier, Lara; Bediou, Benoît; Sander, David

    2014-02-01

    Although brain imaging evidence accumulates to suggest that the amygdala plays a key role in the processing of novel stimuli, only little is known about its role in processing expressed novelty conveyed by surprised faces, and even less about possible interactive encoding of novelty and valence. Those investigations that have already probed human amygdala involvement in the processing of surprised facial expressions either used static pictures displaying negative surprise (as contained in fear) or "neutral" surprise, and manipulated valence by contextually priming or subjectively associating static surprise with either negative or positive information. Therefore, it still remains unresolved how the human amygdala differentially processes dynamic surprised facial expressions displaying either positive or negative surprise. Here, we created new artificial dynamic 3-dimensional facial expressions conveying surprise with an intrinsic positive (wonderment) or negative (fear) connotation, but also intrinsic positive (joy) or negative (anxiety) emotions not containing any surprise, in addition to neutral facial displays either containing ("typical surprise" expression) or not containing ("neutral") surprise. Results showed heightened amygdala activity to faces containing positive (vs. negative) surprise, which may either correspond to a specific wonderment effect as such, or to the computation of a negative expected value prediction error. Findings are discussed in the light of data obtained from a closely matched nonsocial lottery task, which revealed overlapping activity within the left amygdala to unexpected positive outcomes. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  19. Amygdala Functional Connectivity is Reduced After the Cold Pressor Task

    Science.gov (United States)

    Clewett, David; Schoeke, Andrej; Mather, Mara

    2013-01-01

    The amygdala forms a crucial link between central pain and stress systems. There is much evidence that psychological stress affects amygdala activity, but it is less clear how painful stressors influence subsequent amygdala functional connectivity. In the present study, we used pulsed arterial spin labeling (PASL) to investigate differences in healthy male adults’ resting-state amygdala functional connectivity following a cold pressor versus control task, with the stressor and control conditions conducted on different days. During the period of peak cortisol response to acute stress (approximately fifteen to thirty minutes after stressor onset), participants were asked to rest for six minutes with their eyes closed during a PASL scanning sequence. The cold pressor task led to reduced resting-state functional connectivity between the amygdalae and orbitofrontal cortex (OFC) and ventromedial prefrontal cortex (VMPFC), which occurred irrespective of cortisol release. The stressor also induced greater inverse connectivity between the left amygdala and dorsal anterior cingulate cortex (dACC), a brain region implicated in the down-regulation of amygdala responsivity. Furthermore, the degree of post-stressor left amygdala decoupling with the lateral OFC varied according to self-reported pain intensity during the cold pressor task. These findings indicate that the cold pressor task alters amygdala interactions with prefrontal and ACC regions 15–30 minutes after the stressor, and that these altered functional connectivity patterns are related to pain perception rather than cortisol feedback. PMID:23645370

  20. Left posterior BA37 is involved in object recognition: a TMS study

    DEFF Research Database (Denmark)

    Stewart, Lauren; Meyer, Bernd-Ulrich; Frith, Uta

    2001-01-01

    Functional imaging studies have proposed a role for left BA37 in phonological retrieval, semantic processing, face processing and object recognition. The present study targeted the posterior aspect of BA37 to see whether a deficit, specific to one of the above types of processing could be induced...... to name pictures when TMS was given over lBA37 compared to vertex or rBA37. rTMS over lBA37 had no significant effect on word reading, nonword reading or colour naming. The picture naming deficit is suggested to result from a disruption to object recognition processes. This study corroborates the finding...... from a recent imaging study, that the most posterior part of left hemispheric BA37 has a necessary role in object recognition....

  1. Effects of Time-Compressed Speech Training on Multiple Functional and Structural Neural Mechanisms Involving the Left Superior Temporal Gyrus.

    Science.gov (United States)

    Maruyama, Tsukasa; Takeuchi, Hikaru; Taki, Yasuyuki; Motoki, Kosuke; Jeong, Hyeonjeong; Kotozaki, Yuka; Nakagawa, Seishu; Nouchi, Rui; Iizuka, Kunio; Yokoyama, Ryoichi; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Sakaki, Kohei; Sasaki, Yukako; Magistro, Daniele; Kawashima, Ryuta

    2018-01-01

    Time-compressed speech is an artificial form of rapidly presented speech. Training with time-compressed speech (TCSSL) in a second language leads to adaptation toward TCSSL. Here, we newly investigated the effects of 4 weeks of training with TCSSL on diverse cognitive functions and neural systems using the fractional amplitude of spontaneous low-frequency fluctuations (fALFF), resting-state functional connectivity (RSFC) with the left superior temporal gyrus (STG), fractional anisotropy (FA), and regional gray matter volume (rGMV) of young adults by magnetic resonance imaging. There were no significant differences in change of performance of measures of cognitive functions or second language skills after training with TCSSL compared with that of the active control group. However, compared with the active control group, training with TCSSL was associated with increased fALFF, RSFC, and FA and decreased rGMV involving areas in the left STG. These results lacked evidence of a far transfer effect of time-compressed speech training on a wide range of cognitive functions and second language skills in young adults. However, these results demonstrated effects of time-compressed speech training on gray and white matter structures as well as on resting-state intrinsic activity and connectivity involving the left STG, which plays a key role in listening comprehension.

  2. Lifespan anxiety is reflected in human amygdala cortical connectivity

    Science.gov (United States)

    He, Ye; Xu, Ting; Zhang, Wei

    2016-01-01

    Abstract The amygdala plays a pivotal role in processing anxiety and connects to large‐scale brain networks. However, intrinsic functional connectivity (iFC) between amygdala and these networks has rarely been examined in relation to anxiety, especially across the lifespan. We employed resting‐state functional MRI data from 280 healthy adults (18–83.5 yrs) to elucidate the relationship between anxiety and amygdala iFC with common cortical networks including the visual network, somatomotor network, dorsal attention network, ventral attention network, limbic network, frontoparietal network, and default network. Global and network‐specific iFC were separately computed as mean iFC of amygdala with the entire cerebral cortex and each cortical network. We detected negative correlation between global positive amygdala iFC and trait anxiety. Network‐specific associations between amygdala iFC and anxiety were also detectable. Specifically, the higher iFC strength between the left amygdala and the limbic network predicted lower state anxiety. For the trait anxiety, left amygdala anxiety–connectivity correlation was observed in both somatomotor and dorsal attention networks, whereas the right amygdala anxiety–connectivity correlation was primarily distributed in the frontoparietal and ventral attention networks. Ventral attention network exhibited significant anxiety–gender interactions on its iFC with amygdala. Together with findings from additional vertex‐wise analysis, these data clearly indicated that both low‐level sensory networks and high‐level associative networks could contribute to detectable predictions of anxiety behaviors by their iFC profiles with the amygdala. This set of systems neuroscience findings could lead to novel functional network models on neural correlates of human anxiety and provide targets for novel treatment strategies on anxiety disorders. Hum Brain Mapp 37:1178–1193, 2016. © 2015 The Authors Human Brain Mapping

  3. Amygdala Hyperactivity at Rest in Paranoid Individuals With Schizophrenia.

    Science.gov (United States)

    Pinkham, Amy E; Liu, Peiying; Lu, Hanzhang; Kriegsman, Michael; Simpson, Claire; Tamminga, Carol

    2015-08-01

    The amygdala's role in threat perception suggests that increased activation of this region may be related to paranoid ideation. However, investigations of amygdala function in paranoid individuals with schizophrenia, compared with both healthy individuals and nonparanoid individuals with schizophrenia, have consistently reported reduced task-related activation. The reliance of blood-oxygen-level-dependent functional MRI on a contrast between events and baseline, and the inability to quantitatively measure this baseline, may account for these counterintuitive findings. The present study tested for differences in baseline levels of amygdala activity in paranoid and nonparanoid individuals with schizophrenia using arterial spin labeling perfusion MRI. Resting cerebral blood flow (CBF) and task-related activation of the amygdala were measured in 25 healthy individuals, 16 individuals with schizophrenia who were actively paranoid at the time of scanning, and 16 individuals with schizophrenia who were not paranoid. Analysis of relative CBF values extracted from the amygdala bilaterally revealed significantly increased activity in the left amygdala in paranoid patient volunteers compared with healthy comparison subjects and nonparanoid patient volunteers. Increased CBF was also evident in the right amygdala but did not reach the level of statistical significance. Paranoid volunteers also showed significantly decreased task-related activation of the amygdala compared with the two other groups. These findings suggest that amygdala hyperactivation may underlie paranoia in schizophrenia. Additionally, the reported differences between paranoid and nonparanoid patient volunteers emphasize the importance of considering symptom-based subgroups and baseline levels of activity in future investigations of neural activation in schizophrenia.

  4. Isolated amygdala enlargement in temporal lobe epilepsy: A systematic review.

    Science.gov (United States)

    Beh, S M Jessica; Cook, Mark J; D'Souza, Wendyl J

    2016-07-01

    The objective of this study was to compare the seizure characteristics and treatment outcomes in patient groups with temporal lobe epilepsy (TLE) identified with isolated amygdala enlargement (AE) on magnetic resonance imaging studies. PubMed, Embase, and the Cochrane Library were searched for relevant studies using the keywords 'amygdala enlargement', 'epilepsy', and 'seizures' in April 2015. Human studies, written in English, that investigated cohorts of patients with TLE and AE were included. Of 204 abstracts initially identified using the search strategy, 14 studies met the inclusion criteria (11 epilepsy studies and 3 psychiatry studies). Ultimately, 8 full studies on AE and TLE involving 107 unique patients were analyzed. Gender distribution consisted of 50 males and 57 females. Right amygdala enlargement was seen in 39 patients, left enlargement in 58 patients, and bilateral enlargement in 7 patients. Surgical resection was performed in 28 patients, with the most common finding being dysplasia/hamartoma or focal cortical dysplasia. Most studies involved small samples of less than 12 patients. There was a wide discrepancy in the methods used to measure amygdala volume, in both patients and controls, hindering comparisons. Most TLE with AE studies observed a later age of seizure onset (mean: 32.2years) compared with studies involving TLE with HS (mean of mid- to late childhood). A higher frequency of complex partial seizures compared with that of convulsive seizures is seen in patients with AE (67-100% vs. 26-47%), and they have an excellent response to antiepileptic drugs (81.8%-100% of seizure-free patients). All studies that included controls also found a significant difference in frequency of seizure types between their cases and controls. Reliable assessment of amygdala volume remains a critical issue hindering better understanding of the clinical management and research of this focal epilepsy syndrome. Within these limitations, the literature suggests

  5. No Parent Left Behind: Predicting Parental Involvement in Adolescents' Education within a Sociodemographically Diverse Population

    Science.gov (United States)

    Park, Sira; Holloway, Susan D.

    2013-01-01

    Numerous studies have investigated the utility of the Hoover-Dempsey and Sandler (HDS) model for predicting parents' involvement in students' education. Yet, the model has yet to be thoroughly evaluated with respect to youth who are (a) in high school and (b) from sociodemographically diverse families. Using a nationally representative sample of…

  6. Submandibular Gland Involvement in Early Stage Oral Cavity Carcinomas: Can the Gland be left behind

    International Nuclear Information System (INIS)

    Ashfaq, K.; Ashfaq, M.; Ahmed, A.; Khan, M.; Azhar, M.

    2014-01-01

    Objective: To determine the frequency of submandibular gland involvement in early oral cavity tumors. Study Design: Observational study. Place and Duration of Study: ENT Department, CMH, Rawalpindi, from January 2008 to December 2011. Methodology: Data of 110 oral cavity tumors operated over 2008 - 2011 was retrieved from ENT OPD, tumor registry in AFIP and from Head and Neck Oncology Forum Registry. Cases of oral cavity tumors that had undergone elective neck dissections were retrospectively studied for invasion of the submandibular gland, TNM Staging, perineural, perivascular, lymphovascular invasion, site specific frequency of oral cavity tumors and frequency of lymph node metastasis. Results: Tumors of tongue were the most common constituting 42%, squamous cell carcinoma was the histological diagnosis in 90% cases. Sixty eight (61.8%) cases were node negative. Selective neck dissection was done in 55.5% of the cases. Submandibular gland was involved in 2 cases (1.8%). Conclusion: Submandibular gland metastasis from early oral cavity tumors is rare; any neoplastic involvement of the gland usually occurs via direct spread. (author)

  7. 15. Amygdala pain mechanisms

    Science.gov (United States)

    Neugebauer, Volker

    2015-01-01

    A limbic brain area the amygdala plays a key role in emotional responses and affective states and disorders such as learned fear, anxiety and depression. The amygdala has also emerged as an important brain center for the emotional-affective dimension of pain and for pain modulation. Hyperactivity in the laterocapsular division of the central nucleus of the amygdala (CeLC, also termed the “nociceptive amygdala”) accounts for pain-related emotional responses and anxiety-like behavior. Abnormally enhanced output from the CeLC is the consequence of an imbalance between excitatory and inhibitory mechanisms. Impaired inhibitory control mediated by a cluster of GABAergic interneurons in the intercalated cell masses (ITC) allows the development of glutamate- and neuropeptide-driven synaptic plasticity of excitatory inputs from the brainstem (parabrachial area) and from the lateral-basolateral amygdala network (LA-BLA, site of integration of polymodal sensory information). BLA hyperactivity also generates abnormally enhanced feedforward inhibition of principal cells in the medial prefrontal cortex (mPFC), a limbic cortical area that is strongly interconnected with the amygdala. Pain-related mPFC deactivation results in cognitive deficits and failure to engage cortically driven ITC-mediated inhibitory control of amygdala processing. Impaired cortical control allows the uncontrolled persistence of amygdala pain mechanisms. PMID:25846623

  8. Threat-related amygdala functional connectivity is associated with 5-HTTLPR genotype and neuroticism

    DEFF Research Database (Denmark)

    Madsen, Martin Korsbak; Mc Mahon, Brenda; Andersen, Sofie Bech

    2016-01-01

    between right amygdala and mPFC and visual cortex, and between both amygdalae and left lateral orbitofrontal (lOFC) and ventrolateral prefrontal cortex (vlPFC). Notably, 5-HTTLPR moderated the association between neuroticism and functional connectivity between both amygdalae and left l...... is not fully understood. Using functional magnetic resonance imaging, we evaluated independent and interactive effects of the 5-HTTLPR genotype and neuroticism on amygdala functional connectivity during an emotional faces paradigm in 76 healthy individuals. Functional connectivity between left amygdala......Communication between the amygdala and other brain regions critically regulates sensitivity to threat, which has been associated with risk for mood and affective disorders. The extent to which these neural pathways are genetically determined or correlate with risk-related personality measures...

  9. The amygdala: securing pleasure and avoiding pain

    Directory of Open Access Journals (Sweden)

    Anushka B P Fernando

    2013-12-01

    Full Text Available The amygdala has traditionally been associated with fear, mediating the impact of negative emotions on memory. However, this view does not fully encapsulate the function of the amygdala, nor the impact that processing in this structure has on the motivational limbic corticostriatal circuitry of which it is an important structure. Here we discuss the interactions between different amygdala nuclei with cortical and striatal regions involved in motivation; interconnections and parallel circuitries that have become increasingly understood in recent years. We review the evidence that the amygdala stores memories that allow initially motivationally neutral stimuli to become associated through pavlovian conditioning with motivationally relevant outcomes which, importantly, can be either appetitive (e.g. food or aversive (e.g. electric shock. We also consider how different psychological processes supported by the amygdala such as conditioned reinforcement and punishment, conditioned motivation and suppression, and conditioned approach and avoidance behavior, are not only psychologically but also neurobiologically dissociable, being mediated by distinct yet overlapping neural circuits within the limbic corticostriatal circuitry. Clearly the role of the amygdala goes beyond encoding aversive stimuli to also encode the appetitive, requiring an appreciation of the amygdala’s mediation of both appetitive and fearful behavior through diverse psychological processes.

  10. FMRI connectivity analysis of acupuncture effects on an amygdala-associated brain network

    Directory of Open Access Journals (Sweden)

    Zhao Baixiao

    2008-11-01

    Full Text Available Abstract Background Recently, increasing evidence has indicated that the primary acupuncture effects are mediated by the central nervous system. However, specific brain networks underpinning these effects remain unclear. Results In the present study using fMRI, we employed a within-condition interregional covariance analysis method to investigate functional connectivity of brain networks involved in acupuncture. The fMRI experiment was performed before, during and after acupuncture manipulations on healthy volunteers at an acupuncture point, which was previously implicated in a neural pathway for pain modulation. We first identified significant fMRI signal changes during acupuncture stimulation in the left amygdala, which was subsequently selected as a functional reference for connectivity analyses. Our results have demonstrated that there is a brain network associated with the amygdala during a resting condition. This network encompasses the brain structures that are implicated in both pain sensation and pain modulation. We also found that such a pain-related network could be modulated by both verum acupuncture and sham acupuncture. Furthermore, compared with a sham acupuncture, the verum acupuncture induced a higher level of correlations among the amygdala-associated network. Conclusion Our findings indicate that acupuncture may change this amygdala-specific brain network into a functional state that underlies pain perception and pain modulation.

  11. Amygdala and hippocampus enlargement during adolescence in autism.

    NARCIS (Netherlands)

    Groen, W.B.; Teluij, M.; Buitelaar, J.K.; Tendolkar, I.

    2010-01-01

    OBJECTIVE: The amygdala and hippocampus are key components of the neural system mediating emotion perception and regulation and are thought to be involved in the pathophysiology of autism. Although some studies in children with autism suggest that there is an enlargement of amygdala and hippocampal

  12. Amygdala and Hippocampus Enlargement during Adolescence in Autism

    Science.gov (United States)

    Groen, Wouter; Teluij, Michelle; Buitelaar, Jan; Tendolkar, Indira

    2010-01-01

    Objective: The amygdala and hippocampus are key components of the neural system mediating emotion perception and regulation and are thought to be involved in the pathophysiology of autism. Although some studies in children with autism suggest that there is an enlargement of amygdala and hippocampal volume, findings in adolescence are sparse.…

  13. Two Days' Sleep Debt Causes Mood Decline During Resting State Via Diminished Amygdala-Prefrontal Connectivity.

    Science.gov (United States)

    Motomura, Yuki; Katsunuma, Ruri; Yoshimura, Michitaka; Mishima, Kazuo

    2017-10-01

    Sleep debt (SD) has been suggested to evoke emotional instability by diminishing the suppression of the amygdala by the medial prefrontal cortex (MPFC). Here, we investigated how short-term SD affects resting-state functional connectivity between the amygdala and MPFC, self-reported mood, and sleep parameters. Eighteen healthy adult men aged 29 ± 8.24 years participated in a 2-day sleep control session (SC; time in bed [TIB], 9 hours) and 2-day SD session (TIB, 3 hours). On day 2 of each session, resting-state functional magnetic resonance imaging was performed, followed immediately by measuring self-reported mood on the State-Trait Anxiety Inventory-State subscale (STAI-S). STAI-S score was significantly increased, and functional connectivity between the amygdala and MPFC was significantly decreased in SD compared with SC. Significant correlations were observed between reduced rapid eye movement (REM) sleep and reduced left amygdala-MPFC functional connectivity (FCL_amg-MPFC) and between reduced FCL_amg-MPFC and increased STAI-S score in SD compared with SC. These findings suggest that reduced MPFC functional connectivity of amygdala activity is involved in mood deterioration under SD, and that REM sleep reduction is involved in functional changes in the corresponding brain regions. Having adequate REM sleep may be important for mental health maintenance. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

  14. Volumetric associations between uncinate fasciculus, amygdala, and trait anxiety

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    Baur Volker

    2012-01-01

    Full Text Available Abstract Background Recent investigations of white matter (WM connectivity suggest an important role of the uncinate fasciculus (UF, connecting anterior temporal areas including the amygdala with prefrontal-/orbitofrontal cortices, for anxiety-related processes. Volume of the UF, however, has rarely been investigated, but may be an important measure of structural connectivity underlying limbic neuronal circuits associated with anxiety. Since UF volumetric measures are newly applied measures, it is necessary to cross-validate them using further neural and behavioral indicators of anxiety. Results In a group of 32 subjects not reporting any history of psychiatric disorders, we identified a negative correlation between left UF volume and trait anxiety, a finding that is in line with previous results. On the other hand, volume of the left amygdala, which is strongly connected with the UF, was positively correlated with trait anxiety. In addition, volumes of the left UF and left amygdala were inversely associated. Conclusions The present study emphasizes the role of the left UF as candidate WM fiber bundle associated with anxiety-related processes and suggests that fiber bundle volume is a WM measure of particular interest. Moreover, these results substantiate the structural relatedness of UF and amygdala by a non-invasive imaging method. The UF-amygdala complex may be pivotal for the control of trait anxiety.

  15. Impact of family history and depression on amygdala volume.

    LENUS (Irish Health Repository)

    Saleh, Karim

    2012-07-30

    Family history of depression significantly impacts life-long depression risk. Family history could impact the stress and emotion regulation system that involves the amygdala. This study\\'s purpose was to investigate family history\\'s effect on amygdala volumes, and differences in first degree relatives with and without major depressive disorder (MDD). Participants, aged 18-65, were healthy volunteers (N=52) with (n=26) and without (n=26) first degree family history, and patients with MDD (N=48) with (n=27) and without (n=21)first-degree family history recruited for structural magnetic resonance imaging (MRI). Participants underwent clinical assessment followed by manual amygdala tracing. Patients with MDD without family history showed significantly larger right amygdala without a family history of MDD. These effects had larger right amygdala than healthy controls without MDD family history. These effects were pronounced in females. Family history and gender impacted amygdala volumes in all participants, providing a rationale for the inconsistent results in MDD amygdala studies. Higher familial risk in depression seems to be associated with smaller amygdala volumes, whereas depression alone is associated with larger amygdala volumes. Ultimately, these findings highlight consideration of family history and gender in research and treatment strategies.

  16. Sex-specific neural circuits of emotion regulation in the centromedial amygdala.

    Science.gov (United States)

    Wu, Yan; Li, Huandong; Zhou, Yuan; Yu, Jian; Zhang, Yuanchao; Song, Ming; Qin, Wen; Yu, Chunshui; Jiang, Tianzi

    2016-03-23

    Sex-related differences in emotion regulation (ER) in the frequency power distribution within the human amygdala, a brain region involved in emotion processing, have been reported. However, how sex differences in ER are manifested in the brain networks which are seeded on the amygdala subregions is unclear. The goal of this study was to investigate this issue from a brain network perspective. Utilizing resting-state functional connectivity (RSFC) analysis, we found that the sex-specific functional connectivity patterns associated with ER trait level were only seeded in the centromedial amygdala (CM). Women with a higher trait-level ER had a stronger negative RSFC between the right CM and the medial superior frontal gyrus (mSFG), and stronger positive RSFC between the right CM and the anterior insula (AI) and the superior temporal gyrus (STG). But men with a higher trait-level ER was associated with weaker negative RSFC of the right CM-mSFG and positive RSFCs of the right CM-left AI, right CM-right AI/STG, and right CM-left STG. These results provide evidence for the sex-related effects in ER based on CM and indicate that men and women may differ in the neural circuits associated with emotion representation and integration.

  17. Altered Amygdala Resting-State Functional Connectivity and Hemispheric Asymmetry in Patients With Social Anxiety Disorder

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    Ye-Ha Jung

    2018-04-01

    Full Text Available Background: The amygdala plays a key role in emotional hyperreactivity in response to social threat in patients with social anxiety disorder (SAD. We investigated resting-state functional connectivity (rs-FCN of the left and right amygdala with various brain regions and functional lateralization in patients with SAD.Methods: A total of 36 patients with SAD and 42 matched healthy controls underwent functional magnetic resonance imaging (fMRI at rest. Using the left and right amygdala as seed regions, we compared the strength of the rs-FCN in the patient and control groups. Furthermore, we investigated group differences in the hemispheric asymmetry of the functional connectivity maps of the left and right amygdala.Results: Compared with healthy controls, the rs-FCN between the left amygdala and the dorsolateral prefrontal cortex was reduced in patients with SAD, whereas left amygdala connectivity with the fusiform gyrus, anterior insula, supramarginal gyrus, and precuneus was increased or positively deflected in the patient group. Additionally, the strength rs-FCN between the left amygdala and anterior insula was positively associated with the severity of the fear of negative evaluation in patients with SAD (r = 0.338, p = 0.044. The rs-FCN between the right amygdala and medial frontal gyrus was decreased in patients with SAD compared with healthy controls, whereas connectivity with the parahippocampal gyrus was greater in the patient group than in the control group. The hemispheric asymmetry patterns in the anterior insula, intraparietal sulcus (IPS, and inferior frontal gyrus of the patient group were opposite those of the control group, and functional lateralization of the connectivity between the amygdala and the IPS was associated with the severity of social anxiety symptoms (r = 0.365, p = 0.037.Conclusion: Our findings suggest that in addition to impaired fronto-amygdala communication, the functional lateralization of amygdala function

  18. Depression/anxiety disorder and amygdala

    International Nuclear Information System (INIS)

    Iidaka, Tetsuya

    2007-01-01

    Described and discussed are neuro-imaging studies on the amygdala (Am) concerning its volume, neuro-active drug effect on it and its response to repulsive and attractive stress-evoked character/temperament tests in patients mainly with major depression (MD) and anxiety disorder (AD), by functional MRI (fMRI) and positron emission tomography (PET). A recent trend of volumetry of Am is the voxel-based morphometry by MRI, of which results are still controversial in MD. In contrast, many studies by PET and fMRI using neuro-active drugs have revealed that Am activity in MD is stimulated, and this hyperactivity can be improved by anti-depressive drugs. In addition, difference of activities is suggested in Am left and right hemispheres. The hyperactivity in Am has been reported also in AD and phobic disorders, of which symptoms are conceivably expressed by the sensitivity changes in the cerebral limbic system involving Am. The author considers the central region responsible for the depressive mood is present around cortex of anteroinferior genu of corpus callosum where neuro-network with Am is dense. (R.T.)

  19. Left-right symmetry breaking in mice by left-right dynein may occur via a biased chromatid segregation mechanism, without directly involving the Nodal gene

    Energy Technology Data Exchange (ETDEWEB)

    Sauer, Stephan; Klar, Amar J. S., E-mail: sauers@mail.nih.gov, E-mail: klara@mail.nih.gov [Gene Regulation and Chromosome Biology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, MD (United States)

    2012-11-16

    Ever since cloning the classic iv (inversedviscerum) mutation identified the “left-right dynein” (lrd) gene in mice, most research on body laterality determination has focused on its function in motile cilia at the node embryonic organizer. This model is attractive, as it links chirality of cilia architecture to asymmetry development. However, lrd is also expressed in blastocysts and embryonic stem cells, where it was shown to bias the segregation of recombined sister chromatids away from each other in mitosis. These data suggested that lrd is part of a cellular mechanism that recognizes and selectively segregates sister chromatids based on their replication history: old “Watson” versus old “Crick” strands. We previously proposed that the mouse left-right axis is established via an asymmetric cell division prior to/or during gastrulation. In this model, left-right dynein selectively segregates epigenetically differentiated sister chromatids harboring a hypothetical “left-right axis development 1” (“lra1”) gene during the left-right axis establishing cell division. Here, asymmetry development would be ultimately governed by the chirality of the cytoskeleton and the DNA molecule. Our model predicts that randomization of chromatid segregation in lrd mutants should produce embryos with 25% situs solitus, 25% situs inversus, and 50% embryonic death due to heterotaxia and isomerism. Here we confirmed this prediction by using two distinct lrd mutant alleles. Other than lrd, thus far Nodal gene is the most upstream function implicated in visceral organs laterality determination. We next tested whether the Nodal gene constitutes the lra1 gene hypothesized in the model by testing mutant’s effect on 50% embryonic lethality observed in lrd mutants. Since Nodal mutation did not suppress lethality, we conclude that Nodal is not equivalent to the lra1 gene. In summary, we describe the origin of 50% lethality in lrd mutant mice not yet explained by any other

  20. Left-right symmetry breaking in mice by left-right dynein may occur via a biased chromatid segregation mechanism, without directly involving the Nodal gene

    Directory of Open Access Journals (Sweden)

    Stephan eSauer

    2012-11-01

    Full Text Available Ever since cloning the classic iv mutation identified the ‘left-right dynein’ (lrd gene in mice, most research on body laterality determination has focused on its function in motile cilia at the node embryonic organizer. This model is attractive, as it links chirality of cilia architecture to asymmetry development. However, lrd is also expressed in blastocysts and embryonic stem cells, where it was shown to bias the segregation of recombined sister chromatids away from each other in mitosis. These data suggested that lrd is part of a cellular mechanism that recognizes and selectively segregates sister chromatids based on their replication history: old ‘Watson’ vs. old ‘Crick’ strands. We previously proposed that the mouse left-right axis is established via an asymmetric cell division prior to/or during gastrulation. In this model, left-right dynein selectively segregates epigenetically differentiated sister chromatids harboring a hypothetical ‘left-right axis development 1’ (‘lra1’ gene during the left-right axis establishing cell division. Here, asymmetry development would be ultimately governed by the chirality of the cytoskeleton and the DNA molecule. Our model predicts that randomization of chromatid segregation in lrd mutants should produce embryos with 25% situs solitus, 25% situs inversus, and 50% embryonic death due to heterotaxia and isomerism. Here we confirmed this prediction by using two distinct lrd mutant alleles. Other than lrd, thus far Nodal gene is the most upstream function implicated in visceral organs laterality determination. We next tested whether the Nodal gene constitutes the lra1 gene hypothesized in the model by testing mutant’s effect on 50% embryonic lethality observed in lrd mutants. Since Nodal mutation did not suppress lethality, we conclude that Nodal is not equivalent to the lra1 gene. In summary, we describe the origin of 50% lethality in lrd mutant mice not yet explained by any other

  1. Left-right symmetry breaking in mice by left-right dynein may occur via a biased chromatid segregation mechanism, without directly involving the Nodal gene

    International Nuclear Information System (INIS)

    Sauer, Stephan; Klar, Amar J. S.

    2012-01-01

    Ever since cloning the classic iv (inversedviscerum) mutation identified the “left-right dynein” (lrd) gene in mice, most research on body laterality determination has focused on its function in motile cilia at the node embryonic organizer. This model is attractive, as it links chirality of cilia architecture to asymmetry development. However, lrd is also expressed in blastocysts and embryonic stem cells, where it was shown to bias the segregation of recombined sister chromatids away from each other in mitosis. These data suggested that lrd is part of a cellular mechanism that recognizes and selectively segregates sister chromatids based on their replication history: old “Watson” versus old “Crick” strands. We previously proposed that the mouse left-right axis is established via an asymmetric cell division prior to/or during gastrulation. In this model, left-right dynein selectively segregates epigenetically differentiated sister chromatids harboring a hypothetical “left-right axis development 1” (“lra1”) gene during the left-right axis establishing cell division. Here, asymmetry development would be ultimately governed by the chirality of the cytoskeleton and the DNA molecule. Our model predicts that randomization of chromatid segregation in lrd mutants should produce embryos with 25% situs solitus, 25% situs inversus, and 50% embryonic death due to heterotaxia and isomerism. Here we confirmed this prediction by using two distinct lrd mutant alleles. Other than lrd, thus far Nodal gene is the most upstream function implicated in visceral organs laterality determination. We next tested whether the Nodal gene constitutes the lra1 gene hypothesized in the model by testing mutant’s effect on 50% embryonic lethality observed in lrd mutants. Since Nodal mutation did not suppress lethality, we conclude that Nodal is not equivalent to the lra1 gene. In summary, we describe the origin of 50% lethality in lrd mutant mice not yet explained by any other

  2. ABA renewal involves enhancements in both GluA2-lacking AMPA receptor activity and GluA1 phosphorylation in the lateral amygdala.

    Directory of Open Access Journals (Sweden)

    Kyungjoon Park

    Full Text Available Fear renewal, the context-specific relapse of fear following fear extinction, is a leading animal model of post-traumatic stress disorders (PTSD and fear-related disorders. Although fear extinction can diminish fear responses, this effect is restricted to the context where the extinction is carried out, and the extinguished fear strongly relapses when assessed in the original acquisition context (ABA renewal or in a context distinct from the conditioning and extinction contexts (ABC renewal. We have previously identified Ser831 phosphorylation of GluA1 subunit in the lateral amygdala (LA as a key molecular mechanism for ABC renewal. However, molecular mechanisms underlying ABA renewal remain to be elucidated. Here, we found that both the excitatory synaptic efficacy and GluA2-lacking AMPAR activity at thalamic input synapses onto the LA (T-LA synapses were enhanced upon ABA renewal. GluA2-lacking AMPAR activity was also increased during low-threshold potentiation, a potential cellular substrate of renewal, at T-LA synapses. The microinjection of 1-naphtylacetyl-spermine (NASPM, a selective blocker of GluA2-lacking AMPARs, into the LA attenuated ABA renewal, suggesting a critical role of GluA2-lacking AMPARs in ABA renewal. We also found that Ser831 phosphorylation of GluA1 in the LA was increased upon ABA renewal. We developed a short peptide mimicking the Ser831-containing C-tail region of GluA1, which can be phosphorylated upon renewal (GluA1S; thus, the phosphorylated GluA1S may compete with Ser831-phosphorylated GluA1. This GluA1S peptide blocked the low-threshold potentiation when dialyzed into a recorded neuron. The microinjection of a cell-permeable form of GluA1S peptide into the LA attenuated ABA renewal. In support of the GluA1S experiments, a GluA1D peptide (in which the serine at 831 is replaced with a phosphomimetic amino acid, aspartate attenuated ABA renewal when microinjected into the LA. These findings suggest that enhancements

  3. ABA renewal involves enhancements in both GluA2-lacking AMPA receptor activity and GluA1 phosphorylation in the lateral amygdala.

    Science.gov (United States)

    Park, Kyungjoon; Song, Beomjong; Kim, Jeongyeon; Hong, Ingie; Song, Sangho; Lee, Junuk; Park, Sungmo; Kim, Jihye; An, Bobae; Lee, Hyun Woo; Lee, Seungbok; Kim, Hyun; Lee, Justin C; Lee, Sukwon; Choi, Sukwoo

    2014-01-01

    Fear renewal, the context-specific relapse of fear following fear extinction, is a leading animal model of post-traumatic stress disorders (PTSD) and fear-related disorders. Although fear extinction can diminish fear responses, this effect is restricted to the context where the extinction is carried out, and the extinguished fear strongly relapses when assessed in the original acquisition context (ABA renewal) or in a context distinct from the conditioning and extinction contexts (ABC renewal). We have previously identified Ser831 phosphorylation of GluA1 subunit in the lateral amygdala (LA) as a key molecular mechanism for ABC renewal. However, molecular mechanisms underlying ABA renewal remain to be elucidated. Here, we found that both the excitatory synaptic efficacy and GluA2-lacking AMPAR activity at thalamic input synapses onto the LA (T-LA synapses) were enhanced upon ABA renewal. GluA2-lacking AMPAR activity was also increased during low-threshold potentiation, a potential cellular substrate of renewal, at T-LA synapses. The microinjection of 1-naphtylacetyl-spermine (NASPM), a selective blocker of GluA2-lacking AMPARs, into the LA attenuated ABA renewal, suggesting a critical role of GluA2-lacking AMPARs in ABA renewal. We also found that Ser831 phosphorylation of GluA1 in the LA was increased upon ABA renewal. We developed a short peptide mimicking the Ser831-containing C-tail region of GluA1, which can be phosphorylated upon renewal (GluA1S); thus, the phosphorylated GluA1S may compete with Ser831-phosphorylated GluA1. This GluA1S peptide blocked the low-threshold potentiation when dialyzed into a recorded neuron. The microinjection of a cell-permeable form of GluA1S peptide into the LA attenuated ABA renewal. In support of the GluA1S experiments, a GluA1D peptide (in which the serine at 831 is replaced with a phosphomimetic amino acid, aspartate) attenuated ABA renewal when microinjected into the LA. These findings suggest that enhancements in both the

  4. Localization of deformations within the amygdala in individuals with psychopathy.

    Science.gov (United States)

    Yang, Yaling; Raine, Adrian; Narr, Katherine L; Colletti, Patrick; Toga, Arthur W

    2009-09-01

    Despite the repeated findings of impaired fear conditioning and affective recognition in psychopathic individuals, there has been a paucity of brain imaging research on the amygdala and no evidence suggesting which regions within the amygdala may be structurally compromised in individuals with psychopathy. To detect global and regional anatomical abnormalities in the amygdala in individuals with psychopathy. Cross-sectional design using structural magnetic resonance imaging. Participants were recruited from high-risk communities (temporary employment agencies) in the Los Angeles, California, area and underwent imaging at a hospital research facility at the University of Southern California. Twenty-seven psychopathic individuals as defined by the Hare Psychopathy Checklist-Revised and 32 normal controls matched on age, sex, and ethnicity. Amygdala volumes were examined using traditional volumetric analyses and surface-based mesh modeling methods were used to localize regional surface deformations. Individuals with psychopathy showed significant bilateral volume reductions in the amygdala compared with controls (left, 17.1%; right, 18.9%). Surface deformations were localized in regions in the approximate vicinity of the basolateral, lateral, cortical, and central nuclei of the amygdala. Significant correlations were found between reduced amygdala volumes and increased total and facet psychopathy scores, with correlations strongest for the affective and interpersonal facets of psychopathy. Results provide the first evidence, to our knowledge, of focal amygdala abnormalities in psychopathic individuals and corroborate findings from previous lesion studies. Findings support prior hypotheses of amygdala deficits in individuals with psychopathy and indicate that amygdala abnormalities contribute to emotional and behavioral symptoms of psychopathy.

  5. Emotional stimuli-provoked seizures potentially misdiagnosed as psychogenic non-epileptic attacks: A case of temporal lobe epilepsy with amygdala enlargement

    Directory of Open Access Journals (Sweden)

    Hidetaka Tamune

    Full Text Available The association between emotional stimuli and temporal lobe epilepsy (TLE is largely unknown. Here, we report the case of a depressed, 50-year-old female complaining of episodes of a “spaced out” experience precipitated by emotional stimuli. Psychogenic non-epileptic attacks were suspected. However, video-EEG coupled with emotional stimuli-provoked procedures and MRI findings of amygdala enlargement, led to the diagnosis of left TLE. Accurate diagnosis and explanation improved her subjective depression and seizure frequency. This case demonstrated that emotional stimuli can provoke seizures in TLE and suggested the involvement of the enlarged amygdala and the modulation of emotion-related neural circuits. Keywords: Video-EEG, Psychogenic non-epileptic attacks, Temporal lobe epilepsy, Amygdala enlargement, Reflex seizure, Provoked seizure

  6. Chemosensory function of the amygdala.

    Science.gov (United States)

    Gutiérrez-Castellanos, Nicolás; Martínez-Marcos, Alino; Martínez-García, Fernando; Lanuza, Enrique

    2010-01-01

    The chemosensory amygdala has been traditionally divided into two divisions based on inputs from the main (olfactory amygdala) or accessory (vomeronasal amygdala) olfactory bulbs, supposedly playing different and independent functional roles detecting odors and pheromones, respectively. Recently, there has been increased anatomical evidence of convergence inputs from the main and accessory bulbs in some areas of the amygdala, and this is correlated with functional evidence of interrelationships between the olfactory and the vomeronasal systems. This has lead to the characterization of a third division of the chemosensory amygdala, the mixed chemosensory amygdala, providing a new perspective of how chemosensory information is processed in the amygdaloid complex, in particular in relation to emotional behaviors. In this chapter, we analyze the anatomical and functional organization of the chemosensory amygdala from this new perspective. Finally, the evolutionary changes of the chemosensory nuclei of the mammalian amygdala are discussed, paying special attention to the case of primates, including humans. Copyright © 2010 Elsevier Inc. All rights reserved.

  7. Amygdala and ventral striatum make distinct contributions to reinforcement learning

    Science.gov (United States)

    Costa, Vincent D.; Monte, Olga Dal; Lucas, Daniel R.; Murray, Elisabeth A.; Averbeck, Bruno B.

    2016-01-01

    Summary Reinforcement learning (RL) theories posit that dopaminergic signals are integrated within the striatum to associate choices with outcomes. Often overlooked is that the amygdala also receives dopaminergic input and is involved in Pavlovian processes that influence choice behavior. To determine the relative contributions of the ventral striatum (VS) and amygdala to appetitive RL we tested rhesus macaques with VS or amygdala lesions on deterministic and stochastic versions of a two-arm bandit reversal learning task. When learning was characterized with a RL model relative to controls, amygdala lesions caused general decreases in learning from positive feedback and choice consistency. By comparison, VS lesions only affected learning in the stochastic task. Moreover, the VS lesions hastened the monkeys’ choice reaction times, which emphasized a speed-accuracy tradeoff that accounted for errors in deterministic learning. These results update standard accounts of RL by emphasizing distinct contributions of the amygdala and VS to RL. PMID:27720488

  8. Hippocampus and amygdala volumes in patients with vaginismus.

    Science.gov (United States)

    Atmaca, Murad; Baykara, Sema; Ozer, Omer; Korkmaz, Sevda; Akaslan, Unsal; Yildirim, Hanefi

    2016-06-22

    To compare hippocampus and amygdala volumes of patients with vaginismus with those of healthy control subjects. Magnetic resonance imaging was performed on ten patients with vaginismus and ten control subjects matched for age and gender. Volumes of the hippocampus and amygdala were blindly measured. We found that the mean right amygdala volume of patients with vaginismus were smaller than that of the healthy controls. With regard to hippocampus volumes, the mean left and right hippocampus volumes were smaller than those of the healthy controls. Our present findings suggest that there have been hippocampus and amygdala structural abnormalities in patients with vaginismus. These changes provide the notion that vaginismus may be a fear-related condition.

  9. Leiomyosarcoma of inferior vena cava involving bilateral renal veins: Surgical challenges and reconstruction with upfront saphenous vein interposition graft for left renal vein outflow

    Directory of Open Access Journals (Sweden)

    Rishi Nayyar

    2010-01-01

    Full Text Available Leiomyosarcoma of inferior vena cava (IVC involving bilateral renal veins presents a surgical challenge. Herein, we report the successful management of two such cases using restoration of left renal venous outflow by saphenous vein interposition graft as first step of surgery. Then radical resection of tumor and right kidney was done. IVC was lastly reconstructed using Gore-Tex graft. This report highlights the surgical challenges to ensure radical resection. Furthermore, the importance of restoring left renal outflow in presence of concomitant right nephrectomy is discussed. Both the patients were disease free at six months with no loss of left renal glomerular filtration rate.

  10. Altered Amygdala Development and Fear Processing in Prematurely Born Infants

    Science.gov (United States)

    Cismaru, Anca Liliana; Gui, Laura; Vasung, Lana; Lejeune, Fleur; Barisnikov, Koviljka; Truttmann, Anita; Borradori Tolsa, Cristina; Hüppi, Petra S.

    2016-01-01

    Context: Prematurely born children have a high risk of developmental and behavioral disabilities. Cerebral abnormalities at term age have been clearly linked with later behavior alterations, but existing studies did not focus on the amygdala. Moreover, studies of early amygdala development after premature birth in humans are scarce. Objective: To compare amygdala volumes in very preterm infants at term equivalent age (TEA) and term born infants, and to relate premature infants’ amygdala volumes with their performance on the Laboratory Temperament Assessment Battery (Lab-TAB) fear episode at 12 months. Participants: Eighty one infants born between 2008 and 2014 at the University Hospitals of Geneva and Lausanne, taking part in longitudinal and functional imaging studies, who had undergone a magnetic resonance imaging (MRI) scan at TEA enabling manual amygdala delineation. Outcomes: Amygdala volumes assessed by manual segmentation of MRI scans; volumes of cortical and subcortical gray matter, white matter and cerebrospinal fluid (CSF) automatically segmented in 66 infants; scores for the Lab-TAB fear episode for 42 premature infants at 12 months. Results: Amygdala volumes were smaller in preterm infants at TEA than term infants (mean difference 138.03 mm3, p amygdala volumes were larger than left amygdala volumes (mean difference 36.88 mm3, p Amygdala volumes showed significant correlation with the intensity of the escape response to a fearsome toy (rs = 0.38, p = 0.013), and were larger in infants showing an escape response compared to the infants showing no escape response (mean difference 120.97 mm3, p = 0.005). Amygdala volumes were not significantly correlated with the intensity of facial fear, distress vocalizations, bodily fear and positive motor activity in the fear episode. Conclusion: Our results indicate that premature birth is associated with a reduction in amygdala volumes and white matter volumes at TEA, suggesting that altered amygdala development

  11. Altered Amygdala Resting-State Functional Connectivity in Maintenance Hemodialysis End-Stage Renal Disease Patients with Depressive Mood.

    Science.gov (United States)

    Chen, Hui Juan; Wang, Yun Fei; Qi, Rongfeng; Schoepf, U Joseph; Varga-Szemes, Akos; Ball, B Devon; Zhang, Zhe; Kong, Xiang; Wen, Jiqiu; Li, Xue; Lu, Guang Ming; Zhang, Long Jiang

    2017-04-01

    The purpose of this study was to investigate patterns in the amygdala-based emotional processing circuit of hemodialysis patients using resting-state functional MR imaging (rs-fMRI). Fifty hemodialysis patients (25 with depressed mood and 25 without depressed mood) and 26 healthy controls were included. All subjects underwent neuropsychological tests and rs-fMRI, and patients also underwent laboratory tests. Functional connectivity of the bilateral amygdala was compared among the three groups. The relationship between functional connectivity and clinical markers was investigated. Depressed patients showed increased positive functional connectivity of the left amygdala with the left superior temporal gyrus and right parahippocampal gyrus (PHG) but decreased amygdala functional connectivity with the left precuneus, angular gyrus, posterior cingulate cortex (PCC), and left inferior parietal lobule compared with non-depressed patients (P amygdala with bilateral supplementary motor areas and PHG but decreased amygdala functional connectivity with the right superior frontal gyrus, superior parietal lobule, bilateral precuneus, and PCC (P amygdala (P amygdala-prefrontal-PCC-limbic circuits was impaired in depressive hemodialysis patients, with a gradual decrease in ACC between controls, non-depressed, and depressed patients for the right amygdala. This indicates that ACC plays a role in amygdala-based emotional regulatory circuits in these patients.

  12. [MR spectroscopy of amygdala: investigation of methodology].

    Science.gov (United States)

    Tang, Hehan; Yue, Qiang; Gong, Qiyong

    2013-08-01

    This study was aimed to optimize the methods of magnetic resonance spectroscopy (MRS) to improve its quality in amygdala. Forty-three volunteers were examined at right and left amygdala using stimulated-echo acquisition mode (STEAM), and point-resolved spectroscopy series (PRESS) with and without saturation bands. The Cr-SNR, water-suppression level, water full width at half maximum (FWHM) and RMS noise of three sequences were compared. The results showed that (1) the Cr-SNR and water-suppression lelvel of PRESS with saturation bands were better than that of PRESS without saturation bands and STEAM (P<0.001); (2) the left and right RMS noise was significantly different both using PRESS with saturation bands and using STEAM (P<0.05); (3) there was a positive, significant correlation between Cr-SNR and voxel size (P<0.05). Therefore, PRESS with saturation bands is better than PRESS without saturation bands or STEAM for the spectroscopy of amygdala. It is also useful to make the voxel as big as possible to improve the spectral quality.

  13. Effects of fluoxetine on the amygdala and the hippocampus after administration of a single prolonged stress to male Wistar rates: In vivo proton magnetic resonance spectroscopy findings.

    Science.gov (United States)

    Han, Fang; Xiao, Bing; Wen, Lili; Shi, Yuxiu

    2015-05-30

    Posttraumatic stress disorder (PTSD) is an anxiety- and memory-based disorder. The hippocampus and amygdala are key areas in mood regulation. Fluoxetine was found to improve the anxiety-related symptoms of PTSD patients. However, little work has directly examined the effects of fluoxetine on the hippocampus and the amygdala. In the present study, male Wistar rats received fluoxetine or vehicle after exposure to a single prolonged stress (SPS), an animal model of PTSD. In vivo proton magnetic resonance spectroscopy ((1)H-MRS) was performed -1, 1, 4, 7 and 14 days after SPS to examine the effects of fluoxetine on neurometabolite changes in amygdala, hippocampus and thalamus. SPS increased the N-acetylaspartate (NAA)/creatine (Cr) and choline moieties (Cho)/Cr ratios in the bilateral amygdala on day 4, decreased the NAA/Cr ratio in the left hippocampus on day 1, and increased both ratios in the right hippocampus on day 14. But no significant change was found in the thalamus. Fluoxetine treatment corrected the SPS increases in the NAA/Cr and Cho/Cr levels in the amygdala on day 4 and in the hippocampus on day 14, but it failed to normalise SPS-associated decreases in NAA/Cr levels in the left hippocampus on day 1. These results suggested that metabolic abnormalities in the amygdala and the hippocampus were involved in SPS, and different effects of fluoxetine in correcting SPS-induced neurometabolite changes among the three areas. These findings have implications for fluoxetine treatment in PTSD. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  14. Late Ratchet syndrome involving isolated left ventricular lead dislodgement post-cardiac resynchronization therapy defibrillator generator change.

    Science.gov (United States)

    Tan, Vern Hsen; Wong, Kelvin

    2018-04-01

    Lead dislodgement following cardiac implantable electronic device (CIED) generator change is rare. We report a case including the postulate mechanism of an isolated left ventricular lead dislodgement 3 months after cardiac resynchronization therapy defibrillator pulse generator change.

  15. Prefrontal-Amygdala Connectivity and State Anxiety during Fear Extinction Recall in Adolescents

    Directory of Open Access Journals (Sweden)

    Despina E. Ganella

    2017-12-01

    Full Text Available While deficits in fear extinction recall have been suggested to underlie vulnerability to anxiety disorders in adolescents, the neurobiology of these deficits remain underexplored. Here we investigate the functional connectivity (FC of the ventromedial prefrontal cortex (vmPFC and dorsolateral PFC (dlPFC underlying extinction recall in healthy adolescents, and assess associations between FC and state/trait anxiety. Adolescents (17 and adults (14, for comparison completed a fear-learning paradigm involving extinction and extinction recall during a functional magnetic resonance imaging session, in which skin conductance response (SCR was recorded. Psychophysiological interaction analyses revealed that during extinction recall there was significant negative connectivity between the vmPFC and amygdala in adults, but not adolescents. vmPFC-amygdala connectivity was positively correlated with SCR. Adolescents showed significant negative FC between the dlPFC and the left and right hippocampus, and the amygdala, which was positively correlated with state anxiety. Recall was also associated with negative connectivity between the dlPFC and thalamus, posterior cingulate cortex, fusiform gyrus, and pallidum in adolescents. These results demonstrate that fear extinction recall in healthy adolescents is associated with FC between prefrontal and limbic brain regions, and suggest that alterations in connectivity may be associated with vulnerability to anxiety in adolescence.

  16. Altered functional connectivity of amygdala underlying the neuromechanism of migraine pathogenesis.

    Science.gov (United States)

    Chen, Zhiye; Chen, Xiaoyan; Liu, Mengqi; Dong, Zhao; Ma, Lin; Yu, Shengyuan

    2017-12-01

    The amygdala is a large grey matter complex in the limbic system, and it may contribute in the neurolimbic pain network in migraine. However, the detailed neuromechanism remained to be elucidated. The objective of this study is to investigate the amygdala structural and functional changes in migraine and to elucidate the mechanism of neurolimbic pain-modulating in the migraine pathogenesis. Conventional MRI, 3D structure images and resting state functional MRI were performed in 18 normal controls (NC), 18 patients with episodic migraine (EM), and 16 patients with chronic migraine (CM). The amygdala volume was measured using FreeSurfer software and the functional connectivity (FC) of bilateral amygdala was computed over the whole brain. Analysis of covariance was performed on the individual FC maps among groups. The increased FC of left amygdala was observed in EM compared with NC, and the decreased of right amygdala was revealed in CM compared with NC. The increased FC of bilateral amygdala was observed in CM compared with EM. The correlation analysis showed a negative correlation between the score of sleep quality (0, normal; 1, mild sleep disturbance; 2, moderate sleep disturbance; 3, serious sleep disturbance) and the increased FC strength of left amygdala in EM compared with NC, and a positive correlation between the score of sleep quality and the increased FC strength of left amygdala in CM compared with EM, and other clinical variables showed no significant correlation with altered FC of amygdala. The altered functional connectivity of amygdala demonstrated that neurolimbic pain network contribute in the EM pathogenesis and CM chronicization.

  17. Aortic dissection involving the brachio-cephalic trunk, celiac trunk, and left common iliac artery with left kidney ischemia: Case report

    International Nuclear Information System (INIS)

    Paslawski, M.; Krzyzanowski, K.

    2006-01-01

    Acute aortic dissection is one of the most dramatic cardiovascular emergencies. To limit the possibility of death, a detailed morphologic and functional diagnosis must be obtained quickly. Aortography has been the traditional method of assessing suspected aortic dissection; however, concern over the low sensitivity of aortography has prompted the investigation of other imaging techniques for this purpose. Transesophageal echocardiography and magnetic resonance imaging are increasingly used in the evaluation of aortic dissection. A recent study found that the sensitivity and specificity of helical computed tomography compare well with those of MR imaging and transesophageal echocardiography. The 55-year-old patient with acute chest and abdominal pain were examined due to suspected aortic dissection. CT examination of thoracic and abdomial aorta was performed. The examination begins with conventional, unenhanced CT. Both unenhanced CT scans and scans after administering of contrast agent were performed. Enhanced images reveal contrast flow in both the false and true aortic lumen. the intima flap in the ascending aorta, aortic arch, and descending aorta, extending to the brachiocephalic trunk, was seen on axial images. In the abdominal aorta, the intimal flap extended to the celiac trunk, without evidence of its occlusion. In one patient, the occlusion of the left renal artery with renal infract was seen on axial images. The intimal flap calcification enables diagnosis even on unenhanced images. The morphology and extent of the dissection was also seen on MPR and VRT images. Helical CT can be used to study the entire aorta in aortic dissection and for follow-up. This technique allows accurate diagnosis of the type of dissection, atypical forms of aortic dissection, and early and late complications after surgery or medical treatment. In addition, helical CT is useful in the surveillance of abdominal branch-vessel compromise, which can be life-threatening in the acute

  18. Can theories of visual representation help to explain asymmetries in amygdala function?

    OpenAIRE

    McMenamin, Brenton W.; Marsolek, Chad J.

    2013-01-01

    Emotional processing differs between the left and right hemispheres of the brain, and functional differences have been reported more specifically between the left amygdala and right amygdala, subcortical structures heavily implicated in emotional processing. However, the empirical pattern of amygdalar asymmetries is inconsistent with extant theories of emotional asymmetries. Here we review this discrepancy, and we hypothesize that hemispheric differences in visual object processing help to ex...

  19. The amygdala, reward and emotion.

    Science.gov (United States)

    Murray, Elisabeth A

    2007-11-01

    Recent research provides new insights into amygdala contributions to positive emotion and reward. Studies of neuronal activity in the monkey amygdala and of autonomic responses mediated by the monkey amygdala show that, contrary to a widely held view, the amygdala is just as important for processing positive reward and reinforcement as it is for negative. In addition, neuropsychological studies reveal that the amygdala is essential for only a fraction of what might be considered 'stimulus-reward processing', and that the neural substrates for emotion and reward are partially nonoverlapping. Finally, evidence suggests that two systems within the amygdala, operating in parallel, enable reward-predicting cues to influence behavior; one mediates a general, arousing effect of reward and the other links the sensory properties of reward to emotion.

  20. AMYGDALA MICROCIRCUITS CONTROLLING LEARNED FEAR

    Science.gov (United States)

    Duvarci, Sevil; Pare, Denis

    2014-01-01

    We review recent work on the role of intrinsic amygdala networks in the regulation of classically conditioned defensive behaviors, commonly known as conditioned fear. These new developments highlight how conditioned fear depends on far more complex networks than initially envisioned. Indeed, multiple parallel inhibitory and excitatory circuits are differentially recruited during the expression versus extinction of conditioned fear. Moreover, shifts between expression and extinction circuits involve coordinated interactions with different regions of the medial prefrontal cortex. However, key areas of uncertainty remain, particularly with respect to the connectivity of the different cell types. Filling these gaps in our knowledge is important because much evidence indicates that human anxiety disorders results from an abnormal regulation of the networks supporting fear learning. PMID:24908482

  1. Optogenetic dissection of amygdala functioning

    Directory of Open Access Journals (Sweden)

    Ryan eLalumiere

    2014-03-01

    Full Text Available Studies of amygdala functioning have occupied a significant place in the history of understanding how the brain controls behavior and cognition. Early work on the amygdala placed this small structure as a key component in the regulation of emotion and affective behavior. Over time, our understanding of its role in brain processes has expanded, as we have uncovered amygdala influences on memory, reward behavior, and overall functioning in many other brain regions. Studies have indicated that the amygdala has widespread connections with a variety of brain structures, from the prefrontal cortex to regions of the brainstem, that explain its powerful influence on other parts of the brain and behaviors mediated by those regions. Thus, many optogenetic studies have focused on harnessing the powers of this technique to elucidate the functioning of the amygdala in relation to motivation, fear, and memory as well as to determine how the amygdala regulates activity in other structures. For example, studies using optogenetics have examined how specific circuits within amygdala nuclei regulate anxiety. Other work has provided insight into how the basolateral and central amygdala nuclei regulate memory processing underlying aversive learning. Many experiments have taken advantage of optogenetics’ ability to target either genetically distinct subpopulations of neurons or the specific projections from the amygdala to other brain regions. Findings from such studies have provided evidence that particular patterns of activity in basolateral amygdala glutamatergic neurons are related to memory consolidation processes, while other work has indicated the critical nature of amygdala inputs to the prefrontal cortex and nucleus accumbens in regulating behavior dependent on those downstream structures. This review will examine the recent discoveries on amygdala functioning made through experiments using optogenetics, placing these findings in the context of the major

  2. The left inferior frontal gyrus is involved in adjusting response bias during a perceptual decision-making task.

    Science.gov (United States)

    Reckless, Greg E; Ousdal, Olga T; Server, Andres; Walter, Henrik; Andreassen, Ole A; Jensen, Jimmy

    2014-05-01

    Changing the way we make decisions from one environment to another allows us to maintain optimal decision-making. One way decision-making may change is how biased one is toward one option or another. Identifying the regions of the brain that underlie the change in bias will allow for a better understanding of flexible decision-making. An event-related, perceptual decision-making task where participants had to detect a picture of an animal amongst distractors was used during functional magnetic resonance imaging. Positive and negative financial motivation were used to affect a change in response bias, and changes in decision-making behavior were quantified using signal detection theory. Response bias became relatively more liberal during both positive and negative motivated trials compared to neutral trials. For both motivational conditions, the larger the liberal shift in bias, the greater the left inferior frontal gyrus (IFG) activity. There was no relationship between individuals' belief that they used a different strategy and their actual change in response bias. The present findings suggest that the left IFG plays a role in adjusting response bias across different decision environments. This suggests a potential role for the left IFG in flexible decision-making.

  3. Biventricular non-compaction with predominant right ventricular involvement, reduced left ventricular systolic and diastolic function, and pulmonary hypertension in a Hispanic male.

    Science.gov (United States)

    Said, Sarmad; Cooper, Chad J; Quevedo, Karla; Rodriguez, Emmanuel; Hernandez, German T

    2013-01-01

    Male, 22 FINAL DIAGNOSIS: Cardiomyopathy Symptoms: Shortness of breath • dispnoea • chest discomfort - Clinical Procedure: Echocardiogram • cardiac MRI Specialty: Cardiology. Challenging differential diagnosis. Non-compaction cardiomyopathy (NCM) is a rare congenital cardiomyopathy characterized by increased trabeculation in one or more segments of the ventricle. The left ventricle is most commonly affected. However, biventricular involvement or right ventricle predominance has also been described. Clinical features of NCM are non-specific and can range from being asymptomatic to symptoms of congestive heart failure, arrhythmia, and systemic thromboembolism. 22-year-old Hispanic male presented with two month history of chest discomfort. Laboratory workup revealed an elevated brain-natriuretic-peptide of 1768 pg/ml. ECG and chest x-ray was nonspecific. Transthoracic echocardiogram revealed prominent trabeculae and spongiform appearance of the left ventricle (LV) with an ejection-fraction of 15-20%; 5 of 9 segments of the LV were trabeculated with deep intertrabecular recesses also involving the right ventricle (RV) with demonstrated blood flow in these recesses on color-doppler. The biventricular spongiform appearance was morphologically suggestive for NCM with involvement of the RV. Confirmatory cardiac MRI was performed, demonstrating excessive trabeculation of the left-ventricular apex and mid-ventricular segments. Hypertrabecularion was exhibited at the apical and lateral wall of the RV. Cardiac catheterization showed an intact cardiac vessel system. The patient was discharged on heart failure treatment and was placed on the heart transplantation list. NCM is a unique disorder resulting in serious and severe complications. The majority of the reported cases describe the involvement of the left ventricle. However, the right ventricle should be taken into careful consideration. The early diagnosis may help to increase the event-free survival.

  4. A specific role for the human amygdala in olfactory memory.

    Science.gov (United States)

    Buchanan, Tony W; Tranel, Daniel; Adolphs, Ralph

    2003-01-01

    The medial temporal lobe is known to play a role in the processing of olfaction and memory. The specific contribution of the human amygdala to memory for odors has not been addressed, however. The role of this region in memory for odors was assessed in patients with unilateral amygdala damage due to temporal lobectomy (n = 20; 11 left, 9 right), one patient with selective bilateral amygdala damage, and in 20 age-matched normal controls. Fifteen odors were presented, followed 1 h later by an odor-name matching test and an odor-odor recognition test. Signal detection analyses showed that both unilateral groups were impaired in their memory for matching odors with names, these patients were not significantly impaired on odor-odor recognition. Bilateral amygdala damage resulted in severe impairment in both odor-name matching as well as in odor-odor recognition memory. Importantly, none of the patients were impaired on an auditory verbal learning task, suggesting that these findings reflect a specific impairment in olfactory memory, and not merely a more general memory deficit. Taken together, the data provide neuropsychological evidence that the human amygdala is essential for olfactory memory.

  5. Personal involvement is related to increased search motivation and associated with activity in left BA44-a pilot study.

    Science.gov (United States)

    Schaefer, Michael; Rumpel, Franziska; Sadrieh, Abdolkarim; Reimann, Martin; Denke, Claudia

    2015-01-01

    Numerous studies explore consumer perception of brands in a more or less passive way. This may still be representative for many situations or decisions we make each day. Nevertheless, sometimes we often actively search for and use information to make informed and reasoned choices, thus implying a rational and thinking consumer. Researchers suggested describing this distinction as low relative to high involvement consumer behavior. Although the involvement concept has been widely used to explain consumer behavior, behavioral and neural correlates of this concept are poorly understood. The current study aims to describe a behavioral measure that is associated with high involvement, the length of search behavior. A second aim of this study was to explore brain activations associated with involvement by employing functional magnetic resonance imaging (fMRI). We presented participants information cues for different products and told them that they had to answer questions with respect to these products at the end of the experiment. Participants were free to stop the information search if they think they gathered enough information or to continue with collecting information. Behavioral results confirmed our hypothesis of a relationship between searching behavior and personal involvement by demonstrating that the length of search correlated significantly with the degree of personal involvement of the participants. fMRI data revealed that personal involvement was associated with activation in BA44. Since this brain region is known to be involved in semantic memory, the results of this pilot study suggest that high involvement consumer behavior may be linked to cognitive load and attention towards a product.

  6. Personal involvement is related to increased search motivation and associated with activity in left BA44 - a pilot study

    Directory of Open Access Journals (Sweden)

    Michael eSchaefer

    2015-03-01

    Full Text Available Numerous studies explore consumer perception of brands in a more or less passive way. This may still be representative for many situations or decisions we make each day. Nevertheless, sometimes we often actively search for and use information to make informed and reasoned choices, thus implying a rational and thinking consumer. Researchers suggested describing this distinction as low relative to high involvement consumer behavior. Although the involvement concept has been widely used to explain consumer behavior, behavioral and neural correlates of this concept are poorly understood. The current study aims to describe a behavioral measure that is associated with high involvement, the length of search behavior. A second aim of this study was to explore brain activations associated with involvement by employing functional magnetic resonance imaging (fMRI. We presented participants information cues for different products and told them that they had to answer questions with respect to these products at the end of the experiment. Participants were free to stop the information search if they think they gathered enough information or to continue with collecting information. Behavioral results confirmed our hypothesis of a relationship between searching behavior and personal involvement by demonstrating that the length of search correlated significantly with the degree of personal involvement of the participants. FMRI data revealed that personal involvement was associated with activation in BA44. Since this brain region is known to be involved in semantic memory, the results of this pilot study suggest that high involvement consumer behavior may be linked to cognitive load and attention towards a product.

  7. Stress, memory and the amygdala.

    Science.gov (United States)

    Roozendaal, Benno; McEwen, Bruce S; Chattarji, Sumantra

    2009-06-01

    Emotionally significant experiences tend to be well remembered, and the amygdala has a pivotal role in this process. But the efficient encoding of emotional memories can become maladaptive - severe stress often turns them into a source of chronic anxiety. Here, we review studies that have identified neural correlates of stress-induced modulation of amygdala structure and function - from cellular mechanisms to their behavioural consequences. The unique features of stress-induced plasticity in the amygdala, in association with changes in other brain regions, could have long-term consequences for cognitive performance and pathological anxiety exhibited in people with affective disorders.

  8. Meta-analysis reveals a lack of sexual dimorphism in human amygdala volume.

    Science.gov (United States)

    Marwha, Dhruv; Halari, Meha; Eliot, Lise

    2017-02-15

    The amygdala plays a key role in many affective behaviors and psychiatric disorders that differ between men and women. To test whether human amygdala volume (AV) differs reliably between the sexes, we performed a systematic review and meta-analysis of AVs reported in MRI studies of age-matched healthy male and female groups. Using four search strategies, we identified 46 total studies (58 matched samples) from which we extracted effect sizes for the sex difference in AV. All data were converted to Hedges g values and pooled effect sizes were calculated using a random-effects model. Each dataset was further meta-regressed against study year and average participant age. We found that uncorrected amygdala volume is about 10% larger in males, with pooled sex difference effect sizes of g=0.581 for right amygdala (κ=28, n=2022), 0.666 for left amygdala (κ=28, n=2006), and 0.876 for bilateral amygdala (κ=16, n=1585) volumes (all p values brain volume (TBV; g=1.278, pbrain size in males. Among studies reporting AVs normalized for ICV or TBV, sex difference effect sizes were small and not statistically significant: g=0.171 for the right amygdala (p=0.206, κ=13, n=1560); 0.233 for the left amygdala (p=0.092, κ=12, n=1512); and 0.257 for bilateral volume (p=0.131, κ=5, n=1629). These values correspond to less than 0.1% larger corrected right AV and 2.5% larger corrected left AV in males compared to females. In summary, AV is not selectively enhanced in human males, as often claimed. Although we cannot rule out subtle male-female group differences, it is not accurate to refer to the human amygdala as "sexually dimorphic." Copyright © 2016 Elsevier Inc. All rights reserved.

  9. Volumetric MRI analysis of the amygdala and the hippocampus in patients with major depression

    International Nuclear Information System (INIS)

    Xia Jun; Zhou Yicheng; Zhang Jingfeng; Yang Bo; Xia Liming; Wang Chengyuan; Chen Jun

    2005-01-01

    Objective: To study the MRI volume of the amygdala and hippocampus in patients with major depression. Methods: Quantitative MRI of the amygdala and hippocampus was studied in 22 patients with major depression and compared with 13 age-matched controls. Results: Both groups exhibited similar significant hippocampal asymmetry (left smaller than right). The volume of the bilateral hippocampus was significantly smaller in the patient group than that in the controls (left: t=9.96, P<0.01; right: t=11.88, P<0.01). The right amygdala was smaller in the patient group than that in the control group (t=5.50, P<0.01), No correlation was found between the hippocampal volume abnormalities and the course of disease. Conclusion: These findings support the hypothesis that the hippocampus and amygdala within limbic-cortical networks may play a crucial role in the pathogenesis of major depression. (authors)

  10. Williams Syndrome Hypersociability: A Neuropsychological Study of the Amygdala and Prefrontal Cortex Hypotheses

    Science.gov (United States)

    Capitao, Liliana; Sampaio, Adriana; Fernandez, Montse; Sousa, Nuno; Pinheiro, Ana; Goncalves, Oscar F.

    2011-01-01

    Individuals with Williams syndrome display indiscriminate approach towards strangers. Neuroimaging studies conducted so far have linked this social profile to structural and/or functional abnormalities in WS amygdala and prefrontal cortex. In this study, the neuropsychological hypotheses of amygdala and prefrontal cortex involvement in WS…

  11. Preferential responses in amygdala and insula during presentation of facial contempt and disgust.

    Science.gov (United States)

    Sambataro, Fabio; Dimalta, Savino; Di Giorgio, Annabella; Taurisano, Paolo; Blasi, Giuseppe; Scarabino, Tommaso; Giannatempo, Giuseppe; Nardini, Marcello; Bertolino, Alessandro

    2006-10-01

    Some authors consider contempt to be a basic emotion while others consider it a variant of disgust. The neural correlates of contempt have not so far been specifically contrasted with disgust. Using functional magnetic resonance imaging (fMRI), we investigated the neural networks involved in the processing of facial contempt and disgust in 24 healthy subjects. Facial recognition of contempt was lower than that of disgust and of neutral faces. The imaging data indicated significant activity in the amygdala and in globus pallidus and putamen during processing of contemptuous faces. Bilateral insula and caudate nuclei and left as well as right inferior frontal gyrus were engaged during processing of disgusted faces. Moreover, direct comparisons of contempt vs. disgust yielded significantly different activations in the amygdala. On the other hand, disgusted faces elicited greater activation than contemptuous faces in the right insula and caudate. Our findings suggest preferential involvement of different neural substrates in the processing of facial emotional expressions of contempt and disgust.

  12. Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat

    OpenAIRE

    Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan; Li, P. Andy; Sun, Tao

    2013-01-01

    The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral sei...

  13. Wnt11b is involved in cilia-mediated symmetry breakage during Xenopus left-right development.

    Directory of Open Access Journals (Sweden)

    Peter Walentek

    Full Text Available Breakage of bilateral symmetry in amphibian embryos depends on the development of a ciliated epithelium at the gastrocoel roof during early neurulation. Motile cilia at the gastrocoel roof plate (GRP give rise to leftward flow of extracellular fluids. Flow is required for asymmetric gene expression and organ morphogenesis. Wnt signaling has previously been involved in two steps, Wnt/ß-catenin mediated induction of Foxj1, a regulator of motile cilia, and Wnt/planar cell polarity (PCP dependent cilia polarization to the posterior pole of cells. We have studied Wnt11b in the context of laterality determination, as this ligand was reported to activate canonical and non-canonical Wnt signaling. Wnt11b was found to be expressed in the so-called superficial mesoderm (SM, from which the GRP derives. Surprisingly, Foxj1 was only marginally affected in loss-of-function experiments, indicating that another ligand acts in this early step of laterality specification. Wnt11b was required, however, for polarization of GRP cilia and GRP morphogenesis, in line with the known function of Wnt/PCP in cilia-driven leftward flow. In addition Xnr1 and Coco expression in the lateral-most GRP cells, which sense flow and generate the first asymmetric signal, was attenuated in morphants, involving Wnt signaling in yet another process related to symmetry breakage in Xenopus.

  14. Amygdala Activity During Autobiographical Memory Recall in Depressed and Vulnerable Individuals: Association With Symptom Severity and Autobiographical Overgenerality.

    Science.gov (United States)

    Young, Kymberly D; Siegle, Greg J; Bodurka, Jerzy; Drevets, Wayne C

    2016-01-01

    In healthy individuals, autobiographical memory recall is biased toward positive and away from negative events, while the opposite is found in depressed individuals. This study examined amygdala activity during autobiographical memory recall as a putative mechanism underlying biased memory recall and depressive symptoms in currently depressed adults and two vulnerable populations: individuals remitted from depression and otherwise healthy individuals at high familial risk of developing depression. Identification of such vulnerability factors could enable interception strategies that prevent depression onset. Sixty healthy control subjects, 45 unmedicated currently depressed individuals, 25 unmedicated remitted depressed individuals, and 30 individuals at high familial risk of developing depression underwent functional MRI while recalling autobiographical memories in response to emotionally valenced cue words. Amygdala reactivity and connectivity with anatomically defined amygdala regions were examined. During positive recall, depressed participants exhibited significantly decreased left amygdala activity and decreased connectivity with regions of the salience network compared with the other groups. During negative recall, control subjects had significantly decreased left amygdala activity compared with the other groups, while depressed participants exhibited increased amygdala connectivity with the salience network. In depressed participants, left amygdala activity during positive recall correlated significantly with depression severity (r values >-0.38) and percent of positive specific memories recalled (r values >0.59). The results suggest that left amygdala hyperactivity during negative autobiographical recall is a trait-like marker of depression, as both vulnerable groups showed activity similar to the depressed group, while amygdala hypoactivity during positive autobiographical recall is a state marker of depression manifesting in active disease. Treatments

  15. Does the amygdala response correlate with the personality trait 'harm avoidance' while evaluating emotional stimuli explicitly?

    Science.gov (United States)

    Van Schuerbeek, Peter; Baeken, Chris; Luypaert, Robert; De Raedt, Rudi; De Mey, Johan

    2014-05-07

    The affective personality trait 'harm avoidance' (HA) from Cloninger's psychobiological personality model determines how an individual deals with emotional stimuli. Emotional stimuli are processed by a neural network that include the left and right amygdalae as important key nodes. Explicit, implicit and passive processing of affective stimuli are known to activate the amygdalae differently reflecting differences in attention, level of detailed analysis of the stimuli and the cognitive control needed to perform the required task. Previous studies revealed that implicit processing or passive viewing of affective stimuli, induce a left amygdala response that correlates with HA. In this new study we have tried to extend these findings to the situation in which the subjects were required to explicitly process emotional stimuli. A group of healthy female participants was asked to rate the valence of positive and negative stimuli while undergoing fMRI. Afterwards the neural responses of the participants to the positive and to the negative stimuli were separately correlated to their HA scores and compared between the low and high HA participants. Both analyses revealed increased neural activity in the left laterobasal (LB) amygdala of the high HA participants while they were rating the positive and the negative stimuli. Our results indicate that the left amygdala response to explicit processing of affective stimuli does correlate with HA.

  16. Oxytocin Promotes Facial Emotion Recognition and Amygdala Reactivity in Adults with Asperger Syndrome

    Science.gov (United States)

    Domes, Gregor; Kumbier, Ekkehardt; Heinrichs, Markus; Herpertz, Sabine C

    2014-01-01

    The neuropeptide oxytocin has recently been shown to enhance eye gaze and emotion recognition in healthy men. Here, we report a randomized double-blind, placebo-controlled trial that examined the neural and behavioral effects of a single dose of intranasal oxytocin on emotion recognition in individuals with Asperger syndrome (AS), a clinical condition characterized by impaired eye gaze and facial emotion recognition. Using functional magnetic resonance imaging, we examined whether oxytocin would enhance emotion recognition from facial sections of the eye vs the mouth region and modulate regional activity in brain areas associated with face perception in both adults with AS, and a neurotypical control group. Intranasal administration of the neuropeptide oxytocin improved performance in a facial emotion recognition task in individuals with AS. This was linked to increased left amygdala reactivity in response to facial stimuli and increased activity in the neural network involved in social cognition. Our data suggest that the amygdala, together with functionally associated cortical areas mediate the positive effect of oxytocin on social cognitive functioning in AS. PMID:24067301

  17. From circuits to behaviour in the amygdala

    Science.gov (United States)

    Janak, Patricia H.; Tye, Kay M.

    2015-01-01

    The amygdala has long been associated with emotion and motivation, playing an essential part in processing both fearful and rewarding environmental stimuli. How can a single structure be crucial for such different functions? With recent technological advances that allow for causal investigations of specific neural circuit elements, we can now begin to map the complex anatomical connections of the amygdala onto behavioural function. Understanding how the amygdala contributes to a wide array of behaviours requires the study of distinct amygdala circuits. PMID:25592533

  18. Modulation of instrumental responding by a conditioned threat stimulus requires lateral and central amygdala

    Directory of Open Access Journals (Sweden)

    Vincent eCampese

    2015-10-01

    Full Text Available Two studies explored the role of the amygdala in response modulation by an aversive conditioned stimulus (CS in rats. Experiment 1 investigated the role of amygdala circuitry in conditioned suppression using a paradigm in which licking for sucrose was inhibited by a tone CS that had been previously paired with footshock. Electrolytic lesions of the lateral amygdala impaired suppression relative to sham-operated animals, and produced the same pattern of results when applied to central amygdala. In addition, disconnection of the lateral and central amygdala, by unilateral lesion of each on opposite sides of the brain, also impaired suppression relative to control subjects that received lesions of both areas on the same side. In each case, lesions were placed following Pavlovian conditioning and instrumental training, but before testing. This procedure produced within-subjects measures of the effects of lesion on freezing and between-group comparisons for the effects on suppression. Experiment 2 extended this analysis to a task where an aversive CS suppressed shuttling responses that had been previously food reinforced and also found effects of bilateral lesions of the central amygdala in a pre-post design. Together, these studies demonstrate that connections between the lateral and central amygdala constitute a serial circuit involved in processing aversive Pavlovian stimuli, and add to a growing body of findings implicating central amygdala in the modulation of instrumental behavior.

  19. Psilocybin modulates functional connectivity of the amygdala during emotional face discrimination.

    Science.gov (United States)

    Grimm, O; Kraehenmann, R; Preller, K H; Seifritz, E; Vollenweider, F X

    2018-04-24

    Recent studies suggest that the antidepressant effects of the psychedelic 5-HT2A receptor agonist psilocybin are mediated through its modulatory properties on prefrontal and limbic brain regions including the amygdala. To further investigate the effects of psilocybin on emotion processing networks, we studied for the first-time psilocybin's acute effects on amygdala seed-to-voxel connectivity in an event-related face discrimination task in 18 healthy volunteers who received psilocybin and placebo in a double-blind balanced cross-over design. The amygdala has been implicated as a salience detector especially involved in the immediate response to emotional face content. We used beta-series amygdala seed-to-voxel connectivity during an emotional face discrimination task to elucidate the connectivity pattern of the amygdala over the entire brain. When we compared psilocybin to placebo, an increase in reaction time for all three categories of affective stimuli was found. Psilocybin decreased the connectivity between amygdala and the striatum during angry face discrimination. During happy face discrimination, the connectivity between the amygdala and the frontal pole was decreased. No effect was seen during discrimination of fearful faces. Thus, we show psilocybin's effect as a modulator of major connectivity hubs of the amygdala. Psilocybin decreases the connectivity between important nodes linked to emotion processing like the frontal pole or the striatum. Future studies are needed to clarify whether connectivity changes predict therapeutic effects in psychiatric patients. Copyright © 2018 Elsevier B.V. and ECNP. All rights reserved.

  20. MEG evidence for dynamic amygdala modulations by gaze and facial emotions.

    Directory of Open Access Journals (Sweden)

    Thibaud Dumas

    Full Text Available Amygdala is a key brain region for face perception. While the role of amygdala in the perception of facial emotion and gaze has been extensively highlighted with fMRI, the unfolding in time of amydgala responses to emotional versus neutral faces with different gaze directions is scarcely known.Here we addressed this question in healthy subjects using MEG combined with an original source imaging method based on individual amygdala volume segmentation and the localization of sources in the amygdala volume. We found an early peak of amygdala activity that was enhanced for fearful relative to neutral faces between 130 and 170 ms. The effect of emotion was again significant in a later time range (310-350 ms. Moreover, the amygdala response was greater for direct relative averted gaze between 190 and 350 ms, and this effect was selective of fearful faces in the right amygdala.Altogether, our results show that the amygdala is involved in the processing and integration of emotion and gaze cues from faces in different time ranges, thus underlining its role in multiple stages of face perception.

  1. MEG Evidence for Dynamic Amygdala Modulations by Gaze and Facial Emotions

    Science.gov (United States)

    Dumas, Thibaud; Dubal, Stéphanie; Attal, Yohan; Chupin, Marie; Jouvent, Roland; Morel, Shasha; George, Nathalie

    2013-01-01

    Background Amygdala is a key brain region for face perception. While the role of amygdala in the perception of facial emotion and gaze has been extensively highlighted with fMRI, the unfolding in time of amydgala responses to emotional versus neutral faces with different gaze directions is scarcely known. Methodology/Principal Findings Here we addressed this question in healthy subjects using MEG combined with an original source imaging method based on individual amygdala volume segmentation and the localization of sources in the amygdala volume. We found an early peak of amygdala activity that was enhanced for fearful relative to neutral faces between 130 and 170 ms. The effect of emotion was again significant in a later time range (310–350 ms). Moreover, the amygdala response was greater for direct relative averted gaze between 190 and 350 ms, and this effect was selective of fearful faces in the right amygdala. Conclusion Altogether, our results show that the amygdala is involved in the processing and integration of emotion and gaze cues from faces in different time ranges, thus underlining its role in multiple stages of face perception. PMID:24040190

  2. The amygdala and basal forebrain as a pathway for motivationally guided attention.

    Science.gov (United States)

    Peck, Christopher J; Salzman, C Daniel

    2014-10-08

    Visual stimuli associated with rewards attract spatial attention. Neurophysiological mechanisms that mediate this process must register both the motivational significance and location of visual stimuli. Recent neurophysiological evidence indicates that the amygdala encodes information about both of these parameters. Furthermore, the firing rate of amygdala neurons predicts the allocation of spatial attention. One neural pathway through which the amygdala might influence attention involves the intimate and bidirectional connections between the amygdala and basal forebrain (BF), a brain area long implicated in attention. Neurons in the rhesus monkey amygdala and BF were therefore recorded simultaneously while subjects performed a detection task in which the stimulus-reward associations of visual stimuli modulated spatial attention. Neurons in BF were spatially selective for reward-predictive stimuli, much like the amygdala. The onset of reward-predictive signals in each brain area suggested different routes of processing for reward-predictive stimuli appearing in the ipsilateral and contralateral fields. Moreover, neurons in the amygdala, but not BF, tracked trial-to-trial fluctuations in spatial attention. These results suggest that the amygdala and BF could play distinct yet inter-related roles in influencing attention elicited by reward-predictive stimuli. Copyright © 2014 the authors 0270-6474/14/3413757-11$15.00/0.

  3. The Distinct Role of the Amygdala, Superior Colliculus and Pulvinar in Processing of Central and Peripheral Snakes.

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    Inês Almeida

    Full Text Available Visual processing of ecologically relevant stimuli involves a central bias for stimuli demanding detailed processing (e.g., faces, whereas peripheral object processing is based on coarse identification. Fast detection of animal shapes holding a significant phylogenetic value, such as snakes, may benefit from peripheral vision. The amygdala together with the pulvinar and the superior colliculus are implicated in an ongoing debate regarding their role in automatic and deliberate spatial processing of threat signals.Here we tested twenty healthy participants in an fMRI task, and investigated the role of spatial demands (the main effect of central vs. peripheral vision in the processing of fear-relevant ecological features. We controlled for stimulus dependence using true or false snakes; snake shapes or snake faces and for task constraints (implicit or explicit. The main idea justifying this double task is that amygdala and superior colliculus are involved in both automatic and controlled processes. Moreover the explicit/implicit instruction in the task with respect to emotion is not necessarily equivalent to explicit vs. implicit in the sense of endogenous vs. exogenous attention, or controlled vs. automatic processes.We found that stimulus-driven processing led to increased amygdala responses specifically to true snake shapes presented in the centre or in the peripheral left hemifield (right hemisphere. Importantly, the superior colliculus showed significantly biased and explicit central responses to snake-related stimuli. Moreover, the pulvinar, which also contains foveal representations, also showed strong central responses, extending the results of a recent single cell pulvinar study in monkeys. Similar hemispheric specialization was found across structures: increased amygdala responses occurred to true snake shapes presented to the right hemisphere, with this pattern being closely followed by the superior colliculus and the pulvinar

  4. Stress, memory and the amygdala

    NARCIS (Netherlands)

    Roozendaal, Benno; McEwen, Bruce S.; Chattarji, Sumantra

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

  5. Central amygdala, stress and adaption

    NARCIS (Netherlands)

    Roozendaal, Benno

    1992-01-01

    In this thesis the results were presented of studies that were designed to provide more insight in the role of the central nucleus of the amygdala (CEA) in the adaptation to environmental demands. The experiments were performed in several situations, in which rats react either directly to aversive

  6. Amygdala subsystems and control of feeding behavior by learned cues.

    Science.gov (United States)

    Petrovich, Gorica D; Gallagher, Michela

    2003-04-01

    A combination of behavioral studies and a neural systems analysis approach has proven fruitful in defining the role of the amygdala complex and associated circuits in fear conditioning. The evidence presented in this chapter suggests that this approach is also informative in the study of other adaptive functions that involve the amygdala. In this chapter we present a novel model to study learning in an appetitive context. Furthermore, we demonstrate that long-recognized connections between the amygdala and the hypothalamus play a crucial role in allowing learning to modulate feeding behavior. In the first part we describe a behavioral model for motivational learning. In this model a cue that acquires motivational properties through pairings with food delivery when an animal is hungry can override satiety and promote eating in sated rats. Next, we present evidence that a specific amygdala subsystem (basolateral area) is responsible for allowing such learned cues to control eating (override satiety and promote eating in sated rats). We also show that basolateral amygdala mediates these actions via connectivity with the lateral hypothalamus. Lastly, we present evidence that the amygdalohypothalamic system is specific for the control of eating by learned motivational cues, as it does not mediate another function that depends on intact basolateral amygdala, namely, the ability of a conditioned cue to support new learning based on its acquired value. Knowledge about neural systems through which food-associated cues specifically control feeding behavior provides a defined model for the study of learning. In addition, this model may be informative for understanding mechanisms of maladaptive aspects of learned control of eating that contribute to eating disorders and more moderate forms of overeating.

  7. Cannabis use is quantitatively associated with nucleus accumbens and amygdala abnormalities in young adult recreational users.

    Science.gov (United States)

    Gilman, Jodi M; Kuster, John K; Lee, Sang; Lee, Myung Joo; Kim, Byoung Woo; Makris, Nikos; van der Kouwe, Andre; Blood, Anne J; Breiter, Hans C

    2014-04-16

    Marijuana is the most commonly used illicit drug in the United States, but little is known about its effects on the human brain, particularly on reward/aversion regions implicated in addiction, such as the nucleus accumbens and amygdala. Animal studies show structural changes in brain regions such as the nucleus accumbens after exposure to Δ9-tetrahydrocannabinol, but less is known about cannabis use and brain morphometry in these regions in humans. We collected high-resolution MRI scans on young adult recreational marijuana users and nonusing controls and conducted three independent analyses of morphometry in these structures: (1) gray matter density using voxel-based morphometry, (2) volume (total brain and regional volumes), and (3) shape (surface morphometry). Gray matter density analyses revealed greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only. Significant shape differences were detected in the left nucleus accumbens and right amygdala. The left nucleus accumbens showed salient exposure-dependent alterations across all three measures and an altered multimodal relationship across measures in the marijuana group. These data suggest that marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures and is consistent with animal studies of changes in dendritic arborization.

  8. Structural Covariance of Sensory Networks, the Cerebellum, and Amygdala in Autism Spectrum Disorder

    Directory of Open Access Journals (Sweden)

    Garrett J. Cardon

    2017-11-01

    Full Text Available Sensory dysfunction is a core symptom of autism spectrum disorder (ASD, and abnormalities with sensory responsivity and processing can be extremely debilitating to ASD patients and their families. However, relatively little is known about the underlying neuroanatomical and neurophysiological factors that lead to sensory abnormalities in ASD. Investigation into these aspects of ASD could lead to significant advancements in our general knowledge about ASD, as well as provide targets for treatment and inform diagnostic procedures. Thus, the current study aimed to measure the covariation of volumes of brain structures (i.e., structural magnetic resonance imaging that may be involved in abnormal sensory processing, in order to infer connectivity of these brain regions. Specifically, we quantified the structural covariation of sensory-related cerebral cortical structures, in addition to the cerebellum and amygdala by computing partial correlations between the structural volumes of these structures. These analyses were performed in participants with ASD (n = 36, as well as typically developing peers (n = 32. Results showed decreased structural covariation between sensory-related cortical structures, especially between the left and right cerebral hemispheres, in participants with ASD. In contrast, these same participants presented with increased structural covariation of structures in the right cerebral hemisphere. Additionally, sensory-related cerebral structures exhibited decreased structural covariation with functionally identified cerebellar networks. Also, the left amygdala showed significantly increased structural covariation with cerebral structures related to visual processing. Taken together, these results may suggest several patterns of altered connectivity both within and between cerebral cortices and other brain structures that may be related to sensory processing.

  9. Plasticity-related genes in brain development and amygdala-dependent learning.

    Science.gov (United States)

    Ehrlich, D E; Josselyn, S A

    2016-01-01

    Learning about motivationally important stimuli involves plasticity in the amygdala, a temporal lobe structure. Amygdala-dependent learning involves a growing number of plasticity-related signaling pathways also implicated in brain development, suggesting that learning-related signaling in juveniles may simultaneously influence development. Here, we review the pleiotropic functions in nervous system development and amygdala-dependent learning of a signaling pathway that includes brain-derived neurotrophic factor (BDNF), extracellular signaling-related kinases (ERKs) and cyclic AMP-response element binding protein (CREB). Using these canonical, plasticity-related genes as an example, we discuss the intersection of learning-related and developmental plasticity in the immature amygdala, when aversive and appetitive learning may influence the developmental trajectory of amygdala function. We propose that learning-dependent activation of BDNF, ERK and CREB signaling in the immature amygdala exaggerates and accelerates neural development, promoting amygdala excitability and environmental sensitivity later in life. © 2015 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

  10. Functional connectivity between right and left mesial temporal structures.

    Science.gov (United States)

    Lacuey, Nuria; Zonjy, Bilal; Kahriman, Emine S; Kaffashi, Farhad; Miller, Jonathan; Lüders, Hans O

    2015-09-01

    The aim of this study is to investigate functional connectivity between right and left mesial temporal structures using cerebrocerebral evoked potentials. We studied seven patients with drug-resistant focal epilepsy who were explored with stereotactically implanted depth electrodes in bilateral hippocampi. In all patients cerebrocerebral evoked potentials evoked by stimulation of the fornix were evaluated as part of a research project assessing fornix stimulation for control of hippocampal seizures. Stimulation of the fornix elicited responses in the ipsilateral hippocampus in all patients with a mean latency of 4.6 ms (range 2-7 ms). Two patients (29 %) also had contralateral hippocampus responses with a mean latency of 7.5 ms (range 5-12 ms) and without involvement of the contralateral temporal neocortex or amygdala. This study confirms the existence of connections between bilateral mesial temporal structures in some patients and explains seizure discharge spreading between homotopic mesial temporal structures without neocortical involvement.

  11. Fear extinction deficits following acute stress associate with increased spine density and dendritic retraction in basolateral amygdala neurons.

    Science.gov (United States)

    Maroun, Mouna; Ioannides, Pericles J; Bergman, Krista L; Kavushansky, Alexandra; Holmes, Andrew; Wellman, Cara L

    2013-08-01

    Stress-sensitive psychopathologies such as post-traumatic stress disorder are characterized by deficits in fear extinction and dysfunction of corticolimbic circuits mediating extinction. Chronic stress facilitates fear conditioning, impairs extinction, and produces dendritic proliferation in the basolateral amygdala (BLA), a critical site of plasticity for extinction. Acute stress impairs extinction, alters plasticity in the medial prefrontal cortex-to-BLA circuit, and causes dendritic retraction in the medial prefrontal cortex. Here, we examined extinction learning and basolateral amygdala pyramidal neuron morphology in adult male rats following a single elevated platform stress. Acute stress impaired extinction acquisition and memory, and produced dendritic retraction and increased mushroom spine density in basolateral amygdala neurons in the right hemisphere. Unexpectedly, irrespective of stress, rats that underwent fear and extinction testing showed basolateral amygdala dendritic retraction and altered spine density relative to non-conditioned rats, particularly in the left hemisphere. Thus, extinction deficits produced by acute stress are associated with increased spine density and dendritic retraction in basolateral amygdala pyramidal neurons. Furthermore, the finding that conditioning and extinction as such was sufficient to alter basolateral amygdala morphology and spine density illustrates the sensitivity of basolateral amygdala morphology to behavioral manipulation. These findings may have implications for elucidating the role of the amygdala in the pathophysiology of stress-related disorders. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  12. Fear extinction deficits following acute stress associate with increased spine density and dendritic retraction in basolateral amygdala neurons

    Science.gov (United States)

    Maroun, Mouna; Ioannides, Pericles J.; Bergman, Krista L.; Kavushansky, Alexandra; Holmes, Andrew; Wellman, Cara L.

    2013-01-01

    Stress-sensitive psychopathologies such as post-traumatic stress disorder are characterized by deficits in fear extinction and dysfunction of corticolimbic circuits mediating extinction. Chronic stress facilitates fear conditioning, impairs extinction, and produces dendritic proliferation in the basolateral amygdala (BLA), a critical site of plasticity for extinction. Acute stress impairs extinction, alters plasticity in the medial prefrontal cortex-to-BLA circuit, and causes dendritic retraction in the medial prefrontal cortex. Here, we examined extinction learning and basolateral amygdala pyramidal neuron morphology in adult male rats following a single elevated platform stress. Acute stress impaired extinction acquisition and memory, and produced dendritic retraction and increased mushroom spine density in basolateral amygdala neurons in the right hemisphere. Unexpectedly, irrespective of stress, rats that underwent fear and extinction testing showed basolateral amygdala dendritic retraction and altered spine density relative to non-conditioned rats, particularly in the left hemisphere. Thus, extinction deficits produced by acute stress are associated with increased spine density and dendritic retraction in basolateral amygdala pyramidal neurons. Furthermore, the finding that conditioning and extinction as such was sufficient to alter basolateral amygdala morphology and spine density illustrates the sensitivity of basolateral amygdala morphology to behavioral manipulation. These findings may have implications for elucidating the role of the amygdala in the pathophysiology of stress-related disorders. PMID:23714419

  13. NMDA Receptor- and ERK-Dependent Histone Methylation Changes in the Lateral Amygdala Bidirectionally Regulate Fear Memory Formation

    Science.gov (United States)

    Gupta-Agarwal, Swati; Jarome, Timothy J.; Fernandez, Jordan; Lubin, Farah D.

    2014-01-01

    It is well established that fear memory formation requires de novo gene transcription in the amygdala. We provide evidence that epigenetic mechanisms in the form of histone lysine methylation in the lateral amygdala (LA) are regulated by NMDA receptor (NMDAR) signaling and involved in gene transcription changes necessary for fear memory…

  14. Value encoding in single neurons in the human amygdala during decision making.

    Science.gov (United States)

    Jenison, Rick L; Rangel, Antonio; Oya, Hiroyuki; Kawasaki, Hiroto; Howard, Matthew A

    2011-01-05

    A growing consensus suggests that the brain makes simple choices by assigning values to the stimuli under consideration and then comparing these values to make a decision. However, the network involved in computing the values has not yet been fully characterized. Here, we investigated whether the human amygdala plays a role in the computation of stimulus values at the time of decision making. We recorded single neuron activity from the amygdala of awake patients while they made simple purchase decisions over food items. We found 16 amygdala neurons, located primarily in the basolateral nucleus that responded linearly to the values assigned to individual items.

  15. Unique insula subregion resting-state functional connectivity with amygdala complexes in posttraumatic stress disorder and its dissociative subtype.

    Science.gov (United States)

    Nicholson, Andrew A; Sapru, Iman; Densmore, Maria; Frewen, Paul A; Neufeld, Richard W J; Théberge, Jean; McKinnon, Margaret C; Lanius, Ruth A

    2016-04-30

    The insula and amygdala are implicated in the pathophysiology of posttraumatic stress disorder (PTSD), where both have been shown to be hyper/hypoactive in non-dissociative (PTSD-DS) and dissociative subtype (PTSD+DS) PTSD patients, respectively, during symptom provocation. However, the functional connectivity between individual insula subregions and the amygdala has not been investigated in persons with PTSD, with or without the dissociative subtype. We examined insula subregion (anterior, mid, and posterior) functional connectivity with the bilateral amygdala using a region-of-interest seed-based approach via PickAtlas and SPM8. Resting-state fMRI was conducted with (n=61) PTSD patients (n=44 PTSD-DS; n=17 PTSD+DS), and (n=40) age-matched healthy controls. When compared to controls, the PTSD-DS group displayed increased insula connectivity (bilateral anterior, bilateral mid, and left posterior) to basolateral amygdala clusters in both hemispheres, and the PTSD+DS group displayed increased insula connectivity (bilateral anterior, left mid, and left posterior) to the left basolateral amygdala complex. Moreover, as compared to PTSD-DS, increased insula subregion connectivity (bilateral anterior, left mid, and right posterior) to the left basolateral amygdala was found in PTSD+DS. Depersonalization/derealization symptoms and PTSD symptom severity correlated with insula subregion connectivity to the basolateral amygdala within PTSD patients. This study is an important first step in elucidating patterns of neural connectivity associated with unique symptoms of arousal/interoception, emotional processing, and awareness of bodily states, in PTSD and its dissociative subtype. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  16. Peri-pubertal gonadotropin-releasing hormone agonist treatment affects sex biased gene expression of amygdala in sheep.

    Science.gov (United States)

    Nuruddin, Syed; Krogenæs, Anette; Brynildsrud, Ola Brønstad; Verhaegen, Steven; Evans, Neil P; Robinson, Jane E; Haraldsen, Ira Ronit Hebold; Ropstad, Erik

    2013-12-01

    The nature of hormonal involvement in pubertal brain development has attracted wide interest. Structural changes within the brain that occur during pubertal development appear mainly in regions closely linked with emotion, motivation and cognitive functions. Using a sheep model, we have previously shown that peri-pubertal pharmacological blockade of gonadotropin releasing hormone (GnRH) receptors, results in exaggerated sex-differences in cognitive executive function and emotional control, as well as sex and hemisphere specific patterns of expression of hippocampal genes associated with synaptic plasticity and endocrine signaling. In this study, we explored effects of this treatment regime on the gene expression profile of the ovine amygdala. The study was conducted with 30 same-sex twin lambs (14 female and 16 male), half of which were treated with the GnRH agonist (GnRHa) goserelin acetate every 4th week, beginning before puberty, until approximately 50 weeks of age. Gene expression profiles of the left and right amygdala were measured using 8×15 K Agilent ovine microarrays. Differential expression of selected genes was confirmed by qRT-PCR (Quantitative real time PCR). Networking analyses and Gene Ontology (GO) Term analyses were performed with Ingenuity Pathway Analysis (IPA), version 7.5 and DAVID (Database for Annotation, Visualization and integrated Discovery) version 6.7 software packages, respectively. GnRHa treatment was associated with significant sex- and hemisphere-specific differential patterns of gene expression. GnRHa treatment was associated with differential expression of 432 (|logFC|>0.3, adj. p value expressed as a result of GnRHa treatment in the male animals. The results indicated that GnRH may, directly and/or indirectly, be involved in the regulation of sex- and hemisphere-specific differential expression of genes in the amygdala. This finding should be considered when long-term peri-pubertal GnRHa treatment is used in children. Copyright

  17. The Invertibility, Explicit Determinants, and Inverses of Circulant and Left Circulant and g-Circulant Matrices Involving Any Continuous Fibonacci and Lucas Numbers

    Directory of Open Access Journals (Sweden)

    Zhaolin Jiang

    2014-01-01

    Full Text Available Circulant matrices play an important role in solving delay differential equations. In this paper, circulant type matrices including the circulant and left circulant and g-circulant matrices with any continuous Fibonacci and Lucas numbers are considered. Firstly, the invertibility of the circulant matrix is discussed and the explicit determinant and the inverse matrices by constructing the transformation matrices are presented. Furthermore, the invertibility of the left circulant and g-circulant matrices is also studied. We obtain the explicit determinants and the inverse matrices of the left circulant and g-circulant matrices by utilizing the relationship between left circulant, g-circulant matrices and circulant matrix, respectively.

  18. In vivo estimation of normal amygdala volume from structural MRI scans with anatomical-based segmentation.

    Science.gov (United States)

    Siozopoulos, Achilleas; Thomaidis, Vasilios; Prassopoulos, Panos; Fiska, Aliki

    2018-02-01

    Literature includes a number of studies using structural MRI (sMRI) to determine the volume of the amygdala, which is modified in various pathologic conditions. The reported values vary widely mainly because of different anatomical approaches to the complex. This study aims at estimating of the normal amygdala volume from sMRI scans using a recent anatomical definition described in a study based on post-mortem material. The amygdala volume has been calculated in 106 healthy subjects, using sMRI and anatomical-based segmentation. The resulting volumes have been analyzed for differences related to hemisphere, sex, and age. The mean amygdalar volume was estimated at 1.42 cm 3 . The mean right amygdala volume has been found larger than the left, but the difference for the raw values was within the limits of the method error. No intersexual differences or age-related alterations have been observed. The study provides a method for determining the boundaries of the amygdala in sMRI scans based on recent anatomical considerations and an estimation of the mean normal amygdala volume from a quite large number of scans for future use in comparative studies.

  19. Amygdala functional connectivity as a longitudinal biomarker of symptom changes in generalized anxiety.

    Science.gov (United States)

    Makovac, Elena; Watson, David R; Meeten, Frances; Garfinkel, Sarah N; Cercignani, Mara; Critchley, Hugo D; Ottaviani, Cristina

    2016-11-01

    Generalized anxiety disorder (GAD) is characterized by excessive worry, autonomic dysregulation and functional amygdala dysconnectivity, yet these illness markers have rarely been considered together, nor their interrelationship tested longitudinally. We hypothesized that an individual's capacity for emotion regulation predicts longer-term changes in amygdala functional connectivity, supporting the modification of GAD core symptoms. Sixteen patients with GAD (14 women) and individually matched controls were studied at two time points separated by 1 year. Resting-state fMRI data and concurrent measurement of vagally mediated heart rate variability were obtained before and after the induction of perseverative cognition. A greater rise in levels of worry following the induction predicted a stronger reduction in connectivity between right amygdala and ventromedial prefrontal cortex, and enhanced coupling between left amygdala and ventral tegmental area at follow-up. Similarly, amplified physiological responses to the induction predicted increased connectivity between right amygdala and thalamus. Longitudinal shifts in a distinct set of functional connectivity scores were associated with concomitant changes in GAD symptomatology over the course of the year. Results highlight the prognostic value of indices of emotional dysregulation and emphasize the integral role of the amygdala as a critical hub in functional neural circuitry underlying the progression of GAD symptomatology. © The Author (2016). Published by Oxford University Press.

  20. Mindful attention to breath regulates emotions via increased amygdala-prefrontal cortex connectivity.

    Science.gov (United States)

    Doll, Anselm; Hölzel, Britta K; Mulej Bratec, Satja; Boucard, Christine C; Xie, Xiyao; Wohlschläger, Afra M; Sorg, Christian

    2016-07-01

    Mindfulness practice is beneficial for emotion regulation; however, the neural mechanisms underlying this effect are poorly understood. The current study focuses on effects of attention-to-breath (ATB) as a basic mindfulness practice on aversive emotions at behavioral and brain levels. A key finding across different emotion regulation strategies is the modulation of amygdala and prefrontal activity. It is unclear how ATB relevant brain areas in the prefrontal cortex integrate with amygdala activation during emotional stimulation. We proposed that, during emotional stimulation, ATB down-regulates activation in the amygdala and increases its integration with prefrontal regions. To address this hypothesis, 26 healthy controls were trained in mindfulness-based attention-to-breath meditation for two weeks and then stimulated with aversive pictures during both attention-to-breath and passive viewing while undergoing fMRI. Data were controlled for breathing frequency. Results indicate that (1) ATB was effective in regulating aversive emotions. (2) Left dorso-medial prefrontal cortex was associated with ATB in general. (3) A fronto-parietal network was additionally recruited during emotional stimulation. (4) ATB down regulated amygdala activation and increased amygdala-prefrontal integration, with such increased integration being associated with mindfulness ability. Results suggest amygdala-dorsal prefrontal cortex integration as a potential neural pathway of emotion regulation by mindfulness practice. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Effects of the medial or basolateral amygdala upon social anxiety and social recognition in mice.

    Science.gov (United States)

    Wang, Yu; Zhao, Shanshan; Liu, Xu; Fu, Qunying

    2014-01-01

    Though social anxiety and social recognition have been studied extensively, the roles of the medial or basolateral amygdala in the control of social anxiety and social recognition remain to be determined. This study investigated the effects of excitotoxic bilateral medial or basolateral amygdala lesions upon social anxiety and social recognition in-mice. Animals at 9 weeks of age were given bilateral medial or basolateral amygdala lesions via infusion of N-methyl- D-aspartate and then were used for behavioral tests: anxiety-related tests (including open-field test, light-dark test, and elevated-plus maze test), social behavior test in a novel environment, social recognition test, and flavor recognition test. Medial or basolateral amygdala-lesioned mice showed lower levels of anxiety and increased social behaviors in a novel environment. Destruction of the medial or basolateral amygdala neurons impaired social recognition but not flavor recognition. The medial or basolateral amygdala is involved in the control of anxiety-related behavior (social anxiety and social behaviors) in mice. Moreover, both the medial and the basolateral amygdala are essential for social recognition but not flavor recognition in mice.

  2. Amygdala hyperactivation during symptom provocation in obsessive–compulsive disorder and its modulation by distraction

    Directory of Open Access Journals (Sweden)

    Daniela Simon

    2014-01-01

    Full Text Available Anxiety disorders have been linked to a hyperactivated cortico-amygdalar circuitry. Recent findings highlight the amygdala's role in mediating elevated anxiety in obsessive–compulsive disorder (OCD. However, modulation of amygdala hyperactivation by attentional distraction – an effective emotion regulation strategy in healthy individuals – has not yet been examined. While undergoing functional magnetic resonance imaging twenty-one unmedicated OCD patients and 21 controls performed an evaluation and a distraction task during symptom provocation with individually tailored OCD-relevant pictures. To test the specificity of responses, additional aversive and neutral stimuli were included. Significant group-by-picture type interactions were observed within fronto–striato–limbic circuits including the amygdala. In these regions patients showed increased BOLD responses during processing of OCD triggers relative to healthy controls. Amygdala hyperactivation was present across OCD symptom dimensions indicating that it represents a common neural correlate. During distraction, we observed dampening of patients' amygdala hyperactivity to OCD-relevant stimuli. Augmented amygdala involvement in patients during symptom provocation, present across OCD symptom dimensions, might constitute a correlate of fear expression in OCD linking it to other anxiety disorders. Attentional distraction seemed to dampen emotional processing of disorder-relevant stimuli via amygdala downregulation. The clinical impact of this strategy to manage anxiety in OCD should be further elucidated.

  3. Neuroimaging study of the human amygdala. Toward an understanding of emotional and stress responses

    International Nuclear Information System (INIS)

    Iidaka, Tetsuya

    2007-01-01

    The amygdala plays a critical role in the neural system involved in emotional responses and conditioned fear. The dysfunction of this system is thought to be a cause of several neuropsychiatric disorders. A neuroimaging study provides a unique opportunity for noninvasive investigation of the human amygdala. We studied the activity of this structure in normal subjects and patients with schizophrenia by using the face recognition task. Our results showed that the amygdala was activated by presentation of face stimuli, and negative face activated the amygdala to a greater extent than a neutral face. Under the happy face condition, the activation of the amygdala was higher in the schizophrenic patients than in control subjects. A single nucleotide polymorphism in the regulatory region of the serotonin type 3 receptor gene had modulatory effects on the amygdaloid activity. The emotion regulation had a significant impact on neural interaction between the amygdala and prefrontal cortices. Thus, studies on the human amygdala would greatly contribute to the elucidation of the neural system that determines emotional and stress responses. To clarify the relevance of the neural dysfunction and neuropsychiatric disorders, further studies using physiological, genetic, and hormonal approaches are essential. (author)

  4. Amygdala volume linked to individual differences in mental state inference in early childhood and adulthood

    Directory of Open Access Journals (Sweden)

    Katherine Rice

    2014-04-01

    Full Text Available We investigated the role of the amygdala in mental state inference in a sample of adults and in a sample of children aged 4 and 6 years. This period in early childhood represents a time when mentalizing abilities undergo dramatic changes. Both children and adults inferred mental states from pictures of others’ eyes, and children also inferred the mental states of others from stories (e.g., a false belief task. We also collected structural MRI data from these participants, to determine whether larger amygdala volumes (controlling for age and total gray matter volume were related to better face-based and story-based mentalizing. For children, larger amygdala volumes were related to better face-based, but not story-based, mentalizing. In contrast, in adults, amygdala volume was not related to face-based mentalizing. We next divided the face-based items into two subscales: cognitive (e.g., thinking, not believing versus affective (e.g., friendly, kind items. For children, performance on cognitive items was positively correlated with amygdala volume, but for adults, only performance on affective items was positively correlated with amygdala volume. These results indicate that the amygdala's role in mentalizing may be specific to face-based tasks and that the nature of its involvement may change over development.

  5. Brain-derived neurotrophic factor Val66Met genotype modulates amygdala habituation.

    Science.gov (United States)

    Perez-Rodriguez, M Mercedes; New, Antonia S; Goldstein, Kim E; Rosell, Daniel; Yuan, Qiaoping; Zhou, Zhifeng; Hodgkinson, Colin; Goldman, David; Siever, Larry J; Hazlett, Erin A

    2017-05-30

    A deficit in amygdala habituation to repeated emotional stimuli may be an endophenotype of disorders characterized by emotion dysregulation, such as borderline personality disorder (BPD). Amygdala reactivity to emotional stimuli is genetically modulated by brain-derived neurotrophic factor (BDNF) variants. Whether amygdala habituation itself is also modulated by BDNF genotypes remains unknown. We used imaging-genetics to examine the effect of BDNF Val66Met genotypes on amygdala habituation to repeated emotional stimuli. We used functional magnetic resonance imaging (fMRI) in 57 subjects (19 BPD patients, 18 patients with schizotypal personality disorder [SPD] and 20 healthy controls [HC]) during a task involving viewing of unpleasant, neutral, and pleasant pictures, each presented twice to measure habituation. Amygdala responses across genotypes (Val66Met SNP Met allele-carriers vs. Non-Met carriers) and diagnoses (HC, BPD, SPD) were examined with ANOVA. The BDNF 66Met allele was significantly associated with a deficit in amygdala habituation, particularly for emotional pictures. The association of the 66Met allele with a deficit in habituation to unpleasant emotional pictures remained significant in the subsample of BPD patients. Using imaging-genetics, we found preliminary evidence that deficient amygdala habituation may be modulated by BDNF genotype. Copyright © 2017. Published by Elsevier B.V.

  6. Functional Connectivity of the Amygdala Is Disrupted in Preschool-Aged Children With Autism Spectrum Disorder.

    Science.gov (United States)

    Shen, Mark D; Li, Deana D; Keown, Christopher L; Lee, Aaron; Johnson, Ryan T; Angkustsiri, Kathleen; Rogers, Sally J; Müller, Ralph-Axel; Amaral, David G; Nordahl, Christine Wu

    2016-09-01

    The objective of this study was to determine whether functional connectivity of the amygdala is altered in preschool-age children with autism spectrum disorder (ASD) and to assess the clinical relevance of observed alterations in amygdala connectivity. A resting-state functional connectivity magnetic resonance imaging study of the amygdala (and a parallel study of primary visual cortex) was conducted in 72 boys (mean age 3.5 years; n = 43 with ASD; n = 29 age-matched controls). The ASD group showed significantly weaker connectivity between the amygdala and several brain regions involved in social communication and repetitive behaviors, including bilateral medial prefrontal cortex, temporal lobes, and striatum (p amygdala and frontal and temporal lobes was significantly correlated with increased autism severity in the ASD group (p amygdala and regions of the brain important for social communication and language, which might be clinically relevant because weaker connectivity was associated with increased autism severity. Moreover, although amygdala connectivity was associated with behavioral domains that are diagnostic of ASD, altered connectivity of primary visual cortex was related to sensory hypersensitivity. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

  7. Neuroimaging Study of the Human Amygdala - Toward an Understanding of Emotional and Stress Responses -

    Science.gov (United States)

    Iidaka, Tetsuya

    The amygdala plays a critical role in the neural system involved in emotional responses and conditioned fear. The dysfunction of this system is thought to be a cause of several neuropsychiatric disorders. A neuroimaging study provides a unique opportunity for noninvasive investigation of the human amygdala. We studied the activity of this structure in normal subjects and patients with schizophrenia by using the face recognition task. Our results showed that the amygdala was activated by presentation of face stimuli, and negative face activated the amygdala to a greater extent than a neutral face. Under the happy face condition, the activation of the amygdala was higher in the schizophrenic patients than in control subjects. A single nucleotide polymorphism in the regulatory region of the serotonin type 3 receptor gene had modulatory effects on the amygdaloid activity. The emotion regulation had a significant impact on neural interaction between the amygdala and prefrontal cortices. Thus, studies on the human amygdala would greatly contribute to the elucidation of the neural system that determines emotional and stress responses. To clarify the relevance of the neural dysfunction and neuropsychiatric disorders, further studies using physiological, genetic, and hormonal approaches are essential.

  8. Maladaptive social information processing in childhood predicts young men's atypical amygdala reactivity to threat.

    Science.gov (United States)

    Choe, Daniel Ewon; Shaw, Daniel S; Forbes, Erika E

    2015-05-01

    Maladaptive social information processing, such as hostile attributional bias and aggressive response generation, is associated with childhood maladjustment. Although social information processing problems are correlated with heightened physiological responses to social threat, few studies have examined their associations with neural threat circuitry, specifically amygdala activation to social threat. A cohort of 310 boys participated in an ongoing longitudinal study and completed questionnaires and laboratory tasks assessing their social and cognitive characteristics the boys were between 10 and 12 years of age. At age 20, 178 of these young men underwent functional magnetic resonance imaging and a social threat task. At age 22, adult criminal arrest records and self-reports of impulsiveness were obtained. Path models indicated that maladaptive social information-processing at ages 10 and 11 predicted increased left amygdala reactivity to fear faces, an ambiguous threat, at age 20 while accounting for childhood antisocial behavior, empathy, IQ, and socioeconomic status. Exploratory analyses indicated that aggressive response generation - the tendency to respond to threat with reactive aggression - predicted left amygdala reactivity to fear faces and was concurrently associated with empathy, antisocial behavior, and hostile attributional bias, whereas hostile attributional bias correlated with IQ. Although unrelated to social information-processing problems, bilateral amygdala reactivity to anger faces at age 20 was unexpectedly predicted by low IQ at age 11. Amygdala activation did not mediate associations between social information processing and number of criminal arrests, but both impulsiveness at age 22 and arrests were correlated with right amygdala reactivity to anger facial expressions at age 20. Childhood social information processing and IQ predicted young men's amygdala response to threat a decade later, which suggests that childhood social

  9. Role of habenula and amygdala dysfunction in Parkinson disease patients with punding.

    Science.gov (United States)

    Markovic, Vladana; Agosta, Federica; Canu, Elisa; Inuggi, Alberto; Petrovic, Igor; Stankovic, Iva; Imperiale, Francesca; Stojkovic, Tanja; Kostic, Vladimir S; Filippi, Massimo

    2017-06-06

    To assess whether a functional dysregulation of the habenula and amygdala, as modulators of the reward brain circuit, contributes to Parkinson disease (PD) punding. Structural and resting-state functional MRI were obtained from 22 patients with PD punding, 30 patients with PD without any impulsive-compulsive behavior (ICB) matched for disease stage and duration, motor impairment, and cognitive status, and 30 healthy controls. Resting-state functional connectivity of the habenula and amygdala bilaterally was assessed using a seed-based approach. Habenula and amygdala volumes and cortical thickness measures were obtained. Compared to both healthy controls and PD cases without any ICB (PD-no ICB), PD-punding patients showed higher functional connectivity of habenula and amygdala with thalamus and striatum bilaterally, and lower connectivity between bilateral habenula and left frontal and precentral cortices. In PD-punding relative to PD-no ICB patients, a lower functional connectivity between right amygdala and hippocampus was also observed. Habenula and amygdala volumes were not different among groups. PD-punding patients showed a cortical thinning of the left superior frontal and precentral gyri and right middle temporal gyrus and isthmus cingulate compared to healthy controls, and of the right inferior frontal gyrus compared to both controls and PD-no ICB patients. A breakdown of the connectivity among the crucial nodes of the reward circuit (i.e., habenula, amygdala, basal ganglia, frontal cortex) might be a contributory factor to punding in PD. This study provides potential instruments to detect and monitor punding in patients with PD. © 2017 American Academy of Neurology.

  10. Dialectical behavior therapy alters emotion regulation and amygdala activity in patients with borderline personality disorder.

    Science.gov (United States)

    Goodman, Marianne; Carpenter, David; Tang, Cheuk Y; Goldstein, Kim E; Avedon, Jennifer; Fernandez, Nicolas; Mascitelli, Kathryn A; Blair, Nicholas J; New, Antonia S; Triebwasser, Joseph; Siever, Larry J; Hazlett, Erin A

    2014-10-01

    Siever and Davis' (1991) psychobiological framework of borderline personality disorder (BPD) identifies affective instability (AI) as a core dimension characterized by prolonged and intense emotional reactivity. Recently, deficient amygdala habituation, defined as a change in response to repeated relative to novel unpleasant pictures within a session, has emerged as a biological correlate of AI in BPD. Dialectical behavior therapy (DBT), an evidence-based treatment, targets AI by teaching emotion-regulation skills. This study tested the hypothesis that BPD patients would exhibit decreased amygdala activation and improved habituation, as well as improved emotion regulation with standard 12-month DBT. Event-related fMRI was obtained pre- and post-12-months of standard-DBT in unmedicated BPD patients. Healthy controls (HCs) were studied as a benchmark for normal amygdala activity and change over time (n = 11 per diagnostic-group). During each scan, participants viewed an intermixed series of unpleasant, neutral and pleasant pictures presented twice (novel, repeat). Change in emotion regulation was measured with the Difficulty in Emotion Regulation (DERS) scale. fMRI results showed the predicted Group × Time interaction: compared with HCs, BPD patients exhibited decreased amygdala activation with treatment. This post-treatment amygdala reduction in BPD was observed for all three pictures types, but particularly marked in the left hemisphere and during repeated-emotional pictures. Emotion regulation measured with the DERS significantly improved with DBT in BPD patients. Improved amygdala habituation to repeated-unpleasant pictures in patients was associated with improved overall emotional regulation measured by the DERS (total score and emotion regulation strategy use subscale). These findings have promising treatment implications and support the notion that DBT targets amygdala hyperactivity-part of the disturbed neural circuitry underlying emotional dysregulation

  11. Changes in prefrontal and amygdala activity during olanzapine treatment in schizophrenia.

    Science.gov (United States)

    Blasi, Giuseppe; Popolizio, Teresa; Taurisano, Paolo; Caforio, Grazia; Romano, Raffaella; Di Giorgio, Annabella; Sambataro, Fabio; Rubino, Valeria; Latorre, Valeria; Lo Bianco, Luciana; Fazio, Leonardo; Nardini, Marcello; Weinberger, Daniel R; Bertolino, Alessandro

    2009-07-15

    Earlier imaging studies in schizophrenia have reported abnormal amygdala and prefrontal cortex activity during emotion processing. We investigated with functional magnetic resonance imaging (fMRI) during emotion processing changes in activity of the amygdala and of prefrontal cortex in patients with schizophrenia during 8 weeks of olanzapine treatment. Twelve previously drug-free/naive patients with schizophrenia were treated with olanzapine for 8 weeks and underwent two fMRI scans after 4 and 8 weeks of treatment during implicit and explicit emotional processing. Twelve healthy subjects were also scanned twice to control for potential repetition effects. Results showed a diagnosis by time interaction in left amygdala and a diagnosis by time by task interaction in right ventrolateral prefrontal cortex. In particular, activity in left amygdala was greater in patients than in controls at the first scan during both explicit and implicit processing, while it was lower in patients at the second relative to the first scan. Furthermore, during implicit processing, right ventrolateral prefrontal cortex activity was lower in patients than controls at the first scan, while it was greater in patients at the second relative to the first scan. These results suggest that longitudinal treatment with olanzapine may be associated with specific changes in activity of the amygdala and prefrontal cortex during emotional processing in schizophrenia.

  12. An earlier time of scan is associated with greater threat-related amygdala reactivity.

    Science.gov (United States)

    Baranger, David A A; Margolis, Seth; Hariri, Ahmad R; Bogdan, Ryan

    2017-08-01

    Time-dependent variability in mood and anxiety suggest that related neural phenotypes, such as threat-related amygdala reactivity, may also follow a diurnal pattern. Here, using data from 1,043 young adult volunteers, we found that threat-related amygdala reactivity was negatively coupled with time of day, an effect which was stronger in the left hemisphere (β = -0.1083, p-fdr = 0.0012). This effect was moderated by subjective sleep quality (β = -0.0715, p-fdr = 0.0387); participants who reported average and poor sleep quality had relatively increased left amygdala reactivity in the morning. Bootstrapped simulations suggest that similar cross-sectional samples with at least 300 participants would be able to detect associations between amygdala reactivity and time of scan. In control analyses, we found no associations between time and V1 activation. Our results provide initial evidence that threat-related amygdala reactivity may vary diurnally, and that this effect is potentiated among individuals with average to low sleep quality. More broadly, our results suggest that considering time of scan in study design or modeling time of scan in analyses, as well as collecting additional measures of circadian variation, may be useful for understanding threat-related neural phenotypes and their associations with behavior, such as fear conditioning, mood and anxiety symptoms, and related phenotypes. © The Author (2017). Published by Oxford University Press.

  13. Amygdala hypersensitivity in response to emotional faces in Tourette's patients.

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    Neuner, Irene; Kellermann, Thilo; Stöcker, Tony; Kircher, Tilo; Habel, Ute; Shah, Jon N; Schneider, Frank

    2010-10-01

    Tourette's syndrome is characterised by motor and vocal tics as well as a high level of impulsivity and emotional dysregulation. Neuroimaging studies point to structural changes of the basal ganglia, prefrontal cortex and parts of the limbic system. However, there is no link between behavioural symptoms and the structural changes in the amygdala. One aspect of daily social interaction is the perception of emotional facial expressions, closely linked to amgydala function. We therefore investigated via fMRI the implicit discrimination of six emotional facial expressions in 19 adult Tourette's patients. In comparison to healthy control group, Tourette's patients showed significantly higher amygdala activation, especially pronounced for fearful, angry and neutral expressions. The BOLD-activity of the left amygdala correlated negatively with the personality trait extraversion. We will discuss these findings as a result of either deficient frontal inhibition due to structural changes or a desynchronization in the interaction of the cortico-striato-thalamo-cortical network within structures of the limbic system. Our data show an altered pattern of implicit emotion discrimination and emphasize the need to consider motor and non-motor symptoms in Tourette's syndrome in the choice of both behavioural and pharmacological treatment.

  14. MOLECULAR BASIS OF LEARNING IN THE HIPPOCAMPUS AND THE AMYGDALA

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    Łukasz BIJOCH

    2015-12-01

    Full Text Available The hippocampus and the amygdala are structures of mammalian brain both involved in memorizing. However, they are responsible for different types of memory: the hippocampus is involved in creating and storing declarative engrams and the amygdala is engaged in some of non-declarative learning. During memorization, changes of synapses appear and it is believed that they encode information. Long-Term Potentiation (LTP and Long-Term Depression (LTD are two processes which provide to these changes which are called synaptic plasticity. LTP strengthens connections between neurons and because of that it is traditionally linked with learning. LTD as an opposite state is usually treated as forgetting. However, there are some evidences that it is true only for few types of non-declarative engrams. More sophisticated learning (like declarative learning requires cooperation of these processes. Review is focused on functions and detailed signaling pathways of processes of synaptic plasticity.

  15. Asymmetry of Hippocampus and Amygdala Defect in Subjective Cognitive Decline Among the Community Dwelling Chinese

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    Ling Yue

    2018-06-01

    Full Text Available Background: Subjective cognitive decline (SCD may be the first clinical sign of Alzheimer's disease (AD. SCD individuals with normal cognition may already have significant medial temporal lobe atrophy. However, few studies have been devoted to exploring the alteration of left-right asymmetry with hippocampus and amygdala in SCD. The aim of this study was to compare SCD individuals with amnestic mild cognitive impairment (MCI patients and the normal population for volume and asymmetry of hippocampus, amygdala and temporal horn, and to assess their relationship with cognitive function in elderly population living in China.Methods: 111 SCD, 30 MCI, and 67 healthy controls (HC underwent a standard T1-weighted MRI, from which the volumes of the hippocampus and amygdala were calculated and compared. Then we evaluated the pattern and extent of asymmetry in hippocampus and amygdala of these samples. Furthermore, we also investigated the relationship between the altered brain regions and cognitive function.Results: Among the three groups, SCD showed more depressive symptoms (p < 0.001 and higher percentage of heart disease (16.4% vs. 35.1%, p = 0.007 than controls. In terms of brain data, significant differences were found in the volume and asymmetry of both hippocampus and amygdala among the three groups (P < 0.05. In logistic analysis controlled by age, gender, education level, depression symptoms, anxiety symptom, somatic disease and lifestyle in terms of smoking, both SCD and MCI individuals showed significant decreased right hippocampal and amygdala volume than controls. For asymmetry pattern, a ladder-shaped difference of left-larger-than-right asymmetry was found in amygdala with MCI>SCD>HC, and an opposite asymmetry of left-less-than-right pattern was found with HC>SCD>MCI in hippocampus. Furthermore, correlation was shown between the volume of right hippocampus and right amygdala with MMSE and MoCA in SCD group.Conclusion: Our results supported

  16. General and specific responsiveness of the amygdala during explicit emotion recognition in females and males

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    Windischberger Christian

    2009-08-01

    Full Text Available Abstract Background The ability to recognize emotions in facial expressions relies on an extensive neural network with the amygdala as the key node as has typically been demonstrated for the processing of fearful stimuli. A sufficient characterization of the factors influencing and modulating amygdala function, however, has not been reached now. Due to lacking or diverging results on its involvement in recognizing all or only certain negative emotions, the influence of gender or ethnicity is still under debate. This high-resolution fMRI study addresses some of the relevant parameters, such as emotional valence, gender and poser ethnicity on amygdala activation during facial emotion recognition in 50 Caucasian subjects. Stimuli were color photographs of emotional Caucasian and African American faces. Results Bilateral amygdala activation was obtained to all emotional expressions (anger, disgust, fear, happy, and sad and neutral faces across all subjects. However, only in males a significant correlation of amygdala activation and behavioral response to fearful stimuli was observed, indicating higher amygdala responses with better fear recognition, thus pointing to subtle gender differences. No significant influence of poser ethnicity on amygdala activation occurred, but analysis of recognition accuracy revealed a significant impact of poser ethnicity that was emotion-dependent. Conclusion Applying high-resolution fMRI while subjects were performing an explicit emotion recognition task revealed bilateral amygdala activation to all emotions presented and neutral expressions. This mechanism seems to operate similarly in healthy females and males and for both in-group and out-group ethnicities. Our results support the assumption that an intact amygdala response is fundamental in the processing of these salient stimuli due to its relevance detecting function.

  17. Resting-state functional connectivity of the amygdala in suicide attempters with major depressive disorder.

    Science.gov (United States)

    Kang, Seung-Gul; Na, Kyoung-Sae; Choi, Jae-Won; Kim, Jeong-Hee; Son, Young-Don; Lee, Yu Jin

    2017-07-03

    In this study, we investigated the difference in resting-state functional connectivity (RSFC) of the amygdala between suicide attempters and non-suicide attempters with major depressive disorder (MDD) using functional magnetic resonance imaging (fMRI). This study included 19 suicide attempters with MDD and 19 non-suicide attempters with MDD. RSFC was compared between the two groups and the regression analyses were conducted to identify the correlation between RSFC and Scale for Suicide Ideation (SSI) scores in the suicide attempt group. Statistical significance was set at p-value (uncorrected) suicide attempters, suicide attempters showed significantly increased RSFC of the left amygdala with the right insula and left superior orbitofrontal area, and increased RSFC of the right amygdala with the left middle temporal area. The regression analysis showed a significant correlation between the SSI total score and RSFC of the right amygdala with the right parahippocampal area in the suicide attempt group. The present RSFC findings provide evidence of a functional neural basis and will help reveal the pathophysiology underlying suicidality in subjects with MDD. Copyright © 2017. Published by Elsevier Inc.

  18. MRI Amygdala Volume in Williams Syndrome

    Science.gov (United States)

    Capitao, Liliana; Sampaio, Adriana; Sampaio, Cassandra; Vasconcelos, Cristiana; Fernandez, Montse; Garayzabal, Elena; Shenton, Martha E.; Goncalves, Oscar F.

    2011-01-01

    One of the most intriguing characteristics of Williams Syndrome individuals is their hypersociability. The amygdala has been consistently implicated in the etiology of this social profile, particularly given its role in emotional and social behavior. This study examined amygdala volume and symmetry in WS individuals and in age and sex matched…

  19. Amygdala activation as a marker for selective attention toward neutral faces in a chronic traumatic brain injury population.

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    Young, Leanne R; Yu, Weikei; Holloway, Michael; Rodgers, Barry N; Chapman, Sandra B; Krawczyk, Daniel C

    2017-09-01

    There has been great interest in characterizing the response of the amygdala to emotional faces, especially in the context of social cognition. Although amygdala activation is most often associated with fearful or angry stimuli, there is considerable evidence that the response of the amygdala to neutral faces is both robust and reliable. This characteristic of amygdala function is of particular interest in the context of assessing populations with executive function deficits, such as traumatic brain injuries, which can be evaluated using fMRI attention modulation tasks that evaluate prefrontal control over representations, notably faces. The current study tested the hypothesis that the amygdala may serve as a marker of selective attention to neutral faces. Using fMRI, we gathered data within a chronic traumatic brain injury population. Blood Oxygenation Level Dependent (BOLD) signal change within the left and right amygdalae and fusiform face areas was measured while participants viewed neutral faces and scenes, under conditions requiring participants to (1) categorize pictures of faces and scenes, (2) selectively attend to either faces or scenes, or (3) attend to both faces and scenes. Findings revealed that the amygdala is an effective marker for selective attention to neutral faces and, furthermore, it was more face-specific than the fusiform face area. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. vlPFC-vmPFC-Amygdala Interactions Underlie Age-Related Differences in Cognitive Regulation of Emotion.

    Science.gov (United States)

    Silvers, Jennifer A; Insel, Catherine; Powers, Alisa; Franz, Peter; Helion, Chelsea; Martin, Rebecca E; Weber, Jochen; Mischel, Walter; Casey, B J; Ochsner, Kevin N

    2017-07-01

    Emotion regulation is a critical life skill that develops throughout childhood and adolescence. Despite this development in emotional processes, little is known about how the underlying brain systems develop with age. This study examined emotion regulation in 112 individuals (aged 6-23 years) as they viewed aversive and neutral images using a reappraisal task. On "reappraisal" trials, participants were instructed to view the images as distant, a strategy that has been previously shown to reduce negative affect. On "reactivity" trials, participants were instructed to view the images without regulating emotions to assess baseline emotional responding. During reappraisal, age predicted less negative affect, reduced amygdala responses and inverse coupling between the ventromedial prefrontal cortex (vmPFC) and amygdala. Moreover, left ventrolateral prefrontal (vlPFC) recruitment mediated the relationship between increasing age and diminishing amygdala responses. This negative vlPFC-amygdala association was stronger for individuals with inverse coupling between the amygdala and vmPFC. These data provide evidence that vmPFC-amygdala connectivity facilitates vlPFC-related amygdala modulation across development. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Aberrant Functional Connectivity of the Amygdala Complexes in PTSD during Conscious and Subconscious Processing of Trauma-Related Stimuli.

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    Daniela Rabellino

    Full Text Available Post-traumatic stress disorder (PTSD is characterized by altered functional connectivity of the amygdala complexes at rest. However, amygdala complex connectivity during conscious and subconscious threat processing remains to be elucidated. Here, we investigate specific connectivity of the centromedial amygdala (CMA and basolateral amygdala (BLA during conscious and subconscious processing of trauma-related words among individuals with PTSD (n = 26 as compared to non-trauma-exposed controls (n = 20. Psycho-physiological interaction analyses were performed using the right and left amygdala complexes as regions of interest during conscious and subconscious trauma word processing. These analyses revealed a differential, context-dependent responses by each amygdala seed during trauma processing in PTSD. Specifically, relative to controls, during subconscious processing, individuals with PTSD demonstrated increased connectivity of the CMA with the superior frontal gyrus, accompanied by a pattern of decreased connectivity between the BLA and the superior colliculus. During conscious processing, relative to controls, individuals with PTSD showed increased connectivity between the CMA and the pulvinar. These findings demonstrate alterations in amygdala subregion functional connectivity in PTSD and highlight the disruption of the innate alarm network during both conscious and subconscious trauma processing in this disorder.

  2. The Amygdala and the Relevance Detection Theory of Autism: An Evolutionary Perspective

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    Tiziana eZalla

    2013-12-01

    Full Text Available In the last few decades, there has been increasing interest in the role of the amygdala in psychiatric disorders and in particular its contribution to the socio-emotional impairments in autism spectrum disorders (ASDs. Given that the amygdala is a component structure of the social brain, several theoretical explanations compatible with amygdala dysfunction have been proposed to account for socio-emotional impairments in ASDs, including abnormal eye contact, gaze monitoring, face processing, mental state understanding and empathy. Nevertheless, many theoretical accounts, based on the Amygdala Theory of Autism, fail to elucidate the complex pattern of impairments observed in this population, which extends beyond the social domain. As posited by the Relevance Detector theory (Sander, Grafman and Zalla, 2003, the human amygdala is a critical component of a brain circuit involved in the appraisal of self-relevant events that include, but are not restricted to, social stimuli. Here, we propose that the behavioral and social-emotional features of ASDs may be better understood in terms of a disruption in a ‘Relevance Detector Network’ affecting the processing of stimuli that are relevant for the organism’s self-regulating functions. In the present review, we will first summarize the main literature supporting the involvement of the amygdala in socio-emotional disturbances in ASDs. Next, we will present a revised version of the amygdala Relevance Detector hypothesis and we will show that this theoretical framework can provide a better understanding of the heterogeneity of the impairments and symptomatology of ASDs. Finally, we will discuss some predictions of our model, and suggest new directions in the investigation of the role of the amygdala within the more generally disrupted cortical connectivity framework as a model of neural organization of the autistic brain.

  3. Comparison between subjects with long- and short-allele carriers in the BOLD signal within amygdala during emotional tasks

    Science.gov (United States)

    Hadi, Shamil; Siadat, Mohamad R.; Babajani-Feremi, Abbas

    2012-03-01

    Emotional tasks may result in a strong blood oxygen level-dependent (BOLD) signal in the amygdala in 5- HTTLRP short-allele. Reduced anterior cingulate cortex (ACC)-amygdala connectivity in short-allele provides a potential mechanistic account for the observed increase in amygdala activity. In our study, fearful and threatening facial expressions were presented to two groups of 12 subjects with long- and short-allele carriers. The BOLD signals of the left amygdala of each group were averaged to increase the signal-to-noise ratio. A Bayesian approach was used to estimate the model parameters to elucidate the underlying hemodynamic mechanism. Our results showed a positive BOLD signal in the left amygdala for short-allele individuals, and a negative BOLD signal in the same region for long-allele individuals. This is due to the fact that short-allele is associated with lower availability of serotonin transporter (5-HTT) and this leads to an increase of serotonin (5-HT) concentration in the cACC-amygdala synapse.

  4. Smaller amygdala volume and reduced anterior cingulate gray matter density associated with history of post-traumatic stress disorder.

    Science.gov (United States)

    Rogers, Mark A; Yamasue, Hidenori; Abe, Osamu; Yamada, Haruyasu; Ohtani, Toshiyuki; Iwanami, Akira; Aoki, Shigeki; Kato, Nobumasa; Kasai, Kiyoto

    2009-12-30

    Although post-traumatic stress disorder (PTSD) may be seen to represent a failure to extinguish learned fear, significant aspects of the pathophysiology relevant to this hypothesis remain unknown. Both the amygdala and hippocampus are necessary for fear extinction occur, and thus both regions may be abnormal in PTSD. Twenty-five people who experienced the Tokyo subway sarin attack in 1995, nine who later developed PTSD and 16 who did not, underwent magnetic resonance imaging (MRI) with manual tracing to determine bilateral amygdala and hippocampus volumes. At the time of scanning, one had PTSD and eight had a history of PTSD. Results indicated that the group with a history of PTSD had significantly smaller mean bilateral amygdala volume than did the group that did not develop PTSD. Furthermore, left amygdala volume showed a significant negative correlation with severity of PTSD symptomatology as well as reduced gray matter density in the left anterior cingulate cortex. To our knowledge, this is the first observation of an association between PTSD and amygdala volume. Furthermore the apparent interplay between amygdala and anterior cingulate cortex represents support at the level of gross brain morphology for the theory of PTSD as a failure of fear extinction.

  5. Guanfacine modulates the emotional biasing of amygdala-prefrontal connectivity for cognitive control.

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    Schulz, Kurt P; Clerkin, Suzanne M; Newcorn, Jeffrey H; Halperin, Jeffrey M; Fan, Jin

    2014-09-01

    Functional interactions between amygdala and prefrontal cortex provide a cortical entry point for emotional cues to bias cognitive control. Stimulation of α2 adrenoceptors enhances the prefrontal control functions and blocks the amygdala-dependent encoding of emotional cues. However, the impact of this stimulation on amygdala-prefrontal interactions and the emotional biasing of cognitive control have not been established. We tested the effect of the α2 adrenoceptor agonist guanfacine on psychophysiological interactions of amygdala with prefrontal cortex for the emotional biasing of response execution and inhibition. Fifteen healthy adults were scanned twice with event-related functional magnetic resonance imaging while performing an emotional go/no-go task following administration of oral guanfacine (1mg) and placebo in a double-blind, counterbalanced design. Happy, sad, and neutral faces served as trial cues. Guanfacine moderated the effect of face emotion on the task-related functional connectivity of left and right amygdala with left inferior frontal gyrus compared to placebo, by selectively reversing the functional co-activation of the two regions for response execution cued by sad faces. This shift from positively to negatively correlated activation for guanfacine was associated with selective improvements in the relatively low accuracy of responses to sad faces seen for placebo. These results demonstrate the importance of functional interactions between amygdala and inferior frontal gyrus to both bottom-up biasing of cognitive control and top-down control of emotional processing, as well as for the α2 adrenoceptor-mediated modulation of these processes. These mechanisms offer a possibile method to address the emotional reactivity that is common to several psychiatric disorders. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

  6. Preregistered Replication of "Affective Flexibility: Evaluative Processing Goals Shape Amygdala Activity".

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    Lumian, Daniel S; McRae, Kateri

    2017-09-01

    The human amygdala is sensitive to stimulus characteristics, and growing evidence suggests that it is also responsive to cognitive framing in the form of evaluative goals. To examine whether different evaluations of stimulus characteristics shape amygdala activation, we conducted a preregistered replication of Cunningham, Van Bavel, and Johnsen's (2008) study demonstrating flexible mapping of amygdala activation to stimulus characteristics, depending on evaluative goals. Participants underwent functional MRI scanning while viewing famous names under three conditions: They were asked to report their overall attitude toward each name, their positive associations only, or their negative associations only. We observed an interaction between condition and rating type, identified as the effect of interest in Cunningham et al. (2008). Specifically, postscan positivity, but not negativity, ratings predicted left amygdala activation when participants were asked to evaluate positive, but not negative, associations with the names. These results provide convergent evidence that cognitive framing, in the form of evaluative goals, can significantly alter whether amygdala activation indexes positivity or negativity.

  7. Blunted amygdala functional connectivity during a stress task in alcohol dependent individuals: A pilot study

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    Natasha E. Wade, M.S.

    2017-12-01

    Full Text Available Background: Scant research has been conducted on neural mechanisms underlying stress processing in individuals with alcohol dependence (AD. We examined neural substrates of stress in AD individuals compared with controls using an fMRI task previously shown to induce stress, assessing amygdala functional connectivity to medial prefrontal cortex (mPFC. Materials and methods: For this novel pilot study, 10 abstinent AD individuals and 11 controls completed a modified Trier stress task while undergoing fMRI acquisition. The amygdala was used as a seed region for whole-brain seed-based functional connectivity analysis. Results: After controlling for family-wise error (p = 0.05, there was significantly decreased left and right amygdala connectivity with frontal (specifically mPFC, temporal, parietal, and cerebellar regions. Subjective stress, but not craving, increased from pre-to post-task. Conclusions: This study demonstrated decreased connectivity between the amygdala and regions important for stress and emotional processing in long-term abstinent individuals with AD. These results suggest aberrant stress processing in individuals with AD even after lengthy periods of abstinence. Keywords: Alcohol dependence, fMRI, Stress task, Functional connectivity, Amygdala

  8. Molecular Mechanisms of Stress-Induced Increases in Fear Memory Consolidation within the Amygdala.

    Science.gov (United States)

    Aubry, Antonio V; Serrano, Peter A; Burghardt, Nesha S

    2016-01-01

    Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by which stress affects the amygdala and amygdala-dependent fear memories remain unclear. Here we review the literature on the enhancing effects of acute and chronic stress on the acquisition and/or consolidation of a fear memory, as measured by auditory Pavlovian fear conditioning, and discuss potential mechanisms by which these changes occur in the amygdala. We hypothesize that stress-mediated activation of glucocorticoid receptors (GR) and norepinephrine release within the amygdala leads to the mobilization of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors to the synapse, which underlies stress-induced increases in fear memory. We discuss the implications of this hypothesis for evaluating the effects of stress on extinction and for developing treatments for anxiety disorders. Understanding how stress-induced changes in glucocorticoid and norepinephrine signaling might converge to affect emotional learning by increasing the trafficking of AMPA receptors and enhancing amygdala excitability is a promising area for future research.

  9. Molecular Mechanisms of Stress-Induced Increases in Fear Memory Consolidation Within the Amygdala

    Directory of Open Access Journals (Sweden)

    Antonio Aubry

    2016-10-01

    Full Text Available Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by which stress affects the amygdala and amygdala-dependent fear memories remain unclear. Here we review the literature on the enhancing effects of acute and chronic stress on the acquisition and/or consolidation of a fear memory, as measured by auditory Pavlovian fear conditioning, and discuss potential mechanisms by which these changes occur in the amygdala. We hypothesize that stress-mediated activation of glucocorticoid receptors (GR and norepinephrine release within the amygdala leads to the mobilization of AMPA receptors to the synapse, which underlies stress-induced increases in fear memory. We discuss the implications of this hypothesis for evaluating the effects of stress on extinction and for developing treatments for anxiety disorders. Understanding how stress-induced changes in glucocorticoid and norepinephrine signaling might converge to affect emotional learning by increasing the trafficking of AMPA receptors and enhancing amygdala excitability is a promising area for future research.

  10. Direction of Amygdala-Neocortex Interaction During Dynamic Facial Expression Processing.

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    Sato, Wataru; Kochiyama, Takanori; Uono, Shota; Yoshikawa, Sakiko; Toichi, Motomi

    2017-03-01

    Dynamic facial expressions of emotion strongly elicit multifaceted emotional, perceptual, cognitive, and motor responses. Neuroimaging studies revealed that some subcortical (e.g., amygdala) and neocortical (e.g., superior temporal sulcus and inferior frontal gyrus) brain regions and their functional interaction were involved in processing dynamic facial expressions. However, the direction of the functional interaction between the amygdala and the neocortex remains unknown. To investigate this issue, we re-analyzed functional magnetic resonance imaging (fMRI) data from 2 studies and magnetoencephalography (MEG) data from 1 study. First, a psychophysiological interaction analysis of the fMRI data confirmed the functional interaction between the amygdala and neocortical regions. Then, dynamic causal modeling analysis was used to compare models with forward, backward, or bidirectional effective connectivity between the amygdala and neocortical networks in the fMRI and MEG data. The results consistently supported the model of effective connectivity from the amygdala to the neocortex. Further increasing time-window analysis of the MEG demonstrated that this model was valid after 200 ms from the stimulus onset. These data suggest that emotional processing in the amygdala rapidly modulates some neocortical processing, such as perception, recognition, and motor mimicry, when observing dynamic facial expressions of emotion. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  11. fMRI neurofeedback of amygdala response to aversive stimuli enhances prefrontal-limbic brain connectivity.

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    Paret, Christian; Ruf, Matthias; Gerchen, Martin Fungisai; Kluetsch, Rosemarie; Demirakca, Traute; Jungkunz, Martin; Bertsch, Katja; Schmahl, Christian; Ende, Gabriele

    2016-01-15

    Down-regulation of the amygdala with real-time fMRI neurofeedback (rtfMRI NF) potentially allows targeting brain circuits of emotion processing and may involve prefrontal-limbic networks underlying effective emotion regulation. Little research has been dedicated to the effect of rtfMRI NF on the functional connectivity of the amygdala and connectivity patterns in amygdala down-regulation with neurofeedback have not been addressed yet. Using psychophysiological interaction analysis of fMRI data, we present evidence that voluntary amygdala down-regulation by rtfMRI NF while viewing aversive pictures was associated with increased connectivity of the right amygdala with the ventromedial prefrontal cortex (vmPFC) in healthy subjects (N=16). In contrast, a control group (N=16) receiving sham feedback did not alter amygdala connectivity (Group×Condition t-contrast: pneurofeedback to influence functional connectivity in key networks of emotion processing and regulation. This may be beneficial for patients suffering from severe emotion dysregulation by improving neural self-regulation. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Myosin light chain kinase regulates synaptic plasticity and fear learning in the lateral amygdala.

    Science.gov (United States)

    Lamprecht, R; Margulies, D S; Farb, C R; Hou, M; Johnson, L R; LeDoux, J E

    2006-01-01

    Learning and memory depend on signaling molecules that affect synaptic efficacy. The cytoskeleton has been implicated in regulating synaptic transmission but its role in learning and memory is poorly understood. Fear learning depends on plasticity in the lateral nucleus of the amygdala. We therefore examined whether the cytoskeletal-regulatory protein, myosin light chain kinase, might contribute to fear learning in the rat lateral amygdala. Microinjection of ML-7, a specific inhibitor of myosin light chain kinase, into the lateral nucleus of the amygdala before fear conditioning, but not immediately afterward, enhanced both short-term memory and long-term memory, suggesting that myosin light chain kinase is involved specifically in memory acquisition rather than in posttraining consolidation of memory. Myosin light chain kinase inhibitor had no effect on memory retrieval. Furthermore, ML-7 had no effect on behavior when the training stimuli were presented in a non-associative manner. Anatomical studies showed that myosin light chain kinase is present in cells throughout lateral nucleus of the amygdala and is localized to dendritic shafts and spines that are postsynaptic to the projections from the auditory thalamus to lateral nucleus of the amygdala, a pathway specifically implicated in fear learning. Inhibition of myosin light chain kinase enhanced long-term potentiation, a physiological model of learning, in the auditory thalamic pathway to the lateral nucleus of the amygdala. When ML-7 was applied without associative tetanic stimulation it had no effect on synaptic responses in lateral nucleus of the amygdala. Thus, myosin light chain kinase activity in lateral nucleus of the amygdala appears to normally suppress synaptic plasticity in the circuits underlying fear learning, suggesting that myosin light chain kinase may help prevent the acquisition of irrelevant fears. Impairment of this mechanism could contribute to pathological fear learning.

  13. Dopamine in the medial amygdala network mediates human bonding.

    Science.gov (United States)

    Atzil, Shir; Touroutoglou, Alexandra; Rudy, Tali; Salcedo, Stephanie; Feldman, Ruth; Hooker, Jacob M; Dickerson, Bradford C; Catana, Ciprian; Barrett, Lisa Feldman

    2017-02-28

    Research in humans and nonhuman animals indicates that social affiliation, and particularly maternal bonding, depends on reward circuitry. Although numerous mechanistic studies in rodents demonstrated that maternal bonding depends on striatal dopamine transmission, the neurochemistry supporting maternal behavior in humans has not been described so far. In this study, we tested the role of central dopamine in human bonding. We applied a combined functional MRI-PET scanner to simultaneously probe mothers' dopamine responses to their infants and the connectivity between the nucleus accumbens (NAcc), the amygdala, and the medial prefrontal cortex (mPFC), which form an intrinsic network (referred to as the "medial amygdala network") that supports social functioning. We also measured the mothers' behavioral synchrony with their infants and plasma oxytocin. The results of this study suggest that synchronous maternal behavior is associated with increased dopamine responses to the mother's infant and stronger intrinsic connectivity within the medial amygdala network. Moreover, stronger network connectivity is associated with increased dopamine responses within the network and decreased plasma oxytocin. Together, these data indicate that dopamine is involved in human bonding. Compared with other mammals, humans have an unusually complex social life. The complexity of human bonding cannot be fully captured in nonhuman animal models, particularly in pathological bonding, such as that in autistic spectrum disorder or postpartum depression. Thus, investigations of the neurochemistry of social bonding in humans, for which this study provides initial evidence, are warranted.

  14. Reduced amygdala reactivity and impaired working memory during dissociation in borderline personality disorder.

    Science.gov (United States)

    Krause-Utz, Annegret; Winter, Dorina; Schriner, Friederike; Chiu, Chui-De; Lis, Stefanie; Spinhoven, Philip; Bohus, Martin; Schmahl, Christian; Elzinga, Bernet M

    2017-05-19

    Affective hyper-reactivity and impaired cognitive control of emotional material are core features of borderline personality disorder (BPD). A high percentage of individuals with BPD experience stress-related dissociation, including emotional numbing and memory disruptions. So far little is known about how dissociation influences the neural processing of emotional material in the context of a working memory task in BPD. We aimed to investigate whole-brain activity and amygdala functional connectivity (FC) during an Emotional Working Memory Task (EWMT) after dissociation induction in un-medicated BPD patients compared to healthy controls (HC). Using script-driven imagery, dissociation was induced in 17 patients ('BPD_D'), while 12 patients ('BPD_N') and 18 HC were exposed to neutral scripts during fMRI. Afterwards, participants performed the EWMT with neutral vs. negative IAPS pictures vs. no distractors. Main outcome measures were behavioral performance (reaction times, errors) and whole-brain activity during the EWMT. Psychophysiological interaction analysis was used to examine amygdala connectivity during emotional distraction. BPD patients after dissociation induction showed overall WM impairments, a deactivation in bilateral amygdala, and lower activity in left cuneus, lingual gyrus, and posterior cingulate than BPD_N, along with stronger left inferior frontal gyrus activity than HC. Furthermore, reduced amygdala FC with fusiform gyrus and stronger amygdala FC with right middle/superior temporal gyrus and left inferior parietal lobule was observed in BPD_D. Findings suggest that dissociation affects reactivity to emotionally salient material and WM. Altered activity in areas associated with emotion processing, memory, and self-referential processes may contribute to dissociative states in BPD.

  15. [Morphometric features of the structure of the central nucleus of the amygdala in men and women].

    Science.gov (United States)

    Antyukhov, A D

    2015-01-01

    To identify the interhemispheric asymmetry in the structure of the central nucleus of the amygdala in men and women. Morphometric features of the structure of neurons of the central nucleus amygdala complex were studied in histological sections of the brain of 6 men and 6 women (24 hemispheres), aged 19 to 55 years, with no lifetime diagnosis of mental or neurological disease. The value of the profile fields of neurons of the central nucleus amygdala complex in the left and right hemispheres of the brain were investigated. In women, the average value of neurons in the left hemisphere was somewhat greater than in the right hemisphere, while in men this value was greater in the right hemisphere. The interhemispheric morphometric differences were not significant regardless of gender. In addition, the quantity of relevant fields of neurons in the central nucleus of the amygdala in women was significantly larger than that of men in both hemispheres. The authors attempted to associate the results obtained in the study with emotional perception in men and women.

  16. The amygdala, top-down effects, and selective attention to features

    NARCIS (Netherlands)

    Jacobs, Richard H. A. H.; Renken, Remco; Aleman, Andre; Cornelissen, Frans W.

    2012-01-01

    While the amygdalar role in fear conditioning is well established, it also appears to be involved in a wide spectrum of other functions concerning emotional information. For example, the amygdala is thought to be involved in guiding spatial attention to emotionally relevant information such as the

  17. The dynamic right-to-left translocation of Cerl2 is involved in the regulation and termination of Nodal activity in the mouse node.

    Directory of Open Access Journals (Sweden)

    José Manuel Inácio

    Full Text Available The determination of left-right body asymmetry in mouse embryos depends on the interplay of molecules in a highly sensitive structure, the node. Here, we show that the localization of Cerl2 protein does not correlate to its mRNA expression pattern, from 3-somite stage onwards. Instead, Cerl2 protein displays a nodal flow-dependent dynamic behavior that controls the activity of Nodal in the node, and the transmission of the laterality information to the left lateral plate mesoderm (LPM. Our results indicate that Cerl2 initially localizes and prevents the activation of Nodal genetic circuitry on the right side of the embryo, and later its right-to-left translocation shutdowns Nodal activity in the node. The consequent prolonged Nodal activity in the node by the absence of Cerl2 affects local Nodal expression and prolongs its expression in the LPM. Simultaneous genetic removal of both Nodal node inhibitors, Cerl2 and Lefty1, sustains even longer and bilateral this LPM expression.

  18. Optogenetic Examination of Prefrontal-Amygdala Synaptic Development.

    Science.gov (United States)

    Arruda-Carvalho, Maithe; Wu, Wan-Chen; Cummings, Kirstie A; Clem, Roger L

    2017-03-15

    A brain network comprising the medial prefrontal cortex (mPFC) and amygdala plays important roles in developmentally regulated cognitive and emotional processes. However, very little is known about the maturation of mPFC-amygdala circuitry. We conducted anatomical tracing of mPFC projections and optogenetic interrogation of their synaptic connections with neurons in the basolateral amygdala (BLA) at neonatal to adult developmental stages in mice. Results indicate that mPFC-BLA projections exhibit delayed emergence relative to other mPFC pathways and establish synaptic transmission with BLA excitatory and inhibitory neurons in late infancy, events that coincide with a massive increase in overall synaptic drive. During subsequent adolescence, mPFC-BLA circuits are further modified by excitatory synaptic strengthening as well as a transient surge in feedforward inhibition. The latter was correlated with increased spontaneous inhibitory currents in excitatory neurons, suggesting that mPFC-BLA circuit maturation culminates in a period of exuberant GABAergic transmission. These findings establish a time course for the onset and refinement of mPFC-BLA transmission and point to potential sensitive periods in the development of this critical network. SIGNIFICANCE STATEMENT Human mPFC-amygdala functional connectivity is developmentally regulated and figures prominently in numerous psychiatric disorders with a high incidence of adolescent onset. However, it remains unclear when synaptic connections between these structures emerge or how their properties change with age. Our work establishes developmental windows and cellular substrates for synapse maturation in this pathway involving both excitatory and inhibitory circuits. The engagement of these substrates by early life experience may support the ontogeny of fundamental behaviors but could also lead to inappropriate circuit refinement and psychopathology in adverse situations. Copyright © 2017 the authors 0270-6474/17/372976-10$15.00/0.

  19. Significance of exercise-induced ST segment depression in patients with myocardial infarction involving the left circumflex artery. Evaluation by exercise thallium-201 myocardial single photon emission computed tomography

    International Nuclear Information System (INIS)

    Koitabashi, Norimichi; Toyama, Takuji; Hoshizaki, Hiroshi

    2000-01-01

    The significance of exercise-induced ST segment depression in patients with left circumflex artery involvement was investigated by comparing exercise electrocardiography with exercise thallium-201 single photon emission computed tomography (Tl-SPECT) and the wall motion estimated by left ventriculography. Tl-SPECT and exercise electrocardiography were simultaneously performed in 51 patients with left circumflex artery involvement (angina pectoris 30, myocardial infarction 21). In patients with myocardial infarction, exercise-induced ST depression was frequently found in the V 2 , V 3 and V 4 leads. In patients with angina pectoris, ST depression was frequently found in the II, III, aV F , V 5 and V 6 leads. There was no obvious difference in the leads of ST depression in patients with myocardial infarction with ischemia and without ischemia on Tl-SPECT images. In patients with myocardial infarction, the lateral wall motion of the infarcted area evaluated by left ventriculography was more significantly impaired in the patients with ST depression than without ST depression (p<0.01). Exercise-induced ST depression in the precordial leads possibly reflects wall motion abnormality rather than ischemia in the lateral infarcted myocardium. (author)

  20. Comparative distribution of relaxin-3 inputs and calcium-binding protein-positive neurons in rat amygdala

    Directory of Open Access Journals (Sweden)

    Fabio N Santos

    2016-04-01

    Full Text Available The neural circuits involved in mediating complex behaviors are being rapidly elucidated using various newly developed and powerful anatomical and molecular techniques, providing insights into the neural basis for anxiety disorders, depression, addiction, and dysfunctional social behaviors. Many of these behaviors and associated physiological processes involve the activation of the amygdala in conjunction with cortical and hippocampal circuits. Ascending subcortical projections provide modulatory inputs to the extended amygdala and its related nodes (or ‘hubs’ within these key circuits. One such input arises from the nucleus incertus (NI in the tegmentum, which sends amino acid- and peptide-containing projections throughout the forebrain. Notably, a distinct population of GABAergic NI neurons expresses the highly-conserved neuropeptide, relaxin-3, and relaxin-3 signaling has been implicated in the modulation of reward/motivation and anxiety- and depressive-like behaviors in rodents via actions within the extended amygdala. Thus, a detailed description of the relaxin-3 innervation of the extended amygdala would provide an anatomical framework for an improved understanding of NI and relaxin-3 modulation of these and other specific amygdala-related functions. Therefore, in this study, we examined the distribution of NI projections and relaxin-3-positive elements (axons/fibers/terminals within the amygdala, relative to the distribution of neurons expressing the calcium-binding proteins, parvalbumin, calretinin and/or calbindin. Anterograde tracer injections into the NI revealed a topographic distribution of NI efferents within the amygdala that was near identical to the distribution of relaxin-3-immunoreactive fibers. Highest densities of anterogradely-labeled elements and relaxin-3-immunoreactive fibers were observed in the medial nucleus of the amygdala, medial divisions of the bed nucleus of the stria terminalis (BST and in the endopiriform

  1. Relation between Amygdala Structure and Function in Adolescents with Bipolar Disorder

    Science.gov (United States)

    Kalmar, Jessica H.; Wang, Fei; Chepenik, Lara G.; Womer, Fay Y.; Jones, Monique M.; Pittman, Brian; Shah, Maulik P.; Martin, Andres; Constable, R. Todd; Blumberg, Hilary P.

    2009-01-01

    Adolescents with bipolar disorder showed decreased amygdala volume and increased amygdala response to emotional faces. Amygdala volume is inversely related to activation during emotional face processing.

  2. Testosterone reduces amygdala-orbitofrontal cortex coupling

    NARCIS (Netherlands)

    van Wingen, Guido; Mattern, Claudia; Verkes, Robbert Jan; Buitelaar, Jan; Fernández, Guillén

    2010-01-01

    Testosterone influences various aspects of affective behavior, which is mediated by different brain regions within the emotion circuitry. Previous neuroimaging studies have demonstrated that testosterone increases neural activity in the amygdala. To investigate whether this could be due to altered

  3. Age-dependent effects of acute methylphenidate on amygdala reactivity in stimulant treatment-naive patients with Attention Deficit/Hyperactivity Disorder.

    Science.gov (United States)

    Bottelier, Marco A; Schrantee, Anouk; Ferguson, Bart; Tamminga, Hyke G H; Bouziane, Cheima; Kooij, J J Sandra; de Ruiter, Michiel B; Reneman, Liesbeth

    2017-11-30

    In the present study, we investigate whether methylphenidate (MPH) affects emotional processing and whether this effect is modulated by age. We measured amygdala reactivity with functional Magnetic Resonance Imaging (fMRI) during processing of angry and fearful facial expressions in male stimulant treatment-naive patients with ADHD (N = 35 boys; N = 46 men) and 23 healthy control subjects (N = 11 boys; N = 12 men). In ADHD patients, we also measured amygdala reactivity 90min after an acute oral challenge with MPH (0.5mg/kg). Mean amygdala reactivity was analyzed for all subjects using a repeated measures analysis of variance (ANOVA). Whole-brain maps were analyzed for the patients only. At baseline, we found a age*diagnosis effect approaching significance (p = 0.05) in the right amygdala due to lower reactivity in children with Attention Deficit/Hyperactivity Disorder (ADHD) vs. controls (-31%), but higher reactivity in adults with ADHD vs. controls (+31%). MPH significantly reduced right amygdala reactivity in all patients, resulting in further reductions in children. In the left amygdala, reduction of amygdala reactivity was confined to adult ADHD patients whereas there was no change in children with ADHD. MPH-induced decrease of amygdala reactivity in adults might be a promising avenue for managing emotional dysregulation when replicated for chronic MPH treatment. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Structural Connectivity of the Developing Human Amygdala

    Science.gov (United States)

    Saygin, Zeynep M.; Osher, David E.; Koldewyn, Kami; Martin, Rebecca E.; Finn, Amy; Saxe, Rebecca; Gabrieli, John D.E.; Sheridan, Margaret

    2015-01-01

    A large corpus of research suggests that there are changes in the manner and degree to which the amygdala supports cognitive and emotional function across development. One possible basis for these developmental differences could be the maturation of amygdalar connections with the rest of the brain. Recent functional connectivity studies support this conclusion, but the structural connectivity of the developing amygdala and its different nuclei remains largely unstudied. We examined age related changes in the DWI connectivity fingerprints of the amygdala to the rest of the brain in 166 individuals of ages 5-30. We also developed a model to predict age based on individual-subject amygdala connectivity, and identified the connections that were most predictive of age. Finally, we segmented the amygdala into its four main nucleus groups, and examined the developmental changes in connectivity for each nucleus. We observed that with age, amygdalar connectivity becomes increasingly sparse and localized. Age related changes were largely localized to the subregions of the amygdala that are implicated in social inference and contextual memory (the basal and lateral nuclei). The central nucleus’ connectivity also showed differences with age but these differences affected fewer target regions than the basal and lateral nuclei. The medial nucleus did not exhibit any age related changes. These findings demonstrate increasing specificity in the connectivity patterns of amygdalar nuclei across age. PMID:25875758

  5. Intranasal Oxytocin Normalizes Amygdala Functional Connectivity in Posttraumatic Stress Disorder.

    Science.gov (United States)

    Koch, Saskia B J; van Zuiden, Mirjam; Nawijn, Laura; Frijling, Jessie L; Veltman, Dick J; Olff, Miranda

    2016-07-01

    The neuropeptide oxytocin (OT) has been suggested as a promising pharmacological agent for medication-enhanced psychotherapy in posttraumatic stress disorder (PTSD) because of its anxiolytic and prosocial properties. We therefore investigated the behavioral and neurobiological effects of a single intranasal OT administration (40 IU) in PTSD patients. We conducted a randomized, placebo-controlled, cross-over resting-state fMRI study in male and female police officers with (n=37, 21 males) and without PTSD (n=40, 20 males). We investigated OT administration effects on subjective anxiety and functional connectivity of basolateral (BLA) and centromedial (CeM) amygdala subregions with prefrontal and salience processing areas. In PTSD patients, OT administration resulted in decreased subjective anxiety and nervousness. Under placebo, male PTSD patients showed diminished right CeM to left ventromedial prefrontal cortex (vmPFC) connectivity compared with male trauma-exposed controls, which was reinstated after OT administration. Additionally, female PTSD patients showed enhanced right BLA to bilateral dorsal anterior cingulate cortex (dACC) connectivity compared with female trauma-exposed controls, which was dampened after OT administration. Although caution is warranted, our findings tentatively suggest that OT has the potential to diminish anxiety and fear expression of the amygdala in PTSD, either via increased control of the vmPFC over the CeM (males) or via decreased salience processing of the dACC and BLA (females). Our findings add to accumulating evidence that OT administration could potentially enhance treatment response in PTSD.

  6. Fear processing and social networking in the absence of a functional amygdala.

    Science.gov (United States)

    Becker, Benjamin; Mihov, Yoan; Scheele, Dirk; Kendrick, Keith M; Feinstein, Justin S; Matusch, Andreas; Aydin, Merve; Reich, Harald; Urbach, Horst; Oros-Peusquens, Ana-Maria; Shah, Nadim J; Kunz, Wolfram S; Schlaepfer, Thomas E; Zilles, Karl; Maier, Wolfgang; Hurlemann, René

    2012-07-01

    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. 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. 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. 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.

  7. The influence of 5-HTTLPR transporter genotype on amygdala-subgenual anterior cingulate cortex connectivity in autism spectrum disorder

    Directory of Open Access Journals (Sweden)

    Francisco Velasquez

    2017-04-01

    Full Text Available Social deficits in autism spectrum disorder (ASD are linked to amygdala functioning and functional connection between the amygdala and subgenual anterior cingulate cortex (sACC is involved in the modulation of amygdala activity. Impairments in behavioral symptoms and amygdala activation and connectivity with the sACC seem to vary by serotonin transporter-linked polymorphic region (5-HTTLPR variant genotype in diverse populations. The current preliminary investigation examines whether amygdala-sACC connectivity differs by 5-HTTLPR genotype and relates to social functioning in ASD. A sample of 108 children and adolescents (44 ASD completed an fMRI face-processing task. Youth with ASD and low expressing 5-HTTLPR genotypes showed significantly greater connectivity than youth with ASD and higher expressing genotypes as well as typically developing (TD individuals with both low and higher expressing genotypes, in the comparison of happy vs. baseline faces and happy vs. neutral faces. Moreover, individuals with ASD and higher expressing genotypes exhibit a negative relationship between amygdala-sACC connectivity and social dysfunction. Altered amygdala-sACC coupling based on 5-HTTLPR genotype may help explain some of the heterogeneity in neural and social function observed in ASD. This is the first ASD study to combine genetic polymorphism analyses and functional connectivity in the context of a social task.

  8. Personal involvement is related to increased search motivation and associated with activity in left BA44—a pilot study

    Science.gov (United States)

    Schaefer, Michael; Rumpel, Franziska; Sadrieh, Abdolkarim; Reimann, Martin; Denke, Claudia

    2015-01-01

    Numerous studies explore consumer perception of brands in a more or less passive way. This may still be representative for many situations or decisions we make each day. Nevertheless, sometimes we often actively search for and use information to make informed and reasoned choices, thus implying a rational and thinking consumer. Researchers suggested describing this distinction as low relative to high involvement consumer behavior. Although the involvement concept has been widely used to explain consumer behavior, behavioral and neural correlates of this concept are poorly understood. The current study aims to describe a behavioral measure that is associated with high involvement, the length of search behavior. A second aim of this study was to explore brain activations associated with involvement by employing functional magnetic resonance imaging (fMRI). We presented participants information cues for different products and told them that they had to answer questions with respect to these products at the end of the experiment. Participants were free to stop the information search if they think they gathered enough information or to continue with collecting information. Behavioral results confirmed our hypothesis of a relationship between searching behavior and personal involvement by demonstrating that the length of search correlated significantly with the degree of personal involvement of the participants. fMRI data revealed that personal involvement was associated with activation in BA44. Since this brain region is known to be involved in semantic memory, the results of this pilot study suggest that high involvement consumer behavior may be linked to cognitive load and attention towards a product. PMID:25859200

  9. Awareness of Emotional Stimuli Determines the Behavioral Consequences of Amygdala Activation and Amygdala-Prefrontal Connectivity

    Science.gov (United States)

    Lapate, R. C.; Rokers, B.; Tromp, D. P. M.; Orfali, N. S.; Oler, J. A.; Doran, S. T.; Adluru, N.; Alexander, A. L.; Davidson, R. J.

    2016-01-01

    Conscious awareness of negative cues is thought to enhance emotion-regulatory capacity, but the neural mechanisms underlying this effect are unknown. Using continuous flash suppression (CFS) in the MRI scanner, we manipulated visual awareness of fearful faces during an affect misattribution paradigm, in which preferences for neutral objects can be biased by the valence of a previously presented stimulus. The amygdala responded to fearful faces independently of awareness. However, when awareness of fearful faces was prevented, individuals with greater amygdala responses displayed a negative bias toward unrelated novel neutral faces. In contrast, during the aware condition, inverse coupling between the amygdala and prefrontal cortex reduced this bias, particularly among individuals with higher structural connectivity in the major white matter pathway connecting the prefrontal cortex and amygdala. Collectively, these results indicate that awareness promotes the function of a critical emotion-regulatory network targeting the amygdala, providing a mechanistic account for the role of awareness in emotion regulation. PMID:27181344

  10. Headache and Central Positioning Vertigo in a Middle Aged Female-a Case of Solitary Cerebellar Tuberculoma Involving Left Cerebellar Hemisphere

    Directory of Open Access Journals (Sweden)

    Shakya Bhattacharjee

    2012-03-01

    Full Text Available A 48 year old female presented with headache and an illusory sensation of spinning of head in respect to environment for last 8 weeks. Her head spinning or vertigo had no particular direction or not precipitated by any specific head posture. Headache is non- specific in nature and intensified in last few days.Her neurological examination revealed a central positional vertigo with horizontal gaze evoked nystagmus and ataxia. Her MRI scan brain showed the presence of a large solitary ring enhancing lesion in the left cerebellar hemisphere. The lesion was surgically excised and was examined histopathologicaliy that revealed a chronic inflammatory granuloma with caseation necrosis and multinucleated giant cells suggestive of tuberculosis

  11. The amygdala as a neurobiological target for ghrelin in rats: neuroanatomical, electrophysiological and behavioral evidence.

    Directory of Open Access Journals (Sweden)

    Mayte Alvarez-Crespo

    Full Text Available Here, we sought to demonstrate that the orexigenic circulating hormone, ghrelin, is able to exert neurobiological effects (including those linked to feeding control at the level of the amygdala, involving neuroanatomical, electrophysiological and behavioural studies. We found that ghrelin receptors (GHS-R are densely expressed in several subnuclei of the amygdala, notably in ventrolateral (LaVL and ventromedial (LaVM parts of the lateral amygdaloid nucleus. Using whole-cell patch clamp electrophysiology to record from cells in the lateral amygdaloid nucleus, we found that ghrelin reduced the frequency of mEPSCs recorded from large pyramidal-like neurons, an effect that could be blocked by co-application of a ghrelin receptor antagonist. In ad libitum fed rats, intra-amygdala administration of ghrelin produced a large orexigenic response that lasted throughout the 4 hr of testing. Conversely, in hungry, fasted rats ghrelin receptor blockade in the amygdala significantly reduced food intake. Finally, we investigated a possible interaction between ghrelin's effects on feeding control and emotional reactivity exerted at the level of the amygdala. In rats allowed to feed during a 1-hour period between ghrelin injection and anxiety testing (elevated plus maze and open field, intra-amygdala ghrelin had no effect on anxiety-like behavior. By contrast, if the rats were not given access to food during this 1-hour period, a decrease in anxiety-like behavior was observed in both tests. Collectively, these data indicate that the amygdala is a valid target brain area for ghrelin where its neurobiological effects are important for food intake and for the suppression of emotional (anxiety-like behaviors if food is not available.

  12. TOTAL NUMBER, DISTRIBUTION, AND PHENOTYPE OF CELLS EXPRESSING CHONDROITIN SULPHATE PROTEOGLYCANS IN THE NORMAL HUMAN AMYGDALA

    Science.gov (United States)

    Pantazopoulos, Harry; Murray, Elisabeth A.; Berretta, Sabina

    2009-01-01

    Chondroitin sulphate proteoglycans (CSPGs) are a key structural component of the brain extracellular matrix. They are involved in critical neurodevelopmental functions and are one of the main components of pericellular aggregates known as perineuronal nets. As a step toward investigating their functional and pathophysiological roles in the human amygdala, we assessed the pattern of CSPG expression in the normal human amygdala using wisteria floribunda agglutinin (WFA) lectin-histochemistry. Total numbers of WFA-labeled elements were measured in the lateral (LN), basal (BN), accessory basal (ABN) and cortical (CO) nuclei of the amygdala from 15 normal adult human subjects. For interspecies qualitative comparison, we also investigated the pattern of WFA labeling in the amygdala of naïve rats (n=32) and rhesus monkeys (Macaca mulatta; n=6). In human amygdala, WFA lectin-histochemistry resulted in labeling of perineuronal nets and cells with clear glial morphology, while neurons did not show WFA-labeling. Total numbers of WFA-labeled glial cells showed high interindividual variability. These cells aggregated in clusters with a consistent between-subjects spatial distribution. In a subset of human subjects (n=5), dual color fluorescence using an antibody raised against glial fibrillary acidic protein (GFAP) and WFA showed that the majority (93.7%) of WFA-labeled glial cells correspond to astrocytes. In rat and monkey amygdala, WFA histochemistry labeled perineuronal nets, but not glial cells. These results suggest that astrocytes are the main cell type expressing CSPGs in the adult human amygdala. Their highly segregated distribution pattern suggests that these cells serve specialized functions within human amygdalar nuclei. PMID:18374308

  13. Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally.

    Science.gov (United States)

    Barrett, Catherine E; Hennessey, Thomas M; Gordon, Katelyn M; Ryan, Steve J; McNair, Morgan L; Ressler, Kerry J; Rainnie, Donald G

    2017-01-01

    The amygdala controls socioemotional behavior and has consistently been implicated in the etiology of autism spectrum disorder (ASD). Precocious amygdala development is commonly reported in ASD youth with the degree of overgrowth positively correlated to the severity of ASD symptoms. Prenatal exposure to VPA leads to an ASD phenotype in both humans and rats and has become a commonly used tool to model the complexity of ASD symptoms in the laboratory. Here, we examined abnormalities in gene expression in the amygdala and socioemotional behavior across development in the valproic acid (VPA) rat model of ASD. Rat dams received oral gavage of VPA (500 mg/kg) or saline daily between E11 and 13. Socioemotional behavior was tracked across development in both sexes. RNA sequencing and proteomics were performed on amygdala samples from male rats across development. Effects of VPA on time spent in social proximity and anxiety-like behavior were sex dependent, with social abnormalities presenting in males and heightened anxiety in females. Across time VPA stunted developmental and immune, but enhanced cellular death and disorder, pathways in the amygdala relative to saline controls. At postnatal day 10, gene pathways involved in nervous system and cellular development displayed predicted activations in prenatally exposed VPA amygdala samples. By juvenile age, however, transcriptomic and proteomic pathways displayed reductions in cellular growth and neural development. Alterations in immune pathways, calcium signaling, Rho GTPases, and protein kinase A signaling were also observed. As behavioral, developmental, and genomic alterations are similar to those reported in ASD, these results lend support to prenatal exposure to VPA as a useful tool for understanding how developmental insults to molecular pathways in the amygdala give rise to ASD-related syndromes.

  14. Panic Anxiety in Humans with Bilateral Amygdala Lesions: Pharmacological Induction via Cardiorespiratory Interoceptive Pathways.

    Science.gov (United States)

    Khalsa, Sahib S; Feinstein, Justin S; Li, Wei; Feusner, Jamie D; Adolphs, Ralph; Hurlemann, Rene

    2016-03-23

    We previously demonstrated that carbon dioxide inhalation could induce panic anxiety in a group of rare lesion patients with focal bilateral amygdala damage. To further elucidate the amygdala-independent mechanisms leading to aversive emotional experiences, we retested two of these patients (B.G. and A.M.) to examine whether triggering palpitations and dyspnea via stimulation of non-chemosensory interoceptive channels would be sufficient to elicit panic anxiety. Participants rated their affective and sensory experiences following bolus infusions of either isoproterenol, a rapidly acting peripheral β-adrenergic agonist akin to adrenaline, or saline. Infusions were administered during two separate conditions: a panic induction and an assessment of cardiorespiratory interoception. Isoproterenol infusions induced anxiety in both patients, and full-blown panic in one (patient B.G.). Although both patients demonstrated signs of diminished awareness for cardiac sensation, patient A.M., who did not panic, reported a complete lack of awareness for dyspnea, suggestive of impaired respiratory interoception. These findings indicate that the amygdala may play a role in dynamically detecting changes in cardiorespiratory sensation. The induction of panic anxiety provides further evidence that the amygdala is not required for the conscious experience of fear induced via interoceptive sensory channels. We found that monozygotic twins with focal bilateral amygdala lesions report panic anxiety in response to intravenous infusions of isoproterenol, a β-adrenergic agonist similar to adrenaline. Heightened anxiety was evident in both twins, with one twin experiencing a panic attack. The twin who did not panic displayed signs of impaired cardiorespiratory interoception, including a complete absence of dyspnea sensation. These findings highlight that the amygdala is not strictly required for the experience of panic anxiety, and suggest that neural systems beyond the amygdala are also

  15. Trauma exposure relates to heightened stress, altered amygdala morphology and deficient extinction learning: Implications for psychopathology.

    Science.gov (United States)

    Cacciaglia, Raffaele; Nees, Frauke; Grimm, Oliver; Ridder, Stephanie; Pohlack, Sebastian T; Diener, Slawomira J; Liebscher, Claudia; Flor, Herta

    2017-02-01

    Stress exposure causes a structural reorganization in neurons of the amygdala. In particular, animal models have repeatedly shown that both acute and chronic stress induce neuronal hypertrophy and volumetric increase in the lateral and basolateral nuclei of amygdala. These effects are visible on the behavioral level, where stress enhances anxiety behaviors and provokes greater fear learning. We assessed stress and anxiety levels in a group of 18 healthy human trauma-exposed individuals (TR group) compared to 18 non-exposed matched controls (HC group), and related these measurements to amygdala volume. Traumas included unexpected adverse experiences such as vehicle accidents or sudden loss of a loved one. As a measure of aversive learning, we implemented a cued fear conditioning paradigm. Additionally, to provide a biological marker of chronic stress, we measured the sensitivity of the hypothalamus-pituitary-adrenal (HPA) axis using a dexamethasone suppression test. Compared to the HC, the TR group showed significantly higher levels of chronic stress, current stress and trait anxiety, as well as increased volume of the left amygdala. Specifically, we observed a focal enlargement in its lateral portion, in line with previous animal data. Compared to HC, the TR group also showed enhanced late acquisition of conditioned fear and deficient extinction learning, as well as salivary cortisol hypo-suppression to dexamethasone. Left amygdala volumes positively correlated with suppressed morning salivary cortisol. Our results indicate differences in trauma-exposed individuals which resemble those previously reported in animals exposed to stress and in patients with post-traumatic stress disorder and depression. These data provide new insights into the mechanisms through which traumatic stress might prompt vulnerability for psychopathology. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Pattern of distribution of serotonergic fibers to the amygdala and extended amygdala in the rat.

    Science.gov (United States)

    Linley, Stephanie B; Olucha-Bordonau, Francisco; Vertes, Robert P

    2017-01-01

    As is well recognized, serotonergic (5-HT) fibers distribute widely throughout the forebrain, including the amygdala. Although a few reports have examined the 5-HT innervation of select nuclei of the amygdala in the rat, no previous report has described overall 5-HT projections to the amygdala in the rat. Using immunostaining for the serotonin transporter, SERT, we describe the complete pattern of distribution of 5-HT fibers to the amygdala (proper) and to the extended amygdala in the rat. Based on its ontogenetic origins, the amygdala was subdivided into two major parts, pallial and subpallial components, with the pallial component further divided into superficial and deep nuclei (Olucha-Bordonau et al. 2015). SERT + fibers were shown to distributed moderately to densely to the deep and cortical pallial nuclei, but, by contrast, lightly to the subpallial nuclei. Specifically, 1) of the deep pallial nuclei, the lateral, basolateral, and basomedial nuclei contained a very dense concentration of 5-HT fibers; 2) of the cortical pallial nuclei, the anterior cortical and amygdala-cortical transition zone rostrally and the posteromedial and posterolateral nuclei caudally contained a moderate concentration of 5-HT fibers; and 3) of the subpallial nuclei, the anterior nuclei and the rostral part of the medial (Me) nuclei contained a moderate concentration of 5-HT fibers, whereas caudal regions of Me as well as the central nuclei and the intercalated nuclei contained a sparse/light concentration of 5-HT fibers. With regard to the extended amygdala (primarily the bed nucleus of stria terminalis; BST), on the whole, the BST contained moderate numbers of 5-HT fibers, spread fairly uniformly throughout BST. The findings are discussed with respect to a critical serotonergic influence on the amygdala, particularly on the basal complex, and on the extended amygdala in the control of states of fear and anxiety. J. Comp. Neurol. 525:116-139, 2017. © 2016 Wiley Periodicals, Inc.

  17. A study of 1H-MR spectroscopy in the prefrontal cortex and amygdala of heroine abusers

    International Nuclear Information System (INIS)

    Yang Lanying; Wang Yarong; Li Qiang; Xiong Xiaoshuang; Wang Wei; Zhao Wei; Bai Yunliang

    2009-01-01

    Objective: To explore the characteristic findings of 1 H-MR spectroscopy ( 1 H-MRS) in the prefrontal cortex and amygdala of patients with heroine dependence (HD), and the relationship to total cumulative dose of inhaled heroine. Methods: Fourteen male HD patients and 12 healthy controls (HC) underwent 1 H-MRS at the prefrontal cortex and amygdala regions. The total cumulative in haled heroin dose was (852±341) g in HD. Ratios of N-acetylaspartate/creatine(NAA/Cr) and choline/creatine (Cho/Cr) were respectively measured in the prefrontal cortex and bilateral amygdale regions. The student's t test and the linear correlation were employed for statistical analysis. Results: Compared to HC group, HD patients had a significant lower ratio of NAA/Cr in the prefrontal cortex (1.44±0.46 vs 1.50±0.75, t=1.77, P< 0.05), left amygdala region (1.32±0.08 vs 1.42±0.08, t=3.41, P<0.05), and right amygdala region (1.34±0.09 vs 1.44±0.10, t=2.63, P<0.05), the HD patients had a significant increased ratio of Cho/Cr in the prefrontal cortex (0.92±0.06 vs 0.86±0.08, t=2.31, P<0.05), left amygdala region (1.20±0.12 vs 1.07±0.04, t=3.60, P<0.05) and right amygdala region(1.26±0.15 vs 1.12±0.11, t=2.60, P<0.05). There was a negative linear correlation between the total cumulative inhaled heroine dose and the ratio of NAA/Cr in the prefrontal cortex (r=-0.9159, P<0.01), left amygdala region( r= -0.8756, P<0.01), and right amygdala region (r=-0.9399, P<0.01) respectively. Conclusions: The study indicates that neuronal damage and glial proliferation may occur in the prefrontal cortex and amygdala region, which suggests the abnormalities of executive function and emotion in patients with HD. A relationship exists between the heroin-induced metabolic abnormality and the total cumulative dose of inhaled heroine. (authors)

  18. The vomeronasal cortex - afferent and efferent projections of the posteromedial cortical nucleus of the amygdala in mice.

    Science.gov (United States)

    Gutiérrez-Castellanos, Nicolás; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

    2014-01-01

    Most mammals possess a vomeronasal system that detects predominantly chemical signals of biological relevance. Vomeronasal information is relayed to the accessory olfactory bulb (AOB), whose unique cortical target is the posteromedial cortical nucleus of the amygdala. This cortical structure should therefore be considered the primary vomeronasal cortex. In the present work, we describe the afferent and efferent connections of the posteromedial cortical nucleus of the amygdala in female mice, using anterograde (biotinylated dextranamines) and retrograde (Fluorogold) tracers, and zinc selenite as a tracer specific for zinc-enriched (putative glutamatergic) projections. The results show that the posteromedial cortical nucleus of the amygdala is strongly interconnected not only with the rest of the vomeronasal system (AOB and its target structures in the amygdala), but also with the olfactory system (piriform cortex, olfactory-recipient nuclei of the amygdala and entorhinal cortex). Therefore, the posteromedial cortical nucleus of the amygdala probably integrates olfactory and vomeronasal information. In addition, the posteromedial cortical nucleus of the amygdala shows moderate interconnections with the associative (basomedial) amygdala and with the ventral hippocampus, which may be involved in emotional and spatial learning (respectively) induced by chemical signals. Finally, the posteromedial cortical nucleus of the amygdala gives rise to zinc-enriched projections to the ventrolateral septum and the ventromedial striatum (including the medial islands of Calleja). This pattern of intracortical connections (with the olfactory cortex and hippocampus, mainly) and cortico-striatal excitatory projections (with the olfactory tubercle and septum) is consistent with its proposed nature as the primary vomeronasal cortex. © 2013 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  19. Impaired Prefrontal-Amygdala Pathway, Self-Reported Emotion, and Erection in Psychogenic Erectile Dysfunction Patients With Normal Nocturnal Erection

    Directory of Open Access Journals (Sweden)

    Jianhuai Chen

    2018-04-01

    Full Text Available Background: Neuroimaging studies have demonstrated that the prefrontal cortex and amygdala play an important role in sexual arousal (SA. However, little is known about the interactions between the prefrontal and cortex amygdala, which mediate the cognitive regulation of emotion and SA.Objective: We seek to determine whether nocturnal erection of psychogenic erectile dysfunction (pED patients are normal and whether there are changes of topological organization in the prefrontal-amygdala pathway of brain network in pED. In addition, whether there are correlations between network property changes and self-reported emotion and erection.Design, setting, and participants: We used the RigiScan device to evaluate erectile function of patients and employed diffusion MRI and graph theory to construct brain networks of 21 pED patients and 24 healthy controls.Outcome measurements and statistical analysis: We considered four nodal metrics and their asymmetry scores, and nocturnal penile tumescence (NPT parameters, to evaluate the topological properties of brain networks of pED and their relationships with the impaired self-reported emotion and erection.Results and limitations: All the pED patients showed normal nocturnal penile erection, however impaired self-reported erection and negative emotion. In addition, patients showed lower connectivity degree and strength in the left prefrontal-amygdala pathway. We also found that pED exhibited lower leftward asymmetry in the inferior frontal gyrus. Furthermore, patients showed more hub regions and fewer pivotal connections. Moreover, the degree of the left amygdala of pED showed significantly negative correlation with the self-reported erection and positive correlation with the self-reported negative emotion.Conclusions: Together, these results suggest normal nocturnal erection in pED. However, abnormalities of brain network organization in pED, particularly in the left prefrontal-amygdala pathway, are associated

  20. Impaired Prefrontal-Amygdala Pathway, Self-Reported Emotion, and Erection in Psychogenic Erectile Dysfunction Patients With Normal Nocturnal Erection

    Science.gov (United States)

    Chen, Jianhuai; Chen, Yun; Gao, Qingqiang; Chen, Guotao; Dai, Yutian; Yao, Zhijian; Lu, Qing

    2018-01-01

    Background: Neuroimaging studies have demonstrated that the prefrontal cortex and amygdala play an important role in sexual arousal (SA). However, little is known about the interactions between the prefrontal and cortex amygdala, which mediate the cognitive regulation of emotion and SA. Objective: We seek to determine whether nocturnal erection of psychogenic erectile dysfunction (pED) patients are normal and whether there are changes of topological organization in the prefrontal-amygdala pathway of brain network in pED. In addition, whether there are correlations between network property changes and self-reported emotion and erection. Design, setting, and participants: We used the RigiScan device to evaluate erectile function of patients and employed diffusion MRI and graph theory to construct brain networks of 21 pED patients and 24 healthy controls. Outcome measurements and statistical analysis: We considered four nodal metrics and their asymmetry scores, and nocturnal penile tumescence (NPT) parameters, to evaluate the topological properties of brain networks of pED and their relationships with the impaired self-reported emotion and erection. Results and limitations: All the pED patients showed normal nocturnal penile erection, however impaired self-reported erection and negative emotion. In addition, patients showed lower connectivity degree and strength in the left prefrontal-amygdala pathway. We also found that pED exhibited lower leftward asymmetry in the inferior frontal gyrus. Furthermore, patients showed more hub regions and fewer pivotal connections. Moreover, the degree of the left amygdala of pED showed significantly negative correlation with the self-reported erection and positive correlation with the self-reported negative emotion. Conclusions: Together, these results suggest normal nocturnal erection in pED. However, abnormalities of brain network organization in pED, particularly in the left prefrontal-amygdala pathway, are associated with the

  1. Framing effect following bilateral amygdala lesion.

    Science.gov (United States)

    Talmi, Deborah; Hurlemann, René; Patin, Alexandra; Dolan, Raymond J

    2010-05-01

    A paradigmatic example of an emotional bias in decision making is the framing effect, where the manner in which a choice is posed--as a potential loss or a potential gain--systematically biases an ensuing decision. Two fMRI studies have shown that the activation in the amygdala is modulated by the framing effect. Here, contrary to an expectation based on these studies, we show that two patients with Urbach-Wiethe (UW) disease, a rare condition associated with congenital, complete bilateral amygdala degeneration, exhibit an intact framing effect. However, choice preference in these patients did show a qualitatively distinct pattern compared to controls evident in an increased propensity to gamble, indicating that loss of amygdala function does exert an overall influence on risk-taking. These findings suggest either that amygdala does contribute to decision making but does not play a causal role in framing, or that UW is not a pure lesion model of amygdala function. 2010 Elsevier Ltd. All rights reserved.

  2. Stimulus Intensity-dependent Modulations of Hippocampal Long-term Potentiation by Basolateral Amygdala Priming

    Directory of Open Access Journals (Sweden)

    Zexuan eLi

    2012-05-01

    Full Text Available There is growing realization that the relationship between memory and stress/emotionality is complicated, and may include both memory enhancing and memory impairing aspects. It has been suggested that the underlying mechanisms involve amygdalar modulation of hippocampal synaptic plasticity, such as long-term potentiation (LTP. We recently reported that while in CA1 basolateral amygdala (BLA priming impaired theta stimulation induced LTP, it enhanced LTP in the dentate gyrus (DG. However, emotional and stressfull experiences were found to activate synaptic plasticity within the BLA, rasing the possibility that BLA modulation of other brain regions may be altered as well, as it may depend on the way the BLA is activated or is responding. In previous studies BLA priming stimulation was relatively weak (1V, 50 µs pulse duration. In the present study we assessed the effects of two stronger levels of BLA priming stimulation (1V or 2V, 100 µs pulse duration on LTP induction in hippocampal DG and CA1, in anesthetized rats. Results show that 1V-BLA priming stimulation enhanced but 2V-BLA priming stimulation impaired DG LTP; however, both levels of BLA priming stimulation impaired CA1 LTP, suggesting that modulation of hippocampal synaptic plasticity by amygdala is dependent on the degree of amygdala activation. These findings suggest that plasticity induced within the amygdala, by stressful experiences induces a form of metaplasticity that would alter the way the amygdala may modulate memory-related processes in other brain areas, such as the hippocampus.

  3. Fluoxetine pretreatment promotes neuronal survival and maturation after auditory fear conditioning in the rat amygdala.

    Directory of Open Access Journals (Sweden)

    Lizhu Jiang

    Full Text Available The amygdala is a critical brain region for auditory fear conditioning, which is a stressful condition for experimental rats. Adult neurogenesis in the dentate gyrus (DG of the hippocampus, known to be sensitive to behavioral stress and treatment of the antidepressant fluoxetine (FLX, is involved in the formation of hippocampus-dependent memories. Here, we investigated whether neurogenesis also occurs in the amygdala and contributes to auditory fear memory. In rats showing persistent auditory fear memory following fear conditioning, we found that the survival of new-born cells and the number of new-born cells that differentiated into mature neurons labeled by BrdU and NeuN decreased in the amygdala, but the number of cells that developed into astrocytes labeled by BrdU and GFAP increased. Chronic pretreatment with FLX partially rescued the reduction in neurogenesis in the amygdala and slightly suppressed the maintenance of the long-lasting auditory fear memory 30 days after the fear conditioning. The present results suggest that adult neurogenesis in the amygdala is sensitive to antidepressant treatment and may weaken long-lasting auditory fear memory.

  4. Human Neural Stem Cells Overexpressing Choline Acetyltransferase Restore Unconditioned Fear in Rats with Amygdala Injury

    Directory of Open Access Journals (Sweden)

    Kyungha Shin

    2016-01-01

    Full Text Available Amygdala is involved in the fear memory that recognizes certain environmental cues predicting threatening events. Manipulation of neurotransmission within the amygdala affects the expression of conditioned and unconditioned emotional memories such as fear freezing behaviour. We previously demonstrated that F3.ChAT human neural stem cells (NSCs overexpressing choline acetyltransferase (ChAT improve cognitive function of Alzheimer’s disease model rats with hippocampal or cholinergic nerve injuries by increasing acetylcholine (ACh level. In the present study, we examined the effect of F3.ChAT cells on the deficit of unconditioned fear freezing. Rats given N-methyl-d-aspartate (NMDA in their amygdala 2 weeks prior to cat odor exposure displayed very short resting (freezing time compared to normal animals. NMDA induced neuronal degeneration in the amygdala, leading to a decreased ACh concentration in cerebrospinal fluid. However, intracerebroventricular transplantation of F3.ChAT cells attenuated amygdala lesions 4 weeks after transplantation. The transplanted cells were found in the NMDA-injury sites and produced ChAT protein. In addition, F3.ChAT-receiving rats recuperated freezing time staying remote from the cat odor source, according to the recovery of brain ACh concentration. The results indicate that human NSCs overexpressing ChAT may facilitate retrieval of unconditioned fear memory by increasing ACh level.

  5. Implications of newborn amygdala connectivity for fear and cognitive development at 6-months-of-age

    Science.gov (United States)

    Graham, Alice M.; Buss, Claudia; Rasmussen, Jerod M.; Rudolph, Marc D.; Demeter, Damion V.; Gilmore, John H.; Styner, Martin; Entringer, Sonja; Wadhwa, Pathik D.; Fair, Damien A.

    2015-01-01

    The first year of life is an important period for emergence of fear in humans. While animal models have revealed developmental changes in amygdala circuitry accompanying emerging fear, human neural systems involved in early fear development remain poorly understood. To increase understanding of the neural foundations of human fear, it is important to consider parallel cognitive development, which may modulate associations between typical development of early fear and subsequent risk for fear-related psychopathology. We, therefore, examined amygdala functional connectivity with rs-fcMRI in 48 neonates (M=3.65 weeks, SD=1.72), and measured fear and cognitive development at 6-months-of-age. Stronger, positive neonatal amygdala connectivity to several regions, including bilateral anterior insula and ventral striatum, was prospectively associated with higher fear at 6-months. Stronger amygdala connectivity to ventral anterior cingulate/anterior medial prefrontal cortex predicted a specific phenotype of higher fear combined with more advanced cognitive development. Overall, findings demonstrate unique profiles of neonatal amygdala functional connectivity related to emerging fear and cognitive development, which may have implications for normative and pathological fear in later years. Consideration of infant fear in the context of cognitive development will likely contribute to a more nuanced understanding of fear, its neural bases, and its implications for future mental health. PMID:26499255

  6. Enhanced temporal variability of amygdala-frontal functional connectivity in patients with schizophrenia.

    Science.gov (United States)

    Yue, Jing-Li; Li, Peng; Shi, Le; Lin, Xiao; Sun, Hong-Qiang; Lu, Lin

    2018-01-01

    The "dysconnectivity hypothesis" was proposed 20 years ago. It characterized schizophrenia as a disorder with dysfunctional connectivity across a large range of distributed brain areas. Resting-state functional magnetic resonance imaging (rsfMRI) data have supported this theory. Previous studies revealed that the amygdala might be responsible for the emotion regulation-related symptoms of schizophrenia. However, conventional methods oversimplified brain activities by assuming that it remained static throughout the entire scan duration, which may explain why inconsistent results have been reported for the same brain region. An emerging technique is sliding time window analysis, which is used to describe functional connectivity based on the temporal variability of regions of interest (e.g., amygdala) in patients with schizophrenia. Conventional analysis of the static functional connectivity between the amygdala and whole brain was also conducted. Static functional connectivity between the amygdala and orbitofrontal region was impaired in patients with schizophrenia. The variability of connectivity between the amygdala and medial prefrontal cortex was enhanced (i.e., greater dynamics) in patients with schizophrenia. A negative relationship was found between the variability of connectivity and information processing efficiency. A positive correlation was found between the variability of connectivity and symptom severity. The findings suggest that schizophrenia was related to abnormal patterns of fluctuating communication among brain areas that are involved in emotion regulations. Unveiling the temporal properties of functional connectivity could disentangle the inconsistent results of previous functional connectivity studies.

  7. Serca2a and Na(+)/Ca(2+) exchanger are involved in left ventricular function following cardiac remodelling of female rats treated with anabolic androgenic steroid.

    Science.gov (United States)

    Nascimento, Andrews Marques do; Lima, Ewelyne Miranda de; Brasil, Girlandia Alexandre; Caliman, Izabela Facco; Silva, Josiane Fernandes da; Lemos, Virgínia Soares; Andrade, Tadeu Uggere de; Bissoli, Nazaré Souza

    2016-06-15

    Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women. To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats. Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20mg/kg/week for 4weeks); and NDE (trained and treated). The haemodynamic parameters (+dP/dtmax, -dP/dtmin and Tau) were assessed in the left ventricle. The heart was collected for histological analyses and collagen deposition. The gastrocnemius muscle was weighed, and hypertrophy was assessed by the ratio of their weights to gastrocnemius/tibia length. The expression of calcium handling proteins was measured by western blot analysis. ND treatment and physical exercise increased cardiac contractility and relaxation. In addition, ND promoted increases in phospholamban phosphorylated (p-PLB) and isoforms of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, while resistance exercise increased the phosphorylation of PLB and expression of Na(+)/Ca(2+) exchangers (NCX). Cardiac hypertrophy and collagen deposition were observed after ND treatment. Regulatory components of cytosolic calcium, such as SERCA2a and p-PLB, play important roles in modulating the contractility and relaxation effects of ND in females. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. The dosage of the neuroD2 transcription factor regulates amygdala development and emotional learning

    OpenAIRE

    Lin, Chin-Hsing; Hansen, Stacey; Wang, Zhenshan; Storm, Daniel R.; Tapscott, Stephen J.; Olson, James M.

    2005-01-01

    The amygdala is centrally involved in formation of emotional memory and response to fear or risk. We have demonstrated that the lateral and basolateral amygdala nuclei fail to form in neuroD2 null mice and neuroD2 heterozygotes have fewer neurons in this region. NeuroD2 heterozygous mice show profound deficits in emotional learning as assessed by fear conditioning. Unconditioned fear was also diminished in neuroD2 heterozygotes compared to wild-type controls. Several key molecular regulators ...

  9. Amygdala responses to unpleasant pictures are influenced by task demands and positive affect trait

    Directory of Open Access Journals (Sweden)

    Tiago Arruda Sanchez

    2015-03-01

    Full Text Available The role of attention in emotional processing is still the subject of debate. Recent studies have found that high positive affect in approach motivation narrows attention. Furthermore, the positive affect trait has been suggested as an important component for determining human variability in threat reactivity. We employed fMRI to investigate whether different states of attention control would modulate amygdala responses to highly unpleasant pictures relative to neutral and whether this modulation would be influenced by the positive affect trait. Participants (n=22, 12 male were scanned while viewing neutral (people or unpleasant pictures (mutilated bodies flanked by two peripheral bars. They were instructed to (a judge the picture content as unpleasant or neutral or (b to judge the difference in orientation between the bars in an easy condition (0º or 90º orientation difference or (c in a hard condition (0º or 6º orientation difference. Whole brain analysis revealed a task main effect of brain areas related to the experimental manipulation of attentional control, including the amygdala, dorsolateral prefrontal cortex and posterior parietal cortex. ROI analysis showed an inverse correlation (r = -0.51, p < 0.01 between left amygdala activation and positive affect level when participants viewed unpleasant stimuli and judged bar orientation in the easy condition. This result suggests that subjects with high positive affect exhibit lower amygdala reactivity to distracting unpleasant pictures. In conclusion, the current study suggests that positive affect modulates attention effect on unpleasant pictures, therefore attenuating emotional responses.

  10. Blunted amygdala functional connectivity during a stress task in alcohol dependent individuals: A pilot study.

    Science.gov (United States)

    Wade, Natasha E; Padula, Claudia B; Anthenelli, Robert M; Nelson, Erik; Eliassen, James; Lisdahl, Krista M

    2017-12-01

    Scant research has been conducted on neural mechanisms underlying stress processing in individuals with alcohol dependence (AD). We examined neural substrates of stress in AD individuals compared with controls using an fMRI task previously shown to induce stress, assessing amygdala functional connectivity to medial prefrontal cortex (mPFC). For this novel pilot study, 10 abstinent AD individuals and 11 controls completed a modified Trier stress task while undergoing fMRI acquisition. The amygdala was used as a seed region for whole-brain seed-based functional connectivity analysis. After controlling for family-wise error (p = 0.05), there was significantly decreased left and right amygdala connectivity with frontal (specifically mPFC), temporal, parietal, and cerebellar regions. Subjective stress, but not craving, increased from pre-to post-task. This study demonstrated decreased connectivity between the amygdala and regions important for stress and emotional processing in long-term abstinent individuals with AD. These results suggest aberrant stress processing in individuals with AD even after lengthy periods of abstinence.

  11. Emotional arousal impairs association-memory: Roles of amygdala and hippocampus.

    Science.gov (United States)

    Madan, Christopher R; Fujiwara, Esther; Caplan, Jeremy B; Sommer, Tobias

    2017-08-01

    Emotional arousal is well-known to enhance memory for individual items or events, whereas it can impair association memory. The neural mechanism of this association memory impairment by emotion is not known: In response to emotionally arousing information, amygdala activity may interfere with hippocampal associative encoding (e.g., via prefrontal cortex). Alternatively, emotional information may be harder to unitize, resulting in reduced availability of extra-hippocampal medial temporal lobe support for emotional than neutral associations. To test these opposing hypotheses, we compared neural processes underlying successful and unsuccessful encoding of emotional and neutral associations. Participants intentionally studied pairs of neutral and negative pictures (Experiments 1-3). We found reduced association-memory for negative pictures in all experiments, accompanied by item-memory increases in Experiment 2. High-resolution fMRI (Experiment 3) indicated that reductions in associative encoding of emotional information are localizable to an area in ventral-lateral amygdala, driven by attentional/salience effects in the central amygdala. Hippocampal activity was similar during both pair types, but a left hippocampal cluster related to successful encoding was observed only for negative pairs. Extra-hippocampal associative memory processes (e.g., unitization) were more effective for neutral than emotional materials. Our findings suggest that reduced emotional association memory is accompanied by increases in activity and functional coupling within the amygdala. This did not disrupt hippocampal association-memory processes, which indeed were critical for successful emotional association memory formation. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Endocannabinoids in the rat basolateral amygdala enhance memory consolidation and enable glucocorticoid modulation of memory

    NARCIS (Netherlands)

    Campolongo, Patrizia; Roozendaal, Benno; Trezza, Viviana; Hauer, Daniela; Schelling, Gustav; McGaugh, James L.; Cuomo, Vincenzo

    2009-01-01

    Extensive evidence indicates that the basolateral complex of the amygdala (BLA) modulates the consolidation of memories for emotionally arousing experiences, an effect that involves the activation of the glucocorticoid system. Because the BLA expresses high densities of cannabinoid CB1 receptors,

  13. Input from the Medial Geniculate Nucleus Modulates Amygdala Encoding of Fear Memory Discrimination

    Science.gov (United States)

    Ferrara, Nicole C.; Cullen, Patrick K.; Pullins, Shane P.; Rotondo, Elena K.; Helmstetter, Fred J.

    2017-01-01

    Generalization of fear can involve abnormal responding to cues that signal safety and is common in people diagnosed with post-traumatic stress disorder. Differential auditory fear conditioning can be used as a tool to measure changes in fear discrimination and generalization. Most prior work in this area has focused on elevated amygdala activity…

  14. The Amygdala Is Critical for Trace, Delay, and Contextual Fear Conditioning

    Science.gov (United States)

    Kochli, Daniel E.; Thompson, Elaine C.; Fricke, Elizabeth A.; Postle, Abagail F.; Quinn, Jennifer J.

    2015-01-01

    Numerous investigations have definitively shown amygdalar involvement in delay and contextual fear conditioning. However, much less is known about amygdala contributions to trace fear conditioning, and what little evidence exists is conflicting as noted in previous studies. This discrepancy may result from selective targeting of individual nuclei…

  15. Context Fear Learning Specifically Activates Distinct Populations of Neurons in Amygdala and Hypothalamus

    Science.gov (United States)

    Trogrlic, Lidia; Wilson, Yvette M.; Newman, Andrew G.; Murphy, Mark

    2011-01-01

    The identity and distribution of neurons that are involved in any learning or memory event is not known. In previous studies, we identified a discrete population of neurons in the lateral amygdala that show learning-specific activation of a c-"fos"-regulated transgene following context fear conditioning. Here, we have extended these studies to…

  16. A Discrete Population of Neurons in the Lateral Amygdala Is Specifically Activated by Contextual Fear Conditioning

    Science.gov (United States)

    Wilson, Yvette M.; Murphy, Mark

    2009-01-01

    There is no clear identification of the neurons involved in fear conditioning in the amygdala. To search for these neurons, we have used a genetic approach, the "fos-tau-lacZ" (FTL) mouse, to map functionally activated expression in neurons following contextual fear conditioning. We have identified a discrete population of neurons in the lateral…

  17. A Model of Amygdala-Hippocampal-Prefrontal Interaction in Fear Conditioning and Extinction in Animals

    Science.gov (United States)

    Moustafa, Ahmed A.; Gilbertson, Mark W.; Orr, Scott P.; Herzallah, Mohammad M.; Servatius, Richard J.; Myers, Catherine E.

    2013-01-01

    Empirical research has shown that the amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC) are involved in fear conditioning. However, the functional contribution of each brain area and the nature of their interactions are not clearly understood. Here, we extend existing neural network models of the functional roles of the hippocampus…

  18. Adrenal stress hormones, amygdala activation, and memory for emotionally arousing experiences.

    Science.gov (United States)

    Roozendaal, Benno; Barsegyan, Areg; Lee, Sangkwan

    2008-01-01

    Extensive evidence indicates that stress hormones released from the adrenal glands are critically involved in memory consolidation of emotionally arousing experiences. Epinephrine or glucocorticoids administered after exposure to emotionally arousing experiences enhance the consolidation of long-term memories of these experiences. Our findings indicate that adrenal stress hormones influence memory consolidation via interactions with arousal-induced activation of noradrenergic mechanisms within the amygdala. In turn, the amygdala regulates memory consolidation via its efferent projections to many other brain regions. In contrast to the enhancing effects on consolidation, high circulating levels of stress hormones impair memory retrieval and working memory. Such effects also require noradrenergic activation of the amygdala and interactions with other brain regions.

  19. Synchronized Activity in The Main and Accessory Olfactory Bulbs and Vomeronasal Amygdala Elicited by Chemical Signals in Freely Behaving Mice.

    Science.gov (United States)

    Pardo-Bellver, Cecília; Martínez-Bellver, Sergio; Martínez-García, Fernando; Lanuza, Enrique; Teruel-Martí, Vicent

    2017-08-30

    Chemosensory processing in mammals involves the olfactory and vomeronasal systems, but how the activity of both circuits is integrated is unknown. In our study, we recorded the electrophysiological activity in the olfactory bulbs and the vomeronasal amygdala in freely behaving mice exploring a battery of neutral and conspecific stimuli. The exploration of stimuli, including a neutral stimulus, induced synchronic activity in the olfactory bulbs characterized by a dominant theta rhythmicity, with specific theta-gamma coupling, distinguishing between vomeronasal and olfactory structures. The correlated activation of the bulbs suggests a coupling between the stimuli internalization in the nasal cavity and the vomeronasal pumping. In the amygdala, male stimuli are preferentially processed in the medial nucleus, whereas female cues induced a differential response in the posteromedial cortical amygdala. Thus, particular theta-gamma patterns in the olfactory network modulates the integration of chemosensory information in the amygdala, allowing the selection of an appropriate behaviour.

  20. The central amygdala circuits in fear regulation

    Science.gov (United States)

    Li, Bo

    The amygdala is essential for fear learning and expression. The central amygdala (CeA), once viewed as a passive relay between the amygdala complex and downstream fear effectors, has emerged as an active participant in fear conditioning. However, how the CeA contributes to the learning and expression of fear remains unclear. Our recent studies in mice indicate that fear conditioning induces robust plasticity of excitatory synapses onto inhibitory neurons in the lateral subdivision of CeA (CeL). In particular, this plasticity is cell-type specific and is required for the formation of fear memory. In addition, sensory cues that predict threat can cause activation of the somatostatin-positive CeL neurons, which is sufficient to drive freezing behavior. Here I will report our recent findings regarding the circuit and cellular mechanisms underlying CeL function in fear processing.

  1. Reverse redistribution phenomenon on rest 99mTc-tetrofosmin myocardial single photon emission computed tomography involves impaired left ventricular contraction in patients with acute myocardial infarction

    International Nuclear Information System (INIS)

    Kurokawa, Kazuyuki; Ohte, Nobuyuki; Miyabe, Hiromichi; Akita, Sachie; Yajima, Kazuhiro; Hayano, Junichiro; Kimura, Genjiro

    2003-01-01

    The purpose of this study was to investigate the clinical significance of the reverse redistribution (RR) phenomenon on technetium-99m ( 99m Tc)-tetrofosmin myocardial single photon emission computed tomography (SPECT) performed at rest. Twenty-five patients underwent myocardial SPECT 3 weeks after the onset of acute myocardial infarction. Myocardial images were acquired at 40 min (early) and 4 h (delayed) after the injection of 740 MBq of 99m Tc-tetrofosmin. The regional myocardial uptake of the tracer in 26 segments of the left ventricular (LV) wall was visually scored from 0 (no activity) to 3 (normal activity), and then the RR was defined as a decrease of more than 1 point in the activity score on the delayed image compared with that on the early image. Regions with an activity score of 3 on both the early and delayed images were defined as normal, and those with a score of 0 or 1 on the early image were considered to have a fixed defect. The regional myocardial 99m Tc-tetrofosmin uptake and washout rate were also quantitatively assessed in each region. In addition, exercise stress electrocardiograph-gated SPECT with 99m Tc-tetrofosmin was performed within 1 week of the rest study, and the percent count increase (%CI) during myocardial contraction in each corresponding region was studied. RR was observed in 18 of the 25 patients. The regional washout rate of 99m Tc-tetrofosmin was significantly higher in the RR regions (45.0±3.8%) than in either the normal regions (36.4±4.1%, p 99m Tc-tetrofosmin SPECT have severely impaired LV wall contraction after exercise. (author)

  2. Serca2a and Na+/Ca2+ exchanger are involved in left ventricular function following cardiac remodelling of female rats treated with anabolic androgenic steroid

    International Nuclear Information System (INIS)

    Nascimento, Andrews Marques do; Lima, Ewelyne Miranda de; Brasil, Girlandia Alexandre; Caliman, Izabela Facco; Silva, Josiane Fernandes da; Lemos, Virgínia Soares; Andrade, Tadeu Uggere de; Bissoli, Nazaré Souza

    2016-01-01

    Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women. Aim: To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats. Main methods: Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20 mg/kg/week for 4 weeks); and NDE (trained and treated). The haemodynamic parameters (+ dP/dt max , − dP/dt min and Tau) were assessed in the left ventricle. The heart was collected for histological analyses and collagen deposition. The gastrocnemius muscle was weighed, and hypertrophy was assessed by the ratio of their weights to gastrocnemius/tibia length. The expression of calcium handling proteins was measured by western blot analysis. Results: ND treatment and physical exercise increased cardiac contractility and relaxation. In addition, ND promoted increases in phospholamban phosphorylated (p-PLB) and isoforms of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, while resistance exercise increased the phosphorylation of PLB and expression of Na + /Ca 2+ exchangers (NCX). Cardiac hypertrophy and collagen deposition were observed after ND treatment. Conclusion: Regulatory components of cytosolic calcium, such as SERCA2a and p-PLB, play important roles in modulating the contractility and relaxation effects of ND in females. - Highlights: • ND and resistive exercise enhanced the cardiac function and increased expression of cytosolic calcium regulatory components.

  3. The amygdala complex: multiple roles in associative learning and attention.

    OpenAIRE

    Gallagher, M; Holland, P C

    1994-01-01

    Although certain neurophysiological functions of the amygdala complex in learning seem well established, the purpose of this review is to propose that an additional conceptualization of amygdala function is now needed. The research we review provides evidence that a subsystem within the amygdala provides a coordinated regulation of attentional processes. An important aspect of this additional neuropsychology of the amygdala is that it may aid in understanding the importance of connections bet...

  4. Facilitation of Contextual Fear Extinction by Orexin-1 Receptor Antagonism Is Associated with the Activation of Specific Amygdala Cell Subpopulations.

    Science.gov (United States)

    Flores, África; Herry, Cyril; Maldonado, Rafael; Berrendero, Fernando

    2017-08-01

    Orexins are hypothalamic neuropeptides recently involved in the regulation of emotional memory. The basolateral amygdala, an area orchestrating fear memory processes, appears to be modulated by orexin transmission during fear extinction. However, the neuronal types within the basolateral amygdala involved in this modulation remain to be elucidated. We used retrograde tracing combined with immunofluorescence techniques in mice to identify basolateral amygdala projection neurons and cell subpopulations in this brain region influenced by orexin transmission during contextual fear extinction consolidation. Treatment with the orexin-1 receptor antagonist SB334867 increased the activity of basolateral amygdala neurons projecting to infralimbic medial prefrontal cortex during fear extinction. GABAergic interneurons expressing calbindin, but not parvalbumin, were also activated by orexin-1 receptor antagonism in the basolateral amygdala. These data identify neuronal circuits and cell populations of the amygdala associated with the facilitation of fear extinction consolidation induced by the orexin-1 receptor antagonist SB334867. © The Author 2017. Published by Oxford University Press on behalf of CINP.

  5. Self-Regulation of Amygdala Activation Using Real-Time fMRI Neurofeedback

    Science.gov (United States)

    Phillips, Raquel; Alvarez, Ruben P.; Simmons, W. Kyle; Bellgowan, Patrick; Drevets, Wayne C.; Bodurka, Jerzy

    2011-01-01

    Real-time functional magnetic resonance imaging (rtfMRI) with neurofeedback allows investigation of human brain neuroplastic changes that arise as subjects learn to modulate neurophysiological function using real-time feedback regarding their own hemodynamic responses to stimuli. We investigated the feasibility of training healthy humans to self-regulate the hemodynamic activity of the amygdala, which plays major roles in emotional processing. Participants in the experimental group were provided with ongoing information about the blood oxygen level dependent (BOLD) activity in the left amygdala (LA) and were instructed to raise the BOLD rtfMRI signal by contemplating positive autobiographical memories. A control group was assigned the same task but was instead provided with sham feedback from the left horizontal segment of the intraparietal sulcus (HIPS) region. In the LA, we found a significant BOLD signal increase due to rtfMRI neurofeedback training in the experimental group versus the control group. This effect persisted during the Transfer run without neurofeedback. For the individual subjects in the experimental group the training effect on the LA BOLD activity correlated inversely with scores on the Difficulty Identifying Feelings subscale of the Toronto Alexithymia Scale. The whole brain data analysis revealed significant differences for Happy Memories versus Rest condition between the experimental and control groups. Functional connectivity analysis of the amygdala network revealed significant widespread correlations in a fronto-temporo-limbic network. Additionally, we identified six regions — right medial frontal polar cortex, bilateral dorsomedial prefrontal cortex, left anterior cingulate cortex, and bilateral superior frontal gyrus — where the functional connectivity with the LA increased significantly across the rtfMRI neurofeedback runs and the Transfer run. The findings demonstrate that healthy subjects can learn to regulate their amygdala

  6. False memory for face in short-term memory and neural activity in human amygdala.

    Science.gov (United States)

    Iidaka, Tetsuya; Harada, Tokiko; Sadato, Norihiro

    2014-12-03

    Human memory is often inaccurate. Similar to words and figures, new faces are often recognized as seen or studied items in long- and short-term memory tests; however, the neural mechanisms underlying this false memory remain elusive. In a previous fMRI study using morphed faces and a standard false memory paradigm, we found that there was a U-shaped response curve of the amygdala to old, new, and lure items. This indicates that the amygdala is more active in response to items that are salient (hit and correct rejection) compared to items that are less salient (false alarm), in terms of memory retrieval. In the present fMRI study, we determined whether the false memory for faces occurs within the short-term memory range (a few seconds), and assessed which neural correlates are involved in veridical and illusory memories. Nineteen healthy participants were scanned by 3T MRI during a short-term memory task using morphed faces. The behavioral results indicated that the occurrence of false memories was within the short-term range. We found that the amygdala displayed a U-shaped response curve to memory items, similar to those observed in our previous study. These results suggest that the amygdala plays a common role in both long- and short-term false memory for faces. We made the following conclusions: First, the amygdala is involved in detecting the saliency of items, in addition to fear, and supports goal-oriented behavior by modulating memory. Second, amygdala activity and response time might be related with a subject's response criterion for similar faces. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Function of the centromedial amygdala in reward devaluation and open-field activity.

    Science.gov (United States)

    Kawasaki, K; Glueck, A C; Annicchiarico, I; Papini, M R

    2015-09-10

    The present research aimed at determining the role played by the amygdala in reward devaluation using transient inactivation induced by lidocaine microinfusions into the centromedial region. Two situations involving reward devaluation were tested in rats: consummatory successive negative contrast (cSNC) and anticipatory negative contrast (ANC). In cSNC, rats exposed to a downshift from 32% to 4% sucrose consume less 4% sucrose than rats always exposed to 4% sucrose. Extensive evidence suggests that reward devaluation in the cSNC situation is accompanied by negative emotion. In ANC, rats consume less 4% sucrose when each session is closely followed by access to 32% sucrose rather than by 4% sucrose. Evidence suggests that reward devaluation in the ANC situation does not involve negative emotions; rather, ANC appears to involve Pavlovian anticipation of the higher value solution. To test the effects of lidocaine microinfusions in a situation known to induce negative emotion, but unrelated to reward devaluation, animals were also exposed to a lighted open field. Centromedial amygdala inactivation reduced the cSNC effect and increased exploratory behavior in the open field, both effects consistent with a reduction in negative emotional state. However, no detectable effects of amygdala inactivation were observed in the ANC situation. These results suggest that, first, the function of the amygdala is not unique to reward devaluation and, second, it is concerned with tagging the devaluation experience with aversive valence. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. Amygdala habituation to emotional faces in adolescents with internalizing disorders, adolescents with childhood sexual abuse related PTSD and healthy adolescents

    Directory of Open Access Journals (Sweden)

    Bianca G. van den Bulk

    2016-10-01

    Full Text Available Adolescents with internalizing disorders and adolescents with childhood sexual abuse related post-traumatic stress disorder (CSA-related PTSD show a large overlap in symptomatology. In addition, brain research indicated hyper-responsiveness and sustained activation instead of habituation of amygdala activation to emotional faces in both groups. Little is known, however, about whether the same patterns of amygdala habituation are present in these two groups. The current study examined habituation patterns of amygdala activity to emotional faces (fearful, happy and neutral in adolescents with a DSM-IV depressive and/or anxiety disorder (N = 25, adolescents with CSA-related PTSD (N = 19 and healthy controls (N = 26. Behaviourally, the adolescents from the internalizing and CSA-related PTSD group reported more anxiety to fearful and neutral faces than adolescents from the control group and adolescents from the CSA-related PTSD group reacted slower compared to the internalizing group. At the whole brain level, there was a significant interaction between time and group within the left amygdala. Follow-up ROI analysis showed elevated initial activity in the amygdala and rapid habituation in the CSA-related PTSD group compared to the internalizing group. These findings suggest that habituation patterns of amygdala activation provide additional information on problems with emotional face processing. Furthermore, the results suggest there are differences in the underlying neurobiological mechanisms related to emotional face processing for adolescents with internalizing disorders and adolescents with CSA-related PTSD. Possibly CSA-related PTSD is characterized by a stronger primary emotional response driven by the amygdala.

  9. Amygdala habituation to emotional faces in adolescents with internalizing disorders, adolescents with childhood sexual abuse related PTSD and healthy adolescents.

    Science.gov (United States)

    van den Bulk, Bianca G; Somerville, Leah H; van Hoof, Marie-José; van Lang, Natasja D J; van der Wee, Nic J A; Crone, Eveline A; Vermeiren, Robert R J M

    2016-10-01

    Adolescents with internalizing disorders and adolescents with childhood sexual abuse related post-traumatic stress disorder (CSA-related PTSD) show a large overlap in symptomatology. In addition, brain research indicated hyper-responsiveness and sustained activation instead of habituation of amygdala activation to emotional faces in both groups. Little is known, however, about whether the same patterns of amygdala habituation are present in these two groups. The current study examined habituation patterns of amygdala activity to emotional faces (fearful, happy and neutral) in adolescents with a DSM-IV depressive and/or anxiety disorder (N=25), adolescents with CSA-related PTSD (N=19) and healthy controls (N=26). Behaviourally, the adolescents from the internalizing and CSA-related PTSD group reported more anxiety to fearful and neutral faces than adolescents from the control group and adolescents from the CSA-related PTSD group reacted slower compared to the internalizing group. At the whole brain level, there was a significant interaction between time and group within the left amygdala. Follow-up ROI analysis showed elevated initial activity in the amygdala and rapid habituation in the CSA-related PTSD group compared to the internalizing group. These findings suggest that habituation patterns of amygdala activation provide additional information on problems with emotional face processing. Furthermore, the results suggest there are differences in the underlying neurobiological mechanisms related to emotional face processing for adolescents with internalizing disorders and adolescents with CSA-related PTSD. Possibly CSA-related PTSD is characterized by a stronger primary emotional response driven by the amygdala. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Prefrontal control of the amygdala during real-time fMRI neurofeedback training of emotion regulation.

    Directory of Open Access Journals (Sweden)

    Vadim Zotev

    Full Text Available We observed in a previous study (PLoS ONE 6:e24522 that the self-regulation of amygdala activity via real-time fMRI neurofeedback (rtfMRI-nf with positive emotion induction was associated, in healthy participants, with an enhancement in the functional connectivity between the left amygdala (LA and six regions of the prefrontal cortex. These regions included the left rostral anterior cingulate cortex (rACC, bilateral dorsomedial prefrontal cortex (DMPFC, bilateral superior frontal gyrus (SFG, and right medial frontopolar cortex (MFPC. Together with the LA, these six prefrontal regions thus formed the functional neuroanatomical network engaged during the rtfMRI-nf procedure. Here we perform a structural vector autoregression (SVAR analysis of the effective connectivity for this network. The SVAR analysis demonstrates that the left rACC plays an important role during the rtfMRI-nf training, modulating the LA and the other network regions. According to the analysis, the rtfMRI-nf training leads to a significant enhancement in the time-lagged effect of the left rACC on the LA, potentially consistent with the ipsilateral distribution of the monosynaptic projections between these regions. The training is also accompanied by significant increases in the instantaneous (contemporaneous effects of the left rACC on four other regions - the bilateral DMPFC, the right MFPC, and the left SFG. The instantaneous effects of the LA on the bilateral DMPFC are also significantly enhanced. Our results are consistent with a broad literature supporting the role of the rACC in emotion processing and regulation. Our exploratory analysis provides, for the first time, insights into the causal relationships within the network of regions engaged during the rtfMRI-nf procedure targeting the amygdala. It suggests that the rACC may constitute a promising target for rtfMRI-nf training along with the amygdala in patients with affective disorders, particularly posttraumatic stress

  11. Hippocampus and amygdala volumes in parents of children with autistic disorder.

    Science.gov (United States)

    Rojas, Donald C; Smith, J Allegra; Benkers, Tara L; Camou, Suzanne L; Reite, Martin L; Rogers, Sally J

    2004-11-01

    Structural and functional abnormalities in the medial temporal lobe, particularly the hippocampus and amygdala, have been described in people with autism. The authors hypothesized that parents of children with a diagnosis of autistic disorder would show similar changes in these structures. Magnetic resonance imaging scans were performed in 17 biological parents of children with a diagnosis of DSM-IV autistic disorder. The scans were compared with scans from 15 adults with autistic disorder and 17 age-matched comparison subjects with no personal or familial history of autism. The volumes of the hippocampus, amygdala, and total brain were measured in all participants. The volume of the left hippocampus was larger in both the parents of children with autistic disorder and the adults with autistic disorder, relative to the comparison subjects. The hippocampus was significantly larger in the adults with autistic disorder than in the parents of children with autistic disorder. The left amygdala was smaller in the adults with autistic disorder, relative to the other two groups. No differences in total brain volume were observed between the three groups. The finding of larger hippocampal volume in autism is suggestive of abnormal early neurodevelopmental processes but is partly consistent with only one prior study and contradicts the findings of several others. The finding of larger hippocampal volume for the parental group suggests a potential genetic basis for hippocampal abnormalities in autism.

  12. Extending the amygdala in theories of threat processing

    Science.gov (United States)

    Fox, Andrew S.; Oler, Jonathan A.; Tromp, Do P.M.; Fudge, Julie L.; Kalin, Ned H.

    2015-01-01

    The central extended amygdala is an evolutionarily conserved set of interconnected brain regions that play an important role in threat processing to promote survival. Two core components of the central extended amygdala, the central nucleus of the amygdala (Ce) and the lateral bed nucleus of the stria terminalis (BST) are highly similar regions that serve complimentary roles by integrating fear- and anxiety-relevant information. Survival depends on the central extended amygdala's ability to rapidly integrate and respond to threats that vary in their immediacy, proximity, and characteristics. Future studies will benefit from understanding alterations in central extended amygdala function in relation to stress-related psychopathology. PMID:25851307

  13. Noradrenergic enhancement of amygdala responses to fear

    NARCIS (Netherlands)

    Onur, Oezguer A; Walter, Henrik; Schlaepfer, Thomas E; Rehme, Anne K; Schmidt, Christoph; Keysers, Christian; Maier, Wolfgang; Hurlemann, René

    Multiple lines of evidence implicate the basolateral amygdala (BLA) and the noradrenergic (norepinephrine, NE) system in responding to stressful stimuli such as fear signals, suggesting hyperfunction of both in the development of stress-related pathologies including anxiety disorders. However, no

  14. Contribution of amygdala CRF neurons to chronic pain.

    Science.gov (United States)

    Andreoli, Matthew; Marketkar, Tanvi; Dimitrov, Eugene

    2017-12-01

    We investigated the role of amygdala corticotropin-releasing factor (CRF) neurons in the perturbations of descending pain inhibition caused by neuropathic pain. Forced swim increased the tail-flick response latency in uninjured mice, a phenomenon known as stress-induced analgesia (SIA) but did not change the tail-flick response latency in mice with neuropathic pain caused by sciatic nerve constriction. Neuropathic pain also increased the expression of CRF in the central amygdala (CeAmy) and ΔFosB in the dorsal horn of the spinal cord. Next, we injected the CeAmy of CRF-cre mice with cre activated AAV-DREADD (Designer Receptors Exclusively Activated by Designer Drugs) vectors. Activation of CRF neurons by DREADD/Gq did not affect the impaired SIA but inhibition of CRF neurons by DREADD/Gi restored SIA and decreased allodynia in mice with neuropathic pain. The possible downstream circuitry involved in the regulation of SIA was investigated by combined injections of retrograde cre-virus (CAV2-cre) into the locus ceruleus (LC) and cre activated AAV-diphtheria toxin (AAV-FLEX-DTX) virus into the CeAmy. The viral injections were followed by a sciatic nerve constriction ipsilateral or contralateral to the injections. Ablation of amygdala projections to the LC on the side of injury but not on the opposite side, completely restored SIA, decreased allodynia and decreased ΔFosB expression in the spinal cord in mice with neuropathic pain. The possible lateralization of SIA impairment to the side of injury was confirmed by an experiment in which unilateral inhibition of the LC decreased SIA even in uninjured mice. The current view in the field of pain research attributes the process of pain chronification to abnormal functioning of descending pain inhibition. Our results demonstrate that the continuous activity of CRF neurons brought about by persistent pain leads to impaired SIA, which is a symptom of dysregulation of descending pain inhibition. Therefore, an over

  15. A model of amygdala-hippocampal-prefrontal interaction in fear conditioning and extinction in animals

    Science.gov (United States)

    Moustafa, Ahmed A.; Gilbertson, Mark W.; Orr, Scott P.; Herzallah, Mohammad M.; Servatius, Richard. J.; Myers, Catherine E.

    2012-01-01

    Empirical research has shown that the amygdala, hippocampus, and ventromedial prefrontal cortex (vmPFC) are involved in fear conditioning. However, the functional contribution of each brain area and the nature of their interactions are not clearly understood. Here, we extend existing neural network models of the functional roles of the hippocampus in classical conditioning to include interactions with the amygdala and prefrontal cortex. We apply the model to fear conditioning, in which animals learn physiological (e.g. heart rate) and behavioral (e.g. freezing) responses to stimuli that have been paired with a highly aversive event (e.g. electrical shock). The key feature of our model is that learning of these conditioned responses in the central nucleus of the amygdala is modulated by two separate processes, one from basolateral amygdala and signaling a positive prediction error, and one from the vmPFC, via the intercalated cells of the amygdala, and signaling a negative prediction error. In addition, we propose that hippocampal input to both vmPFC and basolateral amygdala is essential for contextual modulation of fear acquisition and extinction. The model is sufficient to account for a body of data from various animal fear conditioning paradigms, including acquisition, extinction, reacquisition, and context specificity effects. Consistent with studies on lesioned animals, our model shows that damage to the vmPFC impairs extinction, while damage to the hippocampus impairs extinction in a different context (e.g., a different conditioning chamber from that used in initial training in animal experiments). We also discuss model limitations and predictions, including the effects of number of training trials on fear conditioning. PMID:23164732

  16. Afferent and Efferent Connections of the Cortex-Amygdala Transition Zone in Mice.

    Science.gov (United States)

    Cádiz-Moretti, Bernardita; Abellán-Álvaro, María; Pardo-Bellver, Cecília; Martínez-García, Fernando; Lanuza, Enrique

    2016-01-01

    The transitional zone between the ventral part of the piriform cortex and the anterior cortical nucleus of the amygdala, named the cortex-amygdala transition zone (CxA), shows two differential features that allow its identification as a particular structure. First, it receives dense cholinergic and dopaminergic innervations as compared to the adjacent piriform cortex and amygdala, and second, it receives projections from the main and accessory olfactory bulbs. In this work we have studied the pattern of afferent and efferent projections of the CxA, which are mainly unknown, by using the retrograde tracer Fluorogold and the anterograde tracer biotinylated dextranamine. The results show that the CxA receives a relatively restricted set of intratelencephalic connections, originated mainly by the olfactory system and basal forebrain, with minor afferents from the amygdala. The only relevant extratelencephalic afference originates in the ventral tegmental area (VTA). The efferent projections of the CxA reciprocate the inputs from the piriform cortex and olfactory amygdala. In addition, the CxA projects densely to the basolateral amygdaloid nucleus and the olfactory tubercle. The extratelencephalic projections of the CxA are very scarce, and target mainly hypothalamic structures. The pattern of connections of the CxA suggests that it is indeed a transitional area between the piriform cortex and the cortical amygdala. Double labeling with choline acetyltransferase indicates that the afferent projection from the basal forebrain is the origin of its distinctive cholinergic innervation, and double labeling with dopamine transporter shows that the projection from the VTA is the source of dopaminergic innervation. These connectivity and neurochemical features, together with the fact that it receives vomeronasal in addition to olfactory information, suggest that the CxA may be involved in processing olfactory information endowed with relevant biological meaning, such as odors

  17. Nesfatin-1/NUCB2 in the amygdala influences visceral sensitivity via glucocorticoid and mineralocorticoid receptors in male maternal separation rats.

    Science.gov (United States)

    Zhou, X-P; Sha, J; Huang, L; Li, T-N; Zhang, R-R; Tang, M-D; Lin, L; Li, X-L

    2016-10-01

    Nesfatin-1, a recently identified satiety molecule derived from nucleobindin 2 (NUCB2), is associated with visceral hypersensitivity in rats and is expressed in the amygdala. We tested the hypothesis that nesfatin-1 expression in the amygdala is involved in the pathogenesis of irritable bowel syndrome (IBS) visceral hypersensitivity. An animal model of IBS-like visceral hypersensitivity was established using maternal separation (MS) during postnatal days 2-16. The role of nesfatin-1 in the amygdala on visceral sensitivity was evaluated. Rats subjected to MS showed a significantly increased mean abdominal withdrawal reflex (AWR) score and electromyographic (EMG) activity at 40, 60, and 80 mmHg colorectal distension. Plasma concentrations of nesfatin-1 and corticosterone were significantly higher than in non-handled (NH) rats. mRNA and protein expression of nesfatin-1/NUCB2 in the amygdala were increased in MS rats, but not in NH rats. In MS rats, AWR scores and EMG activity were significantly decreased after anti-nesfatin-1/NUCB2 injection. In normal rats, mean AWR score, EMG activity, and corticosterone expression were significantly increased after nesfatin-1 injection into the amygdala. Nesfatin-1-induced visceral hypersensitivity was abolished following application of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) antagonists. Elevated expression of nesfatin-1/NUCB2 in the amygdala in MS rats suggests a potential role in the pathogenesis of visceral hypersensitivity, which could potentially take place via activation of GR and MR signaling pathways. © 2016 John Wiley & Sons Ltd.

  18. Pulvinar projections to the striatum and amygdala

    Directory of Open Access Journals (Sweden)

    Jonathan D Day-Brown

    2010-11-01

    Full Text Available Visually-guided movement is possible in the absence of conscious visual perception, a phenomenon referred to as blindsight. Similarly, fearful images can elicit emotional responses in the absence of their conscious perception. Both capabilities are thought to be mediated by pathways from the retina through the superior colliculus (SC and pulvinar nucleus. To define potential pathways that underlie behavioral responses to unperceived visual stimuli, we examined the projections from the pulvinar nucleus to the striatum and amygdala in the tree shrew (Tupaia belangeri, a species considered to be a protypical primate. The tree shrew brain has a large pulvinar nucleus that contains two SC-recipient subdivisions; the dorsal (Pd and central (Pc pulvinar both receive topographic (specific projections from SC, and Pd receives an additional nontopographic (diffuse projection from SC (Chomsung et al., 2008; JCN 510:24-46. Anterograde and retrograde tract tracing revealed that both Pd and Pc project to the caudate and putamen, and Pd, but not Pc, additionally projects to the lateral amygdala. Using immunocytochemical staining for substance P (SP and parvalbumin (PV to reveal the patch/matrix organization of tree shrew striatum, we found that SP-rich/PV-poor patches interlock with a PV-rich/SP-poor matrix. Confocal microscopy revealed that tracer-labeled pulvinostriatal terminals preferentially innervate the matrix. Electron microscopy revealed that the postsynaptic targets of tracer-labeled pulvino-striatal and pulvino-amygdala terminals are spines, demonstrating that the pulvinar nucleus projects to the spiny output cells of the striatum matrix and the lateral amygdala, potentially relaying: 1 topographic visual information from SC to striatum to aid in guiding precise movements, and 2 nontopographic visual information from SC to the amygdala alerting the animal to potentially dangerous visual images.

  19. Posttraumatic stress and alcohol use among veterans: Amygdala and anterior cingulate activation to emotional cues.

    Science.gov (United States)

    Simons, Raluca M; Simons, Jeffrey S; Olson, Dawne; Baugh, Lee; Magnotta, Vincent; Forster, Gina

    2016-11-01

    This fMRI study tested a model of combat trauma, posttraumatic stress symptoms (PTSS), alcohol use, and behavioral and neural responses to emotional cues in 100 OIF/OEF/OND veterans. Multilevel structural equation models were tested for left and right dorsal ACC (dACC), rostral ACC (rACC), and amygdala blood-oxygen- level dependent responses during the emotional counting Stroop test and masked faces task. In the Stroop task, combat exposure moderated the effect of combat stimuli resulting in hyperactivation in the rACC and dACC. Activation in the left amygdala also increased in response to combat stimuli, but effects did not vary as a function of combat severity. In the masked faces task, activation patterns did not vary as a function of stimulus. However, at the between-person level, amygdala activation during the masked faces task was inversely associated with PTSS. In respect to behavioral outcomes, higher PTSS were associated with a stronger Stroop effect, suggesting greater interference associated with combat words. Results are consistent with the premise that combat trauma results in hyperactivation in the ACC in response to combat stimuli, and, via its effect on PTSS, is associated with deficits in cognitive performance in the presence of combat stimuli. Across tasks, predeployment drinking was inversely associated with activation in the dACC but not the rACC or amygdala. Drinking may be a buffering factor, or negatively reinforcing in part because of its effects on normalizing brain response following trauma exposure. Alternatively, drinking may undermine adaptive functioning of the dACC when responding to traumatic stress cues. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  20. Beyond the Classic VTA: Extended Amygdala Projections to DA-Striatal Paths in the Primate.

    Science.gov (United States)

    Fudge, Julie L; Kelly, Emily A; Pal, Ria; Bedont, Joseph L; Park, Lydia; Ho, Brian

    2017-07-01

    The central extended amygdala (CEA) has been conceptualized as a 'macrosystem' that regulates various stress-induced behaviors. Consistent with this, the CEA highly expresses corticotropin-releasing factor (CRF), an important modulator of stress responses. Stress alters goal-directed responses associated with striatal paths, including maladaptive responses such as drug seeking, social withdrawal, and compulsive behavior. CEA inputs to the midbrain dopamine (DA) system are positioned to influence striatal functions through mesolimbic DA-striatal pathways. However, the structure of this amygdala-CEA-DA neuron path to the striatum has been poorly characterized in primates. In primates, we combined neuronal tracer injections into various arms of the circuit through specific DA subpopulations to assess: (1) whether the circuit connecting amygdala, CEA, and DA cells follows CEA intrinsic organization, or a more direct topography involving bed nucleus vs central nucleus divisions; (2) CRF content of the CEA-DA path; and (3) striatal subregions specifically involved in CEA-DA-striatal loops. We found that the amygdala-CEA-DA path follows macrostructural subdivisions, with the majority of input/outputs converging in the medial central nucleus, the sublenticular extended amygdala, and the posterior lateral bed nucleus of the stria terminalis. The proportion of CRF+ outputs is >50%, and mainly targets the A10 parabrachial pigmented nucleus (PBP) and A8 (retrorubal field, RRF) neuronal subpopulations, with additional inputs to the dorsal A9 neurons. CRF-enriched CEA-DA projections are positioned to influence outputs to the 'limbic-associative' striatum, which is distinct from striatal regions targeted by DA cells lacking CEA input. We conclude that the concept of the CEA is supported on connectional grounds, and that CEA termination over the PBP and RRF neuronal populations can influence striatal circuits involved in associative learning.

  1. Amygdala-prefrontal cortex resting-state functional connectivity varies with first depressive or manic episode in bipolar disorder.

    Science.gov (United States)

    Wei, Shengnan; Geng, Haiyang; Jiang, Xiaowei; Zhou, Qian; Chang, Miao; Zhou, Yifang; Xu, Ke; Tang, Yanqing; Wang, Fei

    2017-02-22

    Bipolar disorder (BD) is one of the most complex mental illnesses, characterized by interactive depressive and manic states that are 2 contrary symptoms of disease states. The bilateral amygdala and prefrontal cortex (PFC) appear to play critical roles in BD; however, abnormalities seem to manifest differently in the 2 states and may provide further insight into underlying mechanisms. Sixteen participants with first-episode depressive and 13 participants with first-episode manic states of bipolar disorder as well as 30 healthy control (HC) participants underwent resting-state functional magnetic resonance imaging (fMRI). Resting-state functional connectivity (rsFC) between the bilateral amygdala and PFC was compared among the 3 groups. Compared with depressive state participants of the BD group, manic state participants of the BD group showed a significant decrease in rsFC between the amygdala and right orbital frontal cortex (pamygdala and left middle frontal cortex was significantly decreased in depressive and manic state participants of the BD group when compared with the HC group (pamygdala- left PFC functional connectivity might present the trait feature for BD, while deficits in amygdala- right PFC functional connectivity might be specific to manic episode, compared to depressive episode. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Amygdala modulation of memory-related processes in the hippocampus: potential relevance to PTSD.

    Science.gov (United States)

    Tsoory, M M; Vouimba, R M; Akirav, I; Kavushansky, A; Avital, A; Richter-Levin, G

    2008-01-01

    A key assumption in the study of stress-induced cognitive and neurobiological modifications is that alterations in hippocampal functioning after stress are due to an excessive activity exerted by the amygdala on the hippocampus. Research so far focused on stress-induced impairment of hippocampal plasticity and memory but an exposure to stress may simultaneously also result in strong emotional memories. In fact, under normal conditions emotionally charged events are better remembered compared with neutral ones. Results indicate that under these conditions there is an increase in activity within the amygdala that may lead to memory of a different quality. Studying the way emotionality activates the amygdala and the functional impact of this activation we found that the amygdala modulates memory-related processes in other brain areas, such as the hippocampus. However, this modulation is complex, involving both enhancing and suppressing effects, depending on the way the amygdala is activated and the hippocampal subregion examined. The current review summarizes our findings and attempts to put them in context with the impact of an exposure to a traumatic experience, in which there is a mixture of a strong memory of some aspects of the experience but impaired memory of other aspects of that experience. Toward that end, we have recently developed an animal model for the induction of predisposition to stress-related disorders, focusing on the consequences of exposure to stressors during juvenility on the ability to cope with stress in adulthood. Exposing juvenile-stressed rats to an additional stressful challenge in adulthood revealed their impairment to cope with stress and resulted in significant elevation of the amygdala. Interestingly, and similar to our electrophysiological findings, differential effects were observed between the impact of the emotional challenge on CA1 and dentate gyrus subregions of the hippocampus. Taken together, the results indicate that long

  3. Amygdala EphB2 Signaling Regulates Glutamatergic Neuron Maturation and Innate Fear.

    Science.gov (United States)

    Zhu, Xiao-Na; Liu, Xian-Dong; Zhuang, Hanyi; Henkemeyer, Mark; Yang, Jing-Yu; Xu, Nan-Jie

    2016-09-28

    The amygdala serves as emotional center to mediate innate fear behaviors that are reflected through neuronal responses to environmental aversive cues. However, the molecular mechanism underlying the initial neuron responses is poorly understood. In this study, we monitored the innate defensive responses to aversive stimuli of either elevated plus maze or predator odor in juvenile mice and found that glutamatergic neurons were activated in amygdala. Loss of EphB2, a receptor tyrosine kinase expressed in amygdala neurons, suppressed the reactions and led to defects in spine morphogenesis and fear behaviors. We further found a coupling of spinogenesis with these threat cues induced neuron activation in developing amygdala that was controlled by EphB2. A constitutively active form of EphB2 was sufficient to rescue the behavioral and morphological defects caused by ablation of ephrin-B3, a brain-enriched ligand to EphB2. These data suggest that kinase-dependent EphB2 intracellular signaling plays a major role for innate fear responses during the critical developing period, in which spinogenesis in amygdala glutamatergic neurons was involved. Generation of innate fear responses to threat as an evolutionally conserved brain feature relies on development of functional neural circuit in amygdala, but the molecular mechanism remains largely unknown. We here identify that EphB2 receptor tyrosine kinase, which is specifically expressed in glutamatergic neurons, is required for the innate fear responses in the neonatal brain. We further reveal that EphB2 mediates coordination of spinogenesis and neuron activation in amygdala during the critical period for the innate fear. EphB2 catalytic activity plays a major role for the behavior upon EphB-ephrin-B3 binding and transnucleus neuronal connections. Our work thus indicates an essential synaptic molecular signaling within amygdala that controls synapse development and helps bring about innate fear emotions in the postnatal

  4. Speech Disfluency-dependent Amygdala Activity in Adults Who Stutter: Neuroimaging of Interpersonal Communication in MRI Scanner Environment.

    Science.gov (United States)

    Toyomura, Akira; Fujii, Tetsunoshin; Yokosawa, Koichi; Kuriki, Shinya

    2018-03-15

    Affective states, such as anticipatory anxiety, critically influence speech communication behavior in adults who stutter. However, there is currently little evidence regarding the involvement of the limbic system in speech disfluency during interpersonal communication. We designed this neuroimaging study and experimental procedure to sample neural activity during interpersonal communication between human participants, and to investigate the relationship between the amygdala activity and speech disfluency. Participants were required to engage in live communication with a stranger of the opposite sex in the MRI scanner environment. In the gaze condition, the stranger gazed at the participant without speaking, while in the live conversation condition, the stranger asked questions that the participant was required to answer. The stranger continued to gaze silently at the participant while the participant answered. Adults who stutter reported significantly higher discomfort than fluent controls during the experiment. Activity in the right amygdala, a key anatomical region in the limbic system involved in emotion, was significantly correlated with stuttering occurrences in adults who stutter. Right amygdala activity from pooled data of all participants also showed a significant correlation with discomfort level during the experiment. Activity in the prefrontal cortex, which forms emotion regulation neural circuitry with the amygdala, was decreased in adults who stutter than in fluent controls. This is the first study to demonstrate that amygdala activity during interpersonal communication is involved in disfluent speech in adults who stutter. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Non-compact left ventricle/hypertrabeculated left ventricle

    International Nuclear Information System (INIS)

    Restrepo, Gustavo; Castano, Rafael; Marmol, Alejandro

    2005-01-01

    Non-compact left ventricle/hypertrabeculated left ventricle is a myocardiopatie produced by an arrest of the normal left ventricular compaction process during the early embryogenesis. It is associated to cardiac anomalies (congenital cardiopaties) as well as to extracardial conditions (neurological, facial, hematologic, cutaneous, skeletal and endocrinological anomalies). This entity is frequently unnoticed, being diagnosed only in centers with great experience in the diagnosis and treatment of myocardiopathies. Many cases of non-compact left ventricle have been initially misdiagnosed as hypertrophic myocardiopatie, endocardial fibroelastosis, dilated cardiomyopatie, restrictive cardiomyopathy and endocardial fibrosis. It is reported the case of a 74 years old man with a history of chronic arterial hypertension and diabetes mellitus, prechordial chest pain and mild dyspnoea. An echocardiogram showed signs of non-compact left ventricle with prominent trabeculations and deep inter-trabecular recesses involving left ventricular apical segment and extending to the lateral and inferior walls. Literature on this topic is reviewed

  6. MRI Volumetry of Hippocampus and Amygdala in Normal Aging, Mild Cognitive Impairment and Alzheimer's Disease Subjects

    International Nuclear Information System (INIS)

    Suphaphong, S.; Tritanon, O.; Laothamatas, J.; Sungkarat, W.

    2012-01-01

    The Alzheimer's disease (AD) and mild cognitive impairment (MCI) can affect memory and daily living. Non- invasive diagnostic tools such as MRI can be useful to discriminate the patients from normal group.This study aims to compare the relative volumes of hippocampus and amygdala, to suggest the relative normal volumes, and to evaluate MRI automatic volumetry as a diagnostic tool. The MRI images of 130 subjects were retrospectively studied (Turbo field echo (TFE), acquired with a 3-Tesla Philips scanner). The image data were processed with Free Surfer (automatic segmentation and volumetry). The resultant volumes were corrected for brain size differences with intracranial volumes (ICV), and then analysed with SPSS (v. 17.0). There are differences of hippocampus and amygdala relative volumes between normal, MCI, and AD subjects at p < 0.001. The volume reductions of hippocampus in MCI and AD groups compared to normal group are about 8 % and 28 %, while those of amygdala are about 10 % and 34 %, respectively. The relative volumes of hippocampus (compared to ICV) in normal aging are 0.002617 ± 0.000278 (right) and 0.002553 ± 0.000257 (left), while those of amygdala are 0.001231 ± 0.000165 (right) and 0.001096 ± 0.000144 (left). There are no differences of relative volumes affected by gender in normal, MCI, and AD. There is a highly significant difference of relative volume affected by brain side in normal group (p < 0.001) but not in MCI (p = 0.119 and 0.077) and AD (p = 0.713 and 0.250), for hippocampus and amygdala, respectively. These results demonstrate that there are volume losses of hippocampus and amygdala in both diseases. Automatically measured hippocampus and amygdala volumes can be used as a measure indicating MCI and AD. The abnormal disturbance of volume affected by brain side may indicate the progression of both diseases. The hippocampus and amygdala volumes can be used as one of diagnostic tools to confirm the diagnosis of MCI or AD. The volume

  7. Framing effect following bilateral amygdala lesion

    OpenAIRE

    Talmi, Deborah; Hurlemann, Ren?; Patin, Alexandra; Dolan, Raymond J.

    2010-01-01

    A paradigmatic example of an emotional bias in decision making is the framing effect, where the manner in which a choice is posed ? as a potential loss or a potential gain ? systematically biases an ensuing decision. Two fMRI studies have shown that the activation in the amygdala is modulated by the framing effect. Here, contrary to an expectation based on these studies, we show that two patients with Urbach-Wiethe (UW) disease, a rare condition associated with congenital, complete bilateral ...

  8. Food labels promote healthy choices by a decision bias in the amygdala.

    Science.gov (United States)

    Grabenhorst, Fabian; Schulte, Frank P; Maderwald, Stefan; Brand, Matthias

    2013-07-01

    Food labeling is the major health policy strategy to counter rising obesity rates. Based on traditional economic theory, such strategies assume that detailed nutritional information will necessarily help individuals make better, healthier choices. However, in contrast to the well-known utility of labels in food marketing, evidence for the efficacy of nutritional labeling is mixed. Psychological and behavioral economic theories suggest that successful marketing strategies activate automatic decision biases and emotions, which involve implicit emotional brain systems. Accordingly, simple, intuitive food labels that engage these neural systems could represent a promising approach for promoting healthier choices. Here we used functional MRI to investigate this possibility. Healthy, mildly hungry subjects performed a food evaluation task and a food choice task. The main experimental manipulation was to pair identical foods with simple labels that emphasized either taste benefits or health-related food properties. We found that such labels biased food evaluations in the amygdala, a core emotional brain system. When labels biased the amygdala's evaluations towards health-related food properties, the strength of this bias predicted behavioral shifts towards healthier choices. At the time of decision-making, amygdala activity encoded key decision variables, potentially reflecting active amygdala participation in food choice. Our findings underscore the potential utility of food labeling in health policy and indicate a principal role for emotional brain systems when labels guide food choices. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Reference frames for spatial frequency in face representation differ in the temporal visual cortex and amygdala.

    Science.gov (United States)

    Inagaki, Mikio; Fujita, Ichiro

    2011-07-13

    Social communication in nonhuman primates and humans is strongly affected by facial information from other individuals. Many cortical and subcortical brain areas are known to be involved in processing facial information. However, how the neural representation of faces differs across different brain areas remains unclear. Here, we demonstrate that the reference frame for spatial frequency (SF) tuning of face-responsive neurons differs in the temporal visual cortex and amygdala in monkeys. Consistent with psychophysical properties for face recognition, temporal cortex neurons were tuned to image-based SFs (cycles/image) and showed viewing distance-invariant representation of face patterns. On the other hand, many amygdala neurons were influenced by retina-based SFs (cycles/degree), a characteristic that is useful for social distance computation. The two brain areas also differed in the luminance contrast sensitivity of face-responsive neurons; amygdala neurons sharply reduced their responses to low luminance contrast images, while temporal cortex neurons maintained the level of their responses. From these results, we conclude that different types of visual processing in the temporal visual cortex and the amygdala contribute to the construction of the neural representations of faces.

  10. Amygdala damage eliminates monetary loss aversion.

    Science.gov (United States)

    De Martino, Benedetto; Camerer, Colin F; Adolphs, Ralph

    2010-02-23

    Losses are a possibility in many risky decisions, and organisms have evolved mechanisms to evaluate and avoid them. Laboratory and field evidence suggests that people often avoid risks with losses even when they might earn a substantially larger gain, a behavioral preference termed "loss aversion." The cautionary brake on behavior known to rely on the amygdala is a plausible candidate mechanism for loss aversion, yet evidence for this idea has so far not been found. We studied two rare individuals with focal bilateral amygdala lesions using a series of experimental economics tasks. To measure individual sensitivity to financial losses we asked participants to play a variety of monetary gambles with possible gains and losses. Although both participants retained a normal ability to respond to changes in the gambles' expected value and risk, they showed a dramatic reduction in loss aversion compared to matched controls. The findings suggest that the amygdala plays a key role in generating loss aversion by inhibiting actions with potentially deleterious outcomes.

  11. Blockade of intracellular Zn2+ signaling in the basolateral amygdala affects object recognition memory via attenuation of dentate gyrus LTP.

    Science.gov (United States)

    Fujise, Yuki; Kubota, Mitsuyasu; Suzuki, Miki; Tamano, Haruna; Takeda, Atsushi

    2017-09-01

    Hippocampus-dependent memory is modulated by the amygdala. However, it is unknown whether intracellular Zn 2+ signaling in the amygdala is involved in hippocampus-dependent memory. On the basis of the evidence that intracellular Zn 2+ signaling in dentate granule cells (DGC) is necessary for object recognition memory via LTP at medial perforant pathway (PP)-DGC synapses, the present study examined whether intracellular Zn 2+ signaling in the amygdala influences object recognition memory via modulation of LTP at medial PP-DGC synapses. When ZnAF-2DA (100 μM, 2 μl) was injected into the basolateral amygdala (BLA), intracellular ZnAF-2 locally chelated intracellular Zn 2+ in the amygdala. Recognition memory was affected when training of object recognition test was performed 20 min after ZnAF-2DA injection into the BLA. Twenty minutes after injection of ZnAF-2DA into the BLA, LTP induction at medial PP-DGC synapses was attenuated, while LTP induction at PP-BLA synapses was potentiated and LTP induction at BLA-DGC synapses was attenuated. These results suggest that intracellular Zn 2+ signaling in the BLA is involved in BLA-associated LTP and modulates LTP at medial PP-DGC synapses, followed by modulation of object recognition memory. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Amygdala lesions in rhesus macaques decrease attention to threat

    Science.gov (United States)

    Dal Monte, Olga; Costa, Vincent D.; Noble, Pamela L.; Murray, Elisabeth A.; Averbeck, Bruno B.

    2015-01-01

    Evidence from animal and human studies has suggested that the amygdala plays a role in detecting threat and in directing attention to the eyes. Nevertheless, there has been no systematic investigation of whether the amygdala specifically facilitates attention to the eyes or whether other features can also drive attention via amygdala processing. The goal of the present study was to examine the effects of amygdala lesions in rhesus monkeys on attentional capture by specific facial features, as well as gaze patterns and changes in pupil dilation during free viewing. Here we show reduced attentional capture by threat stimuli, specifically the mouth, and reduced exploration of the eyes in free viewing in monkeys with amygdala lesions. Our findings support a role for the amygdala in detecting threat signals and in directing attention to the eye region of faces when freely viewing different expressions. PMID:26658670

  13. Sliding-window analysis tracks fluctuations in amygdala functional connectivity associated with physiological arousal and vigilance during fear conditioning.

    Science.gov (United States)

    Baczkowski, Blazej M; Johnstone, Tom; Walter, Henrik; Erk, Susanne; Veer, Ilya M

    2017-06-01

    We evaluated whether sliding-window analysis can reveal functionally relevant brain network dynamics during a well-established fear conditioning paradigm. To this end, we tested if fMRI fluctuations in amygdala functional connectivity (FC) can be related to task-induced changes in physiological arousal and vigilance, as reflected in the skin conductance level (SCL). Thirty-two healthy individuals participated in the study. For the sliding-window analysis we used windows that were shifted by one volume at a time. Amygdala FC was calculated for each of these windows. Simultaneously acquired SCL time series were averaged over time frames that corresponded to the sliding-window FC analysis, which were subsequently regressed against the whole-brain seed-based amygdala sliding-window FC using the GLM. Surrogate time series were generated to test whether connectivity dynamics could have occurred by chance. In addition, results were contrasted against static amygdala FC and sliding-window FC of the primary visual cortex, which was chosen as a control seed, while a physio-physiological interaction (PPI) was performed as cross-validation. During periods of increased SCL, the left amygdala became more strongly coupled with the bilateral insula and anterior cingulate cortex, core areas of the salience network. The sliding-window analysis yielded a connectivity pattern that was unlikely to have occurred by chance, was spatially distinct from static amygdala FC and from sliding-window FC of the primary visual cortex, but was highly comparable to that of the PPI analysis. We conclude that sliding-window analysis can reveal functionally relevant fluctuations in connectivity in the context of an externally cued task. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Amygdala-frontal connectivity predicts internalizing symptom recovery among inpatient adolescents.

    Science.gov (United States)

    Venta, Amanda; Sharp, Carla; Patriquin, Michelle; Salas, Ramiro; Newlin, Elizabeth; Curtis, Kaylah; Baldwin, Philip; Fowler, Christopher; Frueh, B Christopher

    2018-01-01

    The possibility of using biological measures to predict the trajectory of symptoms among adolescent psychiatric inpatients has important implications. This study aimed to examine emotion regulation ability (measured via self-report) and a hypothesized proxy in resting-state functional connectivity [RSFC] between the amygdala and frontal brain regions as baseline predictors of internalizing symptom recovery during inpatient care. 196 adolescents (61% female; Mage = 15.20; SD = 1.48) completed the Achenbach Brief Problem Monitor (BPM) each week during their inpatient care. RSFC (n = 45) and self-report data of emotion regulation (n = 196) were collected at baseline. The average internalizing symptom score at admission was high (α 0 = 66.52), exceeding the BPM's clinical cut off score of 65. On average, internalizing symptom scores declined significantly, by 0.40 points per week (p = 0.004). While self-reported emotion regulation was associated with admission levels of internalizing problems, it did not predict change in symptoms. RSFC between left amygdala and left superior frontal gyrus was significantly associated with the intercept-higher connectivity was associated with higher internalizing at admission-and the slope- higher connectivity was associated with a more positive slope (i.e., less decline in symptoms). RSFC between the right amygdala and the left superior frontal gyrus was significantly, positively correlated with the slope parameter. Results indicate the potential of biologically-based measures that can be developed further for personalized care in adolescent psychiatry. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Fear extinction requires infralimbic cortex projections to the basolateral amygdala.

    Science.gov (United States)

    Bloodgood, Daniel W; Sugam, Jonathan A; Holmes, Andrew; Kash, Thomas L

    2018-03-06

    Fear extinction involves the formation of a new memory trace that attenuates fear responses to a conditioned aversive memory, and extinction impairments are implicated in trauma- and stress-related disorders. Previous studies in rodents have found that the infralimbic prefrontal cortex (IL) and its glutamatergic projections to the basolateral amygdala (BLA) and basomedial amygdala (BMA) instruct the formation of fear extinction memories. However, it is unclear whether these pathways are exclusively involved in extinction, or whether other major targets of the IL, such as the nucleus accumbens (NAc) also play a role. To address this outstanding issue, the current study employed a combination of electrophysiological and chemogenetic approaches in mice to interrogate the role of IL-BLA and IL-NAc pathways in extinction. Specifically, we used patch-clamp electrophysiology coupled with retrograde tracing to examine changes in neuronal activity of the IL and prelimbic cortex (PL) projections to both the BLA and NAc following fear extinction. We found that extinction produced a significant increase in the intrinsic excitability of IL-BLA projection neurons, while extinction appeared to reverse fear-induced changes in IL-NAc projection neurons. To establish a causal counterpart to these observations, we then used a pathway-specific Designer Receptors Exclusively Activated by Designer Drugs (DREADD) strategy to selectively inhibit PFC-BLA projection neurons during extinction acquisition. Using this approach, we found that DREADD-mediated inhibition of PFC-BLA neurons during extinction acquisition impaired subsequent extinction retrieval. Taken together, our findings provide further evidence for a critical contribution of the IL-BLA neural circuit to fear extinction.

  16. Cortex and amygdala morphology in psychopathy.

    Science.gov (United States)

    Boccardi, Marina; Frisoni, Giovanni B; Hare, Robert D; Cavedo, Enrica; Najt, Pablo; Pievani, Michela; Rasser, Paul E; Laakso, Mikko P; Aronen, Hannu J; Repo-Tiihonen, Eila; Vaurio, Olli; Thompson, Paul M; Tiihonen, Jari

    2011-08-30

    Psychopathy is characterized by abnormal emotional processes, but only recent neuroimaging studies have investigated its cerebral correlates. The study aim was to map local differences of cortical and amygdalar morphology. Cortical pattern matching and radial distance mapping techniques were used to analyze the magnetic resonance images of 26 violent male offenders (age: 32±8) with psychopathy diagnosed using the Psychopathy Checklist-Revised (PCL-R) and no schizophrenia spectrum disorders, and in matched controls (age: 35± sp="0.12"/>11). The cortex displayed up to 20% reduction in the orbitofrontal and midline structures (corrected pamygdala (corrected p=0.05 on the right; and symmetrical pattern on the left). Psychopathy features specific morphology of the main cerebral structures involved in cognitive and emotional processing, consistent with clinical and functional data, and with a hypothesis of an alternative evolutionary brain development. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  17. Surface morphology of amygdala is associated with trait anxiety.

    Directory of Open Access Journals (Sweden)

    Shuyu Li

    Full Text Available Previous neuroimaging studies have suggested a role of amygdala in trait anxiety level, in which amygdala was typically treated as a whole. To date, it remains unknown whether the morphology of specific subregions of amygdala are associated with trait anxiety. Here, we employed a shape analysis approach to locate the association between its morphology and trait anxiety on the surface of amygdala. 24 healthy young participants were included. The boundary of amygdala for each subject was first manually outlined using high-resolution magnetic resonance (MR image, followed by 3D surface reconstruction and parameterization using spherical harmonic description. Two point-wise metrics, direct displacement between the individual surface and atlas surface and its normal projection, were used to quantify the surface morphology of amygdala. Statistical analysis revealed significant correlations between the two surface metrics and trait anxiety levels, which were located around the lateral and central nucleus of right amygdala. Our results provided localized information for the association between amygdala and trait anxiety, and suggested a central role of the lateral and central nucleus of right amygdala on trait anxiety.

  18. Amygdala Kindling Alters Estrus Cycle and Ovarian Morphology in the Rat.

    Science.gov (United States)

    Pan, Juan; Zhang, Lingwu; Wang, Feng; Liu, Dan; Li, P Andy; Sun, Tao

    2013-11-01

    The objective of this study is to explore the effects of amygdala kindling on estrus cycle and ovarian morphology. Thirty-five female rats at the age of 8 weeks were randomly designated to electrode kindled, sham-kindled, and normal controls. Kindled rats were implanted with kindling electrodes in the left basolateral amygdala and kindled by brief suprathreshold stimulations with a bipolar electrode. Estrous cycles were daily monitored through vaginal smears. Electrographic and behavioral seizures were recorded and ovarian morphology was evaluated by light and electron microscopies. Our results showed that the kindled rats lost their ovarian periodicity displayed significant ovarian enlargement. H&E staining revealed increased number of growing follicles and total follicles, as well as polycysts in the ovaries of the kindled animals compared to sham and control animals. Ultrastructural study detected numerous apoptotic granulosa cells in growing follicles and thecal cell hyperplasia with secretary granules in the thecal cells in the kindled rats. The results suggest that amygdala kindling is a risk factor for the development of polycystic ovary syndrome.

  19. Are Plasma Oxytocin and Vasopressin Levels Reflective of Amygdala Activation during the Processing of Negative Emotions? A Preliminary Study.

    Science.gov (United States)

    Motoki, Kosuke; Sugiura, Motoaki; Takeuchi, Hikaru; Kotozaki, Yuka; Nakagawa, Seishu; Yokoyama, Ryoichi; Kawashima, Ryuta

    2016-01-01

    Plasma oxytocin (OT) and arginine vasopressin (AVP) are associated with individual differences in emotional responses and behaviors. The amygdala is considered to be an important brain region for regulating emotion-based behavior, with OT and AVP modulating activity in the amygdala during the processing of negative emotions. In particular, increased OT levels may diminish amygdala activation (anxiolytic effects) and enhanced AVP levels may augment amygdala activation (anxiogenic effects) when negative emotions are processed. A growing body of research has shown that the effects of OT and AVP are modulated by sex: the aforementioned anxiolytic effects of OT and the anxiogenic effects of AVP occur in men, but not in women. However, we have little knowledge regarding the biological mechanisms underlying OT and AVP plasma levels or their respective anxiogenic and anxiolytic effects; similarly, little is known about the causes and nature of sex differences related to these neuropeptides and their effects on emotional processing. In the current study, we focused on the neural functions associated with the biological mechanisms underlying such effects. We hypothesized that amygdala activation would correlate with trait plasma OT (anxiolytic effects) and AVP (anxiogenic effects) levels because the amygdala is thought to affect the coordinated release of these neuropeptides following affective experiences. We further hypothesized that the effects would be modulated by sex. We assessed 51 participants (male and female) using a paradigm involving negative emotion in conjunction with functional magnetic resonance imaging and measurements of plasma OT and AVP levels. We determined that increased plasma AVP levels were positively associated with amygdala activation (anxiogenic effects) in men, but not in women. These findings highlight the potential underlying neural mechanisms of plasma AVP levels in men.

  20. Are plasma oxytocin and vasopressin levels reflective of amygdala activation during the processing of negative emotions? A preliminary study

    Directory of Open Access Journals (Sweden)

    Kosuke eMotoki

    2016-04-01

    Full Text Available Plasma oxytocin (OT and arginine vasopressin (AVP are associated with individual differences in emotional responses and behaviors. The amygdala is considered to be an important brain region for regulating emotion-based behavior, with OT and AVP modulating activity in the amygdala during the processing of negative emotions. In particular, increased OT levels may diminish amygdala activation (anxiolytic effects and enhanced AVP levels may augment amygdala activation (anxiogenic effects when negative emotions are processed. A growing body of research has shown that the effects of OT and AVP are modulated by sex: the aforementioned anxiolytic effects of OT and the anxiogenic effects of AVP occur in men, but not in women. However, we have little knowledge regarding the biological mechanisms underlying OT and AVP plasma levels or their respective anxiogenic and anxiolytic effects; similarly, little is known about the causes and nature of sex differences related to these neuropeptides and their effects on emotional processing. In the current study, we focused on the neural functions associated with the biological mechanisms underlying such effects. We hypothesized that amygdala activation would correlate with plasma OT (anxiolytic effects and AVP (anxiogenic effects levels because the amygdala is thought to affect the coordinated release of these neuropeptides following affective experiences. We further hypothesized that the effects would be modulated by sex. We assessed 51 participants (male and female using a paradigm involving negative emotion in conjunction with functional magnetic resonance imaging and measurements of plasma OT and AVP levels. We determined that increased plasma AVP levels were positively associated with amygdala activation (anxiogenic effects in men, but not in women. These findings highlight the potential underlying neural mechanisms of plasma AVP levels in men.

  1. Left ventricular rigid body rotation in a diffuse large B-cell lymphoma patient with cardiac involvement: A case from the three-dimensional speckle-tracking echocardiographic MAGYAR-Path Study.

    Science.gov (United States)

    Földeák, Dóra; Kalapos, Anita; Domsik, Péter; Sinkó, Mária; Szeleczki, Nóra; Bagdi, Enikő; Krenács, László; Forster, Tamás; Borbényi, Zita; Nemes, Attila

    2017-02-01

    Secondary myocardial involvement by diffuse large B-cell lymphoma is a rare occurrence. Left ventricular (LV) twist is considered an essential part of LV function. In normal circumstances LV twist results from the movement of two orthogonally oriented muscular bands of a helical myocardial structure with consequent clockwise rotation of the base and counterclockwise rotation of the apex. Three-dimensional (3D) speckle-tracking echocardiography (3DSTE) has been found to be feasible for non-invasive 3D quantification of LV wall motion and rotational mechanics. The present report aimed to assess LV twisting motion in a patient with diffuse large B-cell lymphoma with positron emission tomography/computer tomography-proven cardiac involvement by 3DSTE. During 3DSTE, reduction in some segmental radial, longitudinal, circumferential, area and 3D LV strains were found. Apical and basal LV rotations were found to be in the same counterclockwise direction, confirming near absence of LV twist - so-called rigid body rotation. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  2. Dysfunctional amygdala activation and connectivity with the prefrontal cortex in current cocaine users

    NARCIS (Netherlands)

    Crunelle, C.L.; Kaag, A.M.; van den Munkhof, H.E.; Reneman, L.; Homberg, J.R.; Sabbe, B.; van den Brink, W.; van Wingen, G.

    2015-01-01

    OBJECTIVES: Stimulant use is associated with increased anxiety and a single administration of dexamphetamine increases amygdala activation to biologically salient stimuli in healthy individuals. Here, we investigate how current cocaine use affects amygdala activity and amygdala connectivity with the

  3. Dysfunctional amygdala activation and connectivity with the prefrontal cortex in current cocaine users

    NARCIS (Netherlands)

    Crunelle, Cleo L.; Kaag, Anne Marije; van den Munkhof, Hanna E.; Reneman, Liesbeth; Homberg, Judith R.; Sabbe, Bernard; van den Brink, Wim; van Wingen, Guido

    2015-01-01

    Stimulant use is associated with increased anxiety and a single administration of dexamphetamine increases amygdala activation to biologically salient stimuli in healthy individuals. Here, we investigate how current cocaine use affects amygdala activity and amygdala connectivity with the prefrontal

  4. Reactivations of emotional memory in the hippocampus-amygdala system during sleep.

    Science.gov (United States)

    Girardeau, Gabrielle; Inema, Ingrid; Buzsáki, György

    2017-11-01

    The consolidation of context-dependent emotional memory requires communication between the hippocampus and the basolateral amygdala (BLA), but the mechanisms of this process are unknown. We recorded neuronal ensembles in the hippocampus and BLA while rats learned the location of an aversive air puff on a linear track, as well as during sleep before and after training. We found coordinated reactivations between the hippocampus and the BLA during non-REM sleep following training. These reactivations peaked during hippocampal sharp wave-ripples (SPW-Rs) and involved a subgroup of BLA cells positively modulated during hippocampal SPW-Rs. Notably, reactivation was stronger for the hippocampus-BLA correlation patterns representing the run direction that involved the air puff than for the 'safe' direction. These findings suggest that consolidation of contextual emotional memory occurs during ripple-reactivation of hippocampus-amygdala circuits.

  5. How the amygdala affects emotional memory by altering brain network properties.

    Science.gov (United States)

    Hermans, Erno J; Battaglia, Francesco P; Atsak, Piray; de Voogd, Lycia D; Fernández, Guillén; Roozendaal, Benno

    2014-07-01

    The amygdala has long been known to play a key role in supporting memory for emotionally arousing experiences. For example, classical fear conditioning depends on neural plasticity within this anterior medial temporal lobe region. Beneficial effects of emotional arousal on memory, however, are not restricted to simple associative learning. Our recollection of emotional experiences often includes rich representations of, e.g., spatiotemporal context, visceral states, and stimulus-response associations. Critically, such memory features are known to bear heavily on regions elsewhere in the brain. These observations led to the modulation account of amygdala function, which postulates that amygdala activation enhances memory consolidation by facilitating neural plasticity and information storage processes in its target regions. Rodent work in past decades has identified the most important brain regions and neurochemical processes involved in these modulatory actions, and neuropsychological and neuroimaging work in humans has produced a large body of convergent data. Importantly, recent methodological developments make it increasingly realistic to monitor neural interactions underlying such modulatory effects as they unfold. For instance, functional connectivity network modeling in humans has demonstrated how information exchanges between the amygdala and specific target regions occur within the context of large-scale neural network interactions. Furthermore, electrophysiological and optogenetic techniques in rodents are beginning to make it possible to quantify and even manipulate such interactions with millisecond precision. In this paper we will discuss that these developments will likely lead to an updated view of the amygdala as a critical nexus within large-scale networks supporting different aspects of memory processing for emotionally arousing experiences. Copyright © 2014 Elsevier Inc. All rights reserved.

  6. FKBP5 and emotional neglect interact to predict individual differences in amygdala reactivity.

    Science.gov (United States)

    White, M G; Bogdan, R; Fisher, P M; Muñoz, K E; Williamson, D E; Hariri, A R

    2012-10-01

    Individual variation in physiological responsiveness to stress mediates risk for mental illness and is influenced by both experiential and genetic factors. Common polymorphisms in the human gene for FK506 binding protein 5 (FKBP5), which is involved in transcriptional regulation of the hypothalamic-pituitary-adrenal (HPA) axis, have been shown to interact with childhood abuse and trauma to predict stress-related psychopathology. In the current study, we examined if such gene-environment interaction effects may be related to variability in the threat-related reactivity of the amygdala, which plays a critical role in mediating physiological and behavioral adaptations to stress including modulation of the HPA axis. To this end, 139 healthy Caucasian youth completed a blood oxygen level-dependent functional magnetic resonance imaging probe of amygdala reactivity and self-report assessments of emotional neglect (EN) and other forms of maltreatment. These individuals were genotyped for 6 FKBP5 polymorphisms (rs7748266, rs1360780, rs9296158, rs3800373, rs9470080 and rs9394309) previously associated with psychopathology and/or HPA axis function. Interactions between each SNP and EN emerged such that risk alleles predicted relatively increased dorsal amygdala reactivity in the context of higher EN, even after correcting for multiple testing. Two different haplotype analyses confirmed this relationship as haplotypes with risk alleles also exhibited increased amygdala reactivity in the context of higher EN. Our results suggest that increased threat-related amygdala reactivity may represent a mechanism linking psychopathology to interactions between common genetic variants affecting HPA axis function and childhood trauma. © 2012 The Authors. Genes, Brain and Behavior © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

  7. Input from the medial geniculate nucleus modulates amygdala encoding of fear memory discrimination.

    Science.gov (United States)

    Ferrara, Nicole C; Cullen, Patrick K; Pullins, Shane P; Rotondo, Elena K; Helmstetter, Fred J

    2017-09-01

    Generalization of fear can involve abnormal responding to cues that signal safety and is common in people diagnosed with post-traumatic stress disorder. Differential auditory fear conditioning can be used as a tool to measure changes in fear discrimination and generalization. Most prior work in this area has focused on elevated amygdala activity as a critical component underlying generalization. The amygdala receives input from auditory cortex as well as the medial geniculate nucleus (MgN) of the thalamus, and these synapses undergo plastic changes in response to fear conditioning and are major contributors to the formation of memory related to both safe and threatening cues. The requirement for MgN protein synthesis during auditory discrimination and generalization, as well as the role of MgN plasticity in amygdala encoding of discrimination or generalization, have not been directly tested. GluR1 and GluR2 containing AMPA receptors are found at synapses throughout the amygdala and their expression is persistently up-regulated after learning. Some of these receptors are postsynaptic to terminals from MgN neurons. We found that protein synthesis-dependent plasticity in MgN is necessary for elevated freezing to both aversive and safe auditory cues, and that this is accompanied by changes in the expressions of AMPA receptor and synaptic scaffolding proteins (e.g., SHANK) at amygdala synapses. This work contributes to understanding the neural mechanisms underlying increased fear to safety signals after stress. © 2017 Ferrara et al.; Published by Cold Spring Harbor Laboratory Press.

  8. Amygdala TDP-43 Pathology in Frontotemporal Lobar Degeneration and Motor Neuron Disease.

    Science.gov (United States)

    Takeda, Takahiro; Seilhean, Danielle; Le Ber, Isabelle; Millecamps, Stéphanie; Sazdovitch, Véronique; Kitagawa, Kazuo; Uchihara, Toshiki; Duyckaerts, Charles

    2017-09-01

    TDP-43-positive inclusions are present in the amygdala in frontotemporal lobar degeneration (FTLD) and motor neuron disease (MND) including amyotrophic lateral sclerosis. Behavioral abnormalities, one of the chief symptoms of FTLD, could be, at least partly, related to amygdala pathology. We examined TDP-43 inclusions in the amygdala of patients with sporadic FTLD/MND (sFTLD/MND), FTLD/MND with mutation of the C9ORF72 (FTLD/MND-C9) and FTLD with mutation of the progranulin (FTLD-GRN). TDP-43 inclusions were common in each one of these subtypes, which can otherwise be distinguished on topographical and genetic grounds. Conventional and immunological stainings were performed and we quantified the numerical density of inclusions on a regional basis. TDP-43 inclusions in amygdala could be seen in 10 out of 26 sFTLD/MND cases, 5 out of 9 FTLD/MND-C9 cases, and all 4 FTLD-GRN cases. Their numerical density was lower in FTLD/MND-C9 than in sFTLD/MND and FTLD-GRN. TDP-43 inclusions were more numerous in the ventral region of the basolateral nucleus group in all subtypes. This contrast was apparent in sporadic and C9-mutated FTLD/MND, while it was less evident in FTLD-GRN. Such differences in subregional involvement of amygdala may be related to the region-specific neuronal connections that are differentially affected in FTLD/MND and FTLD-GRN. © 2017 American Association of Neuropathologists, Inc. All rights reserved.

  9. Auditory responses in the amygdala to social vocalizations

    Science.gov (United States)

    Gadziola, Marie A.

    The underlying goal of this dissertation is to understand how the amygdala, a brain region involved in establishing the emotional significance of sensory input, contributes to the processing of complex sounds. The general hypothesis is that communication calls of big brown bats (Eptesicus fuscus) transmit relevant information about social context that is reflected in the activity of amygdalar neurons. The first specific aim analyzed social vocalizations emitted under a variety of behavioral contexts, and related vocalizations to an objective measure of internal physiological state by monitoring the heart rate of vocalizing bats. These experiments revealed a complex acoustic communication system among big brown bats in which acoustic cues and call structure signal the emotional state of a sender. The second specific aim characterized the responsiveness of single neurons in the basolateral amygdala to a range of social syllables. Neurons typically respond to the majority of tested syllables, but effectively discriminate among vocalizations by varying the response duration. This novel coding strategy underscores the importance of persistent firing in the general functioning of the amygdala. The third specific aim examined the influence of acoustic context by characterizing both the behavioral and neurophysiological responses to natural vocal sequences. Vocal sequences differentially modify the internal affective state of a listening bat, with lower aggression vocalizations evoking the greatest change in heart rate. Amygdalar neurons employ two different coding strategies: low background neurons respond selectively to very few stimuli, whereas high background neurons respond broadly to stimuli but demonstrate variation in response magnitude and timing. Neurons appear to discriminate the valence of stimuli, with aggression sequences evoking robust population-level responses across all sound levels. Further, vocal sequences show improved discrimination among stimuli

  10. Dissociable contributions of the amygdala to the immediate and delayed effects of emotional arousal on memory.

    Science.gov (United States)

    Schümann, Dirk; Sommer, Tobias

    2018-06-01

    Emotional arousal enhances memory encoding and consolidation leading to better immediate and delayed memory. Although the central noradrenergic system and the amygdala play critical roles in both effects of emotional arousal, we have recently shown that these effects are at least partly independent of each other, suggesting distinct underlying neural mechanisms. Here we aim to dissociate the neural substrates of both effects in 70 female participants using an emotional memory paradigm to investigate how neural activity, as measured by fMRI, and a polymorphism in the α 2B -noradrenoceptor vary for these effects. To also test whether the immediate and delayed effects of emotional arousal on memory are stable traits, we invited back participants who were a part of a large-scale behavioral memory study ∼3.5 yr ago. We replicated the low correlation of the immediate and delayed emotional enhancement of memory across participants ( r = 0.16) and observed, moreover, that only the delayed effect was, to some degree, stable over time ( r = 0.23). Bilateral amygdala activity, as well as its coupling with the visual cortex and the fusiform gyrus, was related to the preferential encoding of emotional stimuli, which is consistent with affect-biased attention. Moreover, the adrenoceptor genotype modulated the bilateral amygdala activity associated with this effect. The left amygdala and its coupling with the hippocampus was specifically associated with the more efficient consolidation of emotional stimuli, which is consistent with amygdalar modulation of hippocampal consolidation. © 2018 Schümann and Sommer; Published by Cold Spring Harbor Laboratory Press.

  11. Abnormal functional architecture of amygdala-centered networks in adolescent posttraumatic stress disorder.

    Science.gov (United States)

    Aghajani, Moji; Veer, Ilya M; van Hoof, Marie-José; Rombouts, Serge A R B; van der Wee, Nic J; Vermeiren, Robert R J M

    2016-03-01

    Posttraumatic stress disorder (PTSD) is a prevalent, debilitating, and difficult to treat psychiatric disorder. Very little is known of how PTSD affects neuroplasticity in the developing adolescent brain. Whereas multiple lines of research implicate amygdala-centered network dysfunction in the pathophysiology of adult PTSD, no study has yet examined the functional architecture of amygdala subregional networks in adolescent PTSD. Using intrinsic functional connectivity analysis, we investigated functional connectivity of the basolateral (BLA) and centromedial (CMA) amygdala in 19 sexually abused adolescents with PTSD relative to 23 matched controls. Additionally, we examined whether altered amygdala subregional connectivity coincides with abnormal grey matter volume of the amygdaloid complex. Our analysis revealed abnormal amygdalar connectivity and morphology in adolescent PTSD patients. More specifically, PTSD patients showed diminished right BLA connectivity with a cluster including dorsal and ventral portions of the anterior cingulate and medial prefrontal cortices (p < 0.05, corrected). In contrast, PTSD patients showed increased left CMA connectivity with a cluster including the orbitofrontal and subcallosal cortices (p < 0.05, corrected). Critically, these connectivity changes coincided with diminished grey matter volume within BLA and CMA subnuclei (p < 0.05, corrected), with CMA connectivity shifts additionally relating to more severe symptoms of PTSD. These findings provide unique insights into how perturbations in major amygdalar circuits could hamper fear regulation and drive excessive acquisition and expression of fear in PTSD. As such, they represent an important step toward characterizing the neurocircuitry of adolescent PTSD, thereby informing the development of reliable biomarkers and potential therapeutic targets. © 2016 Wiley Periodicals, Inc.

  12. Amygdala, Pulvinar & Inferior Parietal Cortex Contribute to Early Processing of Faces without Awareness

    Directory of Open Access Journals (Sweden)

    Vanessa eTroiani

    2013-06-01

    Full Text Available The goals of the present study were twofold. First, we wished to investigate the neural correlates of stimulus-driven processing of stimuli strongly suppressed from awareness and in the absence of top-down influences. We accomplished this using a novel approach in which participants performed an orthogonal task atop a flash suppression noise image to prevent top-down search. Second, we wished to investigate the extent to which amygdala responses differentiate between suppressed stimuli (fearful faces and houses based on their motivational relevance. Using continuous flash suppression in conjunction with fMRI, we presented fearful faces, houses, and a no stimulus control to one eye while participants performed an orthogonal task that appeared atop the flashing Mondrian image presented to the opposite eye. In 29 adolescents, we show activation in subcortical regions, including the superior colliculus, amygdala, thalamus, and hippocampus for suppressed objects (fearful faces and houses compared to a no stimulus control. Suppressed stimuli showed less activation compared to a no stimulus control in early visual cortex, indicating that object information was being suppressed from this region. Additionally, we find no activation in regions associated with conscious processing of these percepts (fusiform gyrus and/or parahippocampal cortex as assessed by mean activations and multi-voxel patterns. A psychophysiological interaction analysis that seeded the amygdala showed task-specific (fearful faces greater than houses modulation of right pulvinar and left inferior parietal cortex. Taken together, our results support a role for the amygdala in stimulus-driven attentional guidance towards objects of relevance and a potential mechanism for successful suppression of rivalrous stimuli.

  13. Factors that Determine the Non-Linear Amygdala Influence on Hippocampus-Dependent Memory

    OpenAIRE

    Akirav, Irit; Richter-Levin, Gal

    2006-01-01

    Stressful experiences are known to either improve or impair hippocampal-dependent memory tasks and synaptic plasticity. These positive and negative effects of stress on the hippocampus have been largely documented, however little is known about the mechanism involved in the twofold influence of stress on hippocampal functioning and about what factors define an enhancing or inhibitory outcome. We have recently demonstrated that activation of the basolateral amygdala can produce a biphasic effe...

  14. Molecular Mechanisms of Stress-Induced Increases in Fear Memory Consolidation within the Amygdala

    OpenAIRE

    Aubry, Antonio V.; Serrano, Peter A.; Burghardt, Nesha S.

    2016-01-01

    Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by w...

  15. Molecular Mechanisms of Stress-Induced Increases in Fear Memory Consolidation Within the Amygdala

    OpenAIRE

    Antonio Aubry; Antonio Aubry; Peter Serrano; Peter Serrano; Nesha Burghardt; Nesha Burghardt

    2016-01-01

    Stress can significantly impact brain function and increase the risk for developing various psychiatric disorders. Many of the brain regions that are implicated in psychiatric disorders and are vulnerable to the effects of stress are also involved in mediating emotional learning. Emotional learning has been a subject of intense investigation for the past 30 years, with the vast majority of studies focusing on the amygdala and its role in associative fear learning. However, the mechanisms by...

  16. [Hormonal homeostasis and intraocular pressure in chronic emotional stress caused by influences acting on the amygdala].

    Science.gov (United States)

    Isakova, L S; Danilov, G E; Egorkina, S B; Butolin, E G

    1989-01-01

    Changes in intraocular pressure, eye hydrodynamics and the amount of hypophyseal, thyroid, adrenal and pancreatic hormones were studied during continuous stimulation of amygdaloid complex or after administration of angiotensin II into the structure in rabbits. The effects involved changes in hormonal homeostasis and elevation of intraocular pressure due to a hypersecretion of intraocular fluid. The administration of angiotensin II during the amygdala stimulation enhanced the changes.

  17. The joyful, yet balanced, amygdala: moderated responses to positive but not negative stimuli in trait happiness

    OpenAIRE

    Cunningham, William A.; Kirkland, Tabitha

    2013-01-01

    Although much is known about the neural dynamics of maladaptive affective styles, the mechanisms of happiness and well-being are less clear. One possibility is that the neural processes of trait happiness are the opposite of those involved in depression/anxiety: ‘rose-colored glasses’ cause happy people to focus on positive cues while remaining oblivious to threats. Specifically, because negative affective styles have been associated with increased amygdala activation to negative stimuli, it ...

  18. Endocannabinoids in the rat basolateral amygdala enhance memory consolidation and enable glucocorticoid modulation of memory

    OpenAIRE

    Campolongo, Patrizia; Roozendaal, Benno; Trezza, Viviana; Hauer, Daniela; Schelling, Gustav; McGaugh, James L.; Cuomo, Vincenzo

    2009-01-01

    Extensive evidence indicates that the basolateral complex of the amygdala (BLA) modulates the consolidation of memories for emotionally arousing experiences, an effect that involves the activation of the glucocorticoid system. Because the BLA expresses high densities of cannabinoid CB1 receptors, the present experiments investigated whether the endocannabinoid system in the BLA influences memory consolidation and whether glucocorticoids interact with this system. The CB1 receptor agonist WIN5...

  19. Activity alterations in the bed nucleus of the stria terminalis and amygdala during threat anticipation in generalized anxiety disorder.

    Science.gov (United States)

    Buff, Christine; Brinkmann, Leonie; Bruchmann, Maximilian; Becker, Michael P I; Tupak, Sara; Herrmann, Martin J; Straube, Thomas

    2017-11-01

    Sustained anticipatory anxiety is central to Generalized Anxiety Disorder (GAD). During anticipatory anxiety, phasic threat responding appears to be mediated by the amygdala, while sustained threat responding seems related to the bed nucleus of the stria terminalis (BNST). Although sustained anticipatory anxiety in GAD patients was proposed to be associated with BNST activity alterations, firm evidence is lacking. We aimed to explore temporal characteristics of BNST and amygdala activity during threat anticipation in GAD patients. Nineteen GAD patients and nineteen healthy controls (HC) underwent functional magnetic resonance imaging (fMRI) during a temporally unpredictable threat anticipation paradigm. We defined phasic and a systematic variation of sustained response models for blood oxygen level-dependent responses during threat anticipation, to disentangle temporally dissociable involvement of the BNST and the amygdala. GAD patients relative to HC responded with increased phasic amygdala activity to onset of threat anticipation and with elevated sustained BNST activity that was delayed relative to the onset of threat anticipation. Both the amygdala and the BNST displayed altered responses during threat anticipation in GAD patients, albeit with different time courses. The results for the BNST activation hint towards its role in sustained threat responding, and contribute to a deeper understanding of pathological sustained anticipatory anxiety in GAD. © The Author (2017). Published by Oxford University Press.

  20. Serotonin neurons in the dorsal raphe mediate the anticataplectic action of orexin neurons by reducing amygdala activity.

    Science.gov (United States)

    Hasegawa, Emi; Maejima, Takashi; Yoshida, Takayuki; Masseck, Olivia A; Herlitze, Stefan; Yoshioka, Mitsuhiro; Sakurai, Takeshi; Mieda, Michihiro

    2017-04-25

    Narcolepsy is a sleep disorder caused by the loss of orexin (hypocretin)-producing neurons and marked by excessive daytime sleepiness and a sudden weakening of muscle tone, or cataplexy, often triggered by strong emotions. In a mouse model for narcolepsy, we previously demonstrated that serotonin neurons of the dorsal raphe nucleus (DRN) mediate the suppression of cataplexy-like episodes (CLEs) by orexin neurons. Using an optogenetic tool, in this paper we show that the acute activation of DRN serotonin neuron terminals in the amygdala, but not in nuclei involved in regulating rapid eye-movement sleep and atonia, suppressed CLEs. Not only did stimulating serotonin nerve terminals reduce amygdala activity, but the chemogenetic inhibition of the amygdala using designer receptors exclusively activated by designer drugs also drastically decreased CLEs, whereas chemogenetic activation increased them. Moreover, the optogenetic inhibition of serotonin nerve terminals in the amygdala blocked the anticataplectic effects of orexin signaling in DRN serotonin neurons. Taken together, the results suggest that DRN serotonin neurons, as a downstream target of orexin neurons, inhibit cataplexy by reducing the activity of amygdala as a center for emotional processing.

  1. Amygdala temporal dynamics: temperamental differences in the timing of amygdala response to familiar and novel faces

    Directory of Open Access Journals (Sweden)

    Shelton Richard C

    2009-12-01

    Full Text Available Abstract Background Inhibited temperament - the predisposition to respond to new people, places or things with wariness or avoidance behaviors - is associated with increased risk for social anxiety disorder and major depression. Although the magnitude of the amygdala's response to novelty has been identified as a neural substrate of inhibited temperament, there may also be differences in temporal dynamics (latency, duration, and peak. We hypothesized that persons with inhibited temperament would have faster responses to novel relative to familiar neutral faces compared to persons with uninhibited temperament. We used event-related functional magnetic resonance imaging to measure the temporal dynamics of the blood oxygen level dependent (BOLD response to both novel and familiar neutral faces in participants with inhibited or uninhibited temperament. Results Inhibited participants had faster amygdala responses to novel compared with familiar faces, and both longer and greater amygdala response to all faces. There were no differences in peak response. Conclusion Faster amygdala response to novelty may reflect a computational bias that leads to greater neophobic responses and represents a mechanism for the development of social anxiety.

  2. Connections of the corticomedial amygdala in the golden hamster. II. Efferents of the ''olfactory amygdala''

    International Nuclear Information System (INIS)

    Kevetter, G.A.; Winans, S.S.

    1981-01-01

    The anterior cortical (C1) and posterolateral cortical (C2) nuclei of the amygdala are designated the ''olfactory amygdala'' because they each receive direct projections from the main olfactory bulb. The efferents of these nuclei were traced after stereotaxic placement of 1-5 muCi tritiated proline in the corticomedial amygdala of the male golden hamsters. Following survival times of 12, 24, or 48 hours, 20 micron frozen sections of the brains were processed for light microscopic autoradiography. Efferents from C2 terminate in layers II and III of the olfactory tubercle and in layer Ib of pars ventralis and pars medialis of the anterior olfactory nucleus. Fibers from this nucleus also project to layers I and II of the infralimbic cortex and to the molecular layer of the agranular insular cortex. More posteriorly, fibers from C2 terminate in layer I of the dorsolateral entorhinal cortex, and in the endopiriform nucleus. From C1, efferent fibers travel in the stria terminalis and terminate in the precommissural bed nucleus of the stria terminalis and in the mediobasal hypothalamus. Efferents from C1 also innervate the molecular layer of C2, the amygdalo-hippocampal area, and the adjacent piriform cortex. Neurons in both C1 and C2 project to the molecular layer of the medial amygdaloid nucleus and the posteromedial cortical nucleus of the amygdala, the plexiform layer of the ventral subiculum, and the molecular layer of the lateral entorhinal cortex

  3. Gene Network Analysis in Amygdala following Taste Aversion Learning in Rats

    Directory of Open Access Journals (Sweden)

    Siva K. Panguluri

    2013-01-01

    Full Text Available Conditioned taste aversion (CTA is an adaptive behavior that benefits survival of animals including humans and also serves as a powerful model to study the neural mechanisms of learning. Memory formation is a necessary component of CTA learning and involves neural processing and regulation of gene expression in the amygdala. Many studies have been focused on the identification of intracellular signaling cascades involved in CTA, but not late responsive genes underlying the long-lasting behavioral plasticity. In this study, we explored in silico experiments to identify persistent changes in gene expression associated with CTA in rats. We used oligonucleotide microarrays to identify 248 genes in the amygdala regulated by CTA. Pathway Studio and IPA software analyses showed that the differentially expressed genes in the amygdala fall in diverse functional categories such as behavior, psychological disorders, nervous system development and function, and cell-to-cell signaling. Conditioned taste aversion is a complex behavioral trait which involves association of visceral and taste inputs, consolidation of taste and visceral information, memory formation, retrieval of stored information, and extinction phase. In silico analysis of differentially expressed genes is therefore necessary to manipulate specific phase/stage of CTA to understand the molecular insight.

  4. CORTICOTROPIN-RELEASING HORMONE MICROINFUSION IN THE CENTRAL AMYGDALA DIMINISHES A CARDIAC PARASYMPATHETIC OUTFLOW UNDER STRESS-FREE CONDITIONS

    NARCIS (Netherlands)

    WIERSMA, A; BOHUS, B; KOOLHAAS, JM

    1993-01-01

    The central nucleus of the amygdala (CeA) is known to be involved in the regulation of autonomic, neuroendocrine and behavioural responses in stress situations. The CeA contains large numbers of corticotropin-releasing hormone (CRH) cell bodies. Neuroanatomical studies revealed that the majority of

  5. Impaired fear extinction in serotonin transporter knockout rats is associated with increased 5-hydroxymethylcytosine in the amygdala

    NARCIS (Netherlands)

    Shan, L.; Guo, Hang-Yuan; van den Heuvel, Corina N A M; van Heerikhuize, J.J.; Homberg, Judith R

    2018-01-01

    AIMS: One potential risk factor for posttraumatic stress disorder (PTSD) involves the low activity (short; s) allelic variant of the serotonin transporter-linked polymorphic region (5-HTTLPR), possibly due to reduced prefrontal control over the amygdala. Evidence shows that DNA

  6. Roles of the basolateral amygdala and hippocampus in social recognition

    NARCIS (Netherlands)

    Gispen, W.H.; Maaswinkel, H.; Baars, A.M.; Spruijt, B.M.

    1996-01-01

    Lesions of the amygdala or hippocampus have a large impact on social behavior of rats. In this study we investigated whether a social recognition test was also affected by those lesions. An NMDA-induced lesion of the basolateral amygdala did not impair the ability to distinguish a familiar from an

  7. Amygdala reactivity to fearful faces correlates positively with impulsive aggression

    DEFF Research Database (Denmark)

    da Cunha-Bang, Sofi; Fisher, Patrick M; Hjordt, Liv V

    2018-01-01

    Facial expressions robustly activate the amygdala, a brain structure playing a critical role in aggression. Whereas previous studies suggest that amygdala reactivity is related to various measures of impulsive aggression, we here estimate a composite measure of impulsive aggression and evaluate...

  8. Synapse-specific astrocyte gating of amygdala-related behavior.

    Science.gov (United States)

    Martin-Fernandez, Mario; Jamison, Stephanie; Robin, Laurie M; Zhao, Zhe; Martin, Eduardo D; Aguilar, Juan; Benneyworth, Michael A; Marsicano, Giovanni; Araque, Alfonso

    2017-11-01

    The amygdala plays key roles in fear and anxiety. Studies of the amygdala have largely focused on neuronal function and connectivity. Astrocytes functionally interact with neurons, but their role in the amygdala remains largely unknown. We show that astrocytes in the medial subdivision of the central amygdala (CeM) determine the synaptic and behavioral outputs of amygdala circuits. To investigate the role of astrocytes in amygdala-related behavior and identify the underlying synaptic mechanisms, we used exogenous or endogenous signaling to selectively activate CeM astrocytes. Astrocytes depressed excitatory synapses from basolateral amygdala via A 1 adenosine receptor activation and enhanced inhibitory synapses from the lateral subdivision of the central amygdala via A 2A receptor activation. Furthermore, astrocytic activation decreased the firing rate of CeM neurons and reduced fear expression in a fear-conditioning paradigm. Therefore, we conclude that astrocyte activity determines fear responses by selectively regulating specific synapses, which indicates that animal behavior results from the coordinated activity of neurons and astrocytes.

  9. Time-dependent effects of corticosteroids on human amygdala processing

    NARCIS (Netherlands)

    Henckens, M.J.A.G.; van Wingen, G.A.; Joëls, M.; Fernández, G.

    2010-01-01

    Acute stress is associated with a sensitized amygdala. Corticosteroids, released in response to stress, are suggested to restore homeostasis by normalizing/desensitizing brain processing in the aftermath of stress. Here, we investigated the effects of corticosteroids on amygdala processing using

  10. Medial Amygdala and Aggressive Behavior : Interaction Between Testosterone and Vasopressin

    NARCIS (Netherlands)

    Koolhaas, J.M.; Roozendaal, B.; Boorsma, F.; Van Den Brink, T.H.C.

    1990-01-01

    This paper considers the functional significance of the testosterone-dependent vasopressinergic neurons of the medial amygdala (Ame) in intermale aggressive behavior of rats. Local microinfusion of vasopressin into the medial amygdala causes an increase in offensive behavior both in gonadally intact

  11. Amygdala signals subjective appetitiveness and aversiveness of mixed gambles

    DEFF Research Database (Denmark)

    Gelskov, Sofie V.; Henningsson, Susanne; Madsen, Kristoffer Hougaard

    2015-01-01

    People are more sensitive to losses than to equivalent gains when making financial decisions. We used functional magnetic resonance imaging (fMRI) to illuminate how the amygdala contributes to loss aversion. The blood oxygen level dependent (BOLD) response of the amygdala was mapped while healthy...... individuals were responding to 50/50 gambles with varying potential gain and loss amounts. Overall, subjects demanded twice as high potential gain as loss to accept a gamble. The individual level of loss aversion was expressed by the decision boundary, i.e., the gain-loss ratio at which subjects accepted...... and rejected gambles with equal probability. Amygdala activity increased the more the gain-loss ratio deviated from the individual decision boundary showing that the amygdala codes action value. This response pattern was more strongly expressed in loss aversive individuals, linking amygdala activity...

  12. Resilience and amygdala function in older healthy and depressed adults.

    Science.gov (United States)

    Leaver, Amber M; Yang, Hongyu; Siddarth, Prabha; Vlasova, Roza M; Krause, Beatrix; St Cyr, Natalie; Narr, Katherine L; Lavretsky, Helen

    2018-04-25

    Previous studies suggest that low emotional resilience may correspond with increased or over-active amygdala function. Complementary studies suggest that emotional resilience increases with age; older adults tend to have decreased attentional bias to negative stimuli compared to younger adults. Amygdala nuclei and related brain circuits have been linked to negative affect, and depressed patients have been demonstrated to have abnormal amygdala function. In the current study, we correlated psychological resilience measures with amygdala function measured with resting-state arterial spin-labelled (ASL) and blood-oxygenation-level-dependent (BOLD) functional magnetic resonance imaging (fMRI) in older adults with and without depression. Specifically, we targeted the basolateral, centromedial, and superficial nuclei groups of the amygdala, which have different functions and brain connections. High levels of psychological resilience correlated with lower basal levels of amygdala activity measured with ASL fMRI. High resilience also correlated with decreased connectivity between amygdala nuclei and the ventral default-mode network independent of depression status. Instead, lower depression symptoms were associated with higher connectivity between the amygdalae and dorsal frontal networks. Future multi-site studies with larger sample size and improved neuroimaging technologies are needed. Longitudinal studies that target resilience to naturalistic stressors will also be a powerful contribution to the field. Our results suggest that resilience in older adults is more closely related to function in ventral amygdala networks, while late-life depression is related to reduced connectivity between the amygdala and dorsal frontal regions. Copyright © 2018 Elsevier B.V. All rights reserved.

  13. Neuronal Adaptations during Amygdala-Dependent Learning and Memory : Neuronale aanpassingen tijdens Amygdala-afhankelijk leren en geheugen

    NARCIS (Netherlands)

    B.S. Hosseini (Behdokht)

    2016-01-01

    textabstractThe amygdala, a structure deep in the temporal lobe of the brain, is an essential region for emotional and fearful processing. Neuronal coding in the lateral nucleus of the amygdala (LA) endows the brain with the ability to acquire enduring aversive associations, physically represented

  14. Orexin/hypocretin system modulates amygdala-dependent threat learning through the locus coeruleus

    Science.gov (United States)

    Sears, Robert M.; Fink, Ann E.; Wigestrand, Mattis B.; Farb, Claudia R.; de Lecea, Luis; LeDoux, Joseph E.

    2013-01-01

    Survival in a dangerous environment requires learning about stimuli that predict harm. Although recent work has focused on the amygdala as the locus of aversive memory formation, the hypothalamus has long been implicated in emotional regulation, and the hypothalamic neuropeptide orexin (hypocretin) is involved in anxiety states and arousal. Nevertheless, little is known about the role of orexin in aversive memory formation. Using a combination of behavioral pharmacology, slice physiology, and optogenetic techniques, we show that orexin acts upstream of the amygdala via the noradrenergic locus coeruleus to enable threat (fear) learning, specifically during the aversive event. Our results are consistent with clinical studies linking orexin levels to aversive learning and anxiety in humans and dysregulation of the orexin system may contribute to the etiology of fear and anxiety disorders. PMID:24277819

  15. Pubertal testosterone influences threat-related amygdala-orbitofrontal cortex coupling.

    Science.gov (United States)

    Spielberg, Jeffrey M; Forbes, Erika E; Ladouceur, Cecile D; Worthman, Carol M; Olino, Thomas M; Ryan, Neal D; Dahl, Ronald E

    2015-03-01

    Growing evidence indicates that normative pubertal maturation is associated with increased threat reactivity, and this developmental shift has been implicated in the increased rates of adolescent affective disorders. However, the neural mechanisms involved in this pubertal increase in threat reactivity remain unknown. Research in adults indicates that testosterone transiently decreases amygdala-orbitofrontal cortex (OFC) coupling. Consequently, we hypothesized that increased pubertal testosterone disrupts amygdala-OFC coupling, which may contribute to developmental increases in threat reactivity in some adolescents. Hypotheses were tested in a longitudinal study by examining the impact of testosterone on functional connectivity. Findings were consistent with hypotheses and advance our understanding of normative pubertal changes in neural systems instantiating affect/motivation. Finally, potential novel insights into the neurodevelopmental pathways that may contribute to adolescent vulnerability to behavioral and emotional problems are discussed. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  16. Symptom-specific amygdala hyperactivity modulates motor control network in conversion disorder

    Directory of Open Access Journals (Sweden)

    Thomas Hassa

    2017-01-01

    Full Text Available Initial historical accounts as well as recent data suggest that emotion processing is dysfunctional in conversion disorder patients and that this alteration may be the pathomechanistic neurocognitive basis for symptoms in conversion disorder. However, to date evidence of direct interaction of altered negative emotion processing with motor control networks in conversion disorder is still lacking. To specifically study the neural correlates of emotion processing interacting with motor networks we used a task combining emotional and sensorimotor stimuli both separately as well as simultaneously during functional magnetic resonance imaging in a well characterized group of 13 conversion disorder patients with functional hemiparesis and 19 demographically matched healthy controls. We performed voxelwise statistical parametrical mapping for a priori regions of interest within emotion processing and motor control networks. Psychophysiological interaction (PPI was used to test altered functional connectivity of emotion and motor control networks. Only during simultaneous emotional stimulation and passive movement of the affected hand patients displayed left amygdala hyperactivity. PPI revealed increased functional connectivity in patients between the left amygdala and the (pre-supplemental motor area and the subthalamic nucleus, key regions within the motor control network. These findings suggest a novel mechanistic direct link between dysregulated emotion processing and motor control circuitry in conversion disorder.

  17. Symptom-specific amygdala hyperactivity modulates motor control network in conversion disorder.

    Science.gov (United States)

    Hassa, Thomas; Sebastian, Alexandra; Liepert, Joachim; Weiller, Cornelius; Schmidt, Roger; Tüscher, Oliver

    2017-01-01

    Initial historical accounts as well as recent data suggest that emotion processing is dysfunctional in conversion disorder patients and that this alteration may be the pathomechanistic neurocognitive basis for symptoms in conversion disorder. However, to date evidence of direct interaction of altered negative emotion processing with motor control networks in conversion disorder is still lacking. To specifically study the neural correlates of emotion processing interacting with motor networks we used a task combining emotional and sensorimotor stimuli both separately as well as simultaneously during functional magnetic resonance imaging in a well characterized group of 13 conversion disorder patients with functional hemiparesis and 19 demographically matched healthy controls. We performed voxelwise statistical parametrical mapping for a priori regions of interest within emotion processing and motor control networks. Psychophysiological interaction (PPI) was used to test altered functional connectivity of emotion and motor control networks. Only during simultaneous emotional stimulation and passive movement of the affected hand patients displayed left amygdala hyperactivity. PPI revealed increased functional connectivity in patients between the left amygdala and the (pre-)supplemental motor area and the subthalamic nucleus, key regions within the motor control network. These findings suggest a novel mechanistic direct link between dysregulated emotion processing and motor control circuitry in conversion disorder.

  18. Deep brain stimulation of the amygdala alleviates fear conditioning-induced alterations in synaptic plasticity in the cortical-amygdala pathway and fear memory.

    Science.gov (United States)

    Sui, Li; Huang, SiJia; Peng, BinBin; Ren, Jie; Tian, FuYing; Wang, Yan

    2014-07-01

    Deep brain stimulation (DBS) of the amygdala has been demonstrated to modulate hyperactivity of the amygdala, which is responsible for the symptoms of post-traumatic stress disorder (PTSD), and thus might be used for the treatment of PTSD. However, the underlying mechanism of DBS of the amygdala in the modulation of the amygdala is unclear. The present study investigated the effects of DBS of the amygdala on synaptic transmission and synaptic plasticity at cortical inputs to the amygdala, which is critical for the formation and storage of auditory fear memories, and fear memories. The results demonstrated that auditory fear conditioning increased single-pulse-evoked field excitatory postsynaptic potentials in the cortical-amygdala pathway. Furthermore, auditory fear conditioning decreased the induction of paired-pulse facilitation and long-term potentiation, two neurophysiological models for studying short-term and long-term synaptic plasticity, respectively, in the cortical-amygdala pathway. In addition, all these auditory fear conditioning-induced changes could be reversed by DBS of the amygdala. DBS of the amygdala also rescued auditory fear conditioning-induced enhancement of long-term retention of fear memory. These findings suggested that DBS of the amygdala alleviating fear conditioning-induced alterations in synaptic plasticity in the cortical-amygdala pathway and fear memory may underlie the neuromodulatory role of DBS of the amygdala in activities of the amygdala.

  19. Evidence for the involvement of extinction-associated inhibitory learning in the forced swimming test.

    Science.gov (United States)

    Campus, P; Colelli, V; Orsini, C; Sarra, D; Cabib, S

    2015-02-01

    The forced swimming test (FST) remains one of the most used tools for screening antidepressants in rodent models. Nonetheless, the nature of immobility, its main behavioral measure, is still a matter of debate. The present study took advantage of our recent finding that mice of the inbred DBA/2J strain require a functioning left dorsolateral striatum (DLS) to consolidate long-term memory of FST to test whether immobility is the outcome of stress-related learning. Infusion of the GABA-A agonist muscimol in the left DLS immediately after a single experience of FST prevented and infusion in the left or the right amygdala impaired recall of the acquired levels of immobility in a probe test performed 24h later. Post-training left DLS infusion of muscimol, at a dose capable of preventing retention of FST-induced immobility, did not influence 24h retention of inhibitory avoidance training or of the escape response acquired in a water T-maze. However, this same treatment prevented 24h retention of the extinction training of the consolidated escape response. These results indicate that a left DLS-centered memory system selectively mediates memory consolidation of FST and of escape extinction and support the hypothesis that immobility is the result of extinction-like inhibitory learning involving all available escape responses due to the inescapable/unavoidable nature of FST experience. Copyright © 2014 Elsevier B.V. All rights reserved.

  20. Nuclear protein phosphatase-1: an epigenetic regulator of fear memory and amygdala long-term potentiation.

    Science.gov (United States)

    Koshibu, K; Gräff, J; Mansuy, I M

    2011-01-26

    Complex brain diseases and neurological disorders in human generally result from the disturbance of multiple genes and signaling pathways. These disturbances may derive from mutations, deletions, translocations or rearrangements of specific gene(s). However, over the past years, it has become clear that such disturbances may also derive from alterations in the epigenome affecting several genes simultaneously. Our work recently demonstrated that epigenetic mechanisms in the adult brain are in part regulated by protein phosphatase 1 (PP1), a protein Ser/Thr phosphatase that negatively regulates hippocampus-dependent long-term memory (LTM) and synaptic plasticity. PP1 is abundant in brain structures involved in emotional processing like the amygdala, it may therefore be involved in the regulation of fear memory, a form of memory related to post-traumatic stress disorder (PTSD) in human. Here, we demonstrate that PP1 is a molecular suppressor of fear memory and synaptic plasticity in the amygdala that can control chromatin remodeling in neurons. We show that the selective inhibition of the nuclear pool of PP1 in amygdala neurons significantly alters posttranslational modifications (PTMs) of histones and the expression of several memory-associated genes. These alterations correlate with enhanced fear memory, and with an increase in long-term potentiation (LTP) that is transcription-dependent. Our results underscore the importance of nuclear PP1 in the amygdala as an epigenetic regulator of emotional memory, and the relevance of protein phosphatases as potential targets for therapeutic treatment of brain disorders like PTSD. © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

  1. Eyes wide shut: amygdala mediates eyes-closed effect on emotional experience with music.

    Science.gov (United States)

    Lerner, Yulia; Papo, David; Zhdanov, Andrey; Belozersky, Libi; Hendler, Talma

    2009-07-15

    The perceived emotional value of stimuli and, as a consequence the subjective emotional experience with them, can be affected by context-dependent styles of processing. Therefore, the investigation of the neural correlates of emotional experience requires accounting for such a variable, a matter of an experimental challenge. Closing the eyes affects the style of attending to auditory stimuli by modifying the perceptual relationship with the environment without changing the stimulus itself. In the current study, we used fMRI to characterize the neural mediators of such modification on the experience of emotionality in music. We assumed that closed eyes position will reveal interplay between different levels of neural processing of emotions. More specifically, we focused on the amygdala as a central node of the limbic system and on its co-activation with the Locus Ceruleus (LC) and Ventral Prefrontal Cortex (VPFC); regions involved in processing of, respectively, 'low', visceral-, and 'high', cognitive-related, values of emotional stimuli. Fifteen healthy subjects listened to negative and neutral music excerpts with eyes closed or open. As expected, behavioral results showed that closing the eyes while listening to emotional music resulted in enhanced rating of emotionality, specifically of negative music. In correspondence, fMRI results showed greater activation in the amygdala when subjects listened to the emotional music with eyes closed relative to eyes open. More so, by using voxel-based correlation and a dynamic causal model analyses we demonstrated that increased amygdala activation to negative music with eyes closed led to increased activations in the LC and VPFC. This finding supports a system-based model of perceived emotionality in which the amygdala has a central role in mediating the effect of context-based processing style by recruiting neural operations involved in both visceral (i.e. 'low') and cognitive (i.e. 'high') related processes of emotions.

  2. Conservatism and the neural circuitry of threat: economic conservatism predicts greater amygdala-BNST connectivity during periods of threat vs safety.

    Science.gov (United States)

    Pedersen, Walker S; Muftuler, L Tugan; Larson, Christine L

    2018-01-01

    Political conservatism is associated with an increased negativity bias, including increased attention and reactivity toward negative and threatening stimuli. Although the human amygdala has been implicated in the response to threatening stimuli, no studies to date have investigated whether conservatism is associated with altered amygdala function toward threat. Furthermore, although an influential theory posits that connectivity between the amygdala and bed nucleus of the stria terminalis (BNST) is important in initiating the response to sustained or uncertain threat, whether individual differences in conservatism modulate this connectivity is unknown. To test whether conservatism is associated with increased reactivity in neural threat circuitry, we measured participants' self-reported social and economic conservatism and asked them to complete high-resolution fMRI scans while under threat of an unpredictable shock and while safe. We found that economic conservatism predicted greater connectivity between the BNST and a cluster of voxels in the left amygdala during threat vs safety. These results suggest that increased amygdala-BNST connectivity during threat may be a key neural correlate of the enhanced negativity bias found in conservatism. © The Author (2017). Published by Oxford University Press.

  3. Different patterns of amygdala priming differentially affect dentate gyrus plasticity and corticosterone, but not CA1 plasticity.

    Directory of Open Access Journals (Sweden)

    Rose-Marie eVouimba

    2013-05-01

    Full Text Available Stress-induced activation of the amygdala is involved in the modulation of memory processes in the hippocampus. However, stress effects on amygdala and memory remain complex. The activation of the basolateral amygdala (BLA was found to modulate plasticity in other brain areas, including the hippocampus. We previously demonstrated a differential effect of BLA priming on LTP in the CA1 and the dentate gyrus (DG. While BLA priming suppressed long term potentiation (LTP in CA1, it was found to enhance it in the DG. However, since the amygdala itself is amenable to experience-induced plasticity it is thus conceivable that when activity within the amygdala is modified this will have impact on the way the amygdala modulates activity and plasticity in other brain areas. In the current study we examined the effects of different patterns of BLA activation on the modulation of LTP in the DG and CA1, as well as on serum corticosterone (CORT. In CA1, BLA priming impaired LTP induction as was reported before. In contrast, in the DG, varying BLA stimulation intensity and frequency resulted in differential effects on LTP, ranging from no effect to strong impairment or enhancement. Varying BLA stimulation patterns resulted in also differential alterations in Serum CORT, leading to higher CORT levels being positively correlated with LTP magnitude in DG but not in CA1.The results support the notion of a differential role for the DG in aspects of memory, and add to this view the possibility that DG-associated aspects of memory will be enhanced under more emotional or stressful conditions. It is interesting to think of BLA patterns of activation and the differential levels of circulating CORT as two arms of the emotional and stress response that attempt to synchronize brain activity to best meet the challenge. It is foreseeable to think of abnormal such synchronization under extreme conditions, which would lead to the development of maladaptive behavior.

  4. Adolescent alcohol exposure alters lysine demethylase 1 (LSD1) expression and histone methylation in the amygdala during adulthood.

    Science.gov (United States)

    Kyzar, Evan J; Zhang, Huaibo; Sakharkar, Amul J; Pandey, Subhash C

    2017-09-01

    Alcohol exposure in adolescence is an important risk factor for the development of alcoholism in adulthood. Epigenetic processes are implicated in the persistence of adolescent alcohol exposure-related changes, specifically in the amygdala. We investigated the role of histone methylation mechanisms in the persistent effects of adolescent intermittent ethanol (AIE) exposure in adulthood. Adolescent rats were exposed to 2 g/kg ethanol (2 days on/off) or intermittent n-saline (AIS) during postnatal days (PND) 28-41 and used for behavioral and epigenetic studies. We found that AIE exposure caused a long-lasting decrease in mRNA and protein levels of lysine demethylase 1(Lsd1) and mRNA levels of Lsd1 + 8a (a neuron-specific splice variant) in specific amygdaloid structures compared with AIS-exposed rats when measured at adulthood. Interestingly, AIE increased histone H3 lysine 9 dimethylation (H3K9me2) levels in the central nucleus of the amygdala (CeA) and medial nucleus of the amygdala (MeA) in adulthood without producing any change in H3K4me2 protein levels. Acute ethanol challenge (2 g/kg) in adulthood attenuated anxiety-like behaviors and the decrease in Lsd1 + 8a mRNA levels in the amygdala induced by AIE. AIE caused an increase in H3K9me2 occupancy at the brain-derived neurotrophic factor exon IV promoter in the amygdala that returned to baseline after acute ethanol challenge in adulthood. These results indicate that AIE specifically modulates epizymes involved in H3K9 dimethylation in the amygdala in adulthood, which are possibly responsible for AIE-induced chromatin remodeling and adult psychopathology such as anxiety. © Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  5. Neurons in the human amygdala selective for perceived emotion

    Science.gov (United States)

    Wang, Shuo; Tudusciuc, Oana; Mamelak, Adam N.; Ross, Ian B.; Adolphs, Ralph; Rutishauser, Ueli

    2014-01-01

    The human amygdala plays a key role in recognizing facial emotions and neurons in the monkey and human amygdala respond to the emotional expression of faces. However, it remains unknown whether these responses are driven primarily by properties of the stimulus or by the perceptual judgments of the perceiver. We investigated these questions by recording from over 200 single neurons in the amygdalae of 7 neurosurgical patients with implanted depth electrodes. We presented degraded fear and happy faces and asked subjects to discriminate their emotion by button press. During trials where subjects responded correctly, we found neurons that distinguished fear vs. happy emotions as expressed by the displayed faces. During incorrect trials, these neurons indicated the patients’ subjective judgment. Additional analysis revealed that, on average, all neuronal responses were modulated most by increases or decreases in response to happy faces, and driven predominantly by judgments about the eye region of the face stimuli. Following the same analyses, we showed that hippocampal neurons, unlike amygdala neurons, only encoded emotions but not subjective judgment. Our results suggest that the amygdala specifically encodes the subjective judgment of emotional faces, but that it plays less of a role in simply encoding aspects of the image array. The conscious percept of the emotion shown in a face may thus arise from interactions between the amygdala and its connections within a distributed cortical network, a scheme also consistent with the long response latencies observed in human amygdala recordings. PMID:24982200

  6. Oxytocin increases amygdala reactivity to threatening scenes in females.

    Science.gov (United States)

    Lischke, Alexander; Gamer, Matthias; Berger, Christoph; Grossmann, Annette; Hauenstein, Karlheinz; Heinrichs, Markus; Herpertz, Sabine C; Domes, Gregor

    2012-09-01

    The neuropeptide oxytocin (OT) is well known for its profound effects on social behavior, which appear to be mediated by an OT-dependent modulation of amygdala activity in the context of social stimuli. In humans, OT decreases amygdala reactivity to threatening faces in males, but enhances amygdala reactivity to similar faces in females, suggesting sex-specific differences in OT-dependent threat-processing. To further explore whether OT generally enhances amygdala-dependent threat-processing in females, we used functional magnetic resonance imaging (fMRI) in a randomized within-subject crossover design to measure amygdala activity in response to threatening and non-threatening scenes in 14 females following intranasal administration of OT or placebo. Participants' eye movements were recorded to investigate whether an OT-dependent modulation of amygdala activity is accompanied by enhanced exploration of salient scene features. Although OT had no effect on participants' gazing behavior, it increased amygdala reactivity to scenes depicting social and non-social threat. In females, OT may, thus, enhance the detection of threatening stimuli in the environment, potentially by interacting with gonadal steroids, such as progesterone and estrogen. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. Altered amygdala-prefrontal connectivity during emotion perception in schizophrenia.

    Science.gov (United States)

    Bjorkquist, Olivia A; Olsen, Emily K; Nelson, Brady D; Herbener, Ellen S

    2016-08-01

    Individuals with schizophrenia evidence impaired emotional functioning. Abnormal amygdala activity has been identified as an etiological factor underlying affective impairment in this population, but the exact nature remains unclear. The current study utilized psychophysiological interaction analyses to examine functional connectivity between the amygdala and medial prefrontal cortex (mPFC) during an emotion perception task. Participants with schizophrenia (SZ) and healthy controls (HC) viewed and rated positive, negative, and neutral images while undergoing functional neuroimaging. Results revealed a significant group difference in right amygdala-mPFC connectivity during perception of negative versus neutral images. Specifically, HC participants demonstrated positive functional coupling between the amygdala and mPFC, consistent with co-active processing of salient information. In contrast, SZ participants evidenced negative functional coupling, consistent with top-down inhibition of the amygdala by the mPFC. A significant positive correlation between connectivity strength during negative image perception and clinician-rated social functioning was also observed in SZ participants, such that weaker right amygdala-mPFC coupling during negative compared to neutral image perception was associated with poorer social functioning. Overall, results suggest that emotional dysfunction and associated deficits in functional outcome in schizophrenia may relate to abnormal interactions between the amygdala and mPFC during perception of emotional stimuli. This study adds to the growing literature on abnormal functional connections in schizophrenia and supports the functional disconnection hypothesis of schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Prenatal stress alters amygdala functional connectivity in preterm neonates.

    Science.gov (United States)

    Scheinost, Dustin; Kwon, Soo Hyun; Lacadie, Cheryl; Sze, Gordon; Sinha, Rajita; Constable, R Todd; Ment, Laura R

    2016-01-01

    Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.

  9. Amygdala hyperactivation to angry faces in intermittent explosive disorder.

    Science.gov (United States)

    McCloskey, Michael S; Phan, K Luan; Angstadt, Mike; Fettich, Karla C; Keedy, Sarah; Coccaro, Emil F

    2016-08-01

    Individuals with intermittent explosive disorder (IED) were previously found to exhibit amygdala hyperactivation and relatively reduced orbital medial prefrontal cortex (OMPFC) activation to angry faces while performing an implicit emotion information processing task during functional magnetic resonance imaging (fMRI). This study examines the neural substrates associated with explicit encoding of facial emotions among individuals with IED. Twenty unmedicated IED subjects and twenty healthy, matched comparison subjects (HC) underwent fMRI while viewing blocks of angry, happy, and neutral faces and identifying the emotional valence of each face (positive, negative or neutral). We compared amygdala and OMPFC reactivity to faces between IED and HC subjects. We also examined the relationship between amygdala/OMPFC activation and aggression severity. Compared to controls, the IED group exhibited greater amygdala response to angry (vs. neutral) facial expressions. In contrast, IED and control groups did not differ in OMPFC activation to angry faces. Across subjects amygdala activation to angry faces was correlated with number of prior aggressive acts. These findings extend previous evidence of amygdala dysfunction in response to the identification of an ecologically-valid social threat signal (processing angry faces) among individuals with IED, further substantiating a link between amygdala hyperactivity to social signals of direct threat and aggression. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. The Emotional Gatekeeper: A Computational Model of Attentional Selection and Suppression through the Pathway from the Amygdala to the Inhibitory Thalamic Reticular Nucleus

    Science.gov (United States)

    Bullock, Daniel; Barbas, Helen

    2016-01-01

    In a complex environment that contains both opportunities and threats, it is important for an organism to flexibly direct attention based on current events and prior plans. The amygdala, the hub of the brain's emotional system, is involved in forming and signaling affective associations between stimuli and their consequences. The inhibitory thalamic reticular nucleus (TRN) is a hub of the attentional system that gates thalamo-cortical signaling. In the primate brain, a recently discovered pathway from the amygdala sends robust projections to TRN. Here we used computational modeling to demonstrate how the amygdala-TRN pathway, embedded in a wider neural circuit, can mediate selective attention guided by emotions. Our Emotional Gatekeeper model demonstrates how this circuit enables focused top-down, and flexible bottom-up, allocation of attention. The model suggests that the amygdala-TRN projection can serve as a unique mechanism for emotion-guided selection of signals sent to cortex for further processing. This inhibitory selection mechanism can mediate a powerful affective ‘framing’ effect that may lead to biased decision-making in highly charged emotional situations. The model also supports the idea that the amygdala can serve as a relevance detection system. Further, the model demonstrates how abnormal top-down drive and dysregulated local inhibition in the amygdala and in the cortex can contribute to the attentional symptoms that accompany several neuropsychiatric disorders. PMID:26828203

  11. The Emotional Gatekeeper: A Computational Model of Attentional Selection and Suppression through the Pathway from the Amygdala to the Inhibitory Thalamic Reticular Nucleus.

    Directory of Open Access Journals (Sweden)

    Yohan J John

    2016-02-01

    Full Text Available In a complex environment that contains both opportunities and threats, it is important for an organism to flexibly direct attention based on current events and prior plans. The amygdala, the hub of the brain's emotional system, is involved in forming and signaling affective associations between stimuli and their consequences. The inhibitory thalamic reticular nucleus (TRN is a hub of the attentional system that gates thalamo-cortical signaling. In the primate brain, a recently discovered pathway from the amygdala sends robust projections to TRN. Here we used computational modeling to demonstrate how the amygdala-TRN pathway, embedded in a wider neural circuit, can mediate selective attention guided by emotions. Our Emotional Gatekeeper model demonstrates how this circuit enables focused top-down, and flexible bottom-up, allocation of attention. The model suggests that the amygdala-TRN projection can serve as a unique mechanism for emotion-guided selection of signals sent to cortex for further processing. This inhibitory selection mechanism can mediate a powerful affective 'framing' effect that may lead to biased decision-making in highly charged emotional situations. The model also supports the idea that the amygdala can serve as a relevance detection system. Further, the model demonstrates how abnormal top-down drive and dysregulated local inhibition in the amygdala and in the cortex can contribute to the attentional symptoms that accompany several neuropsychiatric disorders.

  12. cAMP response element-binding protein in the amygdala is required for long- but not short-term conditioned taste aversion memory.

    Science.gov (United States)

    Lamprecht, R; Hazvi, S; Dudai, Y

    1997-11-01

    In conditioned taste aversion (CTA) organisms learn to avoid a taste if the first encounter with that taste is followed by transient poisoning. The neural mechanisms that subserve this robust and long-lasting association of taste and malaise have not yet been elucidated, but several brain areas have been implicated in the process, including the amygdala. In this study we investigated the role of amygdala in general, and the cAMP response element-binding protein (CREB) in the amygdala in particular, in CTA learning and memory. Toward that end, we combined antisense technology in vivo with behavioral, molecular, and histochemical analysis. Local microinjection of phosphorothioate-modified oligodeoxynucleotides (ODNs) antisense to CREB into the rat amygdala several hours before CTA training transiently reduced the level of CREB protein during training and impaired CTA memory when tested 3-5 d later. In comparison, sense ODNs had no effect on memory. The effect of antisense was not attributable to differential tissue damage and was site-specific. CREB antisense in the amygdala had no effect on retrieval of CTA memory once it had been formed, and did not affect short-term CTA memory. We propose that the amygdala, specifically the central nucleus, is required for the establishment of long-term CTA memory in the behaving rat; that the process involves long-term changes, subserved by CRE-regulated gene expression, in amygdala neurons; and that the amygdala may retain some CTA-relevant information over time rather than merely modulating the gustatory trace during acquisition of CTA.

  13. Randomized Clinical Trial of Real-Time fMRI Amygdala Neurofeedback for Major Depressive Disorder: Effects on Symptoms and Autobiographical Memory Recall.

    Science.gov (United States)

    Young, Kymberly D; Siegle, Greg J; Zotev, Vadim; Phillips, Raquel; Misaki, Masaya; Yuan, Han; Drevets, Wayne C; Bodurka, Jerzy

    2017-08-01

    Patients with depression show blunted amygdala hemodynamic activity to positive stimuli, including autobiographical memories. The authors examined the therapeutic efficacy of real-time functional MRI neurofeedback (rtfMRI-nf) training aimed at increasing the amygdala's hemodynamic response to positive memories in patients with depression. In a double-blind, placebo-controlled, randomized clinical trial, unmedicated adults with depression (N=36) were randomly assigned to receive two sessions of rtfMRI-nf either from the amygdala (N=19) or from a parietal control region not involved in emotional processing (N=17). Clinical scores and autobiographical memory performance were assessed at baseline and 1 week after the final rtfMRI-nf session. The primary outcome measure was change in score on the Montgomery-Åsberg Depression Rating Scale (MADRS), and the main analytic approach consisted of a linear mixed-model analysis. In participants in the experimental group, the hemodynamic response in the amygdala increased relative to their own baseline and to the control group. Twelve participants in the amygdala rtfMRI-nf group, compared with only two in the control group, had a >50% decrease in MADRS score. Six participants in the experimental group, compared with one in the control group, met conventional criteria for remission at study end, resulting in a number needed to treat of 4. In participants receiving amygdala rtfMRI-nf, the percent of positive specific memories recalled increased relative to baseline and to the control group. rtfMRI-nf training to increase the amygdala hemodynamic response to positive memories significantly decreased depressive symptoms and increased the percent of specific memories recalled on an autobiographical memory test. These data support a role of the amygdala in recovery from depression.

  14. Connections of the corticomedial amygdala in the golden hamster. I. Efferents of the ''vomeronasal amygdala''

    International Nuclear Information System (INIS)

    Kevetter, G.A.; Winans, S.S.

    1981-01-01

    The medial (M) an posteromedial cortical (C3) amygdaloid nuclei and the nucleus of the accessory olfactory tract (NAOT) are designated the ''vomeronasal amygdala'' because they are the only components of the amygdala to receive a direct projection from the accessory olfactory bulb (AOB). The efferents of M and C3 were traced after injections of 3 H-proline into the amygdala in male golden hamsters. Frozen sections of the brains were processed for autoradiography. The efferents of the ''vomeronasal amygdala'' are largely to areas which are primary and secondary terminal areas along the vomeronasal pathway, although the efferents from C3 and M terminate in different layers in these areas than do the projections from the vomeronasal nerve or the AOB. Specifically, C3 projects ipsilaterally to the internal granule cell layer of the AOB, the cellular layer of NAOT, and layer Ib of M. Additional fibers from C3 terminate in a retrocommissural component of the bed nucleus of the strain terminalis (BNST) bilaterally, and in the cellular layers of the contralateral C3. The medial nucleus projects to the cellular layer of the ipsilateral NAOT, layer Ib of C3, and bilaterally to the medial component of BNST. Projections from M to non-vomeronasal areas terminate in the medial preoptic area-anterior hypothalamic junction, ventromedial nucleus of the hypothalamus, ventral premammillary nucleus and possibly in the ventral subiculum. These results demonstrate reciprocal connections between primary and secondary vomeronasal areas between the secondary areas themselves. They suggest that M, but not C3, projects to areas outside this vomeronasal network. The medial amygdaloid nucleus is therefore an important link between the vomeronasal organ and areas of the brain not receiving direct vomeronasal input

  15. Activity dependent protein degradation is critical for the formation and stability of fear memory in the amygdala.

    Directory of Open Access Journals (Sweden)

    Timothy J Jarome

    Full Text Available Protein degradation through the ubiquitin-proteasome system [UPS] plays a critical role in some forms of synaptic plasticity. However, its role in memory formation in the amygdala, a site critical for the formation of fear memories, currently remains unknown. Here we provide the first evidence that protein degradation through the UPS is critically engaged at amygdala synapses during memory formation and retrieval. Fear conditioning results in NMDA-dependent increases in degradation-specific polyubiquitination in the amygdala, targeting proteins involved in translational control and synaptic structure and blocking the degradation of these proteins significantly impairs long-term memory. Furthermore, retrieval of fear memory results in a second wave of NMDA-dependent polyubiquitination that targets proteins involved in translational silencing and synaptic structure and is critical for memory updating following recall. These results indicate that UPS-mediated protein degradation is a major regulator of synaptic plasticity necessary for the formation and stability of long-term memories at amygdala synapses.

  16. Left main percutaneous coronary intervention.

    Science.gov (United States)

    Teirstein, Paul S; Price, Matthew J

    2012-10-23

    The introduction of drug-eluting stents and advances in catheter techniques have led to increasing acceptance of percutaneous coronary intervention (PCI) as a viable alternative to coronary artery bypass graft (CABG) for unprotected left main disease. Current guidelines state that it is reasonable to consider unprotected left main PCI in patients with low to intermediate anatomic complexity who are at increased surgical risk. Data from randomized trials involving patients who are candidates for either treatment strategy provide novel insight into the relative safety and efficacy of PCI for this lesion subset. Herein, we review the current data comparing PCI with CABG for left main disease, summarize recent guideline recommendations, and provide an update on technical considerations that may optimize clinical outcomes in left main PCI. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  17. Amygdala response to emotional faces in seasonal affective disorder

    DEFF Research Database (Denmark)

    Borgsted, Camilla; Ozenne, Brice; Mc Mahon, Brenda

    2018-01-01

    BACKGROUND: Seasonal affective disorder (SAD) is characterized by seasonally recurring depression. Heightened amygdala activation to aversive stimuli is associated with major depressive disorder but its relation to SAD is unclear. We evaluated seasonal variation in amygdala activation in SAD......, we correlated change in symptom severity, assessed with The Hamilton Rating Scale for Depression - Seasonal Affective Disorder version (SIGH-SAD), with change in amygdala activation. RESULTS: We found no season-by-group, season or group effect on our aversive contrast. Independent of season, SAD...... of the presence of depressive symptoms....

  18. Emotion, decision making, and the amygdala.

    Science.gov (United States)

    Seymour, Ben; Dolan, Ray

    2008-06-12

    Emotion plays a critical role in many contemporary accounts of decision making, but exactly what underlies its influence and how this is mediated in the brain remain far from clear. Here, we review behavioral studies that suggest that Pavlovian processes can exert an important influence over choice and may account for many effects that have traditionally been attributed to emotion. We illustrate how recent experiments cast light on the underlying structure of Pavlovian control and argue that generally this influence makes good computational sense. Corresponding neuroscientific data from both animals and humans implicate a central role for the amygdala through interactions with other brain areas. This yields a neurobiological account of emotion in which it may operate, often covertly, to optimize rather than corrupt economic choice.

  19. A Pilot Study of Mindfulness-based Exposure Therapy in OEF/OIF Combat Veterans with PTSD: Altered Medial Frontal Cortex and Amygdala Responses in Social-Emotional Processing

    Directory of Open Access Journals (Sweden)

    Anthony King

    2016-09-01

    Full Text Available Combat-related PTSD is common among returning veterans, and is a serious and debilitating disorder. While highly effective treatments involving trauma exposure exist, difficulties with engagement and early drop may lead to sub-optimal outcomes. Mindfulness training may provide a method for increasing emotional regulation skills that may improve engagement in trauma-focused therapy. Here we examine potential neural correlates of mindfulness training and in vivo exposure (non-trauma focused using a novel group therapy (Mindfulness-based Exposure Therapy in Afghanistan (OEF or Iraq (OIF combat veterans with PTSD. OEF/OIF combat veterans with PTSD (N=23 were treated with MBET (N = 14 or a comparison group therapy (Present-centered group therapy [PCGT], N = 9. PTSD symptoms were assessed at pre- and post-therapy with Clinician Administered PTSD scale (CAPS. Functional neuroimaging (3 Tesla fMRI before and after therapy examined responses to emotional faces (angry, fearful, and neutral faces. Patients treated with MBET had reduced PTSD symptoms (effect size d = .92 but effect was not significantly different from PCGT (d = .43. Improvement in PTSD symptoms from Pre- to Post treatment in both treatment groups was correlated with increased activity in rostral ACC, dorsal medial PFC, and left amygdala. The MBET group showed greater increases in amygdala and fusiform gyrus responses to Angry faces, as well as increased response in left medial PFC to Fearful faces. These preliminary findings provide intriguing evidence that MBET group therapy for PTSD may lead to changes in neural processing of social-emotional threat related to symptom reduction.

  20. Consequences of temporary inhibition of the medial amygdala on social recognition memory performance in mice

    Directory of Open Access Journals (Sweden)

    Julia eNoack

    2015-04-01

    Full Text Available Different lines of investigation suggest that the medial amygdala is causally involved in the processing of information linked to social behaviour in rodents. Here we investigated the consequences of temporary inhibition of the medial amygdala by bilateral injections of lidocaine on long-term social recognition memory as tested in the social discrimination task. Lidocaine or control NaCl solution was infused immediately before learning or before retrieval. Our data show that lidocaine infusion immediately before learning did not affect long-term memory retrieval. However, intra-amygdalar lidocaine infusions immediately before choice interfered with correct memory retrieval. Analysis of the aggressive behaviour measured simultaneously during all sessions in the social recognition memory task support the impression that the lidocaine dosage used here was effective as it – at least partially – reduced the aggressive behaviour shown by the experimental subjects towards the juveniles. Surprisingly, also infusions of NaCl solution blocked recognition memory at both injection time points. The results are interpreted in the context of the importance of the medial amygdala for the processing of non-volatile odours as a major contributor to the olfactory signature for social recognition memory.

  1. Alterations in protein phosphorylation in the amygdala of the 5XFamilial Alzheimer's disease animal model.

    Science.gov (United States)

    Yang, Eun-Jeong; Mahmood, Usman; Kim, Hyunju; Choi, Moonseok; Choi, Yunjung; Lee, Jean-Pyo; Chang, Moon-Jeong; Kim, Hye-Sun

    2017-04-01

    Alzheimer's disease is the most common disease underlying dementia in humans. Two major neuropathological hallmarks of AD are neuritic plaques primarily composed of amyloid beta peptide and neurofibrillary tangles primarily composed of hyperphosphorylated tau. In addition to impaired memory function, AD patients often display neuropsychiatric symptoms and abnormal emotional states such as confusion, delusion, manic/depressive episodes and altered fear status. Brains from AD patients show atrophy of the amygdala which is involved in fear expression and emotional processing as well as hippocampal atrophy. However, which molecular changes are responsible for the altered emotional states observed in AD remains to be elucidated. Here, we observed that the fear response as assessed by evaluating fear memory via a cued fear conditioning test was impaired in 5XFamilial AD (5XFAD) mice, an animal model of AD. Compared to wild-type mice, 5XFAD mice showed changes in the phosphorylation of twelve proteins in the amygdala. Thus, our study provides twelve potential protein targets in the amygdala that may be responsible for the impairment in fear memory in AD. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  2. The central extended amygdala in fear and anxiety: Closing the gap between mechanistic and neuroimaging research.

    Science.gov (United States)

    Fox, Andrew S; Shackman, Alexander J

    2017-11-30

    Anxiety disorders impose a staggering burden on public health, underscoring the need to develop a deeper understanding of the distributed neural circuits underlying extreme fear and anxiety. Recent work highlights the importance of the central extended amygdala, including the central nucleus of the amygdala (Ce) and neighboring bed nucleus of the stria terminalis (BST). Anatomical data indicate that the Ce and BST form a tightly interconnected unit, where different kinds of threat-relevant information can be integrated to assemble states of fear and anxiety. Neuroimaging studies show that the Ce and BST are engaged by a broad spectrum of potentially threat-relevant cues. Mechanistic work demonstrates that the Ce and BST are critically involved in organizing defensive responses to a wide range of threats. Studies in rodents have begun to reveal the specific molecules, cells, and microcircuits within the central extended amygdala that underlie signs of fear and anxiety, but the relevance of these tantalizing discoveries to human experience and disease remains unclear. Using a combination of focal perturbations and whole-brain imaging, a new generation of nonhuman primate studies is beginning to close this gap. This work opens the door to discovering the mechanisms underlying neuroimaging measures linked to pathological fear and anxiety, to understanding how the Ce and BST interact with one another and with distal brain regions to govern defensive responses to threat, and to developing improved intervention strategies. Copyright © 2017. Published by Elsevier B.V.

  3. Amygdala alterations during an emotional conflict task in women recovered from anorexia nervosa.

    Science.gov (United States)

    Bang, Lasse; Rø, Øyvind; Endestad, Tor

    2016-02-28

    The pathophysiology of anorexia nervosa (AN) is not completely understood, but research suggests that alterations in brain circuits related to cognitive control and emotion are central. The aim of this study was to explore neural responses to an emotional conflict task in women recovered from AN. Functional magnetic resonance imaging was used to measure neural responses to an emotional conflict task in 22 women recovered from AN and 21 age-matched healthy controls. The task involved categorizing affective faces while ignoring affective words. Face and word stimuli were either congruent (non-conflict) or incongruent (conflict). Brain responses to emotional conflict did not differ between groups. However, in response to emotional non-conflict, women recovered from AN relative to healthy controls showed significantly less activation in the bilateral amygdala. Specifically, while emotional non-conflict evoked significant activations of the amygdala in healthy controls, recovered AN women did not show such activations. Similar significant group differences were also observed in the hippocampus and basal ganglia. These results suggest that women recovered from AN are characterized by alterations within emotion-related brain circuits. Recovered women's absence of amygdala and hippocampus activation during non-conflict trials possibly reflects an impaired ability to process emotional significant stimuli. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  4. Neurons in the monkey amygdala detect eye-contact during naturalistic social interactions

    Science.gov (United States)

    Mosher, Clayton P.; Zimmerman, Prisca E.; Gothard, Katalin M.

    2014-01-01

    Summary Primates explore the visual world through eye-movement sequences. Saccades bring details of interest into the fovea while fixations stabilize the image [1]. During natural vision, social primates direct their gaze at the eyes of others to communicate their own emotions and intentions and to gather information about the mental states of others [2]. Direct gaze is an integral part of facial expressions that signals cooperation or conflict over resources and social status [3-6]. Despite the great importance of making and breaking eye contact in the behavioral repertoire of primates, little is known about the neural substrates that support these behaviors. Here we show that the monkey amygdala contains neurons that respond selectively to fixations at the eyes of others and to eye contact. These “eye cells” share several features with the canonical, visually responsive neurons in the monkey amygdala, however, they respond to the eyes only when they fall within the fovea of the viewer, either as a result of a deliberate saccade, or as eyes move into the fovea of the viewer during a fixation intended to explore a different feature. The presence of eyes in peripheral vision fails to activate the eye cells. These findings link the primate amygdala to eye-movements involved in the exploration and selection of details in visual scenes that contain socially and emotionally salient features. PMID:25283782

  5. Neurons in the monkey amygdala detect eye contact during naturalistic social interactions.

    Science.gov (United States)

    Mosher, Clayton P; Zimmerman, Prisca E; Gothard, Katalin M

    2014-10-20

    Primates explore the visual world through eye-movement sequences. Saccades bring details of interest into the fovea, while fixations stabilize the image. During natural vision, social primates direct their gaze at the eyes of others to communicate their own emotions and intentions and to gather information about the mental states of others. Direct gaze is an integral part of facial expressions that signals cooperation or conflict over resources and social status. Despite the great importance of making and breaking eye contact in the behavioral repertoire of primates, little is known about the neural substrates that support these behaviors. Here we show that the monkey amygdala contains neurons that respond selectively to fixations on the eyes of others and to eye contact. These "eye cells" share several features with the canonical, visually responsive neurons in the monkey amygdala; however, they respond to the eyes only when they fall within the fovea of the viewer, either as a result of a deliberate saccade or as eyes move into the fovea of the viewer during a fixation intended to explore a different feature. The presence of eyes in peripheral vision fails to activate the eye cells. These findings link the primate amygdala to eye movements involved in the exploration and selection of details in visual scenes that contain socially and emotionally salient features. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Basal μ-opioid receptor availability in the amygdala predicts the inhibition of pain-related brain activity during heterotopic noxious counter-stimulation.

    Science.gov (United States)

    Piché, Mathieu; Watanabe, Nobuhiro; Sakata, Muneyuki; Oda, Keiichi; Toyohara, Jun; Ishii, Kenji; Ishiwata, Kiichi; Hotta, Harumi

    2014-01-01

    The aim of this study was to investigate the association between the magnitude of anti-nociceptive effects induced by heterotopic noxious counter-stimulation (HNCS) and the basal μ-opioid receptor availability in the amygdala. In 8 healthy volunteers (4 females and 4 males), transcutaneous electrical stimulation was applied to the right sural nerve to produce the nociceptive flexion reflex (RIII-reflex), moderate pain, and scalp somatosensory evoked potentials (SEPs). Immersion of the left hand in cold water for 20min was used as HNCS. In a separate session, basal μ-opioid receptor availability was measured using positron emission tomography with the radiotracer [(11)C]carfentanil. HNCS produced a reduction of the P260 amplitude (pbasal μ-opioid receptor availability in the amygdala on the right (R(2)=0.55, p=0.03) with a similar trend on the left (R(2)=0.24, p=0.22). Besides, HNCS did not induce significant changes in pain and RIII-reflex amplitude (p>0.05). These results suggest that activation of μ-opioid receptors in the amygdala may contribute to the anti-nociceptive effects of HNCS. The lack of RIII-reflex modulation further suggests that μ-opioid receptor activation in the amygdala contributes to decrease pain-related brain activity through a cerebral mechanism independent of descending modulation. Copyright © 2014 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  7. Preferential recruitment of the basolateral amygdala during memory encoding of negative scenes in posttraumatic stress disorder.

    Science.gov (United States)

    Patel, Ronak; Girard, Todd A; Pukay-Martin, Nicole; Monson, Candice

    2016-04-01

    The vast majority of functional neuroimaging studies in posttraumatic stress disorder (PTSD) have examined the amygdala as a unitary structure. However, an emerging body of studies indicates that separable functions are subserved by discrete amygdala subregions. The basolateral subdivision (BLA), as compared with the centromedial amygdala (CMA), plays a unique role in learning and memory-based processes for threatening events, and alterations to the BLA have been implicated in the pathogenesis of PTSD. We assessed whether PTSD is associated with differential involvement of the BLA versus the CMA during successful encoding of emotionally charged events. Participants with PTSD (n=11) and a trauma-exposed comparison (TEC) group (n=11) viewed a series of photos that varied in valence (negative versus positive) and arousal (high versus low) while undergoing functional magnetic resonance imaging (fMRI). Subsequently, participants completed an old/new recognition memory test. Using analytic methods based on probabilistic cytoarchitectonic mapping, PTSD was associated with greater activation of the BLA, as compared to the CMA, during successful encoding of negative scenes, a finding which was not observed in the TEC group. Moreover, this memory-related activity in the BLA independently predicted PTSD status. Contrary to hypotheses, there was no evidence of altered BLA activity during memory encoding of high arousing relative to low arousing scenes. Task-related brain activation in PTSD does not appear to be consistent across the entire amygdala. Importantly, memory-related processing of negative information in PTSD is associated with preferential recruitment of the BLA. Copyright © 2016. Published by Elsevier Inc.

  8. TMS over the Left Angular Gyrus Impairs the Ability to Discriminate Left from Right

    Science.gov (United States)

    Hirnstein, Marco; Bayer, Ulrike; Ellison, Amanda; Hausmann, Markus

    2011-01-01

    The underlying cognitive and neural mechanisms of the ability to discriminate left from right are hardly explored. Clinical studies from patients with impairments of left-right discrimination (LRD) and neuroimaging data suggest that the left angular gyrus is particularly involved in LRD. Moreover, it is argued that the often reported sex…

  9. Pre-treatment amygdala volume predicts electroconvulsive therapy response

    NARCIS (Netherlands)

    ten Doesschate, Freek; van Eijndhoven, Philip; Tendolkar, Indira; van Wingen, Guido A.; van Waarde, Jeroen A.

    2014-01-01

    Electroconvulsive therapy (ECT) is an effective treatment for patients with severe depression. Knowledge on factors predicting therapeutic response may help to identify patients who will benefit most from the intervention. Based on the neuroplasticity hypothesis, volumes of the amygdala and

  10. Genoarchitecture of the extended amygdala in zebra finch, and expression of FoxP2 in cell corridors of different genetic profile.

    Science.gov (United States)

    Vicario, Alba; Mendoza, Ezequiel; Abellán, Antonio; Scharff, Constance; Medina, Loreta

    2017-01-01

    We used a battery of genes encoding transcription factors (Pax6, Islet1, Nkx2.1, Lhx6, Lhx5, Lhx9, FoxP2) and neuropeptides to study the extended amygdala in developing zebra finches. We identified different components of the central extended amygdala comparable to those found in mice and chickens, including the intercalated amygdalar cells, the central amygdala, and the lateral bed nucleus of the stria terminalis. Many cells likely originate in the dorsal striatal domain, ventral striatal domain, or the pallidal domain, as is the case in mice and chickens. Moreover, a cell subpopulation of the central extended amygdala appears to originate in the prethalamic eminence. As a general principle, these different cells with specific genetic profiles and embryonic origin form separate or partially intermingled cell corridors along the extended amygdala, which may be involved in different functional pathways. In addition, we identified the medial amygdala of the zebra finch. Like in the chickens and mice, it is located in the subpallium and is rich in cells of pallido-preoptic origin, containing minor subpopulations of immigrant cells from the ventral pallium, alar hypothalamus and prethalamic eminence. We also proposed that the medial bed nucleus of the stria terminalis is composed of several parallel cell corridors with different genetic profile and embryonic origin: preoptic, pallidal, hypothalamic, and prethalamic. Several of these cell corridors with distinct origin express FoxP2, a transcription factor implicated in synaptic plasticity. Our results pave the way for studies using zebra finches to understand the neural basis of social behavior, in which the extended amygdala is involved.

  11. Amygdala Volume and Social Network Size in Humans

    OpenAIRE

    Bickart, Kevin C.; Wright, Christopher I.; Dautoff, Rebecca J.; Dickerson, Bradford C.; Barrett, Lisa Feldman

    2010-01-01

    We demonstrated that amygdala volume (corrected for total intracranial volume) positively correlated with the size and complexity of social networks in adult humans ranging in age from 19 to 83 years. This relationship was specific to the amygdala as compared to other subcortical structures. An exploratory analysis of the entire cortical mantle also revealed an association between social network variables and cortical thickness in three cortical areas, two of which share dense connectivity wi...

  12. Synaptic dysfunction in amygdala in intellectual disorder models.

    Science.gov (United States)

    Aincy, Marianne; Meziane, Hamid; Herault, Yann; Humeau, Yann

    2018-06-08

    The amygdala is a part of the limbic circuit that has been extensively studied in terms of synaptic connectivity, plasticity and cellular organization since decades (Ehrlich et al., 2009; Ledoux, 2000; Maren, 2001). Amygdala sub-nuclei, including lateral, basolateral and central amygdala appear now as "hubs" providing in parallel and in series neuronal processing enabling the animal to elicit freezing or escaping behavior in response to external threats. In rodents, these behaviors are easily observed and quantified following associative fear conditioning. Thus, studies on amygdala circuit in association with threat/fear behavior became very popular in laboratories and are often used among other behavioral tests to evaluate learning abilities of mouse models for various neuropsychiatric conditions including genetically encoded intellectual disabilities (ID). Yet, more than 100 human X-linked genes - and several hundreds of autosomal genes - have been associated with ID in humans. These mutations introduced in mice can generate social deficits, anxiety dysregulations and fear learning impairments (McNaughton et al., 2008; Houbaert et al., 2013; Jayachandran et al., 2014; Zhang et al., 2015). Noteworthy, a significant proportion of the coded ID gene products are synaptic proteins. It is postulated that the loss of function of these proteins could destabilize neuronal circuits by global changes of the balance between inhibitory and excitatory drives onto neurons. However, whereas amygdala related behavioral deficits are commonly observed in ID models, the role of most of these ID-genes in synaptic function and plasticity in the amygdala are only sparsely studied. We will here discuss some of the concepts that emerged from amygdala-targeted studies examining the role of syndromic and non-syndromic ID genes in fear-related behaviors and/or synaptic function. Along describing these cases, we will discuss how synaptic deficits observed in amygdala circuits could impact

  13. Human Amygdala Represents the Complete Spectrum of Subjective Valence

    Science.gov (United States)

    Jin, Jingwen; Zelano, Christina; Gottfried, Jay A.

    2015-01-01

    Although the amygdala is a major locus for hedonic processing, how it encodes valence information is poorly understood. Given the hedonic potency of odor stimuli and the amygdala's anatomical proximity to the peripheral olfactory system, we combined high-resolution fMRI with pattern-based multivariate techniques to examine how valence information is encoded in the amygdala. Ten human subjects underwent fMRI scanning while smelling 9 odorants that systematically varied in perceived valence. Representational similarity analyses showed that amygdala codes the entire dimension of valence, ranging from pleasantness to unpleasantness. This unidimensional representation significantly correlated with self-reported valence ratings but not with intensity ratings. Furthermore, within-trial valence representations evolved over time, prioritizing earlier differentiation of unpleasant stimuli. Together, these findings underscore the idea that both spatial and temporal features uniquely encode pleasant and unpleasant odor valence in the amygdala. The availability of a unidimensional valence code in the amygdala, distributed in both space and time, would create greater flexibility in determining the pleasantness or unpleasantness of stimuli, providing a mechanism by which expectation, context, attention, and learning could influence affective boundaries for guiding behavior. SIGNIFICANCE STATEMENT Our findings elucidate the mechanisms of affective processing in the amygdala by demonstrating that this brain region represents the entire valence dimension from pleasant to unpleasant. An important implication of this unidimensional valence code is that pleasant and unpleasant valence cannot coexist in the amygdale because overlap of fMRI ensemble patterns for these two valence extremes obscures their unique content. This functional architecture, whereby subjective valence maps onto a pattern continuum between pleasant and unpleasant poles, offers a robust mechanism by which context

  14. Elevated amygdala activity to sad facial expressions: a state marker of bipolar but not unipolar depression.

    Science.gov (United States)

    Almeida, Jorge R C; Versace, Amelia; Hassel, Stefanie; Kupfer, David J; Phillips, Mary L

    2010-03-01

    Difficulties in emotion processing and poor social function are common to bipolar disorder (BD) and major depressive disorder (MDD) depression, resulting in many BD depressed individuals being misdiagnosed with MDD. The amygdala is a key region implicated in processing emotionally salient stimuli, including emotional facial expressions. It is unclear, however, whether abnormal amygdala activity during positive and negative emotion processing represents a persistent marker of BD regardless of illness phase or a state marker of depression common or specific to BD and MDD depression. Sixty adults were recruited: 15 depressed with BD type 1 (BDd), 15 depressed with recurrent MDD, 15 with BD in remission (BDr), diagnosed with DSM-IV and Structured Clinical Interview for DSM-IV Research Version criteria; and 15 healthy control subjects (HC). Groups were age- and gender ratio-matched; patient groups were matched for age of illness onset and illness duration; depressed groups were matched for depression severity. The BDd were taking more psychotropic medication than other patient groups. All individuals participated in three separate 3T neuroimaging event-related experiments, where they viewed mild and intense emotional and neutral faces of fear, happiness, or sadness from a standardized series. The BDd-relative to HC, BDr, and MDD-showed elevated left amygdala activity to mild and neutral facial expressions in the sad (p sad and neutral faces might be a depression-specific marker in BD but not MDD, suggesting different pathophysiologic processes for BD versus MDD depression. Copyright 2010 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  15. Inhibitory Gating of Basolateral Amygdala Inputs to the Prefrontal Cortex.

    Science.gov (United States)

    McGarry, Laura M; Carter, Adam G

    2016-09-07

    Interactions between the prefrontal cortex (PFC) and basolateral amygdala (BLA) regulate emotional behaviors. However, a circuit-level understanding of functional connections between these brain regions remains incomplete. The BLA sends prominent glutamatergic projections to the PFC, but the overall influence of these inputs is predominantly inhibitory. Here we combine targeted recordings and optogenetics to examine the synaptic underpinnings of this inhibition in the mouse infralimbic PFC. We find that BLA inputs preferentially target layer 2 corticoamygdala over neighboring corticostriatal neurons. However, these inputs make even stronger connections onto neighboring parvalbumin and somatostatin expressing interneurons. Inhibitory connections from these two populations of interneurons are also much stronger onto corticoamygdala neurons. Consequently, BLA inputs are able to drive robust feedforward inhibition via two parallel interneuron pathways. Moreover, the contributions of these interneurons shift during repetitive activity, due to differences in short-term synaptic dynamics. Thus, parvalbumin interneurons are activated at the start of stimulus trains, whereas somatostatin interneuron activation builds during these trains. Together, these results reveal how the BLA impacts the PFC through a complex interplay of direct excitation and feedforward inhibition. They also highlight the roles of targeted connections onto multiple projection neurons and interneurons in this cortical circuit. Our findings provide a mechanistic understanding for how the BLA can influence the PFC circuit, with important implications for how this circuit participates in the regulation of emotion. The prefrontal cortex (PFC) and basolateral amygdala (BLA) interact to control emotional behaviors. Here we show that BLA inputs elicit direct excitation and feedforward inhibition of layer 2 projection neurons in infralimbic PFC. BLA inputs are much stronger at corticoamygdala neurons compared

  16. Growth hormone biases amygdala network activation after fear learning.

    Science.gov (United States)

    Gisabella, B; Farah, S; Peng, X; Burgos-Robles, A; Lim, S H; Goosens, K A

    2016-11-29

    Prolonged stress exposure is a risk factor for developing posttraumatic stress disorder, a disorder characterized by the 'over-encoding' of a traumatic experience. A potential mechanism by which this occurs is through upregulation of growth hormone (GH) in the amygdala. Here we test the hypotheses that GH promotes the over-encoding of fearful memories by increasing the number of neurons activated during memory encoding and biasing the allocation of neuronal activation, one aspect of the process by which neurons compete to encode memories, to favor neurons that have stronger inputs. Viral overexpression of GH in the amygdala increased the number of amygdala cells activated by fear memory formation. GH-overexpressing cells were especially biased to express the immediate early gene c-Fos after fear conditioning, revealing strong autocrine actions of GH in the amygdala. In addition, we observed dramatically enhanced dendritic spine density in GH-overexpressing neurons. These data elucidate a previously unrecognized autocrine role for GH in the regulation of amygdala neuron function and identify specific mechanisms by which chronic stress, by enhancing GH in the amygdala, may predispose an individual to excessive fear memory formation.

  17. Differential serotonergic innervation of the amygdala in bonobos and chimpanzees.

    Science.gov (United States)

    Stimpson, Cheryl D; Barger, Nicole; Taglialatela, Jared P; Gendron-Fitzpatrick, Annette; Hof, Patrick R; Hopkins, William D; Sherwood, Chet C

    2016-03-01

    Humans' closest living relatives are bonobos (Pan paniscus) and chimpanzees (Pan troglodytes), yet these great ape species differ considerably from each other in terms of social behavior. Bonobos are more tolerant of conspecifics in competitive contexts and often use sexual behavior to mediate social interactions. Chimpanzees more frequently employ aggression during conflicts and actively patrol territories between communities. Regulation of emotional responses is facilitated by the amygdala, which also modulates social decision-making, memory and attention. Amygdala responsiveness is further regulated by the neurotransmitter serotonin. We hypothesized that the amygdala of bonobos and chimpanzees would differ in its neuroanatomical organization and serotonergic innervation. We measured volumes of regions and the length density of serotonin transporter-containing axons in the whole amygdala and its lateral, basal, accessory basal and central nuclei. Results showed that accessory basal nucleus volume was larger in chimpanzees than in bonobos. Of particular note, the amygdala of bonobos had more than twice the density of serotonergic axons than chimpanzees, with the most pronounced differences in the basal and central nuclei. These findings suggest that variation in serotonergic innervation of the amygdala may contribute to mediating the remarkable differences in social behavior exhibited by bonobos and chimpanzees. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  18. Basolateral amygdala lesions abolish mutual reward preferences in rats.

    Science.gov (United States)

    Hernandez-Lallement, Julen; van Wingerden, Marijn; Schäble, Sandra; Kalenscher, Tobias

    2016-01-01

    In a recent study, we demonstrated that rats prefer mutual rewards in a Prosocial Choice Task. Here, employing the same task, we show that the integrity of basolateral amygdala was necessary for the expression of mutual reward preferences. Actor rats received bilateral excitotoxic (n=12) or sham lesions (n=10) targeting the basolateral amygdala and were subsequently tested in a Prosocial Choice Task where they could decide between rewarding ("Both Reward") or not rewarding a partner rat ("Own Reward"), either choice yielding identical reward to the actors themselves. To manipulate the social context and control for secondary reinforcement sources, actor rats were paired with either a partner rat (partner condition) or with an inanimate rat toy (toy condition). Sham-operated animals revealed a significant preference for the Both-Reward-option in the partner condition, but not in the toy condition. Amygdala-lesioned animals exhibited significantly lower Both-Reward preferences than the sham group in the partner but not in the toy condition, suggesting that basolateral amygdala was required for the expression of mutual reward preferences. Critically, in a reward magnitude discrimination task in the same experimental setup, both sham-operated and amygdala-lesioned animals preferred large over small rewards, suggesting that amygdala lesion effects were restricted to decision making in social contexts, leaving self-oriented behavior unaffected. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Extinction of relapsed fear does not require the basolateral amygdala.

    Science.gov (United States)

    Lingawi, Nura W; Westbrook, R Frederick; Laurent, Vincent

    2017-03-01

    It is well established that extinguished fears are restored with the passage of time or a change in physical context. These fear restoration phenomena are believed to mimic the conditions under which relapse occurs in patients that have been treated for anxiety disorders by means of cue-exposure therapy. Here, we used a rodent model to extinguish relapsed fear and assess whether this new extinction prevents further relapse. We found that activity in the basolateral amygdala (BLA) is required to initially extinguish conditioned fear, but this activity was not necessary to subsequently extinguish relapsed fear. That is, extinction of spontaneously recovered or renewed fear was spared by BLA inactivation. Yet, this BLA-independent learning of extinction did not protect against further relapse: extinction of relapsed fear conducted without BLA activity was still likely to return after the passage of time or a shift in physical context. These findings have important clinical implications. They indicate that pharmacological agents with anxiolytic properties may disrupt initial cue-exposure therapy but may be useful when therapy is again needed due to relapse. However, they also suggest that these agents will not protect against further relapse, implying the need for developing drugs that target other brain regions involved in fear inhibition. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. The interplay between the hippocampus and the amygdala in regulating aberrant hippocampal neurogenesis during protracted abstinence from alcohol dependence

    Directory of Open Access Journals (Sweden)

    Chitra D Mandyam

    2013-06-01

    Full Text Available The development of alcohol dependence involves elevated anxiety, low mood, and increased sensitivity to stress, collectively labeled negative affect. Particularly interesting is the recent accumulating evidence that sensitized extrahypothalamic stress systems (e.g., hyperglutamatergic activity, blunted hypothalamic-pituitary-adrenal [HPA] hormonal levels, altered corticotropin-releasing factor signaling, and altered glucocorticoid receptor signaling in the extended amygdala are evident in withdrawn dependent rats, supporting the hypothesis that pathological neuroadaptations in the extended amygdala contribute to the negative affective state. Notably, hippocampal neurotoxicity observed as aberrant dentate gyrus (DG neurogenesis (neurogenesis is a process where neural stem cells in the adult hippocampal subgranular zone generate DG granule cell neurons and DG neurodegeneration are observed in withdrawn dependent rats. These correlations between withdrawal and aberrant neurogenesis in dependent rats suggest that alterations in the DG could be hypothesized to be due to compromised HPA axis activity and associated hyperglutamatergic activity originating from the basolateral amygdala in withdrawn dependent rats. This review discusses a possible link between the neuroadaptations in the extended amygdala stress systems and the resulting pathological plasticity that could facilitate recruitment of new emotional memory circuits in the hippocampus as a function of aberrant DG neurogenesis.

  1. Toxoplasma gondii Infection in Mice Impairs Long-Term Fear Memory Consolidation through Dysfunction of the Cortex and Amygdala.

    Science.gov (United States)

    Ihara, Fumiaki; Nishimura, Maki; Muroi, Yoshikage; Mahmoud, Motamed Elsayed; Yokoyama, Naoaki; Nagamune, Kisaburo; Nishikawa, Yoshifumi

    2016-10-01

    Chronic infection with Toxoplasma gondii becomes established in tissues of the central nervous system, where parasites may directly or indirectly modulate neuronal function. Epidemiological studies have revealed that chronic infection in humans is a risk factor for developing mental diseases. However, the mechanisms underlying parasite-induced neuronal dysfunction in the brain remain unclear. Here, we examined memory associated with conditioned fear in mice and found that T. gondii infection impairs consolidation of conditioned fear memory. To examine the brain pathology induced by T. gondii infection, we analyzed the parasite load and histopathological changes. T. gondii infects all brain areas, yet the cortex exhibits more severe tissue damage than other regions. We measured neurotransmitter levels in the cortex and amygdala because these regions are involved in fear memory expression. The levels of dopamine metabolites but not those of dopamine were increased in the cortex of infected mice compared with those in the cortex of uninfected mice. In contrast, serotonin levels were decreased in the amygdala and norepinephrine levels were decreased in the cortex and amygdala of infected mice. The levels of cortical dopamine metabolites were associated with the time spent freezing in the fear-conditioning test. These results suggest that T. gondii infection affects fear memory through dysfunction of the cortex and amygdala. Our findings provide insight into the mechanisms underlying the neurological changes seen during T. gondii infection. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  2. Amygdala and hippocampus volumes are differently affected by childhood trauma in patients with bipolar disorders and healthy controls.

    Science.gov (United States)

    Janiri, Delfina; Sani, Gabriele; Rossi, Pietro De; Piras, Fabrizio; Iorio, Mariangela; Banaj, Nerisa; Giuseppin, Giulia; Spinazzola, Edoardo; Maggiora, Matteo; Ambrosi, Elisa; Simonetti, Alessio; Spalletta, Gianfranco

    2017-08-01

    Volumetric studies on deep gray matter structures in bipolar disorder (BP) have reported contrasting results. Childhood trauma, a relevant environmental stressor for BP, could account for the variability of the results, modulating differences in the amygdala and hippocampus in patients with BP compared with healthy controls (HC). Our study aimed to test this hypothesis. We assessed 105 outpatients, diagnosed with bipolar disorder type I (BP-I) or bipolar disorder type II (BP-II) according to DSM-IV-TR criteria, and 113 HC subjects. History of childhood trauma was obtained using the Childhood Trauma Questionnaire (CTQ). High-resolution magnetic resonance imaging was performed on all subjects and volumes of the amygdala, hippocampus, nucleus accumbens, caudate, pallidum, putamen, and thalamus were measured using FreeSurfer. Patients with BP showed a global reduction of deep gray matter volumes compared to HCs. However, childhood trauma modulated the impact of the diagnosis specifically on the amygdala and hippocampus. Childhood trauma was associated with bilateral decreased volumes in HCs and increased volumes in patients with BP. The results suggest that childhood trauma may have a different effect in health and disease on volumes of gray matter in the amygdala and hippocampus, which are brain areas specifically involved in response to stress and emotion processing. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Hippocampus and amygdala volumes in children and young adults at high-risk of schizophrenia: research synthesis.

    Science.gov (United States)

    Ganzola, Rossana; Maziade, Michel; Duchesne, Simon

    2014-06-01

    Studies have reported hippocampal and amygdala volume abnormalities in schizophrenic patients. It is necessary to explore the potential for these structures as early disease markers in subjects at high risk (HR) of schizophrenia. We performed a review of 29 magnetic resonance imaging (MRI) studies measuring hippocampal and amygdala volumes in subjects at HR for schizophrenia. We reclassified subjects in 3 new HR categories: presence of only risk symptoms (psychotic moderate symptoms), presence of only risk factors (genetic, developmental or environmental), and presence of combined risk symptoms/factors. Hippocampal volume reductions were detected in subjects with first episode (FE) of psychosis, in all young adults and in adolescents at HR of schizophrenia. The loss of tissue was mainly located in the posterior part of hippocampus and the right side seems more vulnerable in young adults with only risk symptoms. Instead, the anterior sector seems more involved in HR subjects with genetic risks. Abnormal amygdala volumes were found in FE subjects, in children with combined risk symptoms/factors and in older subjects using different inclusion criteria, but not in young adults. Hippocampal and amygdala abnormalities may be present before schizophrenia onset. Further studies should be conducted to clarify whether these abnormalities are causally or effectually related to neurodevelopment. Shape analysis could clarify the impact of environmental, genetic, and developmental factors on the medial temporal structures during the evolution of this disease. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Diazepam reduces excitability of amygdala and further influences auditory cortex following sodium salicylate treatment in rats.

    Science.gov (United States)

    Song, Yu; Liu, Junxiu; Ma, Furong; Mao, Lanqun

    2016-12-01

    Diazepam can reduce the excitability of lateral amygdala and eventually suppress the excitability of the auditory cortex in rats following salicylate treatment, indicating the regulating effect of lateral amygdala to the auditory cortex in the tinnitus procedure. To study the spontaneous firing rates (SFR) of the auditory cortex and lateral amygdala regulated by diazepam in the tinnitus rat model induced by sodium salicylate. This study first created a tinnitus rat modal induced by sodium salicylate, and recorded SFR of both auditory cortex and lateral amygdala. Then diazepam was intraperitoneally injected and the SFR changes of lateral amygdala recorded. Finally, diazepam was microinjected on lateral amygdala and the SFR changes of the auditory cortex recorded. Both SFRs of the auditory cortex and lateral amygdala increased after salicylate treatment. SFR of lateral amygdala decreased after intraperitoneal injection of diazepam. Microinjecting diazepam to lateral amygdala decreased SFR of the auditory cortex ipsilaterally and contralaterally.

  5. Acute effects of LSD on amygdala activity during processing of fearful stimuli in healthy subjects.

    Science.gov (United States)

    Mueller, F; Lenz, C; Dolder, P C; Harder, S; Schmid, Y; Lang, U E; Liechti, M E; Borgwardt, S

    2017-04-04

    Lysergic acid diethylamide (LSD) induces profound changes in various mental domains, including perception, self-awareness and emotions. We used functional magnetic resonance imaging (fMRI) to investigate the acute effects of LSD on the neural substrate of emotional processing in humans. Using a double-blind, randomised, cross-over study design, placebo or 100 μg LSD were orally administered to 20 healthy subjects before the fMRI scan, taking into account the subjective and pharmacological peak effects of LSD. The plasma levels of LSD were determined immediately before and after the scan. The study (including the a priori-defined study end point) was registered at ClinicalTrials.gov before study start (NCT02308969). The administration of LSD reduced reactivity of the left amygdala and the right medial prefrontal cortex relative to placebo during the presentation of fearful faces (PLSD-induced amygdala response to fearful stimuli and the LSD-induced subjective drug effects (PLSD modulates the engagement of brain regions that mediate emotional processing.

  6. Dispositional Mindfulness Co-Varies with Smaller Amygdala and Caudate Volumes in Community Adults

    Science.gov (United States)

    Taren, Adrienne A.; Creswell, J. David; Gianaros, Peter J.

    2013-01-01

    Mindfulness, a psychological process reflecting attention and awareness to what is happening in the present moment, has been associated with increased well-being and decreased depression and anxiety in both healthy and patient populations. However, little research has explored underlying neural pathways. Recent work suggests that mindfulness (and mindfulness training interventions) may foster neuroplastic changes in cortico-limbic circuits responsible for stress and emotion regulation. Building on this work, we hypothesized that higher levels of dispositional mindfulness would be associated with decreased grey matter volume in the amgydala. In the present study, a self-report measure of dispositional mindfulness and structural MRI images were obtained from 155 healthy community adults. Volumetric analyses showed that higher dispositional mindfulness is associated with decreased grey matter volume in the right amygdala, and exploratory analyses revealed that higher dispositional mindfulness is also associated with decreased grey matter volume in the left caudate. Moreover, secondary analyses indicate that these amygdala and caudate volume associations persist after controlling for relevant demographic and individual difference factors (i.e., age, total grey matter volume, neuroticism, depression). Such volumetric differences may help explain why mindful individuals have reduced stress reactivity, and suggest new candidate structural neurobiological pathways linking mindfulness with mental and physical health outcomes. PMID:23717632

  7. Dispositional mindfulness co-varies with smaller amygdala and caudate volumes in community adults.

    Directory of Open Access Journals (Sweden)

    Adrienne A Taren

    Full Text Available Mindfulness, a psychological process reflecting attention and awareness to what is happening in the present moment, has been associated with increased well-being and decreased depression and anxiety in both healthy and patient populations. However, little research has explored underlying neural pathways. Recent work suggests that mindfulness (and mindfulness training interventions may foster neuroplastic changes in cortico-limbic circuits responsible for stress and emotion regulation. Building on this work, we hypothesized that higher levels of dispositional mindfulness would be associated with decreased grey matter volume in the amgydala. In the present study, a self-report measure of dispositional mindfulness and structural MRI images were obtained from 155 healthy community adults. Volumetric analyses showed that higher dispositional mindfulness is associated with decreased grey matter volume in the right amygdala, and exploratory analyses revealed that higher dispositional mindfulness is also associated with decreased grey matter volume in the left caudate. Moreover, secondary analyses indicate that these amygdala and caudate volume associations persist after controlling for relevant demographic and individual difference factors (i.e., age, total grey matter volume, neuroticism, depression. Such volumetric differences may help explain why mindful individuals have reduced stress reactivity, and suggest new candidate structural neurobiological pathways linking mindfulness with mental and physical health outcomes.

  8. Childhood Poverty Predicts Adult Amygdala and Frontal Activity and Connectivity in Response to Emotional Faces

    Directory of Open Access Journals (Sweden)

    Arash eJavanbakht

    2015-06-01

    Full Text Available Childhood poverty negatively impacts physical and mental health in adulthood. Altered brain development in response to social and environmental factors associated with poverty likely contributes to this effect, engendering maladaptive patterns of social attribution and/or elevated physiological stress. In this fMRI study, we examined the association between childhood poverty and neural processing of social signals (i.e., emotional faces in adulthood. 52 subjects from a longitudinal prospective study recruited as children, participated in a brain imaging study at 23-25 years of age using the Emotional Faces Assessment Task (EFAT. Childhood poverty, independent of concurrent adult income, was associated with higher amygdala and mPFC responses to threat vs. happy faces. Also, childhood poverty was associated with decreased functional connectivity between left amygdala and mPFC. This study is unique because it prospectively links childhood poverty to emotional processing during adulthood, suggesting a candidate neural mechanism for negative social-emotional bias. Adults who grew up poor appear to be more sensitive to social threat cues and less sensitive to positive social cues.

  9. The role of the amygdala in incongruity resolution: the case of humor comprehension.

    Science.gov (United States)

    Nakamura, Tagiru; Matsui, Tomoko; Utsumi, Akira; Yamazaki, Mika; Makita, Kai; Harada, Tokiko; Tanabe, Hiroki C; Sadato, Norihiro

    2017-08-21

    A dominant theory of humor comprehension suggests that people understand humor by first perceiving some incongruity in an expression and then resolving it. This is called "the incongruity-resolution theory." Experimental studies have investigated the neural basis of humor comprehension, and multiple neural substrates have been proposed; however, the specific substrate for incongruity resolution is still unknown. The reason may be that the resolution phase, despite its importance in humor comprehension, has not been successfully distinguished from the perception phase because both phases occur almost simultaneously. To reveal the substrate, we conducted a functional magnetic resonance study using 51 healthy participants. We used a humor-producing frame of "Given A, I'd say B, because C" so as to focus on the resolution phase independently by suspending humor processing just after the perception phase. This frame allowed us to separate the two phases. Based on our results, incongruity resolution evoked positive emotion and activated the left amygdala, which is known to be related to positive emotion. On the basis of these findings, we argue that the amygdala plays an important role in humor comprehension, considering its functional role in emotional evaluation, particularly the relevance detection for incoming stimuli.

  10. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids

    Science.gov (United States)

    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-01-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders. PMID:26514583

  11. Amygdala, Hippocampus, and Ventral Medial Prefrontal Cortex Volumes Differ in Maltreated Youth with and without Chronic Posttraumatic Stress Disorder.

    Science.gov (United States)

    Morey, Rajendra A; Haswell, Courtney C; Hooper, Stephen R; De Bellis, Michael D

    2016-02-01

    Posttraumatic stress disorder (PTSD) is considered a disorder of recovery where individuals fail to learn and retain extinction of the traumatic fear response. In maltreated youth, PTSD is common, chronic, and associated with comorbidity. Studies of extinction-related structural volumes (amygdala, hippocampus, anterior cingulate cortex (ACC), and ventral medial prefrontal cortex (vmPFC)) and this stress diathesis, in maltreated youth were not previously investigated. In this cross-sectional study, neuroanatomical volumes associated with extinction in maltreated youth with PTSD (N=31), without PTSD (N=32), and in non-maltreated healthy volunteers (n=57) were examined using magnetic resonance imaging. Groups were sociodemographically similar. Participants underwent extensive assessments for strict inclusion/exclusion criteria and DSM-IV disorders. Maltreated youth with PTSD demonstrated decreased right vmPFC volumes compared with both maltreated youth without PTSD and non-maltreated controls. Maltreated youth without PTSD demonstrated larger left amygdala and right hippocampal volumes compared with maltreated youth with PTSD and non-maltreated control youth. PTSD symptoms inversely correlated with right and left hippocampal and left amygdala volumes. Confirmatory masked voxel base morphometry analyses demonstrated greater medial orbitofrontal cortex gray matter intensity in controls than maltreated youth with PTSD. Volumetric results were not influenced by psychopathology or maltreatment variables. We identified volumetric differences in extinction-related structures between maltreated youth with PTSD from those without PTSD. Alterations of the vmPFC may be one mechanism that mediates the pathway from PTSD to comorbidity. Further longitudinal work is needed to determine neurobiological factors related to chronic and persistent PTSD, and to PTSD resilience despite maltreatment.

  12. Preferential amygdala reactivity to the negative assessment of neutral faces.

    Science.gov (United States)

    Blasi, Giuseppe; Hariri, Ahmad R; Alce, Guilna; Taurisano, Paolo; Sambataro, Fabio; Das, Saumitra; Bertolino, Alessandro; Weinberger, Daniel R; Mattay, Venkata S

    2009-11-01

    Prior studies suggest that the amygdala shapes complex behavioral responses to socially ambiguous cues. We explored human amygdala function during explicit behavioral decision making about discrete emotional facial expressions that can represent socially unambiguous and ambiguous cues. During functional magnetic resonance imaging, 43 healthy adults were required to make complex social decisions (i.e., approach or avoid) about either relatively unambiguous (i.e., angry, fearful, happy) or ambiguous (i.e., neutral) facial expressions. Amygdala activation during this task was compared with that elicited by simple, perceptual decisions (sex discrimination) about the identical facial stimuli. Angry and fearful expressions were more frequently judged as avoidable and happy expressions most often as approachable. Neutral expressions were equally judged as avoidable and approachable. Reaction times to neutral expressions were longer than those to angry, fearful, and happy expressions during social judgment only. Imaging data on stimuli judged to be avoided revealed a significant task by emotion interaction in the amygdala. Here, only neutral facial expressions elicited greater activity during social judgment than during sex discrimination. Furthermore, during social judgment only, neutral faces judged to be avoided were associated with greater amygdala activity relative to neutral faces that were judged as approachable. Moreover, functional coupling between the amygdala and both dorsolateral prefrontal (social judgment > sex discrimination) and cingulate (sex discrimination > social judgment) cortices was differentially modulated by task during processing of neutral faces. Our results suggest that increased amygdala reactivity and differential functional coupling with prefrontal circuitries may shape complex decisions and behavioral responses to socially ambiguous cues.

  13. Paradoxical facilitation of working memory after basolateral amygdala damage.

    Directory of Open Access Journals (Sweden)

    Barak Morgan

    Full Text Available Working memory is a vital cognitive capacity without which meaningful thinking and logical reasoning would be impossible. Working memory is integrally dependent upon prefrontal cortex and it has been suggested that voluntary control of working memory, enabling sustained emotion inhibition, was the crucial step in the evolution of modern humans. Consistent with this, recent fMRI studies suggest that working memory performance depends upon the capacity of prefrontal cortex to suppress bottom-up amygdala signals during emotional arousal. However fMRI is not well-suited to definitively resolve questions of causality. Moreover, the amygdala is neither structurally or functionally homogenous and fMRI studies do not resolve which amygdala sub-regions interfere with working memory. Lesion studies on the other hand can contribute unique causal evidence on aspects of brain-behaviour phenomena fMRI cannot "see". To address these questions we investigated working memory performance in three adult female subjects with bilateral basolateral amygdala calcification consequent to Urbach-Wiethe Disease and ten healthy controls. Amygdala lesion extent and functionality was determined by structural and functional MRI methods. Working memory performance was assessed using the Wechsler Adult Intelligence Scale-III digit span forward task. State and trait anxiety measures to control for possible emotional differences between patient and control groups were administered. Structural MRI showed bilateral selective basolateral amygdala damage in the three Urbach-Wiethe Disease subjects and fMRI confirmed intact functionality in the remaining amygdala sub-regions. The three Urbach-Wiethe Disease subjects showed significant working memory facilitation relative to controls. Control measures showed no group anxiety differences. Results are provisionally interpreted in terms of a 'cooperation through competition' networks model that may account for the observed paradoxical

  14. Acute serotonin 2A receptor blocking alters the processing of fearful faces in the orbitofrontal cortex and amygdala

    DEFF Research Database (Denmark)

    Hornboll, Bettina; Macoveanu, Julian; Rowe, James

    2013-01-01

    judging the gender of neutral, fearful and angry faces. Methods: 5-HT2A receptors were blocked with ketanserin to a variable degree across subjects by adjusting the time between ketanserin-infusion and onset of the fMRI protocol. Neocortical 5-HT2A receptor binding in terms of the binding potential (BPp...... blockade reduced the neural response to fearful faces in the medial orbitofrontal cortex (OFC), independently of 5-HT2A receptor occupancy or neocortical 5-HT2A receptor BPp . The medial OFC also showed increased functional coupling with the left amygdala during processing of fearful faces depending...

  15. Evidence of an IFN-γ by early life stress interaction in the regulation of amygdala reactivity to emotional stimuli.

    Science.gov (United States)

    Redlich, Ronny; Stacey, David; Opel, Nils; Grotegerd, Dominik; Dohm, Katharina; Kugel, Harald; Heindel, Walter; Arolt, Volker; Baune, Bernhard T; Dannlowski, Udo

    2015-12-01

    Since numerous studies have found that exposure to early life stress leads to increased peripheral inflammation and psychiatric disease, it is thought that peripheral immune activation precedes and possibly mediates the onset of stress-associated psychiatric disease. Despite early studies, IFNγ has received little attention relative to other inflammatory cytokines in the context of the pathophysiology of affective disorders. Neuroimaging endophenotypes have emerged recently as a promising means of elucidating these types of complex relationships including the modeling of the interaction between environmental factors and genetic predisposition. Here we investigate the GxE relationship between early-life stress and genetic variants of IFNγ on emotion processing. To investigate the impact of the relationship between genetic variants of IFNγ (rs1861494, rs2069718, rs2430561) and early life stress on emotion processing, a sample of healthy adults (n=409) undergoing an emotional faces paradigm in an fMRI study were genotyped and analysed. Information on early life stress was obtained via Childhood Trauma Questionnaire (CTQ). A positive association between early life stress and amygdala reactivity was found. Specifically, the main effect of genotype of rs1861494 on amygdala reactivity indicates a higher neural response in C allele carriers compared to T homozygotes, while we did not find main effects of rs2069718 and rs2430561. Importantly, interaction analyses revealed a specific interaction between IFNγ genotype (rs1861494) and early life stress affecting amygdala reactivity to emotional faces, resulting from a positive association between CTQ scores and amygdala reactivity in C allele carriers while this association was absent in T homozygotes. Our findings indicate that firstly the genetic variant of IFNγ (rs1861494) is involved with the regulation of amygdala reactivity to emotional stimuli and secondly, that this genetic variant moderates effects of early life

  16. Aphasia following left thalamic hemorrhage

    International Nuclear Information System (INIS)

    Makishita, Hideo; Miyasaka, Motomaro; Tanizaki, Yoshio; Yanagisawa, Nobuo; Sugishita, Morihiro.

    1984-01-01

    We reported 7 patients with left thalamic hemorrhage in the chronic stage (from 1.5 months to 4.5 months), and described language disorders examined by Western Aphasia Battery (WAB) and measured cerebral blood flow by single photon emission CT. Examination of language by WAB revealed 4 aphasics out of 7 cases, and 3 patients had no language deficit. The patient with Wernicke's aphasia showed low density area only in the left posterior thalamus in X-ray CT, and revealed severe low blood flow area extending to left temporal lobe in emission CT. In the case with transcortical sensory aphasia, although X-ray CT showed no obvious low density area, emission CT revealed moderate low flow area in watershed area that involved the territory between posterior cerebral and middle cerebral arteries in the left temporooccipital region in addition to low blood flow at the left thalamus. In one of the two patients classified as anomic aphasia, whose score of repetition (8.4) was higher than that of comprehension (7.4), emission CT showed slight low flow area at the temporo-occipital region similarly as the case with transcortical sensory aphasia. In another case with anomic aphasia, scored 9 on both fluensy and comprehension subtests and 10 on repetition, there was wide low density area all over the left thalamus and midline shift to the right in X-ray CT, and emission CT showed severe low blood flow in the same region spreading widely toward the cerebral surface. On the other hand, in all of the 3 patients without aphasia, emission CT showed low flow region restricted to the left thalamus. (J.P.N.)

  17. Diverting attention suppresses human amygdala responses to faces

    Directory of Open Access Journals (Sweden)

    Carmen eMorawetz

    2010-12-01

    Full Text Available Recent neuroimaging studies disagree as to whether the processing of emotion-laden visual stimuli is dependent upon the availability of attentional resources or entirely capacity-free. Two main factors have been proposed to be responsible for the discrepancies: the differences in the perceptual attentional demands of the tasks used to divert attentional resources from emotional stimuli and the spatial location of the affective stimuli in the visual field. To date, no neuroimaging report addressed these two issues in the same set of subjects. Therefore, the aim of the study was to investigate the effects of high and low attentional load as well as different stimulus locations on face processing in the amygdala using fMRI to provide further evidence for one of the two opposing theories. We were able for the first time to directly test the interaction of attentional load and spatial location. The results revealed a strong attenuation of amygdala activity when the attentional load was high. The eccentricity of the emotional stimuli did not affect responses in the amygdala and no interaction effect between attentional load and spatial location was found. We conclude that the processing of emotional stimuli in the amygdala is strongly dependent on the availability of attentional resources without a preferred processing of stimuli presented in the periphery and provide firm evidence for the concept of the attentional load theory of emotional processing in the amygdala.

  18. The amygdala in schizophrenia: a trimodal magnetic resonance imaging study.

    Science.gov (United States)

    Kalus, Peter; Slotboom, Johannes; Gallinat, Jürgen; Wiest, Roland; Ozdoba, Christoph; Federspiel, Andrea; Strik, Werner K; Buri, Caroline; Schroth, Gerhard; Kiefer, Claus

    2005-03-03

    In schizophrenic psychoses, structural and functional alterations of the amygdala have been demonstrated by several neuroimaging studies. However, postmortem examinations on the brains of schizophrenics did not confirm the volume changes reported by volumetric magnetic resonance imaging (MRI) studies. In order to address these contradictory findings and to further elucidate the possibly underlying pathophysiological process of the amygdala, we employed a trimodal MRI design including high-resolution volumetry, diffusion tensor imaging (DTI), and quantitative magnetization transfer imaging (qMTI) in a sample of 14 schizophrenic patients and 14 matched controls. Three-dimensional MRI volumetry revealed a significant reduction of amygdala raw volumes in the patient group, while amygdala volumes normalized for intracranial volume did not differ between the two groups. The regional diffusional anisotropy of the amygdala, expressed as inter-voxel coherence (COH), showed a marked and significant reduction in schizophrenics. Assessment of qMTI parameters yielded significant group differences for the T2 time of the bound proton pool and the T1 time of the free proton pool, while the semi-quantitative magnetization transfer ratio (MTR) did not differ between the groups. The application of multimodal MRI protocols is diagnostically relevant for the differentiation between schizophrenic patients and controls and provides a new strategy for the detection and characterization of subtle structural alterations in defined regions of the living brain.

  19. Metabolic activation of amygdala, lateral septum and accumbens circuits during food anticipatory behavior.

    Science.gov (United States)

    Olivo, Diana; Caba, Mario; Gonzalez-Lima, Francisco; Rodríguez-Landa, Juan F; Corona-Morales, Aleph A

    2017-01-01

    When food is restricted to a brief fixed period every day, animals show an increase in temperature, corticosterone concentration and locomotor activity for 2-3h before feeding time, termed food anticipatory activity. Mechanisms and neuroanatomical circuits responsible for food anticipatory activity remain unclear, and may involve both oscillators and networks related to temporal conditioning. Rabbit pups are nursed once-a-day so they represent a natural model of circadian food anticipatory activity. Food anticipatory behavior in pups may be associated with neural circuits that temporally anticipate feeding, while the nursing event may produce consummatory effects. Therefore, we used New Zealand white rabbit pups entrained to circadian feeding to investigate the hypothesis that structures related to reward expectation and conditioned emotional responses would show a metabolic rhythm anticipatory of the nursing event, different from that shown by structures related to reward delivery. Quantitative cytochrome oxidase histochemistry was used to measure regional brain metabolic activity at eight different times during the day. We found that neural metabolism peaked before nursing, during food anticipatory behavior, in nuclei of the extended amygdala (basolateral, medial and central nuclei, bed nucleus of the stria terminalis), lateral septum and accumbens core. After pups were fed, however, maximal metabolic activity was expressed in the accumbens shell, caudate, putamen and cortical amygdala. Neural and behavioral activation persisted when animals were fasted by two cycles, at the time of expected nursing. These findings suggest that metabolic activation of amygdala-septal-accumbens circuits involved in temporal conditioning may contribute to food anticipatory activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Cortico-amygdala coupling as a marker of early relapse risk in cocaine-addicted individuals

    Directory of Open Access Journals (Sweden)

    Meredith J Mchugh

    2014-02-01

    Full Text Available Addiction to cocaine is a chronic condition characterized by high rates of early relapse. This study builds on efforts to identify neural markers of relapse risk by studying resting state functional connectivity (rsFC in neural circuits arising from the amygdala; a brain region implicated in relapse-related processes including craving and reactivity to stress following acute and protracted withdrawal from cocaine. Whole-brain resting-state fMRI connectivity (6 min was assessed in 45 cocaine-addicted individuals and 22 healthy controls. Cocaine-addicted individuals completed scans in the final week of a residential treatment episode. To approximate preclinical models of relapse-related circuitry separate seeds were derived for the left and right basolateral (BLA and corticomedial (CMA amygdala. Participants also completed the Iowa Gambling Task, Wisconsin Card Sorting Test, Cocaine Craving Questionnaire, Obsessive Compulsive Cocaine Use scale, Temperament and Character Inventory and the NEO-PI-R. Relapse within the first 30 days post-treatment (n = 24 was associated with reduced rsFC between the left CMA and ventromedial prefrontal cortex/rostral anterior cingulate cortex (vmPFC/rACC relative to cocaine-addicted individuals who remained abstinent (non-relapse, n = 21. Non-relapse participants evidenced reduced rsFC between the bilateral BLA and visual processing regions (lingual gyrus/cuneus compared to controls and relapsed participants. Early relapse was associated with fewer years of education but unrelated to trait reactivity to stress, neurocognitive and clinical characteristics or cocaine use history. Findings suggest that rsFC within neural circuits implicated in preclinical models of relapse may provide a promising marker of relapse risk in cocaine-addicted individuals. Future efforts to replicate the current findings and alter connectivity within these circuits may yield novel interventions and improve treatment outcomes.

  1. Prefrontal and amygdala engagement during emotional reactivity and regulation in generalized anxiety disorder.

    Science.gov (United States)

    Fitzgerald, Jacklynn M; Phan, K Luan; Kennedy, Amy E; Shankman, Stewart A; Langenecker, Scott A; Klumpp, Heide

    2017-08-15

    Emotion dysregulation is prominent in generalized anxiety disorder (GAD), characterized clinically by exaggerated reactivity to negative stimuli and difficulty in down-regulating this response. Although limited research implicates frontolimbic disturbances in GAD, whether neural aberrations occur during emotional reactivity, regulation, or both is not well understood. During functional magnetic resonance imaging (fMRI), 30 individuals with GAD and 30 healthy controls (HC) completed a well-validated explicit emotion regulation task designed to measure emotional reactivity and regulation of reactivity. During the task, participants viewed negative images ('Look-Negative' condition) and, on some trials, used a cognitive strategy to reduce negative affective response ('Reappraise' condition). Results from an Analysis of Variance corrected for whole brain multiple comparisons showed a significant group x condition interaction in the left amygdala and left inferior frontal gyrus (IFG). Results from post-hoc analyses showed that the GAD group engaged these regions to a greater extent than HCs during Look-Negative but not Reappraise. Behaviorally, the GAD group reported feeling more negative than the HC group in each condition, although both groups reported reduced negative affect following regulation. As comorbidity was permitted, the presence of concurrent disorders, like other anxiety disorders and depression, detracts our ability to classify neural engagement particular to GAD alone. Individuals with GAD exhibited over-engagement of amygdala and frontal regions during the viewing of negative images, compared to HCs. Together, these aberrations may indicate that deficits in emotional reactivity rather than regulation contribute to emotion dysregulation in those with GAD. Copyright © 2017. Published by Elsevier B.V.

  2. Evidence for smaller right amygdala volumes in posttraumatic stress disorder following childhood trauma

    NARCIS (Netherlands)

    Veer, I.M.; Oei, N.Y.L.; van Buchem, M.A.; Spinhoven, Ph.; Elzinga, B.M.; Rombouts, S.A.R.B.

    2015-01-01

    Hippocampus and amygdala volumes in posttraumatic stress disorder (PTSD) related to childhood trauma are relatively understudied, albeit the potential importance to the disorder. Whereas some studies reported smaller hippocampal volumes, little evidence was found for abnormal amygdala volumes. Here

  3. Behavioral evidence for left-hemisphere specialization of motor planning

    NARCIS (Netherlands)

    Janssen, L.; Meulenbroek, R.G.; Steenbergen, B.

    2011-01-01

    Recent studies suggest that the left hemisphere is dominant for the planning of motor actions. This left-hemisphere specialization hypothesis was proposed in various lines of research, including patient studies, motor imagery studies, and studies involving neurophysiological techniques. However,

  4. Hippocampus and amygdala morphology in attention-deficit/hyperactivity disorder

    DEFF Research Database (Denmark)

    Plessen, Kerstin J; Bansal, Ravi; Zhu, Hongtu

    2006-01-01

    CONTEXT: Limbic structures are implicated in the genesis of attention-deficit/hyperactivity disorder (ADHD) by the presence of mood and cognitive disturbances in affected individuals and by elevated rates of mood disorders in family members of probands with ADHD. OBJECTIVE: To study the morphology...... of the hippocampus and amygdala in children with ADHD. DESIGN: A cross-sectional case-control study of the hippocampus and amygdala using anatomical magnetic resonance imaging. SETTINGS: University research institute. PATIENTS: One hundred fourteen individuals aged 6 to 18 years, 51 with combined-type ADHD and 63...... healthy controls. MAIN OUTCOME MEASURES: Volumes and measures of surface morphology for the hippocampus and amygdala. RESULTS: The hippocampus was larger bilaterally in the ADHD group than in the control group (t = 3.35; P

  5. Juvenile obesity enhances emotional memory and amygdala plasticity through glucocorticoids.

    Science.gov (United States)

    Boitard, Chloé; Maroun, Mouna; Tantot, Frédéric; Cavaroc, Amandine; Sauvant, Julie; Marchand, Alain; Layé, Sophie; Capuron, Lucile; Darnaudery, Muriel; Castanon, Nathalie; Coutureau, Etienne; Vouimba, Rose-Marie; Ferreira, Guillaume

    2015-03-04

    In addition to metabolic and cardiovascular disorders, obesity is associated with adverse cognitive and emotional outcomes. Its growing prevalence during adolescence is particularly alarming since recent evidence indicates that obesity can affect hippocampal function during this developmental period. Adolescence is a decisive period for maturation of the amygdala and the hypothalamic-pituitary-adrenal (HPA) stress axis, both required for lifelong cognitive and emotional processing. However, little data are available on the impact of obesity during adolescence on amygdala function. Herein, we therefore evaluate in rats whether juvenile high-fat diet (HFD)-induced obesity alters amygdala-dependent emotional memory and whether it depends on HPA axis deregulation. Exposure to HFD from weaning to adulthood, i.e., covering adolescence, enhances long-term emotional memories as assessed by odor-malaise and tone-shock associations. Juvenile HFD also enhances emotion-induced neuronal activation of the basolateral complex of the amygdala (BLA), which correlates with protracted plasma corticosterone release. HFD exposure restricted to adulthood does not modify all these parameters, indicating adolescence is a vulnerable period to the effects of HFD-induced obesity. Finally, exaggerated emotional memory and BLA synaptic plasticity after juvenile HFD are alleviated by a glucocorticoid receptor antagonist. Altogether, our results demonstrate that juvenile HFD alters HPA axis reactivity leading to an enhancement of amygdala-dependent synaptic and memory processes. Adolescence represents a period of increased susceptibility to the effects of diet-induced obesity on amygdala function. Copyright © 2015 the authors 0270-6474/15/354092-12$15.00/0.

  6. The amygdala and ventromedial prefrontal cortex in morality and psychopathy.

    Science.gov (United States)

    Blair, R J R

    2007-09-01

    Recent work has implicated the amygdala and ventromedial prefrontal cortex in morality and, when dysfunctional, psychopathy. This model proposes that the amygdala, through stimulus-reinforcement learning, enables the association of actions that harm others with the aversive reinforcement of the victims' distress. Consequent information on reinforcement expectancy, fed forward to the ventromedial prefrontal cortex, can guide the healthy individual away from moral transgressions. In psychopathy, dysfunction in these structures means that care-based moral reasoning is compromised and the risk that antisocial behavior is used instrumentally to achieve goals is increased.

  7. A neuroplasticity hypothesis of chronic stress in the basolateral amygdala.

    Science.gov (United States)

    Boyle, Lara M

    2013-06-01

    Chronic stress plays a role in the etiology of several affective and anxiety-related disorders. Despite this, its mechanistic effects on the brain are still unclear. Of particular interest is the effect of chronic stress on the amygdala, which plays a key role in the regulation of emotional responses and memory consolidation. This review proposes a neuroplasticity model for the effects of chronic stress in this region, emphasizing the roles of glutamate and BDNF signaling. This model provides a review of recent discoveries of the effects of chronic stress in the amygdala and reveals pathways for future research.

  8. Memory Consolidation within the Central Amygdala Is Not Necessary for Modulation of Cerebellar Learning

    Science.gov (United States)

    Steinmetz, Adam B.; Ng, Ka H.; Freeman, John H.

    2017-01-01

    Amygdala lesions impair, but do not prevent, acquisition of cerebellum-dependent eyeblink conditioning suggesting that the amygdala modulates cerebellar learning. Two-factor theories of eyeblink conditioning posit that a fast-developing memory within the amygdala facilitates slower-developing memory within the cerebellum. The current study tested…

  9. The Physiology of Fear: Reconceptualizing the Role of the Central Amygdala in Fear Learning

    Science.gov (United States)

    Keifer, Orion P.; Hurt, Robert C.; Ressler, Kerry J.

    2015-01-01

    The historically understood role of the central amygdala (CeA) in fear learning is to serve as a passive output station for processing and plasticity that occurs elsewhere in the brain. However, recent research has suggested that the CeA may play a more dynamic role in fear learning. In particular, there is growing evidence that the CeA is a site of plasticity and memory formation, and that its activity is subject to tight regulation. The following review examines the evidence for these three main roles of the CeA as they relate to fear learning. The classical role of the CeA as a routing station to fear effector brain structures like the periaqueductal gray, the lateral hypothalamus, and paraventricular nucleus of the hypothalamus will be briefly reviewed, but specific emphasis is placed on recent literature suggesting that the CeA 1) has an important role in the plasticity underlying fear learning, 2) is involved in regulation of other amygdala subnuclei, and 3) is itself regulated by intra- and extra-amygdalar input. Finally, we discuss the parallels of human and mouse CeA involvement in fear disorders and fear conditioning, respectively. PMID:26328883

  10. Interplay of prefrontal cortex and amygdala during extinction of drug seeking.

    Science.gov (United States)

    Oliva, Valeria; Cartoni, Emilio; Latagliata, Emanuele Claudio; Puglisi-Allegra, Stefano; Baldassarre, Gianluca

    2018-04-01

    Extinction of Pavlovian conditioning is a complex process that involves brain regions such as the medial prefrontal cortex (mPFC), the amygdala and the locus coeruleus. In particular, noradrenaline (NA) coming from the locus coeruleus has been recently shown to play a different role in two subregions of the mPFC, the prelimbic (PL) and the infralimbic (IL) regions. How these regions interact in conditioning and subsequent extinction is an open issue. We studied these processes using two approaches: computational modelling and NA manipulation in a conditioned place preference paradigm (CPP) in mice. In the computational model, NA in PL and IL causes inputs arriving to these regions to be amplified, thus allowing them to modulate learning processes in amygdala. The model reproduces results from studies involving depletion of NA from PL, IL, or both in CPP. In addition, we simulated new experiments of NA manipulations in mPFC, making predictions on the possible results. We searched the parameters of the model and tested the robustness of the predictions by performing a sensitivity analysis. We also present an empirical experiment where, in accord with the model, a double depletion of NA from both PL and IL in CPP with amphetamine impairs extinction. Overall the proposed model, supported by anatomical, physiological, and behavioural data, explains the differential role of NA in PL and IL and opens up the possibility to understand extinction mechanisms more in depth and hence to aid the development of treatments for disorders such as addiction.

  11. Adult-onset hypothyroidism enhances fear memory and upregulates mineralocorticoid and glucocorticoid receptors in the amygdala.

    Science.gov (United States)

    Montero-Pedrazuela, Ana; Fernández-Lamo, Iván; Alieva, María; Pereda-Pérez, Inmaculada; Venero, César; Guadaño-Ferraz, Ana

    2011-01-01

    Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment.

  12. Adult-onset hypothyroidism enhances fear memory and upregulates mineralocorticoid and glucocorticoid receptors in the amygdala.

    Directory of Open Access Journals (Sweden)

    Ana Montero-Pedrazuela

    Full Text Available Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment.

  13. Adult-Onset Hypothyroidism Enhances Fear Memory and Upregulates Mineralocorticoid and Glucocorticoid Receptors in the Amygdala

    Science.gov (United States)

    Montero-Pedrazuela, Ana; Fernández-Lamo, Iván; Alieva, María; Pereda-Pérez, Inmaculada; Venero, César; Guadaño-Ferraz, Ana

    2011-01-01

    Hypothyroidism is the most common hormonal disease in adults, which is frequently accompanied by learning and memory impairments and emotional disorders. However, the deleterious effects of thyroid hormones deficiency on emotional memory are poorly understood and often underestimated. To evaluate the consequences of hypothyroidism on emotional learning and memory, we have performed a classical Pavlovian fear conditioning paradigm in euthyroid and adult-thyroidectomized Wistar rats. In this experimental model, learning acquisition was not impaired, fear memory was enhanced, memory extinction was delayed and spontaneous recovery of fear memory was exacerbated in hypothyroid rats. The potentiation of emotional memory under hypothyroidism was associated with an increase of corticosterone release after fear conditioning and with higher expression of glucocorticoid and mineralocorticoid receptors in the lateral and basolateral nuclei of the amygdala, nuclei that are critically involved in the circuitry of fear memory. Our results demonstrate for the first time that adult-onset hypothyroidism potentiates fear memory and also increases vulnerability to develop emotional memories. Furthermore, our findings suggest that enhanced corticosterone signaling in the amygdala is involved in the pathophysiological mechanisms of fear memory potentiation. Therefore, we recommend evaluating whether inappropriate regulation of fear in patients with post-traumatic stress and other mental disorders is associated with abnormal levels of thyroid hormones, especially those patients refractory to treatment. PMID:22039511

  14. 5-HTTLPR, anxiety and gender interaction moderates right amygdala volume in healthy subjects.

    Science.gov (United States)

    Cerasa, Antonio; Quattrone, Aldo; Piras, Fabrizio; Mangone, Graziella; Magariello, Angela; Fagioli, Sabrina; Girardi, Paolo; Muglia, Maria; Caltagirone, Carlo; Spalletta, Gianfranco

    2014-10-01

    Genetic variants within the serotonin transporter gene (5-HTTLPR) impact the neurobiology and risk for anxiety-related behaviours. There are also gender differences in the prevalence of anxiety-related behaviours. Although numerous studies have investigated the influence of 5-HTTLPR genotype on the neural systems involved in emotional regulation, none have investigated how these effects are modulated by gender and anxiety. We investigated this issue using two complementary region of interest-based structural neuroimaging approaches (voxel-based morphometry and Freesurfer) in 138 healthy individuals categorized into 'no anxiety' and 'subclinical anxiety' groups based on the Hamilton Rating Scale for Anxiety (HAM-A). Preliminarily, using anxiety as a continuous variable, we found a significant interaction effect of genotype by gender on anxiety. Females homozygous for the Short allele showed the highest HAM-A scores and males the lowest. In addition, a three-way significant interaction among genotype, gender and anxiety category was found for the right amygdala volume. Post hoc tests revealed that homozygous females carrying the Short variant with a subclinical anxiety condition had larger volume. The reported interaction effects demonstrate that gender strongly modulates the relationship between 5-HTTLPR genotype and subclinical expression of anxiety acting on amygdala, one region of the emotional neural network specifically involved in the anxiety-like behaviours. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  15. Sex-specific neuroanatomical correlates of fear expression in prefrontal-amygdala circuits.

    Science.gov (United States)

    Gruene, Tina M; Roberts, Elian; Thomas, Virginia; Ronzio, Ashley; Shansky, Rebecca M

    2015-08-01

    The neural projections from the infralimbic region of the prefrontal cortex to the amygdala are important for the maintenance of conditioned fear extinction. Neurons in this pathway exhibit a unique pattern of structural plasticity that is sex-dependent, but the relationship between the morphologic characteristics of these neurons and successful extinction in male and female subjects is unknown. Using classic cued fear conditioning and an extinction paradigm in large cohorts of male and female rats, we identified subpopulations of both sexes that exhibited high (HF) or low (LF) levels of freezing on an extinction retrieval test, representing failed or successful extinction maintenance, respectively. We combined retrograde tracing with fluorescent intracellular microinjections to perform three-dimensional reconstructions of infralimbic neurons that project to the basolateral amygdala in these groups. The HF and LF male rats exhibited neuroanatomical distinctions that were not observed in HF or LF female rats. A retrospective analysis of behavior during fear conditioning and extinction revealed that despite no overall sex differences in freezing behavior, HF and LF phenotypes emerged in male rats during extinction and in female rats during fear conditioning, which does not involve infralimbic-basolateral amygdala neurons. Our results suggest that the neural processes underlying successful or failed extinction maintenance may be sex-specific. These findings are relevant not only to future basic research on sex differences in fear conditioning and extinction but also to exposure-based clinical therapies, which are similar in premise to fear extinction and which are primarily used to treat disorders that are more common in women than in men. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

  16. Early Cardiac Involvement Affects Left Ventricular Longitudinal Function in Females Carrying α-Galactosidase A Mutation: Role of Hybrid Positron Emission Tomography and Magnetic Resonance Imaging and Speckle-Tracking Echocardiography.

    Science.gov (United States)

    Spinelli, Letizia; Imbriaco, Massimo; Nappi, Carmela; Nicolai, Emanuele; Giugliano, Giuseppe; Ponsiglione, Andrea; Diomiaiuti, Tommaso Claudio; Riccio, Eleonora; Duro, Giovanni; Pisani, Antonio; Trimarco, Bruno; Cuocolo, Alberto

    2018-04-01

    Hybrid 18 F-fluorodeoxyglucose (FDG) positron emission tomography and magnetic resonance imaging may differentiate mature fibrosis or scar from fibrosis associated to active inflammation in patients with Anderson-Fabry disease, even in nonhypertrophic stage. This study was designed to compare the results of positron emission tomography and magnetic resonance cardiac imaging with those of speckle-tracking echocardiography in heterozygous Anderson-Fabry disease females. Twenty-four heterozygous females carrying α-galactosidase A mutation and without left ventricular hypertrophy underwent cardiac positron emission tomography and magnetic resonance using 18 F-FDG for glucose uptake and 2-dimensional strain echocardiography. 18 F-FDG myocardial uptake was quantified by measuring the coefficient of variation (COV) of the standardized uptake value using a 17-segment model. Focal 18 F-FDG uptake with COV >0.17 was detected in 13 patients, including 2 patients with late gadolinium enhancement at magnetic resonance. COV was 0.30±0.14 in patients with focal 18 F-FDG uptake and 0.12±0.03 in those without ( P 0.17 compared with those with COV ≤0.17 (-18.5±2.7% versus -22.2±1.8%; P =0.024). For predicting COV >0.17, a global longitudinal strain >-19.8% had 77% sensitivity and 91% specificity and a value >2 dysfunctional segments 92% sensitivity and 100% specificity. In females carrying α-galactosidase A mutation, focal 18 F-FDG uptake represents an early sign of disease-related myocardial damage and is associated with impaired left ventricular longitudinal function. These findings support the hypothesis that inflammation plays an important role in glycosphingolipids storage disorders. © 2018 American Heart Association, Inc.

  17. Contributions of the Nucleus Accumbens Shell in Mediating the Enhancement in Memory Following Noradrenergic Activation of Either the Amygdala or Hippocampus

    Directory of Open Access Journals (Sweden)

    Erin C. Kerfoot

    2018-02-01

    modifications involved in forming new memories. Results show that memory improvement produced by infusing norepinephrine in either the amygdala or hippocampus is attenuated by interrupting neuronal activity in the shell 1 or 7 7 h following amygdala or hippocampus activation. These findings suggest that the accumbens shell plays an integral role modulating information initially processed by the amygdala and hippocampus following exposure to emotionally arousing events. Additionally, results demonstrate that the accumbens is involved in the long-term consolidation processes lasting over 7 h.

  18. Calcitonin gene-related peptide erases the fear memory and facilitates long-term potentiation in the central nucleus of the amygdala in rats.

    Science.gov (United States)

    Wu, Xin; Zhang, Jie-Ting; Liu, Jue; Yang, Si; Chen, Tao; Chen, Jian-Guo; Wang, Fang

    2015-11-01

    Calcitonin gene-related peptide (CGRP) is a 37 amino acid neuropeptide, which plays a critical role in the central nervous system. CGRP binds to G protein-coupled receptors, including CGRP1, which couples positively to adenylyl cyclase (AC) and protein kinase A (PKA) activation. CGRP and CGRP1 receptors are enriched in central nucleus of the amygdala (CeA), the main part of the amygdala, which regulates conditioned fear memories. Here, we reported the importance of CGRP and CGRP1 receptor for synaptic plasticity in the CeA and the extinction of fear memory in rats. Our electrophysiological and behavioral in vitro and in vivo results showed exogenous application of CGRP induced an immediate and lasting long-term potentiation in the basolateral nucleus of amygdala-CeA pathway, but not in the lateral nucleus of amygdala-CeA pathway, while bilateral intra-CeA infusion CGRP (0, 5, 13 and 21 μM/side) dose dependently enhanced fear memory extinction. The effects were blocked by CGRP1 receptor antagonist (CGRP8-37 ), N-methyl-d-aspartate receptors antagonist MK801 and PKA inhibitor H89. These results demonstrate that CGRP can lead to long-term potentiation of basolateral nucleus of amygdala-CeA pathway through a PKA-dependent postsynaptic mechanism that involved N-methyl-d-aspartate receptors and enhance the extinction of fear memory in rats. Together, the results strongly support a pivotal role of CGRP in the synaptic plasticity of CeA and extinction of fear memory. Calcitonin gene-related peptide (CGRP) plays an essential role in synaptic plasticity in the amygdala and fear memory. We found that CGRP-induced chemical long-term potentiation (LTP) in a dose-dependent way in the BLA-CeA (basolateral and central nucleus of amygdala, respectively) pathway and enhanced fear memory extinction in rats through a protein kinase A (PKA)-dependent postsynaptic mechanism that involved NMDA receptors. These results support a pivotal role of CGRP in amygdala. © 2015 International

  19. Contributions of the Nucleus Accumbens Shell in Mediating the Enhancement in Memory Following Noradrenergic Activation of Either the Amygdala or Hippocampus.

    Science.gov (United States)

    Kerfoot, Erin C; Williams, Cedric L

    2018-01-01

    involved in forming new memories. Results show that memory improvement produced by infusing norepinephrine in either the amygdala or hippocampus is attenuated by interrupting neuronal activity in the shell 1 or 7 7 h following amygdala or hippocampus activation. These findings suggest that the accumbens shell plays an integral role modulating information initially processed by the amygdala and hippocampus following exposure to emotionally arousing events. Additionally, results demonstrate that the accumbens is involved in the long-term consolidation processes lasting over 7 h.

  20. A Model of Differential Amygdala Activation in Psychopathy

    Science.gov (United States)

    Moul, Caroline; Killcross, Simon; Dadds, Mark R.

    2012-01-01

    This article introduces a novel hypothesis regarding amygdala function in psychopathy. The first part of this article introduces the concept of psychopathy and describes the main cognitive and affective impairments demonstrated by this population; that is, a deficit in fear-recognition, lower conditioned fear responses and poor performance in…

  1. The Role of the Basolateral Amygdala in Punishment

    Science.gov (United States)

    Dit-Bressel, Philip Jean-Richard; McNally, Gavan P.

    2015-01-01

    Aversive stimuli not only support fear conditioning to their environmental antecedents, they also punish behaviors that cause their occurrence. The amygdala, especially the basolateral nucleus (BLA), has been critically implicated in Pavlovian fear learning but its role in punishment remains poorly understood. Here, we used a within-subjects…

  2. Amygdala activation for eye contact despite complete cortical blindness

    NARCIS (Netherlands)

    Burra, N.; Hervais-Adelman, A.; Kerzel, D.; Tamietto, M.; de Gelder, B.; Pegna, A.J.

    2013-01-01

    Cortical blindness refers to the loss of vision that occurs after destruction of the primary visual cortex. Although there is no sensory cortex and hence no conscious vision, some cortically blind patients show amygdala activation in response to facial or bodily expressions of emotion. Here we

  3. Association between neuroticism and amygdala responsivity emerges under stressful conditions

    NARCIS (Netherlands)

    Everaerd, Daphne; Klumpers, Floris; van Wingen, Guido; Tendolkar, Indira; Fernández, Guillén

    2015-01-01

    Increased amygdala reactivity in response to salient stimuli is seen in patients with affective disorders, in healthy subjects at risk for these disorders, and in stressed individuals, making it a prime target for mechanistic studies into the pathophysiology of affective disorders. However, whereas

  4. Opposing Amygdala and Ventral Striatum Connectivity during Emotion Identification

    Science.gov (United States)

    Satterthwaite, Theodore D.; Wolf, Daniel H.; Pinkham, Amy E.; Ruparel, Kosha; Elliott, Mark A.; Valdez, Jeffrey N.; Overton, Eve; Seubert, Janina; Gur, Raquel E.; Gur, Ruben C.; Loughead, James

    2011-01-01

    Lesion and electrophysiological studies in animals provide evidence of opposing functions for subcortical nuclei such as the amygdala and ventral striatum, but the implications of these findings for emotion identification in humans remain poorly described. Here we report a high-resolution fMRI study in a sample of 39 healthy subjects who performed…

  5. Corticosteroid Induced Decoupling of the Amygdala in Men

    NARCIS (Netherlands)

    Henckens, Marloes J. A. G.; van Wingen, Guido A.; Joëls, Marian; Fernández, Guillén

    2012-01-01

    The amygdala is a key regulator of vigilance and heightens attention toward threat. Its activity is boosted upon threat exposure and contributes to a neuroendocrine stress response via the hypothalamic-pituitary-adrenal (HPA) axis. Corticosteroids are known to control brain activity as well as HPA

  6. The role of the amygdala during emotional processing in Huntington's disease: from pre-manifest to late stage disease.

    Science.gov (United States)

    Mason, Sarah L; Zhang, Jiaxiang; Begeti, Faye; Guzman, Natalie Valle; Lazar, Alpar S; Rowe, James B; Barker, Roger A; Hampshire, Adam

    2015-04-01

    Deficits in emotional processing can be detected in the pre-manifest stage of Huntington's disease and negative emotion recognition has been identified as a predictor of clinical diagnosis. The underlying neuropathological correlates of such deficits are typically established using correlative structural MRI studies. This approach does not take into consideration the impact of disruption to the complex interactions between multiple brain circuits on emotional processing. Therefore, exploration of the neural substrates of emotional processing in pre-manifest HD using fMRI connectivity analysis may be a useful way of evaluating the way brain regions interrelate in the period prior to diagnosis. We investigated the impact of predicted time to disease onset on brain activation when participants were exposed to pictures of faces with angry and neutral expressions, in 20 pre-manifest HD gene carriers and 23 healthy controls. On the basis of the results of this initial study went on to look at amygdala dependent cognitive performance in 79 Huntington's disease patients from a cross-section of disease stages (pre-manifest to late disease) and 26 healthy controls, using a validated theory of mind task: "the Reading the Mind in the Eyes Test" which has been previously been shown to be amygdala dependent. Psychophysiological interaction analysis identified reduced connectivity between the left amygdala and right fusiform facial area in pre-manifest HD gene carriers compared to controls when viewing angry compared to neutral faces. Change in PPI connectivity scores correlated with predicted time to disease onset (r=0.45, pneural networks underlying social cognition and emotional processing can be detected prior to clinical diagnosis in Huntington's disease. Connectivity between the amygdala and other brain regions is impacted by the disease process in pre-manifest HD and may therefore be a useful way of identifying participants who are approaching a clinical diagnosis

  7. Determination of the rCBF in the Amygdala and Rhinal Cortex Using a FAIR-TrueFISP Sequence

    International Nuclear Information System (INIS)

    Ludescher, Burkhard; Martirosian, Petros; Klose, Uwe; Naegele, Thomas; Schick, Fritz; Ernemann, Ulrike

    2011-01-01

    Brain perfusion can be assessed non-invasively by modern arterial spin labeling MRI. The FAIR (flow-sensitive alternating inversion recovery)-TrueFISP (true fast imaging in steady precession) technique was applied for regional assessment of cerebral blood flow in brain areas close to the skull base, since this approach provides low sensitivity to magnetic susceptibility effects. The investigation of the rhinal cortex and the amygdala is a potentially important feature for the diagnosis and research on dementia in its early stages. Twenty-three subjects with no structural or psychological impairment were investigated. FAIR-True-FISP quantitative perfusion data were evaluated in the amygdala on both sides and in the pons. A preparation of the radiofrequency FOCI (frequency offset corrected inversion) pulse was used for slice selective inversion. After a time delay of 1.2 sec, data acquisition began. Imaging slice thickness was 5 mm and inversion slab thickness for slice selective inversion was 12.5 mm. Image matrix size for perfusion images was 64 X 64 with a field of view of 256 X 256 mm, resulting in a spatial resolution of 4 X 4 X 5 mm. Repetition time was 4.8 ms; echo time was 2.4 ms. Acquisition time for the 50 sets of FAIR images was 6:56 min. Data were compared with perfusion data from the literature. Perfusion values in the right amygdala, left amygdala and pons were 65.2 (± 18.2) mL/100 g/minute, 64.6 (± 21.0) mL/100 g/minute, and 74.4 (± 19.3) mL/100 g/minute, respectively. These values were higher than formerly published data using continuous arterial spin labeling but similar to 15O-PET (oxygen-15 positron emission tomography) data. The FAIR-TrueFISP approach is feasible for the quantitative assessment of perfusion in the amygdala. Data are comparable with formerly published data from the literature. The applied technique provided excellent image quality, even for brain regions located at the skull base in the vicinity of marked susceptibility steps.

  8. Determination of the rCBF in the Amygdala and Rhinal Cortex Using a FAIR-TrueFISP Sequence

    Energy Technology Data Exchange (ETDEWEB)

    Ludescher, Burkhard; Martirosian, Petros; Klose, Uwe; Naegele, Thomas; Schick, Fritz; Ernemann, Ulrike [Eberhard-Karls-University, Tuebingen (Germany)

    2011-10-15

    Brain perfusion can be assessed non-invasively by modern arterial spin labeling MRI. The FAIR (flow-sensitive alternating inversion recovery)-TrueFISP (true fast imaging in steady precession) technique was applied for regional assessment of cerebral blood flow in brain areas close to the skull base, since this approach provides low sensitivity to magnetic susceptibility effects. The investigation of the rhinal cortex and the amygdala is a potentially important feature for the diagnosis and research on dementia in its early stages. Twenty-three subjects with no structural or psychological impairment were investigated. FAIR-True-FISP quantitative perfusion data were evaluated in the amygdala on both sides and in the pons. A preparation of the radiofrequency FOCI (frequency offset corrected inversion) pulse was used for slice selective inversion. After a time delay of 1.2 sec, data acquisition began. Imaging slice thickness was 5 mm and inversion slab thickness for slice selective inversion was 12.5 mm. Image matrix size for perfusion images was 64 X 64 with a field of view of 256 X 256 mm, resulting in a spatial resolution of 4 X 4 X 5 mm. Repetition time was 4.8 ms; echo time was 2.4 ms. Acquisition time for the 50 sets of FAIR images was 6:56 min. Data were compared with perfusion data from the literature. Perfusion values in the right amygdala, left amygdala and pons were 65.2 ({+-} 18.2) mL/100 g/minute, 64.6 ({+-} 21.0) mL/100 g/minute, and 74.4 ({+-} 19.3) mL/100 g/minute, respectively. These values were higher than formerly published data using continuous arterial spin labeling but similar to 15O-PET (oxygen-15 positron emission tomography) data. The FAIR-TrueFISP approach is feasible for the quantitative assessment of perfusion in the amygdala. Data are comparable with formerly published data from the literature. The applied technique provided excellent image quality, even for brain regions located at the skull base in the vicinity of marked susceptibility

  9. Role of basal stress hormones and amygdala dimensions in stress coping strategies of male rhesus monkeys in response to a hazard-reward conflict

    Directory of Open Access Journals (Sweden)

    Elaheh Tekieh

    2017-08-01

    Full Text Available Objective(s: In the present study the effect of stress on monkeys that had learned to retrieve food from a five-chamber receptacle, as well as the relationship between their behavior and the serum cortisol and epinephrine levels and relative size of the amygdala was evaluated. Materials and Methods: Six male rhesus monkeys were individually given access to the food reward orderly. They could easily retrieve the rewards from all chambers except for the chamber 4, which a brief, mild electric shock (3 V was delivered to them upon touching the chamber’s interior. The coping behaviors were video-recorded and analyzed offline. Baseline serum cortisol and epinephrine levels were measured before the experiments using monkey enzyme-linked immunosorbent assay kit. One week after the behavioral experiment, the monkeys’ brains were scanned using magnetic resonance imaging under general anesthesia. The cross-sectional area of the left amygdala in sagittal plane relative to the area of the whole brain in the same slice was evaluated by the planimetric method using ImageJ software. Results: Exposure to the distressing condition caused different behavioral responses. Monkeys with higher baseline levels of serum cortisol and epinephrine and larger amygdala behaved more violently in the face of stress, indicating adopting emotion-focused stress-coping strategies. Conversely, those with low plasma epinephrine, moderate cortisol, and smaller amygdala showed perseverative behavior, indicating a problem-focused coping style. Conclusion: In dealing with the same stress, different responses might be observed from nonhuman primates according to their cortisol and epinephrine levels as well as their amygdala dimensions.

  10. Amygdala and dorsal anterior cingulate connectivity during an emotional working memory task in borderline personality disorder patients with interpersonal trauma history

    Directory of Open Access Journals (Sweden)

    Annegret eKrause-Utz

    2014-10-01

    Full Text Available Emotion dysregulation and stress-related cognitive disturbances including dissociation are key features of Borderline Personality Disorder (BPD. Previous research suggests that amygdala hyperreactivity along with a failure to activate frontal brain areas implicated in inhibitory control (e.g., anterior cingulate cortex, ACC may underlie core symptoms of BPD. However, studies investigating interactions of fronto-limbic brain areas during cognitive inhibition of interfering emotional stimuli in BPD patients are still needed. Moreover, very little is known about how dissociation modulates fronto-limbic connectivity during emotional distraction in BPD. We used Psychophysiological Interaction (PPI to analyse amygdala and dorsal ACC (dACC connectivity in 22 un-medicated BPD patients with interpersonal trauma history and 22 healthy controls (HC, who performed a working memory task, while either no distractors or neutral vs. negative interpersonal pictures were presented. A measure of state dissociation was used to predict amygdala as well as dACC connectivity in the BPD group. During emotional distraction, both groups showed disrupted amygdala connectivity with dorsolateral prefrontal cortex, which was more pronounced in the BPD group. Patients further showed stronger amygdala-hippocampus and dACC-insula connectivity during emotional interference and demonstrated a stronger coupling of the dACC with nodes of the default mode network (e.g. posterior cingulate. Dissociation positively predicted amygdala-dACC connectivity and negatively predicted dACC connectivity with insula and posterior cingulate. Our results suggest aberrant connectivity patterns involving brain regions associated with emotion processing, salience detection, and self-referential processes, which may be modulated by dissociation, in BPD. Findings might be related to difficulties in shifting attention away from external (distracting emotional stimuli as well as internal emotional states

  11. Deconstructing white matter connectivity of human amygdala nuclei with thalamus and cortex subdivisions in vivo.

    Science.gov (United States)

    Abivardi, Aslan; Bach, Dominik R

    2017-08-01

    Structural alterations in long-range amygdala connections are proposed to crucially underlie several neuropsychiatric disorders. While progress has been made in elucidating the function of these connections, our understanding of their structure in humans remains sparse and non-systematic. Harnessing diffusion-weighted imaging and probabilistic tractography in humans, we investigate connections between two main amygdala nucleus groups, thalamic nuclei, and cortex. We first parcellated amygdala into deep (basolateral) and superficial (centrocortical) nucleus groups, and thalamus into six subregions, using previously established protocols based on connectivity. Cortex was parcellated based on T1-weighted images. We found substantial amygdala connections to thalamus, with different patterns for the two amygdala nuclei. Crucially, we describe direct subcortical connections between amygdala and paraventricular thalamus. Different from rodents but similar to non-human primates, these are more pronounced for basolateral than centrocortical amygdala. Substantial white-matter connectivity between amygdala and visual pulvinar is also more pronounced for basolateral amygdala. Furthermore, we establish detailed connectivity profiles for basolateral and centrocortical amygdala to cortical regions. These exhibit cascadic connections with sensory cortices as suggested previously based on tracer methods in non-human animals. We propose that the quantitative connectivity profiles provided here may guide future work on normal and pathological function of human amygdala. Hum Brain Mapp 38:3927-3940, 2017. © 2017 Wiley Periodicals, Inc. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

  12. Amygdala reactivity to negative stimuli is influenced by oral contraceptive use.

    Science.gov (United States)

    Petersen, Nicole; Cahill, Larry

    2015-09-01

    The amygdala is a highly interconnected region of the brain that is critically important to emotional processing and affective networks. Previous studies have shown that the response of the amygdala to emotionally arousing stimuli can be modulated by sex hormones. Because oral contraceptive pills dramatically lower circulating sex hormone levels with potent analogs of those hormones, we performed a functional magnetic resonance imaging experiment to measure amygdala reactivity in response to emotional stimuli in women using oral contraceptives, and compared their amygdala reactivity with that of naturally cycling women. Here, we show that women who use oral contraceptive pills have significantly decreased bilateral amygdala reactivity in response to negatively valenced, emotionally arousing stimuli compared with naturally cycling women. We suggest that by modulating amygdala reactivity, oral contraceptive pills may influence behaviors that have previously been shown to be amygdala dependent-in particular, emotional memory. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  13. MRI Overestimates Excitotoxic Amygdala Lesion Damage in Rhesus Monkeys

    Directory of Open Access Journals (Sweden)

    Benjamin M. Basile

    2017-06-01

    Full Text Available Selective, fiber-sparing excitotoxic lesions are a state-of-the-art tool for determining the causal contributions of different brain areas to behavior. For nonhuman primates especially, it is advantageous to keep subjects with high-quality lesions alive and contributing to science for many years. However, this requires the ability to estimate lesion extent accurately. Previous research has shown that in vivo T2-weighted magnetic resonance imaging (MRI accurately estimates damage following selective ibotenic acid lesions of the hippocampus. Here, we show that the same does not apply to lesions of the amygdala. Across 19 hemispheres from 13 rhesus monkeys, MRI assessment consistently overestimated amygdala damage as assessed by microscopic examination of Nissl-stained histological material. Two outliers suggested a linear relation for lower damage levels, and values of unintended amygdala damage from a previous study fell directly on that regression line, demonstrating that T2 hypersignal accurately predicts damage levels below 50%. For unintended damage, MRI estimates correlated with histological assessment for entorhinal cortex, perirhinal cortex and hippocampus, though MRI significantly overestimated the extent of that damage in all structures. Nevertheless, ibotenic acid injections routinely produced extensive intentional amygdala damage with minimal unintended damage to surrounding structures, validating the general success of the technique. The field will benefit from more research into in vivo lesion assessment techniques, and additional evaluation of the accuracy of MRI assessment in different brain areas. For now, in vivo MRI assessment of ibotenic acid lesions of the amygdala can be used to confirm successful injections, but MRI estimates of lesion extent should be interpreted with caution.

  14. Sex Differences and Laterality in Astrocyte Number and Complexity in the Adult Rat Medial Amygdala

    Science.gov (United States)

    JOHNSON, RYAN T.; BREEDLOVE, S. MARC; JORDAN, CYNTHIA L.

    2008-01-01

    The posterodorsal portion of the medial amygdala (MePD) is sexually dimorphic in several rodent species. In several other brain nuclei, astrocytes change morphology in response to steroid hormones. We visualized MePD astrocytes using glial-fibrillary acidic protein (GFAP) immunocytochemistry. We compared the number and process complexity of MePD astrocytes in adult wildtype male and female rats and testicular feminized mutant (TFM) male rats that lack functional androgen receptors (ARs) to determine whether MePD astrocytes are sexually differentiated and whether ARs have a role. Unbiased stereological methods revealed laterality and sex differences in MePD astrocyte number and complexity. The right MePD contained more astrocytes than the left in all three genotypes, and the number of astrocytes was also sexually differentiated in the right MePD, with males having more astrocytes than females. In contrast, the left MePD contained more complex astrocytes than did the right MePD in all three genotypes, and males had more complex astrocytes than females in this hemisphere. TFM males were comparable to wildtype females, having fewer astrocytes on the right and simpler astrocytes on the left than do wildtype males. Taken together, these results demonstrate that astrocytes are sexually dimorphic in the adult MePD and that the nature of the sex difference is hemisphere-dependent: a sex difference in astrocyte number in the right MePD and a sex difference in astrocyte complexity in the left MePD. Moreover, functional ARs appear to be critical in establishing these sex differences in MePD astrocyte morphology. PMID:18853427

  15. Neuropeptide S interacts with the basolateral amygdala noradrenergic system in facilitating object recognition memory consolidation.

    Science.gov (United States)

    Han, Ren-Wen; Xu, Hong-Jiao; Zhang, Rui-San; Wang, Pei; Chang, Min; Peng, Ya-Li; Deng, Ke-Yu; Wang, Rui

    2014-01-01

    The noradrenergic activity in the basolateral amygdala (BLA) was reported to be involved in the regulation of object recognition memory. As the BLA expresses high density of receptors for Neuropeptide S (NPS), we investigated whether the BLA is involved in mediating NPS's effects on object recognition memory consolidation and whether such effects require noradrenergic activity. Intracerebroventricular infusion of NPS (1nmol) post training facilitated 24-h memory in a mouse novel object recognition task. The memory-enhancing effect of NPS could be blocked by the β-adrenoceptor antagonist propranolol. Furthermore, post-training intra-BLA infusions of NPS (0.5nmol/side) improved 24-h memory for objects, which was impaired by co-administration of propranolol (0.5μg/side). Taken together, these results indicate that NPS interacts with the BLA noradrenergic system in improving object recognition memory during consolidation. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Multi-modal neuroimaging of adolescents with non-suicidal self-injury: Amygdala functional connectivity.

    Science.gov (United States)

    Westlund Schreiner, Melinda; Klimes-Dougan, Bonnie; Mueller, Bryon A; Eberly, Lynn E; Reigstad, Kristina M; Carstedt, Patricia A; Thomas, Kathleen M; Hunt, Ruskin H; Lim, Kelvin O; Cullen, Kathryn R

    2017-10-15

    Non-suicidal self-injury (NSSI) is a significant mental health problem among adolescents. Research is needed to clarify the neurobiology of NSSI and identify candidate neurobiological targets for interventions. Based on prior research implicating heightened negative affect and amygdala hyperactivity in NSSI, we pursued a systems approach to characterize amygdala functional connectivity networks during rest (resting-state functional connectivity [RSFC)]) and a task (task functional connectivity [TFC]) in adolescents with NSSI. We examined amygdala networks in female adolescents with NSSI and healthy controls (n = 45) using resting-state fMRI and a negative emotion face-matching fMRI task designed to activate the amygdala. Connectivity analyses included amygdala RSFC, amygdala TFC, and psychophysiological interactions (PPI) between amygdala connectivity and task conditions. Compared to healthy controls, adolescents with NSSI showed atypical amygdala-frontal connectivity during rest and task; greater amygdala RSFC in supplementary motor area (SMA) and dorsal anterior cingulate; and differential amygdala-occipital connectivity between rest and task. After correcting for depression symptoms, amygdala-SMA RSFC abnormalities, among others, remained significant. This study's limitations include its cross-sectional design and its absence of a psychiatric control group. Using a multi-modal approach, we identified widespread amygdala circuitry anomalies in adolescents with NSSI. While deficits in amygdala-frontal connectivity (driven by depression symptoms) replicates prior work in depression, hyperconnectivity between amygdala and SMA (independent of depression symptoms) has not been previously reported. This circuit may represent an important mechanism underlying the link between negative affect and habitual behaviors. These abnormalities may represent intervention targets for adolescents with NSSI. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. CREB regulates spine density of lateral amygdala neurons: implications for memory allocation

    Directory of Open Access Journals (Sweden)

    Derya eSargin

    2013-12-01

    Full Text Available Neurons may compete against one another for integration into a memory trace. Specifically, neurons in the lateral nucleus of the amygdala with relatively higher levels of CREB seem to be preferentially allocated to a fear memory trace, while neurons with relatively decreased CREB function seem to be excluded from a fear memory trace. CREB is a ubiquitous transcription factor that modulates many diverse cellular processes, raising the question as to which of these CREB-mediated processes underlie memory allocation. CREB is implicated in modulating dendritic spine number and morphology. As dendritic spines are intimately involved in memory formation, we investigated whether manipulations of CREB function alter spine number or morphology of neurons at the time of fear conditioning. We used viral vectors to manipulate CREB function in the lateral amygdala principal neurons in mice maintained in their homecages. At the time that fear conditioning normally occurs, we observed that neurons with high levels of CREB had more dendritic spines, while neurons with low CREB function had relatively fewer spines compared to control neurons. These results suggest that the modulation of spine density provides a potential mechanism for preferential allocation of a subset of neurons to the memory trace.

  18. Left heart ventricular angiography

    Science.gov (United States)

    ... blood vessels. These x-ray pictures create a "movie" of the left ventricle as it contracts rhythmically. ... 22578925 www.ncbi.nlm.nih.gov/pubmed/22578925 . Review Date 9/26/2016 Updated by: Michael A. ...

  19. Left heart catheterization

    Science.gov (United States)

    Catheterization - left heart ... to help guide the catheters up into your heart and arteries. Dye (sometimes called "contrast") will be ... in the blood vessels that lead to your heart. The catheter is then moved through the aortic ...

  20. Stress enhances fear by forming new synapses with greater capacity for long-term potentiation in the amygdala.

    Science.gov (United States)

    Suvrathan, Aparna; Bennur, Sharath; Ghosh, Supriya; Tomar, Anupratap; Anilkumar, Shobha; Chattarji, Sumantra

    2014-01-05

    Prolonged and severe stress leads to cognitive deficits, but facilitates emotional behaviour. Little is known about the synaptic basis for this contrast. Here, we report that in rats subjected to chronic immobilization stress, long-term potentiation (LTP) and NMDA receptor (NMDAR)-mediated synaptic responses are enhanced in principal neurons of the lateral amygdala, a brain area involved in fear memory formation. This is accompanied by electrophysiological and morphological changes consistent with the formation of 'silent synapses', containing only NMDARs. In parallel, chronic stress also reduces synaptic inhibition. Together, these synaptic changes would enable amygdalar neurons to undergo further experience-dependent modifications, leading to stronger fear memories. Consistent with this prediction, stressed animals exhibit enhanced conditioned fear. Hence, stress may leave its mark in the amygdala by generating new synapses with greater capacity for plasticity, thereby creating an ideal neuronal substrate for affective disorders. These findings also highlight the unique features of stress-induced plasticity in the amygdala that are strikingly different from the stress-induced impairment of structure and function in the hippocampus.

  1. Context-dependent encoding of fear and extinction memories in a large-scale network model of the basal amygdala.

    Science.gov (United States)

    Vlachos, Ioannis; Herry, Cyril; Lüthi, Andreas; Aertsen, Ad; Kumar, Arvind

    2011-03-01

    The basal nucleus of the amygdala (BA) is involved in the formation of context-dependent conditioned fear and extinction memories. To understand the underlying neural mechanisms we developed a large-scale neuron network model of the BA, composed of excitatory and inhibitory leaky-integrate-and-fire neurons. Excitatory BA neurons received conditioned stimulus (CS)-related input from the adjacent lateral nucleus (LA) and contextual input from the hippocampus or medial prefrontal cortex (mPFC). We implemented a plasticity mechanism according to which CS and contextual synapses were potentiated if CS and contextual inputs temporally coincided on the afferents of the excitatory neurons. Our simulations revealed a differential recruitment of two distinct subpopulations of BA neurons during conditioning and extinction, mimicking the activation of experimentally observed cell populations. We propose that these two subgroups encode contextual specificity of fear and extinction memories, respectively. Mutual competition between them, mediated by feedback inhibition and driven by contextual inputs, regulates the activity in the central amygdala (CEA) thereby controlling amygdala output and fear behavior. The model makes multiple testable predictions that may advance our understanding of fear and extinction memories.

  2. Context-dependent encoding of fear and extinction memories in a large-scale network model of the basal amygdala.

    Directory of Open Access Journals (Sweden)

    Ioannis Vlachos

    2011-03-01

    Full Text Available The basal nucleus of the amygdala (BA is involved in the formation of context-dependent conditioned fear and extinction memories. To understand the underlying neural mechanisms we developed a large-scale neuron network model of the BA, composed of excitatory and inhibitory leaky-integrate-and-fire neurons. Excitatory BA neurons received conditioned stimulus (CS-related input from the adjacent lateral nucleus (LA and contextual input from the hippocampus or medial prefrontal cortex (mPFC. We implemented a plasticity mechanism according to which CS and contextual synapses were potentiated if CS and contextual inputs temporally coincided on the afferents of the excitatory neurons. Our simulations revealed a differential recruitment of two distinct subpopulations of BA neurons during conditioning and extinction, mimicking the activation of experimentally observed cell populations. We propose that these two subgroups encode contextual specificity of fear and extinction memories, respectively. Mutual competition between them, mediated by feedback inhibition and driven by contextual inputs, regulates the activity in the central amygdala (CEA thereby controlling amygdala output and fear behavior. The model makes multiple testable predictions that may advance our understanding of fear and extinction memories.

  3. Serca2a and Na{sup +}/Ca{sup 2+} exchanger are involved in left ventricular function following cardiac remodelling of female rats treated with anabolic androgenic steroid

    Energy Technology Data Exchange (ETDEWEB)

    Nascimento, Andrews Marques do; Lima, Ewelyne Miranda de; Brasil, Girlandia Alexandre; Caliman, Izabela Facco [Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo (Brazil); Silva, Josiane Fernandes da; Lemos, Virgínia Soares [Department of Physiology and Biophysic, Federal University of Minas Gerais, Minas Gerais (Brazil); Andrade, Tadeu Uggere de [Department of Pharmacy, University Vila Velha, Vila Velha, Espirito Santo (Brazil); Bissoli, Nazaré Souza, E-mail: nazarebissoli@gmail.com [Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, Espirito Santo (Brazil)

    2016-06-15

    Anabolic-androgenic steroids are misused, including by women, but little is known about the cardiovascular effects of these drugs on women. Aim: To evaluated the effects of nandrolone decanoate (ND) and resistive physical exercise on cardiac contractility in young female rats. Main methods: Female Wistar rats were separated into 4 groups: C (untrained animals); E (animals were submitted to resistance exercise by jumping in water 5 times per week); ND (animals were treated with ND, 20 mg/kg/week for 4 weeks); and NDE (trained and treated). The haemodynamic parameters (+ dP/dt{sub max}, − dP/dt{sub min} and Tau) were assessed in the left ventricle. The heart was collected for histological analyses and collagen deposition. The gastrocnemius muscle was weighed, and hypertrophy was assessed by the ratio of their weights to gastrocnemius/tibia length. The expression of calcium handling proteins was measured by western blot analysis. Results: ND treatment and physical exercise increased cardiac contractility and relaxation. In addition, ND promoted increases in phospholamban phosphorylated (p-PLB) and isoforms of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2a) expression, while resistance exercise increased the phosphorylation of PLB and expression of Na{sup +}/Ca{sup 2+} exchangers (NCX). Cardiac hypertrophy and collagen deposition were observed after ND treatment. Conclusion: Regulatory components of cytosolic calcium, such as SERCA2a and p-PLB, play important roles in modulating the contractility and relaxation effects of ND in females. - Highlights: • ND and resistive exercise enhanced the cardiac function and increased expression of cytosolic calcium regulatory components.

  4. Activation of protein kinase A in the amygdala modulates anxiety-like behaviors in social defeat exposed mice.

    Science.gov (United States)

    Yang, Liu; Shi, Li-Jun; Yu, Jin; Zhang, Yu-Qiu

    2016-01-08

    Social defeat (SD) stress induces social avoidance and anxiety-like phenotypes. Amygdala is recognized as an emotion-related brain region such as fear, aversion and anxiety. It is conceivable to hypothesize that activation of amygdala is involved in SD-dependent behavioral defects. SD model was established using C57BL/6J mice that were physically defeated by different CD-1 mice for 10 days. Stressed mice exhibited decreased social interaction level in social interaction test and significant anxiety-like behaviors in elevated plus maze and open field tests. Meanwhile, a higher phosphorylation of PKA and CREB with a mutually linear correlation, and increased Fos labeled cells in the basolateral amygdala (BLA) were observed. Activation of PKA in the BLA by 8-Br-cAMP, a PKA activitor, significantly upregulated pCREB and Fos expression. To address the role of PKA activation on SD stress-induced social avoidance and anxiety-like behaviors, 8-Br-cAMP or H-89, a PKA inhibitor, was continuously administered into the bilateral BLA by a micro-osmotic pump system during the 10-day SD period. Neither H-89 nor 8-Br-cAMP affected the social behavior. Differently, 8-Br-cAMP significantly relieved anxiety-like behaviors in both general and moderate SD protocols. H-89 per se did not have anxiogenic effect in naïve mice, but aggravated moderate SD stress-induced anxiety-like behaviors. The antidepressant clomipramine reduced SD-induced anxiety and up-regulated pPKA level in the BLA. These results suggest that SD-driven PKA activation in the basolateral amygdala is actually a compensatory rather than pathogenic response in the homeostasis, and modulating amygdaloid PKA may exhibit potency in the therapy of social derived disorders.

  5. Elevated Hippocampal Cholinergic Neurostimulating Peptide precursor protein (HCNP-pp) mRNA in the amygdala in major depression.

    Science.gov (United States)

    Bassi, Sabrina; Seney, Marianne L; Argibay, Pablo; Sibille, Etienne

    2015-04-01

    The amygdala is innervated by the cholinergic system and is involved in major depressive disorder (MDD). Evidence suggests a hyper-activate cholinergic system in MDD. Hippocampal Cholinergic Neurostimulating Peptide (HCNP) regulates acetylcholine synthesis. The aim of the present work was to investigate expression levels of HCNP-precursor protein (HCNP-pp) mRNA and other cholinergic-related genes in the postmortem amygdala of MDD patients and matched controls (females: N = 16 pairs; males: N = 12 pairs), and in the mouse unpredictable chronic mild stress (UCMS) model that induced elevated anxiety-/depressive-like behaviors (females: N = 6 pairs; males: N = 6 pairs). Results indicate an up-regulation of HCNP-pp mRNA in the amygdala of women with MDD (p < 0.0001), but not males, and of UCMS-exposed mice (males and females; p = 0.037). HCNP-pp protein levels were investigated in the human female cohort, but no difference was found. There were no differences in gene expression of acetylcholinesterase (AChE), muscarinic (mAChRs) or nicotinic receptors (nAChRs) between MDD subjects and controls or UCMS and control mice, except for an up-regulation of AChE in UCMS-exposed mice (males and females; p = 0.044). Exploratory analyses revealed a baseline expression difference of cholinergic signaling-related genes between women and men (p < 0.0001). In conclusion, elevated amygdala HCNP-pp expression may contribute to mechanisms of MDD in women, potentially independently from regulating the cholinergic system. The differential expression of genes between women and men could also contribute to the increased vulnerability of females to develop MDD. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Amygdala Signaling during Foraging in a Hazardous Environment.

    Science.gov (United States)

    Amir, Alon; Lee, Seung-Chan; Headley, Drew B; Herzallah, Mohammad M; Pare, Denis

    2015-09-23

    We recorded basolateral amygdala (BL) neurons in a seminaturalistic foraging task. Rats had to leave their nest to retrieve food in an elongated arena inhabited by a mechanical predator. There were marked trial-to-trial variations in behavior. After poking their head into the foraging arena and waiting there for a while, rats either retreated to their nest or initiated foraging. Before initiating foraging, rats waited longer on trials that followed failed than successful trials indicating that prior experience influenced behavior. Upon foraging initiation, most principal cells (Type-1) reduced their firing rate, while in a minority (Type-2) it increased. When rats aborted foraging, Type-1 cells increased their firing rates, whereas in Type-2 cells it did not change. Surprisingly, the opposite activity profiles of Type-1 and Type-2 units were also seen in control tasks devoid of explicit threats or rewards. The common correlate of BL activity across these tasks was movement velocity, although an influence of position was also observed. Thus depending on whether rats initiated movement or not, the activity of BL neurons decreased or increased, regardless of whether threat or rewards were present. Therefore, BL activity not only encodes threats or rewards, but is closely related to behavioral output. We propose that higher order cortical areas determine task-related changes in BL activity as a function of reward/threat expectations and internal states. Because Type-1 and Type-2 cells likely form differential connections with the central amygdala (controlling freezing), this process would determine whether movement aimed at attaining food or exploration is suppressed or facilitated. Significance statement: For decades, amygdala research has been dominated by pavlovian and operant conditioning paradigms. This work has led to the view that amygdala neurons signal threats or rewards, in turn causing defensive or approach behaviors. However, the artificial circumstances of

  7. Decreased left temporal lobe volume of panic patients measured by magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Uchida, R.R.; Del-Ben, C.M.; Araujo, D.; Crippa, J.A.; Graeff, F.G. [Sao Paulo Univ., Ribeirao Preto, SP (Brazil). Dept. de Neurologia e Psicologia Medica]. E-mail: fgraeff@keynet.com.br; Santos, A.C. [Sao Paulo Univ., Ribeirao Preto, SP (Brazil). Dept. de Clinica Medica; Guimaraes, F.S. [Sao Paulo Univ., Ribeirao Preto, SP (Brazil). Dept. de Farmacologia

    2003-07-01

    Reported neuroimaging studies have shown functional and morphological changes of temporal lobe structures in panic patients, but only one used a volumetric method. The aim of the present study was to determine the volume of temporal lobe structures in patients with panic disorder, measured by magnetic resonance imaging. Eleven panic patients and eleven controls matched for age, sex, handedness, socioeconomic status and years of education participated in the study. The mean volume of the left temporal lobe of panic patients was 9% smaller than that of controls (t{sub 21} = 2.37, P = 0.028). In addition, there was a trend (P values between 0.05 and 0.10) to smaller volumes of the right temporal lobe (7%, t{sub 21} = 1.99, P = 0.06), right amygdala (8%, t{sub 21} = 1.83, P = 0.08), left amygdala (5%, t{sub 21} = 1.78, P 0.09) and left hippocampus (9%, t{sub 21} = 1.93, P = 0.07) in panic patients compared to controls. There was a positive correlation between left hippocampal volume and duration of panic disorder (r = 0.67, P = 0.025), with recent cases showing more reduction than older cases. The present results show that panic patients have a decreased volume of the left temporal lobe and indicate the presence of volumetric abnormalities of temporal lobe structures. (author)

  8. Decreased left temporal lobe volume of panic patients measured by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Uchida, R.R.; Del-Ben, C.M.; Araujo, D.; Crippa, J.A.; Graeff, F.G.; Santos, A.C.; Guimaraes, F.S.

    2003-01-01

    Reported neuroimaging studies have shown functional and morphological changes of temporal lobe structures in panic patients, but only one used a volumetric method. The aim of the present study was to determine the volume of temporal lobe structures in patients with panic disorder, measured by magnetic resonance imaging. Eleven panic patients and eleven controls matched for age, sex, handedness, socioeconomic status and years of education participated in the study. The mean volume of the left temporal lobe of panic patients was 9% smaller than that of controls (t 21 = 2.37, P = 0.028). In addition, there was a trend (P values between 0.05 and 0.10) to smaller volumes of the right temporal lobe (7%, t 21 = 1.99, P = 0.06), right amygdala (8%, t 21 = 1.83, P = 0.08), left amygdala (5%, t 21 = 1.78, P 0.09) and left hippocampus (9%, t 21 = 1.93, P = 0.07) in panic patients compared to controls. There was a positive correlation between left hippocampal volume and duration of panic disorder (r = 0.67, P = 0.025), with recent cases showing more reduction than older cases. The present results show that panic patients have a decreased volume of the left temporal lobe and indicate the presence of volumetric abnormalities of temporal lobe structures. (author)

  9. Obesity is marked by distinct functional connectivity in brain networks involved in food reward and salience.

    Science.gov (United States)

    Wijngaarden, M A; Veer, I M; Rombouts, S A R B; van Buchem, M A; Willems van Dijk, K; Pijl, H; van der Grond, J

    2015-01-01

    We hypothesized that brain circuits involved in reward and salience respond differently to fasting in obese versus lean individuals. We compared functional connectivity networks related to food reward and saliency after an overnight fast (baseline) and after a prolonged fast of 48 h in lean versus obese subjects. We included 13 obese (2 males, 11 females, BMI 35.4 ± 1.2 kg/m(2), age 31 ± 3 years) and 11 lean subjects (2 males, 9 females, BMI 23.2 ± 0.5 kg/m(2), age 28 ± 3 years). Resting-state functional magnetic resonance imaging scans were made after an overnight fast (baseline) and after a prolonged 48 h fast. Functional connectivity of the amygdala, hypothalamus and posterior cingulate cortex (default-mode) networks was assessed using seed-based correlations. At baseline, we found a stronger connectivity between hypothalamus and left insula in the obese subjects. This effect diminished upon the prolonged fast. After prolonged fasting, connectivity of the hypothalamus with the dorsal anterior cingulate cortex (dACC) increased in lean subjects and decreased in obese subjects. Amygdala connectivity with the ventromedial prefrontal cortex was stronger in lean subjects at baseline, which did not change upon the prolonged fast. No differences in posterior cingulate cortex connectivity were observed. In conclusion, obesity is marked by alterations in functional connectivity networks involved in food reward and salience. Prolonged fasting differentially affected hypothalamic connections with the dACC and the insula between obese and lean subjects. Our data support the idea that food reward and nutrient deprivation are differently perceived and/or processed in obesity. Copyright © 2015 Elsevier B.V. All rights reserved.

  10. OCD-like behavior is caused by dysfunction of thalamo-amygdala circuits and upregulated TrkB/ERK-MAPK signaling as a result of SPRED2 deficiency.

    Science.gov (United States)

    Ullrich, M; Weber, M; Post, A M; Popp, S; Grein, J; Zechner, M; Guerrero González, H; Kreis, A; Schmitt, A G; Üçeyler, N; Lesch, K-P; Schuh, K

    2018-02-01

    Obsessive-compulsive disorder (OCD) is a common neuropsychiatric disease affecting about 2% of the general population. It is characterized by persistent intrusive thoughts and repetitive ritualized behaviors. While gene variations, malfunction of cortico-striato-thalamo-cortical (CSTC) circuits, and dysregulated synaptic transmission have been implicated in the pathogenesis of OCD, the underlying mechanisms remain largely unknown. Here we show that OCD-like behavior in mice is caused by deficiency of SPRED2, a protein expressed in various brain regions and a potent inhibitor of Ras/ERK-MAPK signaling. Excessive self-grooming, reflecting OCD-like behavior in rodents, resulted in facial skin lesions in SPRED2 knockout (KO) mice. This was alleviated by treatment with the selective serotonin reuptake inhibitor fluoxetine. In addition to the previously suggested involvement of cortico-striatal circuits, electrophysiological measurements revealed altered transmission at thalamo-amygdala synapses and morphological differences in lateral amygdala neurons of SPRED2 KO mice. Changes in synaptic function were accompanied by dysregulated expression of various pre- and postsynaptic proteins in the amygdala. This was a result of altered gene transcription and triggered upstream by upregulated tropomyosin receptor kinase B (TrkB)/ERK-MAPK signaling in the amygdala of SPRED2 KO mice. Pathway overactivation was mediated by increased activity of TrkB, Ras, and ERK as a specific result of SPRED2 deficiency and not elicited by elevated brain-derived neurotrophic factor levels. Using the MEK inhibitor selumetinib, we suppressed TrkB/ERK-MAPK pathway activity in vivo and reduced OCD-like grooming in SPRED2 KO mice. Altogether, this study identifies SPRED2 as a promising new regulator, TrkB/ERK-MAPK signaling as a novel mediating mechanism, and thalamo-amygdala synapses as critical circuitry involved in the pathogenesis of OCD.

  11. Growth hormone biases amygdala network activation after fear learning

    OpenAIRE

    Gisabella, Barbara; Farah, Shadia; Peng, Xiaoyu; Burgos-Robles, Anthony Noel; Lim, Seh Hong; Goosens, Ki Ann

    2016-01-01

    Prolonged stress exposure is a risk factor for developing posttraumatic stress disorder, a disorder characterized by the ?over-encoding' of a traumatic experience. A potential mechanism by which this occurs is through upregulation of growth hormone (GH) in the amygdala. Here we test the hypotheses that GH promotes the over-encoding of fearful memories by increasing the number of neurons activated during memory encoding and biasing the allocation of neuronal activation, one aspect of the proce...

  12. Social scaffolding of human amygdala-mPFCcircuit development.

    Science.gov (United States)

    Tottenham, Nim

    2015-01-01

    Strong evidence indicates that reciprocal connections between the amygdala and the medial prefrontal cortex (mPFC) support fundamental aspects of emotional behavior in adulthood. However, this circuitry is slow to develop in humans, exhibiting immaturity in childhood. The argument is made that the development of this circuitry in humans is intimately associated with caregiving, such that parental availability during childhood provides important and enduring scaffolding of neuroaffective processes that ultimately form of the nature of the adult phenotype.

  13. Amygdala activity associated with social choice in mice.

    Science.gov (United States)

    Mihara, Takuma; Mensah-Brown, Kobina; Sobota, Rosanna; Lin, Robert; Featherstone, Robert; Siegel, Steven J

    2017-08-14

    Studies suggest that the amygdala is a key region for regulation of anxiety, fear and social function. Therefore, dysfunction of the amygdala has been proposed as a potential mechanism for negative symptoms in schizophrenia. This may be due to NMDA receptor-mediated hypofunction, which is thought to be related to the pathogenesis of schizophrenia. In this study, electroencephalographic amygdala activity was assessed in mice during the three-chamber social test. This activity was also evaluated following exposure to the NMDA receptor antagonist ketamine. Vehicle-treated mice spent significantly more time in the social than the non-social chamber. This social preference was eliminated by ketamine. However, ketamine-treated mice spent significantly less time in the social chamber and significantly more time in the nonsocial chamber than vehicle-treated mice. There were no significant differences in induced powers between social and non-social chamber entries in vehicle-treated mice, except for theta frequencies, which featured greater induced theta power during non-social chamber entry. Ketamine eliminated differences in induced theta power between social and non-social chamber entries. Moreover, ketamine increased the induced gamma power during social chamber entry compared to that of vehicle-treated mice. All other frequency ranges were not significantly influenced by zone or drug condition. All significant findings were upon entry to chambers not during interaction. Results suggest that impaired function of NMDA receptor-mediated glutamate transmission can induce social impairments and amygdala dysfunction, similar to the pattern in schizophrenia. Future studies will utilize this method to evaluate mechanisms of social dysfunction and development of treatments of social impairments in schizophrenia. Copyright © 2017. Published by Elsevier B.V.

  14. Region-specific role of Rac in nucleus accumbens core and basolateral amygdala in consolidation and reconsolidation of cocaine-associated cue memory in rats.

    Science.gov (United States)

    Ding, Zeng-Bo; Wu, Ping; Luo, Yi-Xiao; Shi, Hai-Shui; Shen, Hao-Wei; Wang, Shen-Jun; Lu, Lin

    2013-08-01

    Drug reinforcement and the reinstatement of drug seeking are associated with the pathological processing of drug-associated cue memories that can be disrupted by manipulating memory consolidation and reconsolidation. Ras-related C3 botulinum toxin substrate (Rac) is involved in memory processing by regulating actin dynamics and neural structure plasticity. The nucleus accumbens (NAc) and amygdala have been implicated in the consolidation and reconsolidation of emotional memories. Therefore, we hypothesized that Rac in the NAc and amygdala plays a role in the consolidation and reconsolidation of cocaine-associated cue memory. Conditioned place preference (CPP) and microinjection of Rac inhibitor NSC23766 were used to determine the role of Rac in the NAc and amygdala in the consolidation and reconsolidation of cocaine-associated cue memory in rats. Microinjections of NSC23766 into the NAc core but not shell, basolateral (BLA), or central amygdala (CeA) after each cocaine-conditioning session inhibited the consolidation of cocaine-induced CPP. A microinjection of NSC23766 into the BLA but not CeA, NAc core, or NAc shell immediately after memory reactivation induced by exposure to a previously cocaine-paired context disrupted the reconsolidation of cocaine-induced CPP. The effect of memory disruption on cocaine reconsolidation was specific to reactivated memory, persisted at least 2 weeks, and was not reinstated by a cocaine-priming injection. Our findings indicate that Rac in the NAc core and BLA are required for the consolidation and reconsolidation of cocaine-associated cue memory, respectively.

  15. Memory modulation across neural systems: intra-amygdala glucose reverses deficits caused by intraseptal morphine on a spatial task but not on an aversive task.

    Science.gov (United States)

    McNay, E C; Gold, P E

    1998-05-15

    Based largely on dissociations of the effects of different lesions on learning and memory, memories for different attributes appear to be organized in independent neural systems. Results obtained with direct injections of drugs into one brain region at a time support a similar conclusion. The present experiments investigated the effects of simultaneous pharmacological manipulation of two neural systems, the amygdala and the septohippocampal system, to examine possible interactions of memory modulation across systems. Morphine injected into the medial septum impaired memory both for avoidance training and during spontaneous alternation. When glucose was concomitantly administered to the amygdala, glucose reversed the morphine-induced deficits in memory during alternation but not for avoidance training. These results suggest that the amygdala is involved in modulation of spatial memory processes and that direct injections of memory-modulating drugs into the amygdala do not always modulate memory for aversive events. These findings are contrary to predictions from the findings of lesion studies and of studies using direct injections of drugs into single brain areas. Thus, the independence of neural systems responsible for processing different classes of memory is less clear than implied by studies using lesions or injections of drugs into single brain areas.

  16. Psychopaths show enhanced amygdala activation during fear conditioning

    Directory of Open Access Journals (Sweden)

    Douglas eSchultz

    2016-03-01

    Full Text Available Psychopathy is a personality disorder characterized by emotional deficits and a failure to inhibit impulsive behavior and is often subdivided into primary and secondary psychopathic subtypes. The maladaptive behavior related to primary psychopathy is thought to reflect constitutional fearlessness, while the problematic behavior related to secondary psychopathy is motivated by other factors. The fearlessness observed in psychopathy has often been interpreted as reflecting a fundamental deficit in amygdala function, and previous studies have provided support for a low-fear model of psychopathy. However, many of these studies fail to use appropriate screening procedures, use liberal inclusion criteria, or have used unconventional approaches to assay amygdala function. We measured brain activity with BOLD imaging in primary and secondary psychopaths and non-psychopathic control subjects during Pavlovian fear conditioning. In contrast to the low-fear model, we observed normal fear expression in primary psychopaths. Psychopaths also displayed greater differential BOLD activity in the amygdala relative to matched controls. Inverse patterns of activity were observed in the anterior cingulate cortex (ACC for primary versus secondary psychopaths. Primary psychopaths exhibited a pattern of activity in the dorsal and ventral ACC consistent with enhanced fear expression, while secondary psychopaths exhibited a pattern of activity in these regions consistent with fear inhibition. These results contradict the low-fear model of psychopathy and suggest that the low fear observed for psychopaths in previous studies may be specific to secondary psychopaths.

  17. Effects of early life stress on amygdala and striatal development.

    Science.gov (United States)

    Fareri, Dominic S; Tottenham, Nim

    2016-06-01

    Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS) in the form of the absence of species expected caregiving (i.e., caregiver deprivation), can drastically impact one's social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Effects of early life stress on amygdala and striatal development

    Directory of Open Access Journals (Sweden)

    Dominic S. Fareri

    2016-06-01

    Full Text Available Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS in the form of the absence of species expected caregiving (i.e., caregiver deprivation, can drastically impact one’s social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction.

  19. Prefrontal-amygdala fear networks come into focus

    Directory of Open Access Journals (Sweden)

    Maithe eArruda-Carvalho

    2015-10-01

    Full Text Available The ability to form associations between aversive threats and their predictors is fundamental to survival. However, fear and anxiety in excess are detrimental and are a hallmark of psychiatric diseases such as post-traumatic stress disorder (PTSD. PTSD symptomatology includes persistent and intrusive thoughts of an experienced trauma, suggesting an inability to downregulate fear when a corresponding threat has subsided. Convergent evidence from human and rodent studies supports a role for the medial prefrontal cortex (mPFC-amygdala network in both PTSD and the regulation of fear memory expression. In particular, current models stipulate that the prelimbic and infralimbic subdivisions of the rodent mPFC bidirectionally regulate fear expression via differential recruitment of amygdala neuronal subpopulations. However, an array of recent studies that employ new technical approaches has fundamentally challenged this interpretation. Here we explore how a new emphasis on the contribution of inhibitory neuronal populations, subcortical structures and the passage of time is reshaping our understanding of mPFC-amygdala circuits and their control over fear.

  20. The Amygdala: An Agent of Change in Adolescent Neural Networks

    Science.gov (United States)

    Scherf, K. Suzanne; Smyth, Joshua M.; Delgado, Mauricio R.

    2013-01-01

    A unique component of adolescent development is the need to master new developmental tasks in which peer interactions become primary (for the purposes of becoming autonomous from parents, forming intimate friendships, and romantic/sexual partnerships). Previously, it has been suggested that the ability to master these tasks requires an important re-organization in the relation between perceptual, motivational, affective, and cognitive systems in a very general and broad way that is fundamentally influenced by the infusion of sex hormones during pubertal development (Scherf et al., 2012). Herein, we extend this argument to suggest that the amygdala, which is vastly connected with cortical and subcortical regions and contains sex hormone receptors, may lie at the heart of this re-organization. We propose that during adolescent development there is a shift in the attribution of relevance to existing stimuli and contexts that is mediated by the amygdala (e.g., heightened relevance of peer faces, reduced relevance of physical distance from parents). As a result, amygdala inputs to existing stable neural networks are re-weighted (increased or decreased), which destabilizes the functional interactions among regions within these networks and allows for a critical restructuring of the network functional organization. This process of network re-organization enables processing of qualitatively new kinds of social information and the emergence of novel behaviors that support mastery of adolescent-specific developmental tasks. PMID:23756154

  1. Effects of early life stress on amygdala and striatal development

    Science.gov (United States)

    Fareri, Dominic S.; Tottenham, Nim

    2016-01-01

    Species-expected caregiving early in life is critical for the normative development and regulation of emotional behavior, the ability to effectively evaluate affective stimuli in the environment, and the ability to sustain social relationships. Severe psychosocial stressors early in life (early life stress; ELS) in the form of the absence of species expected caregiving (i.e., caregiver deprivation), can drastically impact one’s social and emotional success, leading to the onset of internalizing illness later in life. Development of the amygdala and striatum, two key regions supporting affective valuation and learning, is significantly affected by ELS, and their altered developmental trajectories have important implications for cognitive, behavioral and socioemotional development. However, an understanding of the impact of ELS on the development of functional interactions between these regions and subsequent behavioral effects is lacking. In this review, we highlight the roles of the amygdala and striatum in affective valuation and learning in maturity and across development. We discuss their function separately as well as their interaction. We highlight evidence across species characterizing how ELS induced changes in the development of the amygdala and striatum mediate subsequent behavioral changes associated with internalizing illness, positing a particular import of the effect of ELS on their interaction. PMID:27174149

  2. Parallel processing of information about location in the amygdala, entorhinal cortex and hippocampus.

    Science.gov (United States)

    Gaskin, Stephane; White, Norman M

    2013-11-01

    The conditioned cue preference paradigm was used to study how rats use extra-maze cues to discriminate between 2 adjacent arms on an 8-arm radial maze, a situation in which most of the same cues can be seen from both arms but only one arm contains food. Since the food-restricted rats eat while passively confined on the food-paired arm no responses are reinforced, so the discrimination is due to Pavlovian stimulus-reward (or outcome) learning. Consistent with other evidence that rats must move around in an environment to acquire a spatial map, we found that learning the adjacent arms CCP (ACCP) required a minimum amount of active exploration of the maze with no reinforcers present prior to passive pairing of the extra-maze cues with the food reinforcer, an instance of latent learning. Temporary inactivation of the hippocampus during the pre-exposure sessions had no effect on ACCP learning, confirming other evidence that the hippocampus is not involved in latent learning. A series of experiments indentified a circuit involving fimbria-fornix and dorsal entorhinal cortex as the neural basis of latent learning in this situation. In contrast, temporary inactivation of the entorhinal cortex or hippocampus during passive training or during testing blocked ACCP learning and expression, respectively, suggesting that these two structures co-operate in using spatial information to learn the location of food on the maze during passive pairing and to express this combined information during testing. In parallel with these processes we found that the amygdala processes information leading to an equal tendency to enter both adjacent arms (even though only one was paired with food) suggesting that the stimulus information available to this structure is not sufficiently precise to discriminate between the ambiguous cues visible from the adjacent arms. Expression of the ACCP in normal rats depends on hippocampus-based learning to avoid the unpaired arm which competes with the

  3. Primate amygdala neurons evaluate the progress of self-defined economic choice sequences.

    Science.gov (United States)

    Grabenhorst, Fabian; Hernadi, Istvan; Schultz, Wolfram

    2016-10-12

    The amygdala is a prime valuation structure yet its functions in advanced behaviors are poorly understood. We tested whether individual amygdala neurons encode a critical requirement for goal-directed behavior: the evaluation of progress during sequential choices. As monkeys progressed through choice sequences toward rewards, amygdala neurons showed phasic, gradually increasing responses over successive choice steps. These responses occurred in the absence of external progress cues or motor preplanning. They were often specific to self-defined sequences, typically disappearing during instructed control sequences with similar reward expectation. Their build-up rate reflected prospectively the forthcoming choice sequence, suggesting adaptation to an internal plan. Population decoding demonstrated a high-accuracy progress code. These findings indicate that amygdala neurons evaluate the progress of planned, self-defined behavioral sequences. Such progress signals seem essential for aligning stepwise choices with internal plans. Their presence in amygdala neurons may inform understanding of human conditions with amygdala dysfunction and deregulated reward pursuit.

  4. Amygdala α-Synuclein Pathology in the Population-Based Vantaa 85+ Study.

    Science.gov (United States)

    Raunio, Anna; Myllykangas, Liisa; Kero, Mia; Polvikoski, Tuomo; Paetau, Anders; Oinas, Minna

    2017-01-01

    We investigated the frequency of Lewy-related pathology (LRP) in the amygdala among the population-based Vantaa 85+ study. Data of amygdala samples (N = 304) immunostained with two α-synuclein antibodies (clone 42 and clone 5G4) was compared with the previously analyzed LRP and AD pathologies from other brain regions. The amygdala LRP was present in one third (33%) of subjects. Only 5% of pure AD subjects, but 85% of pure DLB subjects had LRP in the amygdala. The amygdala LRP was associated with dementia; however, the association was dependent on LRP on other brain regions, and thus was not an independent risk factor. The amygdala-predominant category was a rare (4%) and heterogeneous group.

  5. Serotonin transporter genotype (5-HTTLPR): effects of neutral and undefined conditions on amygdala activation.

    Science.gov (United States)

    Heinz, Andreas; Smolka, Michael N; Braus, Dieter F; Wrase, Jana; Beck, Anne; Flor, Herta; Mann, Karl; Schumann, Gunter; Büchel, Christian; Hariri, Ahmad R; Weinberger, Daniel R

    2007-04-15

    A polymorphism of the human serotonin transporter gene (SCL6A4) has been associated with serotonin transporter expression and with processing of aversive stimuli in the amygdala. Functional imaging studies show that during the presentation of aversive versus neutral cues, healthy carriers of the short (s) allele showed stronger amygdala activation than long (l) carriers. However, a recent report suggested that this interaction is driven by amygdala deactivation during presentation of neutral stimuli in s carriers. Functional MRI was used to assess amygdala activation during the presentation of a fixation cross or affectively aversive or neutral visual stimuli in 29 healthy men. Amygdala activation was increased in s carriers during undefined states such as the presentation of a fixation cross compared with emotionally neutral conditions. This finding suggests that s carriers show stronger amygdala reactivity to stimuli and contexts that are relatively uncertain, which we propose are stressful.

  6. Evidence for endogenous opioid release in the amygdala during positive emotion.

    Science.gov (United States)

    Koepp, M J; Hammers, A; Lawrence, A D; Asselin, M C; Grasby, P M; Bench, C J

    2009-01-01

    Endogenous opioid release has been linked to relief from aversive emotional memories, thereby promoting a euphoric state and subsequent interactions towards social stimuli resulting in the formation of social preferences. However, this theory remains controversial. Using positron emission tomography and [(11)C]diprenorphine (DPN) in healthy volunteers, we found significantly reduced DPN binding to opioid receptor in the hippocampus during positive mood induction compared to neutral mood. Furthermore, the magnitude of positive mood change correlated negatively with DPN binding in the amygdala bilaterally. Our finding of reduced DPN binding is consistent with increased release of endogenous opioids, providing direct evidence that localised release of endogenous opioids is involved in the regulation of positive emotion in humans.

  7. Personality modulates amygdala and insula connectivity during humor appreciation: An event-related fMRI study.

    Science.gov (United States)

    Berger, Philipp; Bitsch, Florian; Nagels, Arne; Straube, Benjamin; Falkenberg, Irina

    2017-11-12

    Previous research and theory implicate that personality traits, such as extraversion and neuroticism, influence the processing of humor, as indicated by alterations in the activation of fronto-temporal and mesocorticolimbic brain regions during humor processing. In the current study, we sought to complement these findings by testing whether inter-individual differences in functional connectivity of humor-related brain regions are modulated by stable personality characteristics during humor processing. Using fMRI techniques, we studied 19 healthy subjects during the processing of standardized humorous and neutral cartoons. In order to isolate the specific effects of humor appreciation, subjective funniness ratings, collected during the scanning procedure, were implemented in the analysis as parametric modulation. Two distinct clusters in the right amygdala and the left insula were identified. Seed-to-voxel connectivity analysis investigating the effects of personality on inter-individual differences in functional connectivity revealed that amygdala and insula connectivity with brain areas previously related to humor comprehension (e.g. middle temporal gyrus) and appreciation (e.g. caudate nucleus) were significantly modulated by personality dimensions. These results underscore the sensitivity of humor processing to moderating influences, such as personality, and call attention to the importance of brain connectivity measures for the investigation of inter-individual differences in the processing of humor.

  8. Bi-Directional Tuning of Amygdala Sensitivity in Combat Veterans Investigated with fMRI

    Science.gov (United States)

    Brashers-Krug, Tom; Jorge, Ricardo

    2015-01-01

    Objectives Combat stress can be followed by persistent emotional consequences. It is thought that these emotional consequences are caused in part by increased amygdala reactivity. It is also thought that amygdala hyper-reactivity results from decreased inhibition from portions of the anterior cingulate cortex (ACC) in which activity is negatively correlated with activity in the amygdala. However, experimental support for these proposals has been inconsistent. Methods We showed movies of combat and civilian scenes during a functional magnetic resonance imaging (fMRI) session to 50 veterans of recent combat. We collected skin conductance responses (SCRs) as measures of emotional arousal. We examined the relation of blood oxygenation-level dependent (BOLD) signal in the amygdala and ACC to symptom measures and to SCRs. Results Emotional arousal, as measured with SCR, was greater during the combat movie than during the civilian movie and did not depend on symptom severity. As expected, amygdala signal during the less-arousing movie increased with increasing symptom severity. Surprisingly, during the more-arousing movie amygdala signal decreased with increasing symptom severity. These differences led to the unexpected result that amygdala signal in highly symptomatic subjects was lower during the more-arousing movie than during the less-arousing movie. Also unexpectedly, we found no significant inverse correlation between any portions of the amygdala and ACC. Rather, signal throughout more than 80% of the ACC showed a strong positive correlation with signal throughout more than 90% of the amygdala. Conclusions Amygdala reactivity can be tuned bi-directionally, either up or down, in the same person depending on the stimulus and the degree of post-traumatic symptoms. The exclusively positive correlations in BOLD activity between the amygdala and ACC contrast with findings that have been cited as evidence for inhibitory control of the amygdala by the ACC. The

  9. Amygdala reactivity to negative stimuli is influenced by oral contraceptive use

    OpenAIRE

    Petersen, Nicole; Cahill, Larry

    2015-01-01

    The amygdala is a highly interconnected region of the brain that is critically important to emotional processing and affective networks. Previous studies have shown that the response of the amygdala to emotionally arousing stimuli can be modulated by sex hormones. Because oral contraceptive pills dramatically lower circulating sex hormone levels with potent analogs of those hormones, we performed a functional magnetic resonance imaging experiment to measure amygdala reactivity in response to ...

  10. Basolateral amygdala and stress-induced hyperexcitability affect motivated behaviors and addiction

    OpenAIRE

    Sharp, B M

    2017-01-01

    The amygdala integrates and processes incoming information pertinent to reward and to emotions such as fear and anxiety that promote survival by warning of potential danger. Basolateral amygdala (BLA) communicates bi-directionally with brain regions affecting cognition, motivation and stress responses including prefrontal cortex, hippocampus, nucleus accumbens and hindbrain regions that trigger norepinephrine-mediated stress responses. Disruption of intrinsic amygdala and BLA regulatory neuro...

  11. No Community Left Behind

    Science.gov (United States)

    Schlechty, Phillip C.

    2008-01-01

    The debate over the reauthorization of No Child Left Behind (NCLB) generally overlooks--or looks past--what may be the most fundamental flaw in that legislation. As the law is now written, decisions regarding what the young should know and be able to do are removed from the hands of parents and local community leaders and turned over to officials…

  12. The Children Left Behind

    Science.gov (United States)

    Gillard, Sarah A.; Gillard, Sharlett

    2012-01-01

    This article explores some of the deficits in our educational system in regard to non-hearing students. It has become agonizingly clear that non-hearing students are being left out of the gallant sweep to enrich our children's educations. The big five areas of literacy, at best, present unique challenges for non-hearing students and, in some…

  13. Left atrial appendage occlusion

    Directory of Open Access Journals (Sweden)

    Ahmad Mirdamadi

    2013-01-01

    Full Text Available Left atrial appendage (LAA occlusion is a treatment strategy to prevent blood clot formation in atrial appendage. Although, LAA occlusion usually was done by catheter-based techniques, especially percutaneous trans-luminal mitral commissurotomy (PTMC, it can be done during closed and open mitral valve commissurotomy (CMVC, OMVC and mitral valve replacement (MVR too. Nowadays, PTMC is performed as an optimal management of severe mitral stenosis (MS and many patients currently are treated by PTMC instead of previous surgical methods. One of the most important contraindications of PTMC is presence of clot in LAA. So, each patient who suffers of severe MS is evaluated by Trans-Esophageal Echocardiogram to rule out thrombus in LAA before PTMC. At open heart surgery, replacement of the mitral valve was performed for 49-year-old woman. Also, left atrial appendage occlusion was done during surgery. Immediately after surgery, echocardiography demonstrates an echo imitated the presence of a thrombus in left atrial appendage area, although there was not any evidence of thrombus in pre-pump TEE. We can conclude from this case report that when we suspect of thrombus of left atrial, we should obtain exact history of previous surgery of mitral valve to avoid misdiagnosis clotted LAA, instead of obliterated LAA. Consequently, it can prevent additional evaluations and treatments such as oral anticoagulation and exclusion or postponing surgeries including PTMC.

  14. Understanding amygdala responsiveness to fearful expressions through the lens of psychopathy and altruism.

    Science.gov (United States)

    Marsh, Abigail A

    2016-06-01

    Because the face is the central focus of human social interactions, emotional facial expressions provide a unique window into the emotional lives of others. They play a particularly important role in fostering empathy, which entails understanding and responding to others' emotions, especially distress-related emotions such as fear. This Review considers how fearful facial as well as vocal and postural expressions are interpreted, with an emphasis on the role of the amygdala. The amygdala may be best known for its role in the acquisition and expression of conditioned fear, but it also supports the perception and recognition of others' fear. Various explanations have been supplied for the amygdala's role in interpreting and responding to fearful expressions. They include theories that amygdala responses to fearful expressions 1) reflect heightened vigilance in response to uncertain danger, 2) promote heightened attention to the eye region of faces, 3) represent a response to an unconditioned aversive stimulus, or 4) reflect the generation of an empathic fear response. Among these, only empathic fear explains why amygdala lesions would impair fear recognition across modalities. Supporting the possibility of a link between fundamental empathic processes and amygdala responses to fear is evidence that impaired fear recognition in psychopathic individuals results from amygdala dysfunction, whereas enhanced fear recognition in altruistic individuals results from enhanced amygdala function. Empathic concern and caring behaviors may be fostered by sensitivity to signs of acute distress in others, which relies on intact functioning of the amygdala. © 2015 Wiley Periodicals, Inc.

  15. Age-related reduced prefrontal-amygdala structural connectivity is associated with lower trait anxiety.

    Science.gov (United States)

    Clewett, David; Bachman, Shelby; Mather, Mara

    2014-07-01

    A current neuroanatomical model of anxiety posits that greater structural connectivity between the amygdala and ventral prefrontal cortex (vPFC) facilitates regulatory control over the amygdala and helps reduce anxiety. However, some neuroimaging studies have reported contradictory findings, demonstrating a positive rather than negative association between trait anxiety and amygdala-vPFC white matter integrity. To help reconcile these findings, we tested the regulatory hypothesis of anxiety circuitry using aging as a model of white matter decline in the amygdala-vPFC pathway. We used probabilistic tractography to trace connections between the amygdala and vPFC in 21 younger, 18 middle-aged, and 15 healthy older adults. The resulting tract estimates were used to extract 3 indices of white-matter integrity: fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD). The relationship between these amygdala-vPFC structural connectivity measures and age and State-Trait Anxiety Inventory (STAI) scores were assessed. The tractography results revealed age-related decline in the FA (p = .005) and radial diffusivity (p = .002) of the amygdala-vPFC pathway. Contrary to the regulatory hypothesis, we found a positive rather than negative association between trait anxiety and right amygdala-vPFC FA (p = .01). These findings argue against the notion that greater amygdala-vPFC structural integrity facilitates better anxiety outcomes in healthy adults. Instead, our results suggest that white matter degeneration in this network relates to lower anxiety in older adults.

  16. Amygdala activity related to enhanced memory for pleasant and aversive stimuli.

    Science.gov (United States)

    Hamann, S B; Ely, T D; Grafton, S T; Kilts, C D

    1999-03-01

    Pleasant or aversive events are better remembered than neutral events. Emotional enhancement of episodic memory has been linked to the amygdala in animal and neuropsychological studies. Using positron emission tomography, we show that bilateral amygdala activity during memory encoding is correlated with enhanced episodic recognition memory for both pleasant and aversive visual stimuli relative to neutral stimuli, and that this relationship is specific to emotional stimuli. Furthermore, data suggest that the amygdala enhances episodic memory in part through modulation of hippocampal activity. The human amygdala seems to modulate the strength of conscious memory for events according to emotional importance, regardless of whether the emotion is pleasant or aversive.

  17. Age-related reduced prefrontal-amygdala structural connectivity is associated with lower trait anxiety

    Science.gov (United States)

    Clewett, David; Bachman, Shelby; Mather, Mara

    2014-01-01

    Objective A current neuroanatomical model of anxiety posits that greater structural connectivity between the amygdala and ventral prefrontal cortex (vPFC) facilitates regulatory control over the amygdala and helps reduce anxiety. However, some neuroimaging studies have reported contradictory findings, demonstrating a positive rather than negative association between trait anxiety and amygdala-vPFC white matter integrity. To help reconcile these findings, we tested the regulatory hypothesis of anxiety circuitry using aging as a model of white matter decline in the amygdala-vPFC pathway. Methods We used probabilistic tractography to trace connections between the amygdala and vPFC in 21 younger, 18 middle-aged, and 15 healthy older adults. The resulting tract estimates were used to extract three indices of white-matter integrity: fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD). The relationship between these amygdala-vPFC structural connectivity measures and age and State-Trait Anxiety Inventory (STAI) scores were assessed. Results The tractography results revealed age-related decline in the FA (p = .005) and radial diffusivity (p = .002) of the amygdala-vPFC pathway. Contrary to the regulatory hypothesis, we found a positive rather than negative association between trait anxiety and right amygdala-vPFC FA (p = .01). Conclusion These findings argue against the notion that greater amygdala-vPFC structural integrity facilitates better anxiety outcomes in healthy adults. Instead, our results suggest that white matter degeneration in this network relates to lower anxiety in older adults. PMID:24635708

  18. Hypoplastic left heart syndrome

    Directory of Open Access Journals (Sweden)

    Thiagarajan Ravi

    2007-05-01

    Full Text Available Abstract Hypoplastic left heart syndrome(HLHS refers to the abnormal development of the left-sided cardiac structures, resulting in obstruction to blood flow from the left ventricular outflow tract. In addition, the syndrome includes underdevelopment of the left ventricle, aorta, and aortic arch, as well as mitral atresia or stenosis. HLHS has been reported to occur in approximately 0.016 to 0.036% of all live births. Newborn infants with the condition generally are born at full term and initially appear healthy. As the arterial duct closes, the systemic perfusion becomes decreased, resulting in hypoxemia, acidosis, and shock. Usually, no heart murmur, or a non-specific heart murmur, may be detected. The second heart sound is loud and single because of aortic atresia. Often the liver is enlarged secondary to congestive heart failure. The embryologic cause of the disease, as in the case of most congenital cardiac defects, is not fully known. The most useful diagnostic modality is the echocardiogram. The syndrome can be diagnosed by fetal echocardiography between 18 and 22 weeks of gestation. Differential diagnosis includes other left-sided obstructive lesions where the systemic circulation is dependent on ductal flow (critical aortic stenosis, coarctation of the aorta, interrupted aortic arch. Children with the syndrome require surgery as neonates, as they have duct-dependent systemic circulation. Currently, there are two major modalities, primary cardiac transplantation or a series of staged functionally univentricular palliations. The treatment chosen is dependent on the preference of the institution, its experience, and also preference. Although survival following initial surgical intervention has improved significantly over the last 20 years, significant mortality and morbidity are present for both surgical strategies. As a result pediatric cardiologists continue to be challenged by discussions with families regarding initial decision

  19. Early experience of a novel-environment in isolation primes a fearful phenotype characterized by persistent amygdala activation.

    Science.gov (United States)

    Daskalakis, Nikolaos P; Diamantopoulou, Anastasia; Claessens, Sanne E F; Remmers, Elisa; Tjälve, Marika; Oitzl, Melly S; Champagne, Danielle L; de Kloet, E Ronald

    2014-01-01

    Prolonged maternal separation (MS) activates the neonate's hypothalamus-pituitary-adrenal axis causing elevated basal and stress-induced corticosterone levels that may initiate amygdala-dependent fear learning. Here we test the hypothesis that the adult fearful phenotype is programmed by the pup's stressful experience during prolonged MS rather than by prolonged maternal absence per se. For this purpose, Wistar rat pups were exposed, on postnatal-day (pnd) 3, to: (i) repeated-MS in home-environment (HOME-SEP), 8h-MS daily for three days with the pups remaining together in the home-cage; (ii) repeated-MS in a novel-environment (NOVEL-SEP), with the same separation procedure, but now the pups were individually housed in a novel-environment during the 8h dam's absence; (iii) repeated handling, which consisted of daily brief (15 min instead of 8h) MS in the home-altogether or in a novel-environment individually (HOME-HAN and NOVEL-HAN, respectively); (iv) no-separation/no-handling (NON-SEP/NON-HAN) control condition, in which pups were left undisturbed in their home-cage. Compared to HOME-SEP rats, the NOVEL-SEP rats showed one day after the last MS enhanced stress-induced amygdala c-Fos expression and ACTH-release, despite of reduced adrenal corticosterone secretion. The higher amygdala c-Fos expression, ACTH-release and reduced corticosterone output observed postnatally, persisted into adulthood of the NOVEL-SEP animals. Behaviorally, NOVEL-SEP juvenile rats displayed deficits in social play, had intact spatial memory in the peri-pubertal period and showed more contextual fear memory compared to HOME-SEP in adulthood. Finally, NOVEL-HAN, compared to HOME-HAN, displayed increased stress-induced corticosterone output, no deficits in social play and reduced contextual fear. In conclusion, programming of an adult fearful phenotype linked to amygdala priming develops if pups are repeatedly isolated from peers in a novel-environment, while away from the dam for a prolonged

  20. Rethinking the fear circuit: the central nucleus of the amygdala is required for the acquisition, consolidation, and expression of Pavlovian fear conditioning

    DEFF Research Database (Denmark)

    Wilensky, Ann E; Schafe, Glenn E; Kristensen, Morten Pilgaard

    2006-01-01

    of the amygdala (CE), which serves as the principal output nucleus for the expression of conditioned fear responses. In the present study, we reexamined the roles of LA and CE. Specifically, we asked whether CE, like LA, might also be involved in fear learning and memory consolidation. Using functional...... inactivation methods, we first show that CE is involved not only in the expression but also the acquisition of fear conditioning. Next, we show that inhibition of protein synthesis in CE after training impairs fear memory consolidation. These findings indicate that CE is not only involved in fear expression...... but, like LA, is also involved in the learning and consolidation of pavlovian fear conditioning....

  1. Tracking the fear memory engram: discrete populations of neurons within amygdala, hypothalamus, and lateral septum are specifically activated by auditory fear conditioning

    Science.gov (United States)

    Wilson, Yvette M.; Gunnersen, Jenny M.; Murphy, Mark

    2015-01-01

    Memory formation is thought to occur via enhanced synaptic connectivity between populations of neurons in the brain. However, it has been difficult to localize and identify the neurons that are directly involved in the formation of any specific memory. We have previously used fos-tau-lacZ (FTL) transgenic mice to identify discrete populations of neurons in amygdala and hypothalamus, which were specifically activated by fear conditioning to a context. Here we have examined neuronal activation due to fear conditioning to a more specific auditory cue. Discrete populations of learning-specific neurons were identified in only a small number of locations in the brain, including those previously found to be activated in amygdala and hypothalamus by context fear conditioning. These populations, each containing only a relatively small number of neurons, may be directly involved in fear learning and memory. PMID:26179231

  2. Neural hyperactivity in the amygdala induced by chronic treatment of rats with analgesics may elucidate the mechanisms underlying psychiatric comorbidities associated with medication-overuse headache.

    Science.gov (United States)

    Wanasuntronwong, Aree; Jansri, Ukkrit; Srikiatkhachorn, Anan

    2017-01-03

    Patients with medication-overuse headache suffer not only from chronic headache, but often from psychiatric comorbidities, such as anxiety and depression. The mechanisms underlying these comorbidities are unclear, but the amygdala is likely to be involved in their pathogenesis. To investigate the mechanisms underlying the comorbidities we used elevated plus maze and open field tests to assess anxiety-like behavior in rats chronically treated with analgesics. We measured the electrical properties of neurons in the amygdala, and examined the cortical spreading depression (CSD)-evoked expression of Fos in the trigeminal nucleus caudalis (TNC) and amygdala of rats chronically treated with analgesics. CSD, an analog of aura, evokes Fos expression in the TNC of rodents suggesting trigeminal nociception, considered to be a model of migraine. Increased anxiety-like behavior was seen both in elevated plus maze and open field tests in a model of medication overuse produced in male rats by chronic treatment with aspirin or acetaminophen. The time spent in the open arms of the maze by aspirin- or acetaminophen-treated rats (53 ± 36.1 and 37 ± 29.5 s, respectively) was significantly shorter than that spent by saline-treated vehicle control rats (138 ± 22.6 s, P amygdala as indicated by their more negative threshold for action potential generation (-54.6 ± 5.01 mV for aspirin-treated, -55.2 ± 0.97 mV for acetaminophen-treated, and -31.50 ± 5.34 mV for saline-treated rats, P amygdala [18 ± 10.2 Fos-immunoreactive (IR) neurons per slide in the amygdala of rats treated with aspirin, 11 ± 5.4 IR neurons per slide in rats treated with acetaminophen, and 4 ± 3.7 IR neurons per slide in saline-treated control rats, P amygdala, which could underlie the anxiety seen in patients with medication-overuse headache.

  3. Cannabinoids prevent the differential long-term effects of exposure to severe stress on hippocampal- and amygdala-dependent memory and plasticity.

    Science.gov (United States)

    Shoshan, Noa; Segev, Amir; Abush, Hila; Mizrachi Zer-Aviv, Tomer; Akirav, Irit

    2017-10-01

    Exposure to excessive or uncontrolled stress is a major factor associated with various diseases including posttraumatic stress disorder (PTSD). The consequences of exposure to trauma are affected not only by aspects of the event itself, but also by the frequency and severity of trauma reminders. It was suggested that in PTSD, hippocampal-dependent memory is compromised while amygdala-dependent memory is strengthened. Several lines of evidence support the role of the endocannabinoid (eCB) system as a modulator of the stress response. In this study we aimed to examine cannabinoids modulation of the long-term effects (i.e., 1 month) of exposure to a traumatic event on memory and plasticity in the hippocampus and amygdala. Following exposure to the shock and reminders model of PTSD in an inhibitory avoidance light-dark apparatus rats demonstrated: (i) enhanced fear retrieval and impaired inhibitory extinction (Ext), (ii) no long-term potentiation (LTP) in the CA1, (iii) impaired hippocampal-dependent short-term memory in the object location task, (iv) enhanced LTP in the amygdala, and (v) enhanced amygdala-dependent conditioned taste aversion memory. The cannabinoid CB1/2 receptor agonist WIN55-212,2 (0.5mg/kg, i.p.) and the fatty acid amide hydrolase (FAAH) inhibitor URB597 (0.3mg/kg, i.p.), administered 2 hr after shock exposure prevented these opposing effects on hippocampal- and amygdala-dependent processes. Moreover, the effects of WIN55-212,2 and URB597 on Ext and acoustic startle were prevented by co-administration of a low dose of the CB1 receptor antagonist AM251 (0.5mg/kg, i.p.), suggesting that the preventing effects of both drugs are mediated by CB1 receptors. Exposure to shock and reminders increased CB1 receptor levels in the CA1 and basolateral amygdala 1 month after shock exposure and this increase was also prevented by administering WIN55-212,2 or URB597. Taken together, these findings suggest the involvement of the eCB system, and specifically CB1

  4. Activation of ERK2 in basolateral amygdala underlies the promoting influence of stress on fear memory and anxiety: influence of midazolam pretreatment.

    Science.gov (United States)

    Maldonado, N M; Espejo, P J; Martijena, I D; Molina, V A

    2014-02-01

    Exposure to emotionally arousing experiences elicits a robust and persistent memory and enhances anxiety. The amygdala complex plays a key role in stress-induced emotional processing and in the fear memory formation. It is well known that ERK activation in the amygdala is a prerequisite for fear memory consolidation. Moreover, stress elevates p-ERK2 levels in several areas of the brain stress circuitry. Therefore, given that the ERK1/2 cascade is activated following stress and that the role of this cascade is critical in the formation of fear memory, the present study investigated the potential involvement of p-ERK2 in amygdala subnuclei in the promoting influence of stress on fear memory formation and on anxiety-like behavior. A robust and persistent ERK2 activation was noted in the Basolateral amygdala (BLA), which was evident at 5min after restraint and lasted at least one day after the stressful experience. Midazolam, a short-acting benzodiazepine ligand, administered prior to stress prevented the increase in the p-ERK2 level in the BLA. Pretreatment with intra-BLA infusion of U0126 (MEK inhibitor), but not into the adjacent central nucleus of the amygdala, attenuated the stress-induced promoting influence on fear memory formation. Finally, U0126 intra-BLA infusion prevented the enhancement of anxiety-like behavior in stressed animals. These findings suggest that the selective ERK2 activation in BLA following stress exposure is an important mechanism for the occurrence of the promoting influence of stress on fear memory and on anxiety-like behavior. © 2013 Published by Elsevier B.V. and ECNP.

  5. Opposing effects of traumatic brain injury on excitatory synaptic function in the lateral amygdala in the absence and presence of preinjury stress.

    Science.gov (United States)

    Klein, Rebecca C; Acheson, Shawn K; Qadri, Laura H; Dawson, Alina A; Rodriguiz, Ramona M; Wetsel, William C; Moore, Scott D; Laskowitz, Daniel T; Dawson, Hana N

    2016-06-01

    Traumatic brain injury (TBI) is a leading cause of death and disability among young adults and is highly prevalent among recently deployed military personnel. Survivors of TBI often experience cognitive and emotional deficits, suggesting that long-term effects of injury may disrupt neuronal function in critical brain regions, including the amygdala, which is involved in emotion and fear memory. Amygdala hyperexcitability has been reported in both TBI and posttraumatic stress disorder patients, yet little is known regarding the effects of combined stress and TBI on amygdala structure and function at the neuronal level. The present study seeks to determine how the long-term effects of preinjury foot-shock stress and TBI interact to influence synaptic plasticity in the lateral amygdala (LA) of adult male C57BL/6J mice by using whole-cell patch clamp electrophysiology 2-3 months postinjury. In the absence of stress, TBI resulted in a significant increase in membrane excitability and spontaneous excitatory postsynaptic currents (sEPSCs) in LA pyramidal-like neurons. Foot-shock stress in the absence of TBI also resulted in increased sEPSC activity. In contrast, when preinjury stress and TBI occurred in combination, sEPSC activity was significantly decreased compared with either condition alone. There were no significant differences in inhibitory activity or total dendritic length among any of the treatment groups. These results demonstrate that stress and TBI may be contributing to amygdala hyperexcitability via different mechanisms and that these pathways may counterbalance each other with respect to long-term pathophysiology in the LA. © 2015 Wiley Periodicals, Inc.

  6. Intra- and interobserver variability of MRI-based volume measurements of the hippocampus and amygdala using the manual ray-tracing method

    International Nuclear Information System (INIS)

    Achten, E.; Deblaere, K.; Damme, F. van; Kunnen, M.; Wagter, C. de; Boon, P.; Reuck, J. de

    1998-01-01

    We studied the intra- and interobserver variability of volume measurments of the hippocampus (HC) and the amygdala as applied to the detection of HC atrophy in patients with complex partial seizures (CPE), measuring the volumes of the HC and amygdala of 11 normal volunteers and 12 patients with presumed CPE, using the manual ray-tracing method. Two independent observers performed these measurements twice each using home-made software. The intra- and interobserver variability of the absolute volumes and of the normalised left-to-right volume differences (δV) between the HC (δV HC ), the amygdala (δV A ) and the sum of both (δV HCA) were assessed. In our mainly right-handed normals, the right HC and amygdala were on average 0.05 and 0.03 ml larger respectively than on the left. The interobserver variability for volume measurements in normal subjects was 1.80 ml for the HC and 0.82 ml for the amygdala, the intraobserver variability roughly one third of these values. The interobserver variability coefficient in normals was 3.6 % for δV HCA , 4.7 % for δV HC and 7.3 % for δV A . The intraobserver variability coefficient was 3.4 % for δV HCA , 4.2 % for δV HC amd 5.6 % for δV A . The variability in patients was the same for volume differences less than 5 % either side of the interval for normality, but was higher when large volume differences were encountered, is probably due to the lack of thresholding and/or normalisation. Cutoff values for lateralisation with the δV were defined. No intra- or interobserver lateralisation differences were encountered with δV HCA and δV HC . From these observations we conclude that the manual ray-tracing method is a robust method for lateralisation in patients with TLE. Due to its higher variability, this method is less suited to measure absolute volumes. (orig.) (orig.)

  7. Intra- and interobserver variability of MRI-based volume measurements of the hippocampus and amygdala using the manual ray-tracing method

    Energy Technology Data Exchange (ETDEWEB)

    Achten, E.; Deblaere, K.; Damme, F. van; Kunnen, M. [MR Department 1K12, University Hospital Gent (Belgium); Wagter, C. de [Department of Radiotherapy and Nuclear Medicine, University Hospital Gent (Belgium); Boon, P.; Reuck, J. de [Department of Neurology, University Hospital Gent (Belgium)

    1998-09-01

    We studied the intra- and interobserver variability of volume measurments of the hippocampus (HC) and the amygdala as applied to the detection of HC atrophy in patients with complex partial seizures (CPE), measuring the volumes of the HC and amygdala of 11 normal volunteers and 12 patients with presumed CPE, using the manual ray-tracing method. Two independent observers performed these measurements twice each using home-made software. The intra- and interobserver variability of the absolute volumes and of the normalised left-to-right volume differences ({delta}V) between the HC ({delta}V{sub HC}), the amygdala ({delta}V{sub A}) and the sum of both ({delta}V{sub HCA)} were assessed. In our mainly right-handed normals, the right HC and amygdala were on average 0.05 and 0.03 ml larger respectively than on the left. The interobserver variability for volume measurements in normal subjects was 1.80 ml for the HC and 0.82 ml for the amygdala, the intraobserver variability roughly one third of these values. The interobserver variability coefficient in normals was 3.6 % for {delta}V{sub HCA}, 4.7 % for {delta}V{sub HC} and 7.3 % for {delta}V{sub A}. The intraobserver variability coefficient was 3.4 % for {delta}V{sub HCA}, 4.2 % for {delta}V{sub HC} amd 5.6 % for {delta}V{sub A}. The variability in patients was the same for volume differences less than 5 % either side of the interval for normality, but was higher when large volume differences were encountered, is probably due to the lack of thresholding and/or normalisation. Cutoff values for lateralisation with the {delta}V were defined. No intra- or interobserver lateralisation differences were encountered with {delta}V{sub HCA} and {delta}V{sub HC}. From these observations we conclude that the manual ray-tracing method is a robust method for lateralisation in patients with TLE. Due to its higher variability, this method is less suited to measure absolute volumes. (orig.) (orig.) With 2 figs., 7 tabs., 23 refs.

  8. Progressively Disrupted Intrinsic Functional Connectivity of Basolateral Amygdala in Very Early Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Marion Ortner

    2016-09-01

    Full Text Available Abstract:Very early Alzheimer’s disease (AD - i.e., AD at stages of mild cognitive impairment (MCI and mild dementia - is characterized by progressive structural and neuropathologic changes such as atrophy or tangle deposition in medial temporal lobes, including hippocampus and entorhinal cortex but also adjacent amygdala. While progressively disrupted intrinsic connectivity of hippocampus with other brain areas has been demonstrated by many studies, amygdala connectivity was rarely investigated in AD, notwithstanding its known relevance for emotion processing and mood disturbances, which are both important in early AD. Intrinsic functional connectivity (iFC patterns of hippocampus and amygdala overlap in healthy persons. Thus, we hypothesized that increased alteration of iFC patterns along AD is not limited to the hippocampus but also concerns the amygdala, independent from atrophy. To address this hypothesis, we applied structural and functional resting-state MRI in healthy controls (CON, n=33 and patients with AD in the stages of MCI (AD-MCI, n=38 and mild dementia (AD-D, n=36. Outcome measures were voxel-based morphometry (VBM values and region of interest-based intrinsic functional connectivity maps (iFC of basolateral amygdala, which has extended cortical connectivity. Amygdala VBM values were progressively reduced in patients (CON > AD-MCI and AD-D. Amygdala iFC was progressively reduced along impairment severity (CON > AD-MCI > AD-D, particularly for hippocampus, temporal lobes, and fronto-parietal areas. Notably, decreased iFC was independent of amygdala atrophy. Results demonstrate progressively impaired amygdala intrinsic connectivity in temporal and fronto-parietal lobes independent from increasing amygdala atrophy in very early AD. Data suggest that early AD disrupts intrinsic connectivity of medial temporal lobe key regions including that of amygdala.

  9. White matter integrity deficits in prefrontal-amygdala pathways in Williams syndrome.

    Science.gov (United States)

    Avery, Suzanne N; Thornton-Wells, Tricia A; Anderson, Adam W; Blackford, Jennifer Urbano

    2012-01-16

    Williams syndrome is a neurodevelopmental disorder associated with significant non-social fears. Consistent with this elevated non-social fear, individuals with Williams syndrome have an abnormally elevated amygdala response when viewing threatening non-social stimuli. In typically-developing individuals, amygdala activity is inhibited through dense, reciprocal white matter connections with the prefrontal cortex. Neuroimaging studies suggest a functional uncoupling of normal prefrontal-amygdala inhibition in individuals with Williams syndrome, which might underlie both the extreme amygdala activity and non-social fears. This functional uncoupling might be caused by structural deficits in underlying white matter pathways; however, prefrontal-amygdala white matter deficits have yet to be explored in Williams syndrome. We used diffusion tensor imaging to investigate prefrontal-amygdala white matter integrity differences in individuals with Williams syndrome and typically-developing controls with high levels of non-social fear. White matter pathways between the amygdala and several prefrontal regions were isolated using probabilistic tractography. Within each pathway, we tested for between-group differences in three measures of white matter integrity: fractional anisotropy (FA), radial diffusivity (RD), and parallel diffusivity (λ(1)). Individuals with Williams syndrome had lower FA, compared to controls, in several of the prefrontal-amygdala pathways investigated, indicating a reduction in white matter integrity. Lower FA in Williams syndrome was explained by significantly higher RD, with no differences in λ(1), suggestive of lower fiber density or axon myelination in prefrontal-amygdala pathways. These results suggest that deficits in the structural integrity of prefrontal-amygdala white matter pathways might underlie the increased amygdala activity and extreme non-social fears observed in Williams syndrome. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. Left Ventricular Assist Devices

    Directory of Open Access Journals (Sweden)

    Khuansiri Narajeenron

    2017-04-01

    Full Text Available Audience: The audience for this classic team-based learning (cTBL session is emergency medicine residents, faculty, and students; although this topic is applicable to internal medicine and family medicine residents. Introduction: A left ventricular assist device (LVAD is a mechanical circulatory support device that can be placed in critically-ill patients who have poor left ventricular function. After LVAD implantation, patients have improved quality of life.1 The number of LVAD patients worldwide continues to rise. Left-ventricular assist device patients may present to the emergency department (ED with severe, life-threatening conditions. It is essential that emergency physicians have a good understanding of LVADs and their complications. Objectives: Upon completion of this cTBL module, the learner will be able to: 1 Properly assess LVAD patients’ circulatory status; 2 appropriately resuscitate LVAD patients; 3 identify common LVAD complications; 4 evaluate and appropriately manage patients with LVAD malfunctions. Method: The method for this didactic session is cTBL.

  11. Reduced amygdala and ventral striatal activity to happy faces in PTSD is associated with emotional numbing.

    Directory of Open Access Journals (Sweden)

    Kim L Felmingham

    Full Text Available There has been a growing recognition of the importance of reward processing in PTSD, yet little is known of the underlying neural networks. This study tested the predictions that (1 individuals with PTSD would display reduced responses to happy facial expressions in ventral striatal reward networks, and (2 that this reduction would be associated with emotional numbing symptoms. 23 treatment-seeking patients with Posttraumatic Stress Disorder were recruited from the treatment clinic at the Centre for Traumatic Stress Studies, Westmead Hospital, and 20 trauma-exposed controls were recruited from a community sample. We examined functional magnetic resonance imaging responses during the presentation of happy and neutral facial expressions in a passive viewing task. PTSD participants rated happy facial expression as less intense than trauma-exposed controls. Relative to controls, PTSD participants revealed lower activation to happy (-neutral faces in ventral striatum and and a trend for reduced activation in left amygdala. A significant negative correlation was found between emotional numbing symptoms in PTSD and right ventral striatal regions after controlling for depression, anxiety and PTSD severity. This study provides initial evidence that individuals with PTSD have lower reactivity to happy facial expressions, and that lower activation in ventral striatal-limbic reward networks may be associated with symptoms of emotional numbing.

  12. Increased amygdala response to shame in remitted major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Erdem Pulcu

    Full Text Available Proneness to self-blaming moral emotions such as shame and guilt is increased in major depressive disorder (MDD, and may play an important role in vulnerability even after symptoms have subsided. Social psychologists have argued that shame-proneness is relevant for depression vulnerability and is distinct from guilt. Shame depends on the imagined critical perception of others, whereas guilt results from one's own judgement. The neuroanatomy of shame in MDD is unknown. Using fMRI, we compared 21 participants with MDD remitted from symptoms with no current co-morbid axis-I disorders, and 18 control participants with no personal or family history of MDD. The MDD group exhibited higher activation of the right amygdala and posterior insula for shame relative to guilt (SPM8. This neural difference was observed despite equal levels of rated negative emotional valence and frequencies of induced shame and guilt experience across groups. These same results were found in the medication-free MDD subgroup (N = 15. Increased amygdala and posterior insula activations, known to be related to sensory perception of emotional stimuli, distinguish shame from guilt responses in remitted MDD. People with MDD thus exhibit changes in the neural response to shame after symptoms have subsided. This supports the hypothesis that shame and guilt play at least partly distinct roles in vulnerability to MDD. Shame-induction may be a more sensitive probe of residual amygdala hypersensitivity in MDD compared with facial emotion-evoked responses previously found to normalize on remission.

  13. Visual Attention to Suffering After Compassion Training Is Associated With Decreased Amygdala Responses

    Directory of Open Access Journals (Sweden)

    Helen Y. Weng

    2018-05-01

    Full Text Available Compassion meditation training is hypothesized to increase the motivational salience of cues of suffering, while also enhancing equanimous attention and decreasing emotional reactivity to suffering. However, it is currently unknown how compassion meditation impacts visual attention to suffering, and how this impacts neural activation in regions associated with motivational salience as well as aversive responses, such as the amygdala. Healthy adults were randomized to 2 weeks of compassion or reappraisal training. We measured BOLD fMRI responses before and after training while participants actively engaged in their assigned training to images depicting human suffering or non-suffering. Eye-tracking data were recorded concurrently, and we computed looking time for socially and emotionally evocative areas of the images, and calculated visual preference for suffering vs. non-suffering. Increases in visual preference for suffering due to compassion training were associated with decreases in the amygdala, a brain region involved in negative valence, arousal, and physiological responses typical of fear and anxiety states. This pattern was specifically in the compassion group, and was not found in the reappraisal group. In addition, compassion training-related increases in visual preference for suffering were also associated with decreases in regions sensitive to valence and empathic distress, spanning the anterior insula and orbitofrontal cortex (while the reappraisal group showed the opposite effect. Examining visual attention alone demonstrated that engaging in compassion in general (across both time points resulted in visual attention preference for suffering compared to engaging in reappraisal. Collectively, these findings suggest that compassion meditation may cultivate visual preference for suffering while attenuating neural responses in regions typically associated with aversive processing of negative stimuli, which may cultivate a more

  14. The Effect of Reversible Abolition of Basolateral Amygdala on Hippocampal Dependent Spatial Memory Processes in Mice

    Directory of Open Access Journals (Sweden)

    A Rashidy-Pour

    2004-04-01

    Full Text Available Introduction: Many evidences have suggested that the Basolateral Amygdala (BLA are probably involved in emotional learning and modulation of spatial memory processes. The aim of this present study was assessment of the effect of reversible abolition of BLA on spatial memory processes in a place avoidance learning model in a stable environment. Methods and Materials: Long-Evans strain rats (280-320 gr. were selected and cannulae aimed at the BLA were surgically implanted bilaterally. The mice were trained to avoid a 60° segment of the arena by punishing with a mild foot shock upon entering the area. The punished sector was defined by room cues during the place avoidance training, which occurred in a single 30-mi