Mechanisms Contributing to the Induction and Storage of Pavlovian Fear Memories in the Lateral Amygdala

ERIC Educational Resources Information Center

Kim, Dongbeom; Pare, Denis; Nair, Satish S.

2013-01-01

The relative contributions of plasticity in the amygdala vs. its afferent pathways to conditioned fear remain controversial. Some believe that thalamic and cortical neurons transmitting information about the conditioned stimulus (CS) to the lateral amygdala (LA) serve a relay function. Others maintain that thalamic and/or cortical plasticity is…

A dissociation of dorso-lateral striatum and amygdala function on the same stimulus-response habit task.

PubMed

McDonald, R J; Hong, N S

2004-01-01

This experiment tested the idea that the amygdala-based learning and memory system covertly acquires a stimulus-reward (stimulus-outcome) association during acquisition of a stimulus-response (S-R) habit task developed for the eight-arm radial maze. Groups of rats were given dorso-lateral striatal or amygdala lesions and then trained on the S-R habit task on the eight-arm radial maze. Rats with neurotoxic damage to the dorso-lateral striatum were severely impaired on the acquisition of the S-R habit task but showed a conditioned-cue preference for the stimulus reinforced during S-R habit training. Rats with neurotoxic damage to the amygdala were able to acquire the S-R habit task but did not show a conditioned-cue preference for the stimulus reinforced during S-R habit training. This pattern of results represents a dissociation of learning and memory functions of the dorsal striatum and amygdala on the same task.

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

PubMed Central

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

Childhood Cumulative Risk Exposure and Adult Amygdala Volume and Function

PubMed Central

Evans, Gary W.; Swain, James E.; King, Anthony P.; Wang, Xin; Javanbakht, Arash; Ho, S. Shaun; Angstadt, Michael; Phan, K. Luan; Xie, Hong; Liberzon, Israel

2015-01-01

Considerable work indicates that early cumulative risk exposure is aversive to human development, but very little research has examined neurological underpinnings of these robust findings. We investigated amygdala volume and reactivity to facial stimuli among adults (M = 23.7 years, n = 54) as a function of cumulative risk exposure during childhood (ages 9 and 13). In addition, we tested whether expected, cumulative risk elevations in amygdala volume would mediate functional reactivity of the amygdala during socio-emotional processing. Risks included substandard housing quality, noise, crowding, family turmoil, child separation from family, and violence. Total and left hemisphere adult amygdala volumes, respectively were positively related to cumulative risk exposure during childhood. The links between childhood cumulative risk exposure and elevated amygdala responses to emotionally neutral facial stimuli in adulthood were mediated by the respective amygdala volumes. Cumulative risk exposure in later adolescence (17 years), however, was unrelated to subsequent, adult amygdala volume or function. Physical and socioemotional risk exposures early in life appear to alter amygdala development, rendering adults more reactive to ambiguous stimuli such as neutral faces. These stress-related differences in childhood amygdala development might contribute to well-documented psychological distress as a function of early risk exposure. PMID:26469872

Childhood Cumulative Risk Exposure and Adult Amygdala Volume and Function.

PubMed

Evans, Gary W; Swain, James E; King, Anthony P; Wang, Xin; Javanbakht, Arash; Ho, S Shaun; Angstadt, Michael; Phan, K Luan; Xie, Hong; Liberzon, Israel

2016-06-01

Considerable work indicates that early cumulative risk exposure is aversive to human development, but very little research has examined the neurological underpinnings of these robust findings. This study investigates amygdala volume and reactivity to facial stimuli among adults (mean 23.7 years of age, n = 54) as a function of cumulative risk exposure during childhood (9 and 13 years of age). In addition, we test to determine whether expected cumulative risk elevations in amygdala volume would mediate functional reactivity of the amygdala during socioemotional processing. Risks included substandard housing quality, noise, crowding, family turmoil, child separation from family, and violence. Total and left hemisphere adult amygdala volumes were positively related to cumulative risk exposure during childhood. The links between childhood cumulative risk exposure and elevated amygdala responses to emotionally neutral facial stimuli in adulthood were mediated by the corresponding amygdala volumes. Cumulative risk exposure in later adolescence (17 years of age), however, was unrelated to subsequent adult amygdala volume or function. Physical and socioemotional risk exposures early in life appear to alter amygdala development, rendering adults more reactive to ambiguous stimuli such as neutral faces. These stress-related differences in childhood amygdala development might contribute to the well-documented psychological distress as a function of early risk exposure. © 2015 Wiley Periodicals, Inc.

Increased amygdala reactivity following early life stress: a potential resilience enhancer role.

PubMed

Yamamoto, Tetsuya; Toki, Shigeru; Siegle, Greg J; Takamura, Masahiro; Takaishi, Yoshiyuki; Yoshimura, Shinpei; Okada, Go; Matsumoto, Tomoya; Nakao, Takashi; Muranaka, Hiroyuki; Kaseda, Yumiko; Murakami, Tsuneji; Okamoto, Yasumasa; Yamawaki, Shigeto

2017-01-18

Amygdala hyper-reactivity is sometimes assumed to be a vulnerability factor that predates depression; however, in healthy people, who experience early life stress but do not become depressed, it may represent a resilience mechanism. We aimed to test these hypothesis examining whether increased amygdala activity in association with a history of early life stress (ELS) was negatively or positively associated with depressive symptoms and impact of negative life event stress in never-depressed adults. Twenty-four healthy participants completed an individually tailored negative mood induction task during functional magnetic resonance imaging (fMRI) assessment along with evaluation of ELS. Mood change and amygdala reactivity were increased in never-depressed participants who reported ELS compared to participants who reported no ELS. Yet, increased amygdala reactivity lowered effects of ELS on depressive symptoms and negative life events stress. Amygdala reactivity also had positive functional connectivity with the bilateral DLPFC, motor cortex and striatum in people with ELS during sad memory recall. Increased amygdala activity in those with ELS was associated with decreased symptoms and increased neural features, consistent with emotion regulation, suggesting that preservation of robust amygdala reactions may reflect a stress buffering or resilience enhancing factor against depression and negative stressful events.

Context and Auditory Fear are Differentially Regulated by HDAC3 Activity in the Lateral and Basal Subnuclei of the Amygdala

PubMed Central

Kwapis, Janine L; Alaghband, Yasaman; López, Alberto J; White, André O; Campbell, Rianne R; Dang, Richard T; Rhee, Diane; Tran, Ashley V; Carl, Allison E; Matheos, Dina P; Wood, Marcelo A

2017-01-01

Histone acetylation is a fundamental epigenetic mechanism that is dynamically regulated during memory formation. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) compete to modulate histone acetylation, allowing for rapid changes in acetylation in response to a learning event. HDACs are known to be powerful negative regulators of memory formation, but it is not clear whether this function depends on HDAC enzymatic activity per se. Here, we tested whether the enzymatic activity of an individual Class I HDAC, HDAC3, has a role in fear memory formation in subregions of the hippocampus and amygdala. We found that fear conditioning drove expression of the immediate early genes cFos and Nr4a2 in the hippocampus, which coincided with reduced HDAC3 occupancy at these promoters. Using a dominant-negative, deacetylase-dead point mutant virus (AAV-HDAC3(Y298H)-v5), we found that selectively blocking HDAC3 deacetylase activity in either the dorsal hippocampus or basal nucleus of the amygdala enhanced context fear without affecting tone fear. Blocking HDAC3 activity in the lateral nucleus of the amygdala, on the other hand, enhanced tone, but not context fear memory. These results show for the first time that the enzymatic activity of HDAC3 functions to negatively regulate fear memory formation. Further, HDAC3 activity regulates different aspects of fear memory in the basal and lateral subregions of the amygdala. Thus, the deacetylase activity of HDAC3 is a powerful negative regulator of fear memory formation in multiple subregions of the fear circuit. PMID:27924874

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

ERIC Educational Resources Information Center

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…

Lateralized interactive social content and valence processing within the human amygdala

PubMed Central

Vrtička, Pascal; Sander, David; Vuilleumier, Patrik

2013-01-01

In the past, the amygdala has generally been conceptualized as a fear-processing module. Recently, however, it has been proposed to respond to all stimuli that are relevant with respect to the current needs, goals, and values of an individual. This raises the question of whether the human amygdala may differentiate between separate kinds of relevance. A distinction between emotional (vs. neutral) and social (vs. non-social) relevance is supported by previous studies showing that the human amygdala preferentially responds to both emotionally and socially significant information, and these factors might even display interactive encoding properties. However, no investigation has yet probed a full 2 (positive vs. negative valence) × 2 (social vs. non-social content) processing pattern, with neutral images as an additional baseline. Applying such an extended orthogonal factorial design, our fMRI study demonstrates that the human amygdala is (1) more strongly activated for neutral social vs. non-social information, (2) activated at a similar level when viewing social positive or negative images, but (3) displays a valence effect (negative vs. positive) for non-social images. In addition, this encoding pattern is not influenced by cognitive or behavioral emotion regulation mechanisms, and displays a hemispheric lateralization with more pronounced effects on the right side. Finally, the same valence × social content interaction was found in three additional cortical regions, namely the right fusiform gyrus, right anterior superior temporal gyrus, and medial orbitofrontal cortex. Overall, these findings suggest that valence and social content processing represent distinct kinds of relevance that interact within the human amygdala as well as in a more extensive cortical network, likely subserving a key role in relevance detection. PMID:23346054

Optogenetic Activation of Presynaptic Inputs in Lateral Amygdala Forms Associative Fear Memory

ERIC Educational Resources Information Center

Kwon, Jeong-Tae; Nakajima, Ryuichi; Hyung-Su, Kim; Jeong, Yire; Augustine, George J.; Han, Jin-Hee

2014-01-01

In Pavlovian fear conditioning, the lateral amygdala (LA) has been highlighted as a key brain site for association between sensory cues and aversive stimuli. However, learning-related changes are also found in upstream sensory regions such as thalamus and cortex. To isolate the essential neural circuit components for fear memory association, we…

Hypothalamic-pituitary-adrenal axis genetic variation and early stress moderates amygdala function.

PubMed

Di Iorio, Christina R; Carey, Caitlin E; Michalski, Lindsay J; Corral-Frias, Nadia S; Conley, Emily Drabant; Hariri, Ahmad R; Bogdan, Ryan

2017-06-01

Early life stress may precipitate psychopathology, at least in part, by influencing amygdala function. Converging evidence across species suggests that links between childhood stress and amygdala function may be dependent upon hypothalamic-pituitary-adrenal (HPA) axis function. Using data from college-attending non-Hispanic European-Americans (n=308) who completed the Duke Neurogenetics Study, we examined whether early life stress (ELS) and HPA axis genetic variation interact to predict threat-related amygdala function as well as psychopathology symptoms. A biologically-informed multilocus profile score (BIMPS) captured HPA axis genetic variation (FKBP5 rs1360780, CRHR1 rs110402; NR3C2 rs5522/rs4635799) previously associated with its function (higher BIMPS are reflective of higher HPA axis activity). BOLD fMRI data were acquired while participants completed an emotional face matching task. ELS and depression and anxiety symptoms were measured using the childhood trauma questionnaire and the mood and anxiety symptom questionnaire, respectively. The interaction between HPA axis BIMPS and ELS was associated with right amygdala reactivity to threat-related stimuli, after accounting for multiple testing (empirical-p=0.016). Among individuals with higher BIMPS (i.e., the upper 21.4%), ELS was positively coupled with threat-related amygdala reactivity, which was absent among those with average or low BIMPS. Further, higher BIMPS were associated with greater self-reported anxious arousal, though there was no evidence that amygdala function mediated this relationship. Polygenic variation linked to HPA axis function may moderate the effects of early life stress on threat-related amygdala function and confer risk for anxiety symptomatology. However, what, if any, neural mechanisms may mediate the relationship between HPA axis BIMPS and anxiety symptomatology remains unclear. Copyright © 2017 Elsevier Ltd. All rights reserved.

Functional Connectivity of the Amygdala in Early Childhood Onset Depression

PubMed Central

Luking, Katherine R.; Repovs, Grega; Belden, Andy C.; Gaffrey, Michael S.; Botteron, Kelly N.; Luby, Joan L.; Barch, Deanna M.

2011-01-01

Objective Adult major depressive disorder (MDD) is associated with reduced cortico-limbic functional connectivity thought to indicate decreased top-down control of emotion. However, it is unclear whether such connectivity alterations are also present in early childhood onset MDD. Method Fifty-one children ages 7–11 years, prospectively studied since preschool age, completed resting state fMRI and were assigned to four groups: 1) C-MDD (N=13) personal history of early childhood onset MDD; 2) M-MDD (N=11) a maternal history of affective disorders; 3) CM-MDD (N=13) both maternal and early childhood onset MDD or 4) CON (N=14) without either a personal or maternal history. We used seed-based resting state functional connectivity (rsfcMRI) analysis in an independent sample of adults to identify networks showing both positive (e.g., limbic regions) and negative (e.g., dorsal frontal/parietal regions) connectivity with the amygdala. These regions were then used in ROI based analyses of our child sample. Results We found a significant interaction between maternal affective disorder history and the child's MDD history for both positive and negative rsfcMRI networks. Specifically, when copared to CON, we found reduced connectivity between the amygdala and the “Negative Network” in children with C-MDD, M-MDD and CM-MDD. Children with either C-MDD or a maternal history of MDD (but not CM-MDD) displayed reduced connectivity between the amygdala and the “Positive Network”. Conclusions Our finding of an attenuated relationship between the amygdala, a region affected in MDD and involved in emotion processing, and cognitive control regions is consistent with a hypothesis of altered regulation of emotional processing in C-MDD suggesting developmental continuity of this alteration into early childhood. PMID:21961777

Amygdala subnuclei response and connectivity during emotional processing.

PubMed

Hrybouski, Stanislau; Aghamohammadi-Sereshki, Arash; Madan, Christopher R; Shafer, Andrea T; Baron, Corey A; Seres, Peter; Beaulieu, Christian; Olsen, Fraser; Malykhin, Nikolai V

2016-06-01

The involvement of the human amygdala in emotion-related processing has been studied using functional magnetic resonance imaging (fMRI) for many years. However, despite the amygdala being comprised of several subnuclei, most studies investigated the role of the entire amygdala in processing of emotions. Here we combined a novel anatomical tracing protocol with event-related high-resolution fMRI acquisition to study the responsiveness of the amygdala subnuclei to negative emotional stimuli and to examine intra-amygdala functional connectivity. The greatest sensitivity to the negative emotional stimuli was observed in the centromedial amygdala, where the hemodynamic response amplitude elicited by the negative emotional stimuli was greater and peaked later than for neutral stimuli. Connectivity patterns converge with extant findings in animals, such that the centromedial amygdala was more connected with the nuclei of the basal amygdala than with the lateral amygdala. Current findings provide evidence of functional specialization within the human amygdala. Copyright © 2016 Elsevier Inc. All rights reserved.

MEG Evidence for Dynamic Amygdala Modulations by Gaze and Facial Emotions

PubMed Central

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

Diazepam reduces excitability of amygdala and further influences auditory cortex following sodium salicylate treatment in rats.

PubMed

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.

Preschool negative emotionality predicts activity and connectivity of the fusiform face area and amygdala in later childhood.

PubMed

Kann, Sarah J; O'Rawe, Jonathan F; Huang, Anna S; Klein, Daniel N; Leung, Hoi-Chung

2017-09-01

Negative emotionality (NE) refers to individual differences in the propensity to experience and react with negative emotions and is associated with increased risk of psychological disorder. However, research on the neural bases of NE has focused almost exclusively on amygdala activity during emotional face processing. This study broadened this framework by examining the relationship between observed NE in early childhood and subsequent neural responses to emotional faces in both the amygdala and the fusiform face area (FFA) in a late childhood/early adolescent sample. Measures of NE were obtained from children at age 3 using laboratory observations, and functional magnetic resonance imaging (fMRI) data were collected when these children were between the ages of 9 and 12 while performing a visual stimulus identity matching task with houses and emotional faces as stimuli. Multiple regression analyses revealed that higher NE at age 3 is associated with significantly greater activation in the left amygdala and left FFA but lower functional connectivity between these two regions during the face conditions. These findings suggest that those with higher early NE have subsequent alterations in both activity and connectivity within an extended network during face processing. © The Author (2017). Published by Oxford University Press.

Community violence exposure in early adolescence: Longitudinal associations with hippocampal and amygdala volume and resting state connectivity.

PubMed

Saxbe, Darby; Khoddam, Hannah; Piero, Larissa Del; Stoycos, Sarah A; Gimbel, Sarah I; Margolin, Gayla; Kaplan, Jonas T

2018-06-11

Community violence exposure is a common stressor, known to compromise youth cognitive and emotional development. In a diverse, urban sample of 22 adolescents, participants reported on community violence exposure (witnessing a beating or illegal drug use, hearing gun shots, or other forms of community violence) in early adolescence (average age 12.99), and underwent a neuroimaging scan 3-5 years later (average age 16.92). Community violence exposure in early adolescence predicted smaller manually traced left and right hippocampal and amygdala volumes in a model controlling for age, gender, and concurrent community violence exposure, measured in late adolescence. Community violence continued to predict hippocampus (but not amygdala) volumes after we also controlled for family aggression exposure in early adolescence. Community violence exposure was also associated with stronger resting state connectivity between the right hippocampus (using the manually traced structure as a seed region) and bilateral frontotemporal regions including the superior temporal gyrus and insula. These resting state connectivity results held after controlling for concurrent community violence exposure, SES, and family aggression. Although this is the first study focusing on community violence in conjunction with brain structure and function, these results dovetail with other research linking childhood adversity with smaller subcortical volumes in adolescence and adulthood, and with altered frontolimbic resting state connectivity. Our findings suggest that even community-level exposure to neighborhood violence can have detectable neural correlates in adolescents. © 2018 John Wiley & Sons Ltd.

Sex differences in amygdala activation during the perception of facial affect.

PubMed

Killgore, W D; Yurgelun-Todd, D A

2001-08-08

The cognitive and affective systems of the cerebral cortex are often more lateralized in males than females, but it is unclear whether these differences extend to subcortical systems. We used fMRI to examine sex differences in lateralized amygdala activity during happy and fearful face perception. Amygdala activation differed for men and women depending on the valence of the expression. Overall, males were more lateralized than females, but the direction differed between valence conditions. Happy faces produced greater right than left amygdala activation for males but not females. Both sexes showed greater left amygdala activation for fearful faces. These findings suggest that the lateralization of affective function may extend beyond the cortex to subcortical regions such as the amygdala.

mGluR2/3 in the Lateral Amygdala is Required for Fear Extinction: Cortical Input Synapses onto the Lateral Amygdala as a Target Site of the mGluR2/3 Action

PubMed Central

Kim, Jihye; An, Bobae; Kim, Jeongyeon; Park, Sewon; Park, Sungmo; Hong, Ingie; Lee, Sukwon; Park, Kyungjoon; Choi, Sukwoo

2015-01-01

Various subtypes of metabotropic glutamate receptors (mGluRs) have been implicated in fear extinction, but mGluR2/3 subtype has not been tested. Here, we found that microinjection of an mGluR2/3 antagonist, LY341495, into the lateral amygdala (LA), but not into the adjacent central amygdala (CeA), impaired extinction retention without affecting within-session extinction. In contrast, we failed to detect any significant changes in motility and anxiety during a period when extinction training or retention was performed after LY341495 injection, suggesting that the effect of LY341495 is specific to conditioned responses. Subsequently, on the basis of a previous finding that a long-term potentiation of presynaptic efficacy at cortical input synapses onto the lateral amygdala (C-LA synapses) supports conditioned fear, we tested the hypothesis that activation of mGluR2/3 leads to fear extinction via a long-term weakening of presynaptic functions at C-LA synapses. Fear extinction produced a decrease in C-LA synaptic efficacy, whereas LY341495 infusion into the LA blocked this extinction-induced C-LA efficacy decrease without altering synaptic efficacy at other LA synapses. Furthermore, extinction enhanced paired pulse ratio (PPR) of EPSCs, which inversely correlates with presynaptic release probability, whereas LY341495 infusion into the LA attenuated the extinction-induced increase in PPR, suggesting the presence of mGluR2/3-dependent presynaptic changes after extinction. Consistently, extinction occluded a presynaptic form of depression at C-LA synapses, whereas the LY341495 infusion into the LA rescued this occlusion. Together, our findings suggest that mGluR2/3 is required for extinction retention and that the mGluR2/3 action is mediated by the long-term weakening of release probability at C-LA synapses. PMID:26081171

Differential Expression of Phosphorylated Mitogen-Activated Protein Kinase (pMAPK) in the Lateral Amygdala of Mice Selectively Bred for High and Low Fear

DTIC Science & Technology

2013-07-02

amygdala induced by hippocampal formation stimulation in vivo. The Journal of neuroscience: the official journal of the Society for Neuroscience 15...6 Figure 1.3. Schematic model of the neural circuitry of Pavlovian auditory fear conditioning. Model shows how an auditory conditioned...stimulus and a nociceptive unconditioned foot shock stimulus converge in the lateral amygdala (LA) via auditory thalamus and cortex and somatosensory

Metabolic activation of amygdala, lateral septum and accumbens circuits during food anticipatory behavior.

PubMed

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.

Long-Term Synaptic Changes in Two Input Pathways into the Lateral Nucleus of the Amygdala Underlie Fear Extinction

ERIC Educational Resources Information Center

Park, Junchol; Choi, June-Seek

2010-01-01

Plasticity in two input pathways into the lateral nucleus of the amygdala (LA), the medial prefrontal cortex (mPFC) and the sensory thalamus, have been suggested to underlie extinction, suppression of a previously acquired conditioned response (CR) following repeated presentations of the conditioned stimulus (CS). However, little is known about…

Evidence of an IFN-γ by early life stress interaction in the regulation of amygdala reactivity to emotional stimuli.

PubMed

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

Learning Enhances Intrinsic Excitability in a Subset of Lateral Amygdala Neurons

ERIC Educational Resources Information Center

Sehgal, Megha; Ehlers, Vanessa L.; Moyer, James R., Jr.

2014-01-01

Learning-induced modulation of neuronal intrinsic excitability is a metaplasticity mechanism that can impact the acquisition of new memories. Although the amygdala is important for emotional learning and other behaviors, including fear and anxiety, whether learning alters intrinsic excitability within the amygdala has received very little…

Amygdala Damage Affects Event-Related Potentials for Fearful Faces at Specific Time Windows

PubMed Central

Rotshtein, Pia; Richardson, Mark P; Winston, Joel S; Kiebel, Stefan J; Vuilleumier, Patrik; Eimer, Martin; Driver, Jon; Dolan, Raymond J

2010-01-01

The amygdala is known to influence processing of threat-related stimuli in distant brain regions, including visual cortex. The time-course of these distant influences is unknown, although this information is important for resolving debates over likely pathways mediating an apparent rapidity in emotional processing. To address this, we recorded event-related potentials (ERPs) to seen fearful face expressions, in preoperative patients with medial temporal lobe epilepsy who had varying degrees of amygdala pathology, plus healthy volunteers. We found that amygdala damage diminished ERPs for fearful versus neutral faces within the P1 time-range, ∼100–150 ms, and for a later component at ∼500–600 ms. Individual severity of amygdala damage determined the magnitude of both these effects, consistent with a causal amygdala role. By contrast, amygdala damage did not affect explicit perception of fearful expressions nor a distinct emotional ERP effect at 150–250 ms. These results demonstrate two distinct time-points at which the amygdala influences fear processing. The data also demonstrate that while not all aspects of expression processing are disrupted by amygdala damage, there is a crucial impact on an early P1 component. These findings are consistent with the existence of multiple processing stages or routes for fearful faces that vary in their dependence on amygdala function. Hum Brain Mapp, 2010. © 2009 Wiley-Liss, Inc. PMID:20017134

15. Amygdala pain mechanisms

PubMed Central

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

Protracted dendritic growth in the typically developing human amygdala and increased spine density in young ASD brains.

PubMed

Weir, R K; Bauman, M D; Jacobs, B; Schumann, C M

2018-02-01

The amygdala is a medial temporal lobe structure implicated in social and emotional regulation. In typical development (TD), the amygdala continues to increase volumetrically throughout childhood and into adulthood, while other brain structures are stable or decreasing in volume. In autism spectrum disorder (ASD), the amygdala undergoes rapid early growth, making it volumetrically larger in children with ASD compared to TD children. Here we explore: (a) if dendritic arborization in the amygdala follows the pattern of protracted growth in TD and early overgrowth in ASD and (b), if spine density in the amygdala in ASD cases differs from TD from youth to adulthood. The amygdala from 32 postmortem human brains (7-46 years of age) were stained using a Golgi-Kopsch impregnation. Ten principal neurons per case were selected in the lateral nucleus and traced using Neurolucida software in their entirety. We found that both ASD and TD individuals show a similar pattern of increasing dendritic length with age well into adulthood. However, spine density is (a) greater in young ASD cases compared to age-matched TD controls (<18 years old) and (b) decreases in the amygdala as people with ASD age into adulthood, a phenomenon not found in TD. Therefore, by adulthood, there is no observable difference in spine density in the amygdala between ASD and TD age-matched adults (≥18 years old). Our findings highlight the unique growth trajectory of the amygdala and suggest that spine density may contribute to aberrant development and function of the amygdala in children with ASD. © 2017 Wiley Periodicals, Inc.

[Significance of CRF and dopamine receptors in amygdala for reinforcing effects of opiates and opioids on self-stimulation of lateral hypothalamus in rats].

PubMed

Shabanov, P D; Lebedev, A A; Liubimov, A V; Kornilov, V A

2011-01-01

Bipolar electrodes were implanted in the lateral hypothalamus in a group of 44 Wistar male rats in order to study self-stimulation reaction in the Skinner box. Simultaneously, microcanules were implanted into the central nucleus of the amygdala to inject the drugs (1 microl per injection). The blockade of corticoliberin (CRF) receptors (astressin, 1 microg) or Na+influx currents (xycaine or lidocain 1 microg) by the intrastructural administration of drugs into the amygdala decreased self-stimulation reaction of the lateral hypothalamus in rats by 29-55%. The inhibition of D1 and D2 dopamine receptors in the amygdala with SCH23390 (1 microg) or sulpiride (1 microg) respectively, also reduced self-stimulation but to a lower degree. On the background of blockade of CRF (astressin) and dopamine (sulpiride) receptors as well as sodium influx ionic currents (lidocain) in the amygdala neurons, psychomotor stimulant amphetamine (1 mg/kg) and barbiturate sodium ethaminal (5 mg/kg) retained their psychoactivating effect on self-stimulation (+30-37%), while fentanyl (0.1 mg/kg) and leu-enkephaline (0.1 mg/kg) did not produce this effect. Fentanyl moderately activated self-stimulation only after the blockade of D1 dopamine receptors with SCH23390. After the blockade of CRF receptors, leu-enkephaline strengthened its depressant effect on self-stimulation reaction (-89%). Therefore, if the modulating action of amygdala on the hypothalamus is eliminated, the enhancing effects of opiates (fentanyl) and opioids (leu-encephaline) are blocked, but the effects of psychomotor stimulant amphetamine and barbiturate sodium ethaminal are retained.

Delta Subunit-Containing Gamma-Aminobutyric Acid A Receptor Disinhibits Lateral Amygdala and Facilitates Fear Expression in Mice.

PubMed

Liu, Zhi-Peng; He, Qing-Hai; Pan, Han-Qing; Xu, Xiao-Bin; Chen, Wen-Bing; He, Ye; Zhou, Jin; Zhang, Wen-Hua; Zhang, Jun-Yu; Ying, Xiao-Ping; Han, Ren-Wen; Li, Bao-Ming; Gao, Tian-Ming; Pan, Bing-Xing

2017-06-15

Maintaining gamma-aminobutyric acidergic (GABAergic) inhibition in the amygdala within a physiological range is critical for the appropriate expression of emotions such as fear and anxiety. The synaptic GABA type A receptor (GABA A R) is generally known to mediate the primary component of amygdala inhibition and prevent inappropriate expression of fear. However, little is known about the contribution of the extrasynaptic GABA A R to amygdala inhibition and fear. By using mice expressing green fluorescent protein in interneurons (INs) and lacking the δ subunit-containing GABA A R (GABA A (δ)R), which is exclusively situated in the extrasynaptic membrane, we systematically investigated the role of GABA A (δ)R in regulating inhibition in the lateral amygdala (LA) and fear learning using the combined approaches of immunohistochemistry, electrophysiology, and behavior. In sharp contrast to the established role of synaptic GABA A R in mediating LA inhibition, we found that either pharmacological or physiological recruitment of GABA A (δ)R resulted in the weakening of GABAergic transmission onto projection neurons in LA while leaving the glutamatergic transmission unaltered, suggesting disinhibition by GABA A (δ)R. The disinhibition arose from IN-specific expression of GABA A (δ)R with its activation decreasing the input resistance of local INs and suppressing their activation. Genetic deletion of GABA A (δ)R attenuated its role in suppressing LA INs and disinhibiting LA. Importantly, the GABA A (δ)R facilitated long-term potentiation in sensory afferents to LA and permitted the expression of learned fear. Our findings suggest that GABA A (δ)R serves as a brake rather than a mediator of GABAergic inhibition in LA. The disinhibition by GABA A (δ)R may help to prevent excessive suppression of amygdala activity and thus ensure the expression of emotion. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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

PubMed Central

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

Parvalbumin interneurons constrain the size of the lateral amygdala engram.

PubMed

Morrison, Dano J; Rashid, Asim J; Yiu, Adelaide P; Yan, Chen; Frankland, Paul W; Josselyn, Sheena A

2016-11-01

Memories are thought to be represented by discrete physiological changes in the brain, collectively referred to as an engram, that allow patterns of activity present during learning to be reactivated in the future. During the formation of a conditioned fear memory, a subset of principal (excitatory) neurons in the lateral amygdala (LA) are allocated to a neuronal ensemble that encodes an association between an initially neutral stimulus and a threatening aversive stimulus. Previous experimental and computational work suggests that this subset consists of only a small proportion of all LA neurons, and that this proportion remains constant across different memories. Here we examine the mechanisms that contribute to the stability of the size of the LA component of an engram supporting a fear memory. Visualizing expression of the activity-dependent gene Arc following memory retrieval to identify neurons allocated to an engram, we first show that the overall size of the LA engram remains constant across conditions of different memory strength. That is, the strength of a memory was not correlated with the number of LA neurons allocated to the engram supporting that memory. We then examine potential mechanisms constraining the size of the LA engram by expressing inhibitory DREADDS (designer receptors exclusively activated by designer drugs) in parvalbumin-positive (PV + ) interneurons of the amygdala. We find that silencing PV + neurons during conditioning increases the size of the engram, especially in the dorsal subnucleus of the LA. These results confirm predictions from modeling studies regarding the role of inhibition in shaping the size of neuronal memory ensembles and provide additional support for the idea that neurons in the LA are sparsely allocated to the engram based on relative neuronal excitability. Copyright © 2016 Elsevier Inc. All rights reserved.

The amygdala and decision-making.

PubMed

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.

A phenotype of early infancy predicts reactivity of the amygdala in male adults.

PubMed

Schwartz, C E; Kunwar, P S; Greve, D N; Kagan, J; Snidman, N C; Bloch, R B

2012-10-01

One of the central questions that has occupied those disciplines concerned with human development is the nature of continuities and discontinuities from birth to maturity. The amygdala has a central role in the processing of novelty and emotion in the brain. Although there is considerable variability among individuals in the reactivity of the amygdala to novel and emotional stimuli, the origin of these individual differences is not well understood. Four-month old infants called high reactive (HR) demonstrate a distinctive pattern of vigorous motor activity and crying to specific unfamiliar visual, auditory and olfactory stimuli in the laboratory. Low-reactive infants show the complementary pattern. Here, we demonstrate that the HR infant phenotype predicts greater amygdalar reactivity to novel faces almost two decades later in adults. A prediction of individual differences in brain function at maturity can be made on the basis of a single behavioral assessment made in the laboratory at 4 months of age. This is the earliest known human behavioral phenotype that predicts individual differences in patterns of neural activity at maturity. These temperamental differences rooted in infancy may be relevant to understanding individual differences in vulnerability and resilience to clinical psychiatric disorder. Males who were HR infants showed particularly high levels of reactivity to novel faces in the amygdala that distinguished them as adults from all other sex/temperament subgroups, suggesting that their amygdala is particularly prone to engagement by unfamiliar faces. These findings underline the importance of taking gender into account when studying the developmental neurobiology of human temperament and anxiety disorders. The genetic study of behavioral and biologic intermediate phenotypes (or 'endophenotypes') indexing anxiety-proneness offers an important alternative to examining phenotypes based on clinically defined disorder. As the HR phenotype is characterized

Matrix metalloproteinase 9 (MMP-9) is indispensable for long term potentiation in the central and basal but not in the lateral nucleus of the amygdala.

PubMed

Gorkiewicz, Tomasz; Balcerzyk, Marcin; Kaczmarek, Leszek; Knapska, Ewelina

2015-01-01

It has been shown that matrix metalloproteinase 9 (MMP-9) is required for synaptic plasticity, learning and memory. In particular, MMP-9 involvement in long-term potentiation (LTP, the model of synaptic plasticity) in the hippocampus and prefrontal cortex has previously been demonstrated. Recent data suggest the role of MMP-9 in amygdala-dependent learning and memory. Nothing is known, however, about its physiological correlates in the specific pathways in the amygdala. In the present study we show that LTP in the basal and central but not lateral amygdala (LA) is affected by MMP-9 knock-out. The MMP-9 dependency of LTP was confirmed in brain slices treated with a specific MMP-9 inhibitor. The results suggest that MMP-9 plays different roles in synaptic plasticity in different nuclei of the amygdala.

Structural Connectivity of the Developing Human Amygdala

PubMed Central

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

Structural connectivity of the developing human amygdala.

PubMed

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.

Extending the amygdala in theories of threat processing

PubMed Central

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

Disentangling the roles of arousal and amygdala activation in emotional declarative memory

PubMed Central

Fernández, Guillén; Hermans, Erno J.

2016-01-01

A large body of evidence in animals and humans implicates the amygdala in promoting memory for arousing experiences. Although the amygdala can trigger threat-related noradrenergic-sympathetic arousal, in humans amygdala activation and noradrenergic-sympathetic arousal do not always concur. This raises the question how these two processes play a role in enhancing emotional declarative memory. This study was designed to disentangle these processes in a combined subsequent-memory/fear-conditioning paradigm with neutral items belonging to two conceptual categories as conditioned stimuli. Functional MRI, skin conductance (index of sympathetic activity), and pupil dilation (indirect index of central noradrenergic activity) were acquired throughout procedures. Recognition memory for individual items was tested 24 h later. We found that pupil dilation and skin conductance responses were higher on CS+ (associated with a shock) compared with CS− trials, irrespective of later memory for those items. By contrast, amygdala activity was only higher for CS+ items that were later confidently remembered compared with CS+ items that were later forgotten. Thus, amygdala activity and not noradrenergic-sympathetic arousal, predicted enhanced declarative item memory. This dissociation is in line with animal models stating that the amygdala integrates arousal-related neuromodulatory changes to alter mnemonic processes elsewhere in the brain. PMID:27217115

Familial Risk and a Genome-Wide Supported DRD2 Variant for Schizophrenia Predict Lateral Prefrontal-Amygdala Effective Connectivity During Emotion Processing.

PubMed

Quarto, Tiziana; Paparella, Isabella; De Tullio, Davide; Viscanti, Giovanna; Fazio, Leonardo; Taurisano, Paolo; Romano, Raffaella; Rampino, Antonio; Masellis, Rita; Popolizio, Teresa; Selvaggi, Pierluigi; Pergola, Giulio; Bertolino, Alessandro; Blasi, Giuseppe

2017-09-16

The brain functional mechanisms translating genetic risk into emotional symptoms in schizophrenia (SCZ) may include abnormal functional integration between areas key for emotion processing, such as the amygdala and the lateral prefrontal cortex (LPFC). Indeed, investigation of these mechanisms is also complicated by emotion processing comprising different subcomponents and by disease-associated state variables. Here, our aim was to investigate the relationship between risk for SCZ and effective connectivity between the amygdala and the LPFC during different subcomponents of emotion processing. Thus, we first characterized with dynamic causal modeling (DCM) physiological patterns of LPFC-amygdala effective connectivity in healthy controls (HC) during implicit and explicit emotion processing. Then, we compared DCM patterns in a subsample of HC, in patients with SCZ and in healthy siblings of patients (SIB), matched for demographics. Finally, we investigated in HC association of LPFC-amygdala effective connectivity with a genome-wide supported variant increasing genetic risk for SCZ and possibly relevant to emotion processing (DRD2 rs2514218). In HC, we found that a "bottom-up" amygdala-to-LPFC pattern during implicit processing and a "top-down" LPFC-to-amygdala pattern during explicit processing were the most likely directional models of effective connectivity. Differently, implicit emotion processing in SIB, SCZ, and HC homozygous for the SCZ risk rs2514218 C allele was associated with decreased probability for the "bottom-up" as well as with increased probability for the "top-down" model. These findings suggest that task-specific anomaly in the directional flow of information or disconnection between the amygdala and the LPFC is a good candidate endophenotype of SCZ. © The Author 2017. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

[(35)S]-GTPgammaS autoradiography reveals alpha(2) adrenoceptor-mediated G-protein activation in amygdala and lateral septum.

PubMed

Newman-Tancredi, A; Chaput, C; Touzard, M; Millan, M J

2000-04-03

alpha(2)-adrenoceptor-mediated G-protein activation was examined by [(35)S]-GTPgammaS autoradiography. In alpha(2)-adrenoceptor-rich regions (amygdala, lateral septum), noradrenaline stimulated [(35)S]-GTPgammaS binding. These actions were abolished by the selective alpha(2) antagonist, atipamezole. Conversely, in caudate nucleus, which expresses few alpha(2) receptors, noradrenaline-induced stimulation was not inhibited by atipamezole, suggesting that it is not mediated by alpha(2)-adrenoceptors.

Tracking the fear engram: the lateral amygdala is an essential locus of fear memory storage.

PubMed

Schafe, Glenn E; Doyère, Valérie; LeDoux, Joseph E

2005-10-26

Although it is believed that different types of memories are localized in discreet regions of the brain, concrete experimental evidence of the existence of such engrams is often elusive. Despite being one of the best characterized memory systems of the brain, the question of where fear memories are localized in the brain remains a hotly debated issue. Here, we combine site-specific behavioral pharmacology with multisite electrophysiological recording techniques to show that the lateral nucleus of the amygdala, long thought to be critical for the acquisition of fear memories, is also an essential locus of fear memory storage.

Synapse-specific astrocyte gating of amygdala-related behavior.

PubMed

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.

Kainate receptor-mediated depression of glutamatergic transmission involving protein kinase A in the lateral amygdala.

PubMed

Negrete-Díaz, José Vicente; Duque-Feria, Paloma; Andrade-Talavera, Yuniesky; Carrión, Miriam; Flores, Gonzalo; Rodríguez-Moreno, Antonio

2012-04-01

Kainate receptors (KARs) have been described as modulators of synaptic transmission at different synapses. However, this role of KARs has not been well characterized in the amygdala. We have explored the effect of kainate receptor activation at the synapse established between fibers originating at medial geniculate nucleus and the principal cells in the lateral amygdala. We have observed an inhibition of evoked excitatory postsynaptic currents (eEPSCs) amplitude after a brief application of KARs agonists KA and ATPA. Paired-pulse recordings showed a clear pair pulse facilitation that was enhanced after KA or ATPA application. When postsynaptic cells were loaded with BAPTA, the depression of eEPSC amplitude observed after the perfusion of KAR agonists was not prevented. We have also observed that the inhibition of the eEPSCs by KARs agonists was prevented by protein kinase A but not by protein kinase C inhibitors. Taken together our results indicate that KARs present at this synapse are pre-synaptic and their activation mediate the inhibition of glutamate release through a mechanism that involves the activation of protein kinase A. © 2012 The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.

Early Adverse Experience Increases Emotional Reactivity in Juvenile Rhesus Macaques: Relation to Amygdala Volume

PubMed Central

Howell, B.R.; Grand, A. P.; McCormack, K. M.; Shi, Y.; LaPrarie, J.; Maestripieri, D.; Styner, M. A.; Sanchez, M. M.

2015-01-01

This study investigated the impact of infant maltreatment on juvenile rhesus monkeys’ behavioral reactivity to novel stimuli and its associations with amygdala volume. Behavioral reactivity to novel stimuli of varying threat intensity was measured using Approach/Avoidance (AA) and Human Intruder (HI) tasks. In vivo magnetic resonance imaging (MRI) was used to measure amygdala volume. Interestingly, group behavioral differences were context-dependent. When exposed to a human intruder, maltreated subjects displayed more anxious behaviors than controls; however, when presented with fear-evoking objects, maltreated animals exhibited increased aggression and a shorter latency to inspect the objects. Finally, under testing conditions with the lowest levels of threat (neutral novel objects) maltreated animals also showed shorter latencies to inspect objects, and reduced avoidance and increased exploration compared to controls. This suggests alterations in threat assessment and less behavioral inhibition in animals with early adverse experience compared to controls. Some of these behavioral responses were associated with amygdala volume, which was positively correlated with abuse rates received during infancy, particularly reflecting a relationship with exploration, consistent with previous studies. PMID:25196846

High early life stress and aberrant amygdala activity: risk factors for elevated neuropsychiatric symptoms in HIV+ adults.

PubMed

Clark, Uraina S; Sweet, Lawrence H; Morgello, Susan; Philip, Noah S; Cohen, Ronald A

2017-06-01

Relative to HIV-negative adults, HIV+ adults report elevated levels of early life stress (ELS). In non-HIV samples, high ELS has been linked to abnormalities in brain structure and function, as well as increased risk of neuropsychiatric symptoms. Yet, little is known about the neural effects of high ELS, and their relation to elevated neuropsychiatric symptoms, in HIV+ adults. Recent studies have revealed combined effects of HIV and high ELS on amygdala morphometry. Aberrant amygdala activity is prominently implicated in studies of neuropsychiatric symptomology in non-HIV samples. Hence, this preliminary study examined: 1) the combined effects of HIV and high ELS on amygdala activity, and 2) the relation between amygdala activity and neuropsychiatric symptoms in HIV+ adults. We included 28 HIV+ adults and 25 demographically-matched HIV-negative control (HC) adults. ELS exposure was quantified using a retrospective ELS questionnaire, which defined four groups: HIV+ Low-ELS (N = 15); HIV+ High-ELS (N = 13); HC Low-ELS (N = 16); and HC High-ELS (N = 9). Participants completed a battery of neuropsychiatric measures. BOLD fMRI assessed amygdala reactivity during explicit observation of fearful/angry faces. High-ELS participants demonstrated reduced levels of amygdala reactivity relative to Low-ELS participants. HIV+ High-ELS participants reported higher levels of neuropsychiatric symptoms than all other groups. In the HIV+ group, lower amygdala responses were associated with higher neuropsychiatric symptoms, particularly depression, anxiety, and alexithymia. Collectively, these results suggest that high ELS exposure is a significant risk factor for neuropsychiatric symptoms in HIV+ adults. Furthermore, our results implicate ELS-related abnormalities in amygdala activity in the etiology of neuropsychiatric symptoms in HIV+ adults.

Phosphorylation of ERK/MAP Kinase Is Required for Long-Term Potentiation in Anatomically Restricted Regions of the Lateral Amygdala in Vivo

ERIC Educational Resources Information Center

Schafe, Glenn E.; Swank, Michael W.; Rodriguez, Sarina M.; Debiec, Jacek; Doyere, Valerie

2008-01-01

We have previously shown that the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/ MAPK) is transiently activated in anatomically restricted regions of the lateral amygdala (LA) following Pavlovian fear conditioning and that blockade of ERK/MAPK activation in the LA impairs both fear memory consolidation and long-term…

Bidirectional communication between amygdala and fusiform gyrus during facial recognition.

PubMed

Herrington, John D; Taylor, James M; Grupe, Daniel W; Curby, Kim M; Schultz, Robert T

2011-06-15

Decades of research have documented the specialization of fusiform gyrus (FG) for facial information processes. Recent theories indicate that FG activity is shaped by input from amygdala, but effective connectivity from amygdala to FG remains undocumented. In this fMRI study, 39 participants completed a face recognition task. 11 participants underwent the same experiment approximately four months later. Robust face-selective activation of FG, amygdala, and lateral occipital cortex were observed. Dynamic causal modeling and Bayesian Model Selection (BMS) were used to test the intrinsic connections between these structures, and their modulation by face perception. BMS results strongly favored a dynamic causal model with bidirectional, face-modulated amygdala-FG connections. However, the right hemisphere connections diminished at time 2, with the face modulation parameter no longer surviving Bonferroni correction. These findings suggest that amygdala strongly influences FG function during face perception, and that this influence is shaped by experience and stimulus salience. Copyright © 2011 Elsevier Inc. All rights reserved.

Disentangling the roles of arousal and amygdala activation in emotional declarative memory.

PubMed

de Voogd, Lycia D; Fernández, Guillén; Hermans, Erno J

2016-09-01

A large body of evidence in animals and humans implicates the amygdala in promoting memory for arousing experiences. Although the amygdala can trigger threat-related noradrenergic-sympathetic arousal, in humans amygdala activation and noradrenergic-sympathetic arousal do not always concur. This raises the question how these two processes play a role in enhancing emotional declarative memory. This study was designed to disentangle these processes in a combined subsequent-memory/fear-conditioning paradigm with neutral items belonging to two conceptual categories as conditioned stimuli. Functional MRI, skin conductance (index of sympathetic activity), and pupil dilation (indirect index of central noradrenergic activity) were acquired throughout procedures. Recognition memory for individual items was tested 24 h later. We found that pupil dilation and skin conductance responses were higher on CS+ (associated with a shock) compared with CS- trials, irrespective of later memory for those items. By contrast, amygdala activity was only higher for CS+ items that were later confidently remembered compared with CS+ items that were later forgotten. Thus, amygdala activity and not noradrenergic-sympathetic arousal, predicted enhanced declarative item memory. This dissociation is in line with animal models stating that the amygdala integrates arousal-related neuromodulatory changes to alter mnemonic processes elsewhere in the brain. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Human amygdala engagement moderated by early life stress exposure is a biobehavioral target for predicting recovery on antidepressants.

PubMed

Goldstein-Piekarski, Andrea N; Korgaonkar, Mayuresh S; Green, Erin; Suppes, Trisha; Schatzberg, Alan F; Hastie, Trevor; Nemeroff, Charles B; Williams, Leanne M

2016-10-18

Amygdala circuitry and early life stress (ELS) are both strongly and independently implicated in the neurobiology of depression. Importantly, animal models have revealed that the contribution of ELS to the development and maintenance of depression is likely a consequence of structural and physiological changes in amygdala circuitry in response to stress hormones. Despite these mechanistic foundations, amygdala engagement and ELS have not been investigated as biobehavioral targets for predicting functional remission in translational human studies of depression. Addressing this question, we integrated human neuroimaging and measurement of ELS within a controlled trial of antidepressant outcomes. Here we demonstrate that the interaction between amygdala activation engaged by emotional stimuli and ELS predicts functional remission on antidepressants with a greater than 80% cross-validated accuracy. Our model suggests that in depressed people with high ELS, the likelihood of remission is highest with greater amygdala reactivity to socially rewarding stimuli, whereas for those with low-ELS exposure, remission is associated with lower amygdala reactivity to both rewarding and threat-related stimuli. This full model predicted functional remission over and above the contribution of demographics, symptom severity, ELS, and amygdala reactivity alone. These findings identify a human target for elucidating the mechanisms of antidepressant functional remission and offer a target for developing novel therapeutics. The results also offer a proof-of-concept for using neuroimaging as a target for guiding neuroscience-informed intervention decisions at the level of the individual person.

Experience-dependent modification of a central amygdala fear circuit

PubMed Central

Li, Haohong; Penzo, Mario A.; Taniguchi, Hiroki; Kopec, Charles D.; Huang, Z. Josh; Li, Bo

2013-01-01

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 CeA contributes to the learning and expression of fear is unclear. Here we show in mice that fear conditioning induces robust plasticity of excitatory synapses onto inhibitory neurons in the lateral subdivision of CeA (CeL). This experience-dependent plasticity is cell-specific, bidirectional, and expressed presynaptically by inputs from the lateral amygdala. In particular, preventing synaptic potentiation onto somatostatin-positive neurons impairs fear memory formation. Furthermore, activation of these neurons is necessary for fear memory recall and sufficient to drive fear responses. Our findings support a model in which the fear conditioning-induced synaptic modifications in CeL favor the activation of somatostatin-positive neurons, which inhibit CeL output thereby disinhibiting the medial subdivision of CeA and releasing fear expression. PMID:23354330

Enhanced Right Amygdala Activity in Adolescents during Encoding of Positively-Valenced Pictures

PubMed Central

Vasa, Roma A.; Pine, Daniel S.; Thorn, Julia M.; Nelson, Tess E.; Spinelli, Simona; Nelson, Eric; Maheu, Francoise S.; Ernst, Monique; Bruck, Maggie; Mostofsky, Stewart H.

2010-01-01

While studies among adults implicate the amygdala and interconnecting brain regions in encoding emotional stimuli, few studies have examined whether developmental changes occur within this emotional-memory network during adolescence. The present study examined whether adolescents and adults differentially engaged the amygdala and hippocampus during successful encoding of emotional pictures, with either positive or negative valence. Eighteen adults and twelve adolescents underwent event-related fMRI while encoding emotional pictures. Approximately 30 minutes later, outside the scanner, subjects were asked to recall the pictures seen during the scan. Age group differences in brain activity in the amygdala and hippocampus during encoding of the pictures that were later successfully and unsuccessfully recalled were separately compared for the positive and negative pictures. Adolescents, relative to adults, demonstrated enhanced activity in the right amygdala during encoding of positive pictures that were later recalled compared to not recalled. There were no age group differences in amygdala or hippocampal activity during successful encoding of negative pictures. The findings of preferential activity within the adolescent right amygdala during successful encoding of positive pictures may have implications for the increased reward and novelty seeking behavior, as well as elevated rates of psychopathology, observed during this distinct developmental period. PMID:21127721

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

PubMed

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. �

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

PubMed

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.

The long reach of early adversity: Parenting, stress, and neural pathways to antisocial behavior in adulthood.

PubMed

Gard, Arianna M; Waller, Rebecca; Shaw, Daniel S; Forbes, Erika E; Hariri, Ahmad R; Hyde, Luke W

2017-10-01

Early life adversities including harsh parenting, maternal depression, neighborhood deprivation, and low family economic resources are more prevalent in low-income urban environments and are potent predictors of psychopathology, including, for boys, antisocial behavior (AB). However, little research has examined how these stressful experiences alter later neural function. Moreover, identifying genetic markers of greater susceptibility to adversity is critical to understanding biopsychosocial pathways from early adversity to later psychopathology. Within a sample of 310 low-income boys followed from age 1.5 to 20, multimethod assessments of adversities were examined at age 2 and age 12. At age 20, amygdala reactivity to emotional facial expressions was assessed using fMRI, and symptoms of Antisocial Personality Disorder were assessed via structured clinical interview. Genetic variability in cortisol signaling ( CRHR1 ) was examined as a moderator of pathways to amygdala reactivity. Observed parenting and neighborhood deprivation at age 2 each uniquely predicted amygdala reactivity to emotional faces at age 20 over and above other adversities measured at multiple developmental periods. Harsher parenting and greater neighborhood deprivation in toddlerhood predicted clinically-significant symptoms of AB via less amygdala reactivity to fearful facial expressions and this pathway was moderated by genetic variation in CRHR1 . These results elucidate a pathway linking early adversity to less amygdala reactivity to social signals of interpersonal distress 18 years later, which in turn increased risk for serious AB. Moreover, these findings suggest a genetic marker of youth more susceptible to adversity.

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

PubMed

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.

Age-Related Changes in Amygdala-Frontal Connectivity during Emotional Face Processing from Childhood into Young Adulthood

PubMed Central

Wu, Minjie; Kujawa, Autumn; Lu, Lisa H.; Fitzgerald, Daniel A.; Klumpp, Heide; Fitzgerald, Kate D.; Monk, Christopher S.; Phan, K. Luan

2016-01-01

The ability to process and respond to emotional facial expressions is a critical skill for healthy social and emotional development. There has been growing interest in understanding the neural circuitry underlying development of emotional processing, with previous research implicating functional connectivity between amygdala and frontal regions. However, existing work has focused on threatening emotional faces, raising questions regarding the extent to which these developmental patterns are specific to threat or to emotional face processing more broadly. In the current study, we examined age-related changes in brain activity and amygdala functional connectivity during an fMRI emotional face matching task (including angry, fearful and happy faces) in 61 healthy subjects aged 7–25 years. We found age-related decreases in ventral medial prefrontal cortex (vmPFC) activity in response to happy faces but not to angry or fearful faces, and an age-related change (shifting from positive to negative correlation) in amygdala-anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) functional connectivity to all emotional faces. Specifically, positive correlations between amygdala and ACC/mPFC in children changed to negative correlations in adults, which may suggest early emergence of bottom-up amygdala excitatory signaling to ACC/mPFC in children and later development of top-down inhibitory control of ACC/mPFC over amygdala in adults. Age-related changes in amygdala-ACC/mPFC connectivity did not vary for processing of different facial emotions, suggesting changes in amygdala-ACC/mPFC connectivity may underlie development of broad emotional processing, rather than threat-specific processing. PMID:26931629

Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation

PubMed Central

Pagliaccio, David; Luby, Joan L.; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S.; Belden, Andrew C.; Botteron, Kelly N.; Harms, Michael P.; Barch, Deanna M.

2015-01-01

Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within four hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9–14 year olds; N=120). Whole-brain regression analyses indicated that increasing genetic ‘risk’ predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic ‘risk’ and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. PMID:26595470

Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation.

PubMed

Pagliaccio, David; Luby, Joan L; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S; Belden, Andrew C; Botteron, Kelly N; Harms, Michael P; Barch, Deanna M

2015-11-01

Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within 4 hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9- to 14-year-olds; N = 120). Whole-brain regression analyses indicated that increasing genetic "risk" predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic "risk" and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. (c) 2015 APA, all rights reserved).

Ventral striatum and amygdala activity as convergence sites for early adversity and conduct disorder

PubMed Central

Boecker-Schlier, Regina; Buchmann, Arlette F.; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Plichta, Michael M.; Cattrell, Anna; Schumann, Gunter; Esser, Günter; Schmidt, Martin; Buitelaar, Jan; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

2017-01-01

Abstract Childhood family adversity (CFA) increases the risk for conduct disorder (CD) and has been associated with alterations in regions of affective processing like ventral striatum (VS) and amygdala. However, no study so far has demonstrated neural converging effects of CFA and CD in the same sample. At age 25 years, functional MRI data during two affective tasks, i.e. a reward (N = 171) and a face-matching paradigm (N = 181) and anatomical scans (N = 181) were acquired in right-handed currently healthy participants of an epidemiological study followed since birth. CFA during childhood was determined using a standardized parent interview. Disruptive behaviors and CD diagnoses during childhood and adolescence were obtained by diagnostic interview (2–19 years), temperamental reward dependence was assessed by questionnaire (15 and 19 years). CFA predicted increased CD and amygdala volume. Both exposure to CFA and CD were associated with a decreased VS response during reward anticipation and blunted amygdala activity during face-matching. CD mediated the effect of CFA on brain activity. Temperamental reward dependence was negatively correlated with CFA and CD and positively with VS activity. These findings underline the detrimental effects of CFA on the offspring's affective processing and support the importance of early postnatal intervention programs aiming to reduce childhood adversity factors. PMID:27694318

Dynamic Changes in Amygdala Activation and Functional Connectivity in Children and Adolescents with Anxiety Disorders

PubMed Central

Swartz, Johnna R.; Phan, K. Luan; Angstadt, Mike; Fitzgerald, Kate D.; Monk, Christopher S.

2015-01-01

Anxiety disorders are associated with abnormalities in amygdala function and prefrontal cortex-amygdala connectivity. The majority of fMRI studies have examined mean group differences in amygdala activation or connectivity in children and adolescents with anxiety disorders relative to controls, but emerging evidence suggests that abnormalities in amygdala function are dependent on the timing of the task and may vary across the course of a scanning session. The goal of the present study was to extend our knowledge of the dynamics of amygdala dysfunction by examining whether changes in amygdala activation and connectivity over scanning differ in pediatric anxiety disorder patients relative to typically developing controls during an emotion processing task. Examining changes in activation over time allows for a comparison of how brain function differs during initial exposure to novel stimuli versus more prolonged exposure. Participants included 34 anxiety disorder patients and 19 controls 7 to 19 years old. Participants performed an emotional face matching task during fMRI scanning and the task was divided into thirds in order to examine change in activation over time. Results demonstrated that patients exhibited an abnormal pattern of amygdala activation characterized by an initially heightened amygdala response relative to controls at the beginning of scanning, followed by significant decreases in activation over time. In addition, controls evidenced greater prefrontal cortex-amygdala connectivity during the beginning of scanning relative to patients. These results indicate that differences in emotion processing between the groups vary from initial exposure to novel stimuli relative to more prolonged exposure. Implications are discussed regarding how this pattern of neural activation may relate to altered early-occurring or anticipatory emotion-regulation strategies and maladaptive later-occurring strategies in children and adolescents with anxiety disorders. PMID

The NO-cGMP-PKG Signaling Pathway Regulates Synaptic Plasticity and Fear Memory Consolidation in the Lateral Amygdala via Activation of ERK/MAP Kinase

ERIC Educational Resources Information Center

Ota, Kristie T.; Pierre, Vicki J.; Ploski, Jonathan E.; Queen, Kaila; Schafe, Glenn E.

2008-01-01

Recent studies have shown that nitric oxide (NO) signaling plays a crucial role in memory consolidation of Pavlovian fear conditioning and in synaptic plasticity in the lateral amygdala (LA). In the present experiments, we examined the role of the cGMP-dependent protein kinase (PKG), a downstream effector of NO, in fear memory consolidation and…

Cornering the fear engram: long-term synaptic changes in the lateral nucleus of the amygdala after fear conditioning.

PubMed

Kwon, Jeong-Tae; Choi, June-Seek

2009-08-05

Use-dependent synaptic modifications in the lateral nucleus of the amygdala (LA) have been suggested to be the cellular analog of memory trace after pavlovian fear conditioning. However, whether neurophysiological changes in the LA are produced as a direct consequence of associative learning awaits additional proof. Using microstimulation of the medial geniculate nucleus of the thalamus as the conditioned stimulus (CS), we demonstrated that contingent pairings of the brain-stimulation CS and a footshock unconditioned stimulus lead to enhanced synaptic efficacy in the thalamic input to the LA, supporting the hypothesis that localized synaptic alterations underlie fear memory formation.

Effect of Hippocampal and Amygdala Connectivity on the Relationship Between Preschool Poverty and School-Age Depression.

PubMed

Barch, Deanna; Pagliaccio, David; Belden, Andy; Harms, Michael P; Gaffrey, Michael; Sylvester, Chad M; Tillman, Rebecca; Luby, Joan

2016-06-01

In this study, the authors tested the hypothesis that poverty experienced in early childhood, as measured by income-to-needs ratio, has an impact on functional brain connectivity at school age, which in turn mediates influences on child negative mood/depression. Participants were from a prospective longitudinal study of emotion development. Preschoolers 3-5 years of age were originally ascertained from primary care and day care sites in the St. Louis area and then underwent annual behavioral assessments for up to 12 years. Healthy preschoolers and those with a history of depression symptoms underwent neuroimaging at school age. Using functional MRI, the authors examined whole brain resting-state functional connectivity with the left and right hippocampus and amygdala. Lower income-to-needs ratio at preschool age was associated with reduced connectivity between hippocampus and amygdala and a number of regions at school age, including the superior frontal cortex, lingual gyrus, posterior cingulate, and putamen. Lower income-to-needs ratio predicted greater negative mood/depression severity at school age, as did connectivity between the left hippocampus and the right superior frontal cortex and between the right amygdala and the right lingual gyrus. Connectivity mediated the relationship between income-to-needs ratio and negative mood/depression at the time of scanning. These findings suggest that poverty in early childhood, as assessed by at least one measure, may influence the development of hippocampal and amygdala connectivity in a manner leading to negative mood symptoms during later childhood.

Age-related changes in amygdala-frontal connectivity during emotional face processing from childhood into young adulthood.

PubMed

Wu, Minjie; Kujawa, Autumn; Lu, Lisa H; Fitzgerald, Daniel A; Klumpp, Heide; Fitzgerald, Kate D; Monk, Christopher S; Phan, K Luan

2016-05-01

The ability to process and respond to emotional facial expressions is a critical skill for healthy social and emotional development. There has been growing interest in understanding the neural circuitry underlying development of emotional processing, with previous research implicating functional connectivity between amygdala and frontal regions. However, existing work has focused on threatening emotional faces, raising questions regarding the extent to which these developmental patterns are specific to threat or to emotional face processing more broadly. In the current study, we examined age-related changes in brain activity and amygdala functional connectivity during an fMRI emotional face matching task (including angry, fearful, and happy faces) in 61 healthy subjects aged 7-25 years. We found age-related decreases in ventral medial prefrontal cortex activity in response to happy faces but not to angry or fearful faces, and an age-related change (shifting from positive to negative correlation) in amygdala-anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC) functional connectivity to all emotional faces. Specifically, positive correlations between amygdala and ACC/mPFC in children changed to negative correlations in adults, which may suggest early emergence of bottom-up amygdala excitatory signaling to ACC/mPFC in children and later development of top-down inhibitory control of ACC/mPFC over amygdala in adults. Age-related changes in amygdala-ACC/mPFC connectivity did not vary for processing of different facial emotions, suggesting changes in amygdala-ACC/mPFC connectivity may underlie development of broad emotional processing, rather than threat-specific processing. Hum Brain Mapp 37:1684-1695, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effects of Chronic Ethanol Consumption on Rat GABAA and Strychnine-sensitive Glycine Receptors Expressed by Lateral/Basolateral Amygdala Neurons

PubMed Central

McCool, Brian A.; Frye, Gerald D.; Pulido, Marisa D.; Botting, Shaleen K.

2010-01-01

It is well known that the anxiolytic potential of ethanol is maintained during chronic exposure. We have confirmed this using a light-dark box paradigm following chronic ethanol ingestion via a liquid diet. However, cessation from chronic ethanol exposure is known to cause severe withdrawal anxiety. These opposing effects on anxiety likely result from neuro-adaptations of neurotransmitter systems within the brain regions regulating anxiety. Recent work highlights the importance of amygdala ligand-gated chloride channels in the expression of anxiety. We have therefore examined the effects of chronic ethanol exposure on GABAA and strychnine-sensitive glycine receptors expressed by acutely isolated adult rat lateral/basolateral amygdala neurons. Chronic ethanol exposure increased the functional expression of GABAA receptors in acutely isolated basolateral amygdala neurons without altering strychnine-sensitive glycine receptors. Neither the acute ethanol nor benzodiazepine sensitivity of either receptor system was affected. We explored the likelihood that subunit composition might influence each receptor’s response to chronic ethanol. Importantly, when expressed in a mammalian heterologous system, GABAA receptors composed of unique α subunits were differentially sensitive to acute ethanol. Likewise, the presence of the β subunit appeared to influence the acute ethanol sensitivity of glycine receptors containing the α2 subunit. Our results suggest that the facilitation of GABAA receptors during chronic ethanol exposure may help explain the maintenance of ethanol’s anti-anxiety effects during chronic ethanol exposure. Furthermore, the subunit composition of GABAA and strychnine-sensitive glycine receptors may ultimately influence the response of each system to chronic ethanol exposure. PMID:12560122

Cannabis use in early adolescence: Evidence of amygdala hypersensitivity to signals of threat.

PubMed

Spechler, Philip A; Orr, Catherine A; Chaarani, Bader; Kan, Kees-Jan; Mackey, Scott; Morton, Aaron; Snowe, Mitchell P; Hudson, Kelsey E; Althoff, Robert R; Higgins, Stephen T; Cattrell, Anna; Flor, Herta; Nees, Frauke; Banaschewski, Tobias; Bokde, Arun L W; Whelan, Robert; Büchel, Christian; Bromberg, Uli; Conrod, Patricia; Frouin, Vincent; Papadopoulos, Dimitri; Gallinat, Jurgen; Heinz, Andreas; Walter, Henrik; Ittermann, Bernd; Gowland, Penny; Paus, Tomáš; Poustka, Luise; Martinot, Jean-Luc; Artiges, Eric; Smolka, Michael N; Schumann, Gunter; Garavan, Hugh

2015-12-01

Cannabis use in adolescence may be characterized by differences in the neural basis of affective processing. In this study, we used an fMRI affective face processing task to compare a large group (n=70) of 14-year olds with a history of cannabis use to a group (n=70) of never-using controls matched on numerous characteristics including IQ, SES, alcohol and cigarette use. The task contained short movies displaying angry and neutral faces. Results indicated that cannabis users had greater reactivity in the bilateral amygdalae to angry faces than neutral faces, an effect that was not observed in their abstinent peers. In contrast, activity levels in the cannabis users in cortical areas including the right temporal-parietal junction and bilateral dorsolateral prefrontal cortex did not discriminate between the two face conditions, but did differ in controls. Results did not change after excluding subjects with any psychiatric symptomology. Given the high density of cannabinoid receptors in the amygdala, our findings suggest cannabis use in early adolescence is associated with hypersensitivity to signals of threat. Hypersensitivity to negative affect in adolescence may place the subject at-risk for mood disorders in adulthood. Copyright © 2015. Published by Elsevier Ltd.

Hunger-Dependent Enhancement of Food Cue Responses in Mouse Postrhinal Cortex and Lateral Amygdala.

PubMed

Burgess, Christian R; Ramesh, Rohan N; Sugden, Arthur U; Levandowski, Kirsten M; Minnig, Margaret A; Fenselau, Henning; Lowell, Bradford B; Andermann, Mark L

2016-09-07

The needs of the body can direct behavioral and neural processing toward motivationally relevant sensory cues. For example, human imaging studies have consistently found specific cortical areas with biased responses to food-associated visual cues in hungry subjects, but not in sated subjects. To obtain a cellular-level understanding of these hunger-dependent cortical response biases, we performed chronic two-photon calcium imaging in postrhinal association cortex (POR) and primary visual cortex (V1) of behaving mice. As in humans, neurons in mouse POR, but not V1, exhibited biases toward food-associated cues that were abolished by satiety. This emergent bias was mirrored by the innervation pattern of amygdalo-cortical feedback axons. Strikingly, these axons exhibited even stronger food cue biases and sensitivity to hunger state and trial history. These findings highlight a direct pathway by which the lateral amygdala may contribute to state-dependent cortical processing of motivationally relevant sensory cues. Published by Elsevier Inc.

The central amygdala circuits in fear regulation

NASA Astrophysics Data System (ADS)

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.

Effects of chronic ethanol consumption on rat GABA(A) and strychnine-sensitive glycine receptors expressed by lateral/basolateral amygdala neurons.

PubMed

McCool, Brian A; Frye, Gerald D; Pulido, Marisa D; Botting, Shaleen K

2003-02-14

It is well known that the anxiolytic potential of ethanol is maintained during chronic exposure. We have confirmed this using a light-dark box paradigm following chronic ethanol ingestion via a liquid diet. However, cessation from chronic ethanol exposure is known to cause severe withdrawal anxiety. These opposing effects on anxiety likely result from neuro-adaptations of neurotransmitter systems within the brain regions regulating anxiety. Recent work highlights the importance of amygdala ligand-gated chloride channels in the expression of anxiety. We have therefore examined the effects of chronic ethanol exposure on GABA(A) and strychnine-sensitive glycine receptors expressed by acutely isolated adult rat lateral/basolateral amygdala neurons. Chronic ethanol exposure increased the functional expression of GABA(A) receptors in acutely isolated basolateral amygdala neurons without altering strychnine-sensitive glycine receptors. Neither the acute ethanol nor benzodiazepine sensitivity of either receptor system was affected. We explored the likelihood that subunit composition might influence each receptor's response to chronic ethanol. Importantly, when expressed in a mammalian heterologous system, GABA(A) receptors composed of unique alpha subunits were differentially sensitive to acute ethanol. Likewise, the presence of the beta subunit appeared to influence the acute ethanol sensitivity of glycine receptors containing the alpha(2) subunit. Our results suggest that the facilitation of GABA(A) receptors during chronic ethanol exposure may help explain the maintenance of ethanol's anti-anxiety effects during chronic ethanol exposure. Furthermore, the subunit composition of GABA(A) and strychnine-sensitive glycine receptors may ultimately influence the response of each system to chronic ethanol exposure.

Otitis Media in Early Childhood and Later Language.

ERIC Educational Resources Information Center

Roberts, Joanne E.; And Others

1991-01-01

The relationship between early otitis media with effusion (OME) and later language development was examined in a prospective cohort of 30 children from middle class families and 33 children from low income families. Findings suggested no reliable relationship between early OME experience and later language development. (Author/DB)

Amygdala Functional Connectivity is Reduced After the Cold Pressor Task

PubMed Central

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

Neonatal Amygdala Functional Connectivity at Rest in Healthy and Preterm Infants and Early Internalizing Symptoms.

PubMed

Rogers, Cynthia E; Sylvester, Chad M; Mintz, Carrie; Kenley, Jeanette K; Shimony, Joshua S; Barch, Deanna M; Smyser, Christopher D

2017-02-01

Alterations in the normal developmental trajectory of amygdala resting state functional connectivity (rs-FC) have been associated with atypical emotional processes and psychopathology. Little is known, however, regarding amygdala rs-FC at birth or its relevance to outcomes. This study examined amygdala rs-FC in healthy, full-term (FT) infants and in very preterm (VPT) infants, and tested whether variability of neonatal amygdala rs-FC predicted internalizing symptoms at age 2 years. Resting state fMRI data were obtained shortly after birth from 65 FT infants (gestational age [GA] ≥36 weeks) and 57 VPT infants (GA <30 weeks) at term equivalent. Voxelwise correlation analyses were performed using individual-specific bilateral amygdala regions of interest. Total internalizing symptoms and the behavioral inhibition, depression/withdrawal, general anxiety, and separation distress subdomains were assessed in a subset (n = 44) at age 2 years using the Infant Toddler Social Emotional Assessment. In FT and VPT infants, the amygdala demonstrated positive correlations with subcortical and limbic structures and negative correlations with cortical regions, although magnitudes were decreased in VPT infants. Neonatal amygdala rs-FC predicted internalizing symptoms at age 2 years with regional specificity consistent with known pathophysiology in older populations: connectivity with the anterior insula related to depressive symptoms, with the dorsal anterior cingulate related to generalized anxiety, and with the medial prefrontal cortex related to behavioral inhibition. Amygdala rs-FC is well established in neonates. Variability in regional neonatal amygdala rs-FC predicted internalizing symptoms at 2 years, suggesting that risk for internalizing symptoms may be established in neonatal amygdala functional connectivity patterns. Copyright © 2016 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

Localization of deformations within the amygdala in individuals with psychopathy.

PubMed

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.

Synaptic Plasticity and NO-cGMP-PKG Signaling Coordinately Regulate ERK-Driven Gene Expression in the Lateral Amygdala and in the Auditory Thalamus Following Pavlovian Fear Conditioning

ERIC Educational Resources Information Center

Ota, Kristie T.; Monsey, Melissa S.; Wu, Melissa S.; Young, Grace J.; Schafe, Glenn E.

2010-01-01

We have recently hypothesized that NO-cGMP-PKG signaling in the lateral nucleus of the amygdala (LA) during auditory fear conditioning coordinately regulates ERK-driven transcriptional changes in both auditory thalamic (MGm/PIN) and LA neurons that serve to promote pre- and postsynaptic alterations at thalamo-LA synapses, respectively. In the…

Neuronal populations in the basolateral nuclei of the amygdala are differentially increased in humans compared with apes: a stereological study.

PubMed

Barger, Nicole; Stefanacci, Lisa; Schumann, Cynthia M; Sherwood, Chet C; Annese, Jacopo; Allman, John M; Buckwalter, Joseph A; Hof, Patrick R; Semendeferi, Katerina

2012-09-01

In human and nonhuman primates, the amygdala is known to play critical roles in emotional and social behavior. Anatomically, individual amygdaloid nuclei are connected with many neural systems that are either differentially expanded or conserved over the course of primate evolution. To address amygdala evolution in humans and our closest living relatives, the apes, we used design-based stereological methods to obtain neuron counts for the amygdala and each of four major amygdaloid nuclei (the lateral, basal, accessory basal, and central nuclei) in humans, all great ape species, lesser apes, and one monkey species. Our goal was to determine whether there were significant differences in the number or percent of neurons distributed to individual nuclei among species. Additionally, regression analyses were performed on independent contrast data to determine whether any individual species deviated from allometric trends. There were two major findings. In humans, the lateral nucleus contained the highest number of neurons in the amygdala, whereas in apes the basal nucleus contained the highest number of neurons. Additionally, the human lateral nucleus contained 59% more neurons than predicted by allometric regressions on nonhuman primate data. Based on the largest sample ever analyzed in a comparative study of the hominoid amygdala, our findings suggest that an emphasis on the lateral nucleus is the main characteristic of amygdala specialization over the course of human evolution. Copyright © 2012 Wiley Periodicals, Inc.

Neuronal Populations in the Basolateral Nuclei of the Amygdala Are Differentially Increased in Humans Compared With Apes: A Stereological Study

PubMed Central

Barger, Nicole; Stefanacci, Lisa; Schumann, Cynthia M.; Sherwood, Chet C.; Annese, Jacopo; Allman, John M.; Buckwalter, Joseph A.; Hof, Patrick R.; Semendeferi, Katerina

2016-01-01

In human and nonhuman primates, the amygdala is known to play critical roles in emotional and social behavior. Anatomically, individual amygdaloid nuclei are connected with many neural systems that are either differentially expanded or conserved over the course of primate evolution. To address amygdala evolution in humans and our closest living relatives, the apes, we used design-based stereological methods to obtain neuron counts for the amygdala and each of four major amygdaloid nuclei (the lateral, basal, accessory basal, and central nuclei) in humans, all great ape species, lesser apes, and one monkey species. Our goal was to determine whether there were significant differences in the number or percent of neurons distributed to individual nuclei among species. Additionally, regression analyses were performed on independent contrast data to determine whether any individual species deviated from allometric trends. There were two major findings. In humans, the lateral nucleus contained the highest number of neurons in the amygdala, whereas in apes the basal nucleus contained the highest number of neurons. Additionally, the human lateral nucleus contained 59% more neurons than predicted by allometric regressions on nonhuman primate data. Based on the largest sample ever analyzed in a comparative study of the hominoid amygdala, our findings suggest that an emphasis on the lateral nucleus is the main characteristic of amygdala specialization over the course of human evolution. PMID:22473387

Amygdala Lesions Reduce Cataplexy in Orexin KO mice

PubMed Central

Burgess, C.R.; Oishi, Y.; Mochizuki, T.; Peever, J.H.; Scammell, T.E.

2013-01-01

Narcolepsy is characterized by excessive sleepiness and cataplexy, sudden episodes of muscle weakness during waking that are thought to be an intrusion of REM sleep muscle atonia into wakefulness. One of the most striking aspects of cataplexy is that it is often triggered by strong, generally positive emotions, but little is known about the neural pathways through which positive emotions trigger muscle atonia. We hypothesized that the amygdala is functionally important for cataplexy because the amygdala has a role in processing emotional stimuli and it contains neurons that are active during cataplexy. Using anterograde and retrograde tracing in mice, we found that GABAergic neurons in the central nucleus of the amygdala heavily innervate neurons that maintain waking muscle tone such as those in the ventrolateral periaqueductal grey, lateral pontine tegmentum, locus coeruleus, and dorsal raphe. We then found that bilateral, excitotoxic lesions of the amygdala markedly reduced cataplexy in orexin knockout mice, a model of narcolepsy. These lesions did not alter basic sleep/wake behavior, but substantially reduced the triggering of cataplexy. Lesions also reduced the cataplexy events triggered by conditions associated with high arousal and positive emotions (i.e., wheel running and chocolate). These observations demonstrate that the amygdala is a functionally important part of the circuitry underlying cataplexy and suggest that increased amygdala activity in response to emotional stimuli could directly trigger cataplexy by inhibiting brainstem regions that suppress muscle atonia. PMID:23739970

Extinction of cued fear memory involves a distinct form of depotentiation at cortical input synapses onto the lateral amygdala.

PubMed

Hong, Ingie; Song, Beomjong; Lee, Sukwon; Kim, Jihye; Kim, Jeongyeon; Choi, Sukwoo

2009-12-03

The amygdala is known to be a critical storage site of conditioned fear memory. Among the two major pathways to the lateral amygdala (LA), the cortical pathway is known to display a presynaptic long-term potentiation which is occluded with fear conditioning. Here we show that fear extinction results in a net depression of conditioning-induced potentiation at cortical input synapses onto the LA (C-LA synapses). Fear conditioning induced a significant potentiation of excitatory postsynaptic currents at C-LA synapses compared with naïve and unpaired controls, whereas extinction apparently reversed this potentiation. Paired-pulse low-frequency stimulation (pp-LFS) induced synaptic depression in the C-LA pathway of fear-conditioned rats, but not in naïve or unpaired controls, indicating that the pp-LFS-induced depression is specific to associative learning-induced changes (pp-LFS-induced depotentiation(ex vivo)). Importantly, extinction occluded pp-LFS-induced depotentiation(ex vivo), suggesting that extinction shares some mechanisms with the depotentiation. pp-LFS-induced depotentiation(ex vivo) required NMDA receptor (NMDAR) activity, consistent with a previous finding that blockade of amygdala NMDARs impaired fear extinction. In addition, pp-LFS-induced depotentiation(ex vivo) required activity of group II metabotropic glutamate receptors (mGluRs), known to be present at presynaptic terminals, but not AMPAR internalization, consistent with a presynaptic mechanism for pp-LFS-induced depotentiation(ex vivo). This result is in contrast with another form of ex vivo depotentiation in the thalamic pathway that requires both group I mGluR activity and AMPAR internalization. We thus suggest that extinction of conditioned fear involves a distinct form of depotentiation at C-LA synapses, which depends upon both NMDARs and group II mGluRs.

5-HT1A-receptor agonist modified amygdala activity and amygdala-associated social behavior in a valproate-induced rat autism model.

PubMed

Wang, Chao-Chuan; Lin, Hui-Ching; Chan, Yun-Han; Gean, Po-Wu; Yang, Yen Kung; Chen, Po See

2013-10-01

Accumulating evidence suggests that dysfunction of the amygdala is related to abnormal fear processing, anxiety, and social behaviors noted in autistic spectrum disorders (ASDs). In addition, studies have shown that disrupted brain serotonin homeostasis is linked to ASD. With a valproate (VPA)-induced rat ASD model, we investigated the possible role of amygdala serotonin homeostasis in autistic phenotypes and further explored the underlying mechanism. We first discovered that the distribution of tryptophan hydroxylase immunoreactivity in the caudal raphe system was modulated on postnatal day (PD) 28 of the VPA-exposed offspring. Then, we found a significantly higher serotonin transporter availability in the amygdala of the VPA-exposed offspring on PD 56 by using single photon emission computed tomography and computed tomography co-registration following injection of (123)I-labeled 2-((2-(dimethylamino)methyl)phenyl)thio)-5-iodophenylamine((123)I[ADAM]). Furthermore, treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist, increased social interaction and improved fear memory extinction in the VPA-exposed offspring. 8-OH-DPAT treatment also reversed the characteristics of miniature excitatory post-synaptic currents as well as paired pulse facilitation observed in lateral amygdala slices. These results provided further evidence to support the role of the amygdala in characteristic behavioral changes in the rat ASD model. The serotonergic projections that modulate the amygdala function might play a certain role in the development and treatment of behavioral symptoms exhibited in individuals with ASD.

Resting-state functional connectivity of the amygdala and longitudinal changes in depression severity in adolescent depression.

PubMed

Connolly, Colm G; Ho, Tiffany C; Blom, Eva Henje; LeWinn, Kaja Z; Sacchet, Matthew D; Tymofiyeva, Olga; Simmons, Alan N; Yang, Tony T

2017-01-01

The incidence of major depressive disorder (MDD) rises during adolescence, yet the neural mechanisms of MDD during this key developmental period are unclear. Altered amygdala resting-state functional connectivity (RSFC) has been associated with both adolescent and adult MDD, as well as symptom improvement in response to treatment in adults. However, no study to date has examined whether amygdala RSFC is associated with changes in depressive symptom severity in adolescents. We examined group differences in amygdala RSFC between medication-naïve depressed adolescents (N=48) and well-matched healthy controls (N=53) cross-sectionally. We then longitudinally examined whether baseline amygdala RSFC was associated with change in depression symptoms three months later in a subset of the MDD group (N=24). Compared to healthy controls, depressed adolescents showed reduced amygdala-based RSFC with the dorsolateral prefrontal cortex (DLPFC)and the ventromedial prefrontal cortex (VMPFC). Within the depressed group, more positive baseline RSFC between the amygdala and insulae was associated with greater reduction in depression symptoms three months later. Only a subset of depressed participants was assessed at follow-up and treatment type and delivery were not standardized. Adolescent depression may be characterized by dysfunction of frontolimbic circuits (amygdala-DLPFC, amygdala-VMPFC) underpinning emotional regulation, whereas those circuits (amygdala-insula) subserving affective integration may index changes in depression symptom severity and may therefore potentially serve as a candidate biomarker for treatment response. Furthermore, these results suggest that the biomarkers of MDD presence are distinct from those associated with change in depression symptoms over time. Copyright © 2016 Elsevier B.V. All rights reserved.

An "egr-1" ("zif268") Antisense Oligodeoxynucleotide Infused into the Amygdala Disrupts Fear Conditioning

ERIC Educational Resources Information Center

Donley, Melanie P.; Rosen, Jeffrey B.; Malkani, Seema; Wallace, Karin J.

2004-01-01

Studies of gene expression following fear conditioning have demonstrated that the inducible transcription factor, "egr-1," is increased in the lateral nucleus of the amygdala shortly following fear conditioning. These studies suggest that "egr-1" and its protein product Egr-1 in the amygdala are important for learning and memory of fear. To…

Amygdala volume and verbal memory performance in schizophrenia and bipolar disorder.

PubMed

Killgore, William D S; Rosso, Isabelle M; Gruber, Staci A; Yurgelun-Todd, Deborah A

2009-03-01

To clarify the relationship between amygdala-hippocampal volume and cognitive performance in schizophrenia and bipolar disorder. Abnormalities of the amygdala-hippocampal complex and memory deficits have been reported in both schizophrenia and bipolar illness. We examined memory performance and its relationship to the volumes of the whole brain, lateral ventricles, hippocampus, and amygdala using morphometric magnetic resonance imaging in 19 patients with schizophrenia, 11 bipolar patients, and 20 healthy controls. Schizophrenia patients performed more poorly than bipolar patients and controls on indices of memory functioning, whereas patients with bipolar disorder showed milder impairments relative to controls. The schizophrenia group showed reduced total cerebral volume and enlarged ventricles relative to controls, but no group differences were found for amygdala or hippocampal volume. Left amygdala volume was predictive of memory performance in both groups, correlating positively with better immediate and delayed verbal memory for bipolar patients and negatively with immediate and delayed verbal recall for schizophrenia patients. Amygdala volume was unrelated to memory performance in healthy subjects. Schizophrenia and bipolar disorder both seem to be associated with anomalous and differential limbic volume-function relationships, such that the amygdala may facilitate hippocampal-dependent memory processes in bipolar disorder but impair these same processes in schizophrenia.

Estradiol shifts interactions between the infralimbic cortex and central amygdala to enhance fear extinction memory in female rats.

PubMed

Maeng, Lisa Y; Cover, Kara K; Taha, Mohamad B; Landau, Aaron J; Milad, Mohammed R; Lebrón-Milad, Kelimer

2017-01-02

There is growing evidence that estradiol (E2) enhances fear extinction memory consolidation. However, it is unclear how E2 influences the nodes of the fear extinction network to enhance extinction memory. This study begins to delineate the neural circuits underlying the influence of E2 on fear extinction acquisition and consolidation in female rats. After fear conditioning (day 1), naturally cycling female rats underwent extinction learning (day 2) in a low-E2 state, receiving a systemic administration of either E2 or vehicle prior to extinction training. Extinction memory recall was then tested 24 hr later (day 3). We measured immediate early gene c-fos expression within the extinction network during fear extinction learning and extinction recall. During extinction learning, E2 treatment increased centrolateral amygdala c-fos activity and reduced lateral amygdala activity relative to vehicle. During extinction recall, E2-treated rats exhibited reduced c-fos expression in the centromedial amygdala. There were no group differences in c-fos expression within the medial prefrontal cortex or dorsal hippocampus. Examining c-fos ratios with the infralimbic cortex (IL) revealed that, despite the lack of group differences within the IL, E2 treatment induced greater IL activity relative to both prelimbic cortex and central amygdala (CeA) activity during extinction memory recall. Only the relationship between IL and CeA activity positively correlated with extinction retention. In conclusion, E2 appears to modify interactions between the IL and the CeA in females, shifting from stronger amygdalar modulation of fear during extinction learning to stronger IL control during extinction recall. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Differential serotonergic innervation of the amygdala in bonobos and chimpanzees

PubMed Central

Barger, Nicole; Taglialatela, Jared P.; Gendron-Fitzpatrick, Annette; Hof, Patrick R.; Hopkins, William D.; Sherwood, Chet C.

2016-01-01

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. PMID:26475872

Predicting Later-Life Outcomes of Early-Life Exposures

EPA Science Inventory

Background: In utero exposure of the fetus to a stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later-life expression of early-life events.Objectives: We examined the current state of understanding of later-life diseases resulting from ea...

Categorization of biologically relevant chemical signals in the medial amygdala

PubMed Central

Samuelsen, Chad L.; Meredith, Michael

2009-01-01

Many species employ chemical signals to convey messages between members of the same species (conspecific), but chemosignals may also provide information to another species (heterospecific). Here, we found that conspecific chemosignals (male, female mouse urine) increased immediate early gene-protein (IEG) expression in both anterior and posterior medial amygdala of male mice, whereas most heterospecific chemosignals (e.g.: hamster vaginal fluid, steer urine) increased expression only in anterior medial amygdala. This categorization of responses in medial amygdala conforms to our previously reported findings in male hamsters. The same characteristic pattern of IEG expression appears in the medial amygdala of each species in response to conspecific stimuli for that species. These results suggest that the amygdala categorizes stimuli according to the biological relevance for the tested species. Thus, a heterospecific predator (cat collar) stimulus, which elicited behavioral avoidance in mice, increased IEG expression in mouse posterior medial amygdala (like conspecific stimuli). Further analysis suggests reproduction related and potentially threatening stimuli produce increased IEG expression in different sub-regions of posterior medial amygdala (dorsal and ventral, respectively). These patterns of IEG expression in medial amygdala may provide glimpses of a tertiary sorting of chemosensory signals beyond the primary-level selectivity of chemosensory neurons and the secondary sorting in main and accessory olfactory bulbs. PMID:19368822

Lower amygdala volume in men is associated with childhood aggression, early psychopathic traits, and future violence.

PubMed

Pardini, Dustin A; Raine, Adrian; Erickson, Kirk; Loeber, Rolf

2014-01-01

Reduced amygdala volume has been implicated in the development of severe and persistent aggression and the development of psychopathic personality. With longitudinal data, the current study examined whether male subjects with lower amygdala volume have a history of aggression and psychopathic features dating back to childhood and are at increased risk for engaging in future aggression/violence. Participants were selected from a longitudinal study of 503 male subjects initially recruited when they were in the first grade in 1986-1987. At age 26, a subsample of 56 men with varying histories of violence was recruited for a neuroimaging substudy. Automated segmentation was used to index individual differences in amygdala volume. Analyses examined the association between amygdala volume and levels of aggression and psychopathic features of participants measured in childhood and adolescence. Analyses also examined whether amygdala volume was associated with violence and psychopathic traits assessed at a 3-year follow-up. Men with lower amygdala volume exhibited higher levels of aggression and psychopathic features from childhood to adulthood. Lower amygdala volume was also associated with aggression, violence, and psychopathic traits at a 3-year follow-up, even after controlling for earlier levels of these features. All effects remained after accounting for several potential confounds. This represents the first prospective study to demonstrate that men with lower amygdala volume have a longstanding history of aggression and psychopathic features and are at increased risk for committing future violence. Studies should further examine whether specific amygdala abnormalities might be a useful biomarker for severe and persistent aggression. Copyright © 2014 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Amygdala lesions reduce cataplexy in orexin knock-out mice.

PubMed

Burgess, Christian R; Oishi, Yo; Mochizuki, Takatoshi; Peever, John H; Scammell, Thomas E

2013-06-05

Narcolepsy is characterized by excessive sleepiness and cataplexy, sudden episodes of muscle weakness during waking that are thought to be an intrusion of rapid eye movement sleep muscle atonia into wakefulness. One of the most striking aspects of cataplexy is that it is often triggered by strong, generally positive emotions, but little is known about the neural pathways through which positive emotions trigger muscle atonia. We hypothesized that the amygdala is functionally important for cataplexy because the amygdala has a role in processing emotional stimuli and it contains neurons that are active during cataplexy. Using anterograde and retrograde tracing in mice, we found that GABAergic neurons in the central nucleus of the amygdala heavily innervate neurons that maintain waking muscle tone such as those in the ventrolateral periaqueductal gray, lateral pontine tegmentum, locus ceruleus, and dorsal raphe. We then found that bilateral, excitotoxic lesions of the amygdala markedly reduced cataplexy in orexin knock-out mice, a model of narcolepsy. These lesions did not alter basic sleep-wake behavior but substantially reduced the triggering of cataplexy. Lesions also reduced the cataplexy events triggered by conditions associated with high arousal and positive emotions (i.e., wheel running and chocolate). These observations demonstrate that the amygdala is a functionally important part of the circuitry underlying cataplexy and suggest that increased amygdala activity in response to emotional stimuli could directly trigger cataplexy by inhibiting brainstem regions that suppress muscle atonia.

Altruism costs—the cheap signal from amygdala

PubMed Central

Sundberg, Marcus; Maeder, Johanna; Fransson, Peter; Petrovic, Predrag; Isacsson, Gunnar; Karlström, Anders; Ingvar, Martin

2014-01-01

When people state their willingness to pay for something, the amount usually differs from the behavior in a real purchase situation. The discrepancy between a hypothetical answer and the real act is called hypothetical bias. We investigated neural processes of hypothetical bias regarding monetary donations to public goods using fMRI with the hypothesis that amygdala codes for real costs. Real decisions activated amygdala more than hypothetical decisions. This was observed for both accepted and rejected proposals. The more the subjects accepted real donation proposals the greater was the activity in rostral anterior cingulate cortex—a region known to control amygdala but also neural processing of the cost-benefit difference. The presentation of a charitable donation goal evoked an insula activity that predicted the later decision to donate. In conclusion, we have identified the neural mechanisms underlying real donation behavior, compatible with theories on hypothetical bias. Our findings imply that the emotional system has an important role in real decision making as it signals what kind of immediate cost and reward an outcome is associated with. PMID:23945997

Levetiracetam attenuates hippocampal expression of synaptic plasticity-related immediate early and late response genes in amygdala-kindled rats

PubMed Central

2010-01-01

Background The amygdala-kindled rat is a model for human temporal lobe epilepsy and activity-dependent synaptic plasticity. Hippocampal RNA isolated from amygdala-kindled rats at different kindling stages was analyzed to identify kindling-induced genes. Furthermore, effects of the anti-epileptic drug levetiracetam on kindling-induced gene expression were examined. Results Cyclooxygenase-2 (Cox-2), Protocadherin-8 (Pcdh8) and TGF-beta-inducible early response gene-1 (TIEG1) were identified and verified as differentially expressed transcripts in the hippocampus of kindled rats by in situ hybridization and quantitative RT-PCR. In addition, we identified a panel of 16 additional transcripts which included Arc, Egr3/Pilot, Homer1a, Ania-3, MMP9, Narp, c-fos, NGF, BDNF, NT-3, Synaptopodin, Pim1 kinase, TNF-α, RGS2, Egr2/krox-20 and β-A activin that were differentially expressed in the hippocampus of amygdala-kindled rats. The list consists of many synaptic plasticity-related immediate early genes (IEGs) as well as some late response genes encoding transcription factors, neurotrophic factors and proteins that are known to regulate synaptic remodelling. In the hippocampus, induction of IEG expression was dependent on the afterdischarge (AD) duration. Levetiracetam, 40 mg/kg, suppressed the development of kindling measured as severity of seizures and AD duration. In addition, single animal profiling also showed that levetiracetam attenuated the observed kindling-induced IEG expression; an effect that paralleled the anti-epileptic effect of the drug on AD duration. Conclusions The present study provides mRNA expression data that suggest that levetiracetam attenuates expression of genes known to regulate synaptic remodelling. In the kindled rat, levetiracetam does so by shortening the AD duration thereby reducing the seizure-induced changes in mRNA expression in the hippocampus. PMID:20105316

Differential serotonergic innervation of the amygdala in bonobos and chimpanzees.

PubMed

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.

Cortico-Amygdala Coupling as a Marker of Early Relapse Risk in Cocaine-Addicted Individuals

PubMed Central

McHugh, Meredith J.; Demers, Catherine H.; Salmeron, Betty Jo; Devous, Michael D.; Stein, Elliot A.; Adinoff, Bryon

2014-01-01

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 functional magnetic resonance imaging 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 and Personality Inventory. 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. PMID

Amygdala volume in combat-exposed veterans with and without posttraumatic stress disorder: a cross-sectional study.

PubMed

Kuo, Janice R; Kaloupek, Danny G; Woodward, Steven H

2012-10-01

Data from animal models demonstrate a link between stress exposure and hypertrophic changes in the amygdala; however, studies of adults with posttraumatic stress disorder (PTSD) have failed to find analogous structural alterations. To compare amygdala volumes between a sample of combat veterans with and without PTSD (analysis 1) and examine whether our observation of larger amygdala volume in individuals with PTSD could be accounted for by the presence of trauma exposure in childhood and the severity of combat exposure in adulthood (analysis 2). Cross-sectional magnetic resonance imaging. Veterans Affairs Palo Alto Health Care System Inpatient Trauma Recovery Program and Veterans Affairs New England Health Care System Outpatient PTSD program. Ninety-nine combat-exposed veterans from the Vietnam Conflict or the Persian Gulf War who had been exposed to substantial military operational stress. Amygdala volume adjusted for total cerebral volume, Life Events Checklist, and the Combat Exposure Scale. Analysis 1 indicated that combat-exposed individuals with PTSD exhibited larger total amygdala volume compared with their non-PTSD counterparts (99 individuals, P = .047). Analysis 2 indicated that greater severity of combat exposure (87 individuals, P = .02), as well as the interaction between the presence of early life trauma and the severity of combat exposure (87 individuals, P = .008), were significantly associated with smaller total amygdala volume. The PTSD diagnosis continued to explain larger amygdala volume (87 individuals, P = .006). Posttraumatic stress disorder is associated with enlarged amygdala volume, above the variance accounted for by a history of early life trauma and severity of adult trauma exposure. The discrepancy between our and prior findings may be explained by variability in these trauma indices in previous investigations. These findings support additional study of amygdala structure in human stress disorders and further delineation of the role of

Glutamic acid decarboxylase 65: a link between GABAergic synaptic plasticity in the lateral amygdala and conditioned fear generalization.

PubMed

Lange, Maren D; Jüngling, Kay; Paulukat, Linda; Vieler, Marc; Gaburro, Stefano; Sosulina, Ludmila; Blaesse, Peter; Sreepathi, Hari K; Ferraguti, Francesco; Pape, Hans-Christian

2014-08-01

An imbalance of the gamma-aminobutyric acid (GABA) system is considered a major neurobiological pathomechanism of anxiety, and the amygdala is a key brain region involved. Reduced GABA levels have been found in anxiety patients, and genetic variations of glutamic acid decarboxylase (GAD), the rate-limiting enzyme of GABA synthesis, have been associated with anxiety phenotypes in both humans and mice. These findings prompted us to hypothesize that a deficiency of GAD65, the GAD isoform controlling the availability of GABA as a transmitter, affects synaptic transmission and plasticity in the lateral amygdala (LA), and thereby interferes with fear responsiveness. Results indicate that genetically determined GAD65 deficiency in mice is associated with (1) increased synaptic length and release at GABAergic connections, (2) impaired efficacy of GABAergic synaptic transmission and plasticity, and (3) reduced spillover of GABA to presynaptic GABAB receptors, resulting in a loss of the associative nature of long-term synaptic plasticity at cortical inputs to LA principal neurons. (4) In addition, training with high shock intensities in wild-type mice mimicked the phenotype of GAD65 deficiency at both the behavioral and synaptic level, indicated by generalization of conditioned fear and a loss of the associative nature of synaptic plasticity in the LA. In conclusion, GAD65 is required for efficient GABAergic synaptic transmission and plasticity, and for maintaining extracellular GABA at a level needed for associative plasticity at cortical inputs in the LA, which, if disturbed, results in an impairment of the cue specificity of conditioned fear responses typifying anxiety disorders.

Glutamic Acid Decarboxylase 65: A Link Between GABAergic Synaptic Plasticity in the Lateral Amygdala and Conditioned Fear Generalization

PubMed Central

Lange, Maren D; Jüngling, Kay; Paulukat, Linda; Vieler, Marc; Gaburro, Stefano; Sosulina, Ludmila; Blaesse, Peter; Sreepathi, Hari K; Ferraguti, Francesco; Pape, Hans-Christian

2014-01-01

An imbalance of the gamma-aminobutyric acid (GABA) system is considered a major neurobiological pathomechanism of anxiety, and the amygdala is a key brain region involved. Reduced GABA levels have been found in anxiety patients, and genetic variations of glutamic acid decarboxylase (GAD), the rate-limiting enzyme of GABA synthesis, have been associated with anxiety phenotypes in both humans and mice. These findings prompted us to hypothesize that a deficiency of GAD65, the GAD isoform controlling the availability of GABA as a transmitter, affects synaptic transmission and plasticity in the lateral amygdala (LA), and thereby interferes with fear responsiveness. Results indicate that genetically determined GAD65 deficiency in mice is associated with (1) increased synaptic length and release at GABAergic connections, (2) impaired efficacy of GABAergic synaptic transmission and plasticity, and (3) reduced spillover of GABA to presynaptic GABAB receptors, resulting in a loss of the associative nature of long-term synaptic plasticity at cortical inputs to LA principal neurons. (4) In addition, training with high shock intensities in wild-type mice mimicked the phenotype of GAD65 deficiency at both the behavioral and synaptic level, indicated by generalization of conditioned fear and a loss of the associative nature of synaptic plasticity in the LA. In conclusion, GAD65 is required for efficient GABAergic synaptic transmission and plasticity, and for maintaining extracellular GABA at a level needed for associative plasticity at cortical inputs in the LA, which, if disturbed, results in an impairment of the cue specificity of conditioned fear responses typifying anxiety disorders. PMID:24663011

Spared Anterograde Memory for Shock-Probe Fear Conditioning After Inactivation of the Amygdala

PubMed Central

Lehmann, Hugo; Treit, Dallas; Parent, Marise B.

2003-01-01

Previous studies have shown that amygdala lesions impair avoidance of an electrified probe. This finding has been interpreted as indicating that amygdala lesions reduce fear. It is unclear, however, whether amygdala-lesioned rats learn that the probe is associated with shock. If the lesions prevent the formation of this association, then pretraining reversible inactivation of the amygdala should impair both acquisition and retention performance. To test this hypothesis, the amygdala was inactivated (tetrodotoxin; TTX; 1 ng/side) before a shock-probe acquisition session, and retention was tested 4 d later. The data indicated that, compared with rats infused with vehicle, rats infused with TTX received more shocks during the acquisition session, but more importantly, were not impaired on the retention test. In Experiment 2, we assessed whether the spared memory on the retention test was caused by overtraining during acquisition. We used the same procedure as in Experiment 1, with the exception that the number of shocks the rats received during the acquisition session was limited to four. Again the data indicated that amygdala inactivation did not impair performance on the retention test. These results indicate that amygdala inactivation does not prevent the formation of an association between the shock and the probe and that shock-probe deficits during acquisition likely reflect the amygdala's involvement in other processes. PMID:12888544

The interplay of attention and emotion: top-down attention modulates amygdala activation in psychopathy.

PubMed

Larson, Christine L; Baskin-Sommers, Arielle R; Stout, Daniel M; Balderston, Nicholas L; Curtin, John J; Schultz, Douglas H; Kiehl, Kent A; Newman, Joseph P

2013-12-01

Psychopathic behavior has long been attributed to a fundamental deficit in fear that arises from impaired amygdala function. Growing evidence has demonstrated that fear-potentiated startle (FPS) and other psychopathy-related deficits are moderated by focus of attention, but to date, no work on adult psychopathy has examined attentional modulation of the amygdala or concomitant recruitment of relevant attention-related circuitry. Consistent with previous FPS findings, here we report that psychopathy-related differences in amygdala activation appear and disappear as a function of goal-directed attention. Specifically, decreased amygdala activity was observed in psychopathic offenders only when attention was engaged in an alternative goal-relevant task prior to presenting threat-relevant information. Under this condition, psychopaths also exhibited greater activation in selective-attention regions of the lateral prefrontal cortex (LPFC) than did nonpsychopaths, and this increased LPFC activation mediated psychopathy's association with decreased amygdala activation. In contrast, when explicitly attending to threat, amygdala activation did not differ in psychopaths and nonpsychopaths. This pattern of amygdala activation highlights the potential role of LPFC in mediating the failure of psychopathic individuals to process fear and other important information when it is peripheral to the primary focus of goal-directed attention.

Effects of intranasal oxytocin on amygdala reactivity to emotional faces in recently trauma-exposed individuals.

PubMed

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

2016-02-01

There is a need for effective, early post-trauma preventive interventions for post-traumatic stress disorder (PTSD). Attenuating amygdala hyperreactivity early post-trauma, a likely PTSD vulnerability factor, may decrease PTSD risk. Since oxytocin modulates amygdala reactivity to emotional stimuli, oxytocin administration early post-trauma may be a promising candidate for PTSD prevention. In a randomized double-blind placebo-controlled fMRI study, we investigated effects of a single intranasal oxytocin administration (40 IU) on amygdala reactivity to happy, neutral and fearful faces in 41 recently trauma-exposed men and women showing moderate to high distress after initial post-trauma screening. We explored treatment interactions with sex. Participants were scanned within 11 days post-trauma. Compared with placebo, oxytocin significantly increased right amygdala reactivity to fearful faces. There was a significant treatment by sex interaction on amygdala reactivity to neutral faces, with women showing increased left amygdala reactivity after oxytocin. These findings indicate that a single oxytocin administration may enhance fearful faces processing in recently trauma-exposed individuals and neutral faces processing in recently trauma-exposed women. These observations may be explained by oxytocin-induced increased salience processing. Clinical implications of these findings for PTSD prevention should be further investigated. Netherlands Trial Registry; Boosting Oxytocin after trauma: Neurobiology and the Development of Stress-related psychopathology (BONDS); NTR3190; http://www.trialregister.nl/trialreg/admin/rctview.asp?TC = 3190. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Elevated Arc/Arg 3.1 protein expression in the basolateral amygdala following auditory trace-cued fear conditioning.

PubMed

Chau, Lily S; Prakapenka, Alesia; Fleming, Stephen A; Davis, Ashley S; Galvez, Roberto

2013-11-01

The underlying neuronal mechanisms of learning and memory have been heavily explored using associative learning paradigms. Two of the more commonly employed learning paradigms have been contextual and delay fear conditioning. In fear conditioning, a subject learns to associate a neutral stimulus (conditioned stimulus; CS), such as a tone or the context of the room, with a fear provoking stimulus (unconditioned stimulus; US), such as a mild footshock. Utilizing these two paradigms, various analyses have elegantly demonstrated that the amygdala plays a role in both fear-related associative learning paradigms. However, the amygdala's involvement in trace fear conditioning, a forebrain-dependent fear associative learning paradigm that has been suggested to tap into higher cognitive processes, has not been closely investigated. Furthermore, to our knowledge, the specific amygdala nuclei involved with trace fear conditioning has not been examined. The present study used Arc expression as an activity marker to determine the amygdala's involvement in trace fear associative learning and to further explore involvement of specific amygdalar nuclei. Arc is an immediate early gene that has been shown to be associated with neuronal activation and is believed to be necessary for neuronal plasticity. Findings from the present study demonstrated that trace-conditioned mice, compared to backward-conditioned (stimulation-control), delay-conditioned and naïve mice, exhibited elevated amygdalar Arc expression in the basolateral (BLA) but not the central (CeA) or the lateral amygdala (LA). These findings are consistent with previous reports demonstrating that the amygdala plays a critical role in trace conditioning. Furthermore, these findings parallel studies demonstrating hippocampal-BLA activation following contextual fear conditioning, suggesting that trace fear conditioning and contextual fear conditioning may involve similar amygdala nuclei. Together, findings from this study

An intra-amygdala circuit specifically regulates social fear learning

PubMed Central

Twining, Robert C.; Vantrease, Jaime E.; Love, Skyelar; Padival, Mallika; Rosenkranz, J. Amiel

2016-01-01

Adaptive social behavior requires transmission and reception of salient social information. Impairment of this reciprocity is a cardinal symptom of autism. The amygdala is a critical mediator of social behavior and is implicated in social symptoms of autism. Here we found that a specific amygdala circuit, from the lateral nucleus to the medial nucleus (LA-MeA), is required for using social cues to learn about environmental cues that signal imminent threats. Disruption of the LA-MeA circuit impaired valuation of these environmental cues and subsequent ability to use this cue to guide behavior. Rats with impaired social guidance of behavior due to knockout of Nrxn1, an analog to autism-associated genes (NRXN), exhibited marked LA-MeA deficits. Chemogenetic activation of this circuit reversed these impaired social behaviors. These findings identify an amygdala circuit required to guide emotional responses to socially significant cues and identify a novel exploratory target for disorders associated with social impairments. PMID:28114293

Identification of distinct telencephalic progenitor pools for neuronal diversity in the amygdala

PubMed Central

Hirata, Tsutomu; Li, Peijun; Lanuza, Guillermo M.; Cocas, Laura A.; Huntsman, Molly M.; Corbin, Joshua G.

2009-01-01

Development of the amygdala, a central structure of the limbic system, remains poorly understood. Using mouse as a model, our studies reveal that two spatially distinct and early specified telencephalic progenitor pools marked by the homeodomain transcription factor Dbx1 are major sources of neuronal cell diversity in the mature amygdala. We find that Dbx1+ cells of the ventral pallium (VP) generate excitatory neurons of the basolateral complex and cortical amygdala nuclei. Moreover, Dbx1-derived cells comprise a novel migratory stream that emanates from the preoptic area (POA), a ventral telencephalic domain adjacent to the diencephalic border. The Dbx1+ POA-derived population migrates specifically to the amygdala, and as defined by both immunochemical and electrophysiological criteria, generates a unique subclass of inhibitory neurons in the medial amygdala nucleus. Thus, this POA-derived population represents a novel progenitor pool dedicated to the limbic system. PMID:19136974

Identification of distinct telencephalic progenitor pools for neuronal diversity in the amygdala.

PubMed

Hirata, Tsutomu; Li, Peijun; Lanuza, Guillermo M; Cocas, Laura A; Huntsman, Molly M; Corbin, Joshua G

2009-02-01

The development of the amygdala, a central structure of the limbic system, remains poorly understood. We found that two spatially distinct and early-specified telencephalic progenitor pools marked by the homeodomain transcription factor Dbx1 are major sources of neuronal cell diversity in the mature mouse amygdala. We found that Dbx1-positive cells of the ventral pallium generate the excitatory neurons of the basolateral complex and cortical amygdala nuclei. Moreover, Dbx1-derived cells comprise a previously unknown migratory stream that emanates from the preoptic area (POA), a ventral telencephalic domain adjacent to the diencephalic border. The Dbx1-positive, POA-derived population migrated specifically to the amygdala and, as defined by both immunochemical and electrophysiological criteria, generated a unique subclass of inhibitory neurons in the medial amygdala nucleus. Thus, this POA-derived population represents a previously unknown progenitor pool dedicated to the limbic system.

NMDA receptor- and ERK-dependent histone methylation changes in the lateral amygdala bidirectionally regulate fear memory formation.

PubMed

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

2014-07-01

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 consolidation. Here we found increases in histone H3 lysine 9 dimethylation (H3K9me2) levels in the LA at 1 h following auditory fear conditioning, which continued to be temporally regulated up to 25 h following behavioral training. Additionally, we demonstrate that inhibiting the H3K9me2 histone lysine methyltransferase G9a (H/KMTs-G9a) in the LA impaired fear memory, while blocking the H3K9me2 histone lysine demethylase LSD1 (H/KDM-LSD1) enhanced fear memory, suggesting that H3K9me2 in the LA can bidirectionally regulate fear memory formation. Furthermore, we show that NMDAR activity differentially regulated the recruitment of H/KMT-G9a, H/KDM-LSD1, and subsequent H3K9me2 levels at a target gene promoter. This was largely regulated by GluN2B- but not GluN2A-containing NMDARs via ERK activation. Moreover, fear memory deficits associated with NMDAR or ERK blockade were successfully rescued through pharmacologically inhibiting LSD1, suggesting that enhancements of H3K9me2 levels within the LA can rescue fear memory impairments that result from hypofunctioning NMDARs or loss of ERK signaling. Together, the present study suggests that histone lysine methylation regulation in the LA via NMDAR-ERK-dependent signaling is involved in fear memory formation. © 2014 Gupta-Agarwal et al.; Published by Cold Spring Harbor Laboratory Press.

Sensitive periods of amygdala development: the role of maltreatment in preadolescence.

PubMed

Pechtel, Pia; Lyons-Ruth, Karlen; Anderson, Carl M; Teicher, Martin H

2014-08-15

The amygdala is vulnerable to stress-dependent disruptions in neural development. Animal models have shown that stress increases dendritic arborization leading to larger amygdala volumes. Human studies of early stress and amygdala volume, however, remain inconclusive. This study compared amygdala volume in adults with childhood maltreatment to that in healthy controls. Eighteen participants from a longitudinal cohort and 33 cross-sectional controls (17 M/34 F, 25.5±3.1 years) completed a structural magnetic resonance imagining scan and the Maltreatment and Abuse Chronology of Exposure scale. Random forest regression with conditional trees was used to assess relative importance of exposure to adversity at each age on amygdala, thalamic or caudate volume. Severity of exposure to adversity across age accounted for 27% of the variance in right amygdala volume. Peak sensitivity occurred at 10-11 years of age, and importance of exposure at this time was highly significant based on permutation tests (p=0.003). The regression model showed that exposure during this sensitive period resulted in steep dose-response function with maximal response to even modest levels of exposure. Subjects in the highest exposure quartile (MACE-11, range=11-54) had a 9.1% greater right amygdala volume than subjects in the lowest exposure quartile (MACE-11, ≤3.5). No associations emerged between age of exposure and volume of the left amygdala or bilateral caudate or thalamus. Severity of adversity experienced at age 10-11 contributed to larger right but not left amygdala volume in adulthood. Results provide preliminary evidence that the amygdala may have a developmental sensitive period in preadolescence. Copyright © 2014 Elsevier Inc. All rights reserved.

Morphological, structural, and functional alterations of the prefrontal cortex and the basolateral amygdala after early lesion of the rat mediodorsal thalamus.

PubMed

Ouhaz, Zakaria; Ba-M'hamed, Saadia; Bennis, Mohamed

2017-08-01

Early postnatal damage to the mediodorsal thalamus (MD) produces deficits in cognition and behavior believed to be associated with early prefrontal cortical maldevelopment. We assessed the role of MD afferents during development on the morphological and functional maturation of the prefrontal cortex (PFC) and the basolateral amygdala (BLA). Sprague-Dawley rat pups (n = 56) received a bilateral electrolytic lesion of the MD or a MD Sham lesion on postnatal day 4. 7 weeks later, all rats were tested in anxiety-related and cognitive paradigms using the elevated plus maze and novel object recognition tests. Following behavioral testing (P70), rats were killed and the baseline expression of C-Fos protein and the number of GABAergic neurons were evaluated in the PFC and the BLA. The dendritic morphology and spine density in the PFC using Golgi-Cox staining was also evaluated. Adult rats with early postnatal bilateral MD damage exhibited disrupted recognition memory and increased anxiety-like behaviors. The lesion also caused a significant diminution of C-Fos immunolabeling and an increase of the number of GABAergic neurons in the PFC. In the BLA, the number of GABAergic neurons was significantly reduced, associated with an increase in C-Fos immunolabeling. Furthermore, in the PFC the lesion induced a significant reduction in dendritic branching and spine density. Our data are consistent with the hypothesis that the MD plays a role in the development of the PFC and, therefore, may be a good animal model to investigate cognitive symptoms associated with schizophrenia.

The influence of negative life events on hippocampal and amygdala volumes in old age: a life-course perspective.

PubMed

Gerritsen, L; Kalpouzos, G; Westman, E; Simmons, A; Wahlund, L O; Bäckman, L; Fratiglioni, L; Wang, H X

2015-04-01

Psychosocial stress has been related to changes in the nervous system, with both adaptive and maladaptive consequences. The aim of this study was to examine the relationship of negative events experienced throughout the entire lifespan and hippocampal and amygdala volumes in older adults. In 466 non-demented old adults (age range 60-96 years, 58% female), hippocampal and amygdala volumes were segmented using Freesurfer. Negative life events and the age at which these events occurred were assessed by means of a structured questionnaire. Using generalized linear models, hippocampal and amygdala volumes were estimated with life events as independent variables. The statistical analyses were adjusted for age, gender, intracranial volume, lifestyle factors, cardiovascular risk factors, depressive symptoms, and cognitive functioning. Total number of negative life events and of late-life events, but not of early-life, early-adulthood, or middle-adulthood events, was related to larger amygdala volume. There were interactions of early-life events with age and gender. Participants who reported two or more early-life events had significantly smaller amygdala and hippocampal volumes with increasing age. Furthermore, smaller hippocampal volume was found in men who reported two or more early-life events, but not in women. These results suggest that the effect of negative life events on the brain depends on the time when the events occurred, with the strongest effects observed during the critical time periods of early and late life.

Extended fear conditioning reveals a role for both N-methyl-D-aspartic acid and non-N-methyl-D-aspartic acid receptors in the amygdala in the acquisition of conditioned fear.

PubMed

Pistell, P J; Falls, W A

2008-09-09

Pavlovian conditioning is a useful tool for elucidating the neural mechanisms involved with learning and memory, especially in regard to the stimuli associated with aversive events. The amygdala has been repeatedly implicated as playing a significant role in the acquisition and expression of fear. If the amygdala is critical for the acquisition of fear, then it should contribute to this processes regardless of the parameters used to induce or evaluate conditioned fear. A series of experiments using reversible inactivation techniques evaluated the role of the amygdala in the acquisition of conditioned fear when training was conducted over several days in rats. Fear-potentiated startle was used to evaluate the acquisition of conditioned fear. Pretraining infusions of N-methyl-d-aspartic acid (NMDA) or non-NMDA receptor antagonists alone into the amygdala interfered with the acquisition of fear early in training, but not later. Pretraining infusions of a cocktail consisting of both an NMDA and non-NMDA antagonist interfered with the acquisition of conditioned fear across all days of training. Taken together these results suggest the amygdala may potentially be critical for the acquisition of conditioned fear regardless of the parameters utilized.

Strychnine and taurine modulation of amygdala-associated anxiety-like behavior is 'state' dependent.

PubMed

McCool, Brian A; Chappell, Ann

2007-03-12

Strychnine-sensitive glycine receptors are expressed in many adult forebrain regions, yet the biological function of these receptors outside the spinal cord/brainstem is poorly understood. We have recently shown that rat lateral/basolateral amygdala neurons express strychnine-sensitive glycine-gated currents whose pharmacological and molecular characteristics are consistent with those established for classic ligand-gated chloride channels. The current studies were undertaken to establish the behavioral role, if any, of these strychnine-sensitive glycine receptors. Adult Long-Evans male rats were implanted with guide cannulae targeted at the lateral amygdala and were microinjected with standard artificial cerebrospinal fluid with or without various doses of strychnine or taurine. Anxiety-like behaviors were assessed with the elevated plus maze or the light/dark box. In the elevated plus maze, strychnine decreased closed-arm time and increased open-arm time, suggestive of an anxiolytic effect. Similarly, strychnine produced a modest anxiolytic effect in the light/dark box. Post hoc analysis of 'open-arm' time and 'light-side' time indicated that aCSF-treated animals were distributed into two apparent groups that displayed either high or low amounts of anxiety-like behavior in a given apparatus. Surprisingly, the pharmacological effects of both strychnine and taurine in these assays were dependent upon a given animal's behavioral phenotype. Together, these findings are significant because they suggest that the basal 'emotional state' of the animal could influence the behavioral outcome associated with drug application directly into the lateral/basolateral amygdala. Furthermore, our findings also suggest that compounds acting at amygdala strychnine-sensitive glycine receptors may actively modulate this basal anxiety-like state.

The Interplay of Attention and Emotion: Top-down Attention Modulates Amygdala Activation in Psychopathy

PubMed Central

Larson, Christine L.; Baskin-Sommers, Arielle R.; Stout, Daniel M.; Balderston, Nicholas L.; Curtin, John J.; Schultz, Douglas H.; Kiehl, Kent A.; Newman, Joseph P.

2013-01-01

Psychopathic behavior has long been attributed to a fundamental deficit in fear that arises from impaired amygdala function. Growing evidence demonstrates that fear potentiated startle (FPS) and other psychopathy-related deficits are moderated by focus of attention but, to date, no work on adult psychopathy has examined attentional modulation of the amygdala, or concomitant recruitment of relevant attention-related circuitry. Consistent with previous FPS findings, here we report that psychopathy-related differences in amygdala activation appear and disappear as a function of goal-directed attention. Specifically, decreased amygdala activity was observed in psychopathic offenders only when attention was engaged in an alternative goal-relevant task prior to presenting threat-relevant information. Under this condition, psychopaths also exhibited greater activation in selective attention regions of the lateral prefrontal cortex (LPFC) than non-psychopaths, and this increased LPFC activation mediated psychopathy’s association with decreased amygdala activation. In contrast, when explicitly attending to threat, amygdala activation in psychopaths did not differ from non-psychopaths. This pattern of amygdala activation highlights the potential role of LPFC in mediating the failure of psychopathic individuals to process fear and other important information when it is peripheral to the primary focus of goal-directed attention. PMID:23712665

Unilateral block of NMDA receptors in the amygdala prevents predator stress-induced lasting increases in anxiety-like behavior and unconditioned startle--effective hemisphere depends on the behavior.

PubMed

Adamec, R E; Burton, P; Shallow, T; Budgell, J

Lasting increases in anxiety-like behavior (ALB) in the elevated plus-maze are produced by a single 5-min exposure of a rat to a cat. Rats become more anxious in the plus-maze for up to 3 weeks after the exposure. The first study in this series demonstrated that blockade of NMDA receptors in rats with MK-801, AP7, or CPP, given systemically 30 min prior to exposure to a cat prevents the increase in ALB assessed 1 week later in the elevated plus-maze. To localize the site of action of systemic MK-801, MK-801 was injected in the amygdala 30 min prior to predator stress. Injections were given either unilaterally in either hemisphere, or bilaterally in both hemispheres. The target of the injection was the basolateral amygdala. The effects of injection depended on both the type of behavior and the hemisphere of injection. Injections of MK-801 in a variety of sites in the basolateral amygdala had no effect on the suppression of open-arm exploration produced by predator stress. Other amygdala nuclei or other limbic sites likely mediate the effects of systemically administered MK-801 on this behavior. In contrast, NMDA receptors in the left lateral amygdala mediate lasting suppression of risk assessment. MK-801, in a variety of sites in the left but not right lateral amygdala, blocked the effects of predator stress on risk assessment. This is clear evidence of separability of neural mechanisms controlling open-arm exploration and risk assessment. Different NMDA-dependent amygdala circuitry mediated effects of predator stress on unconditioned acoustic startle 1 week after cat exposure. The data indicate that integrity of the left lateral amygdala is necessary for potentiation of startle amplitude by predator stress, though NMDA receptors are not involved in this function. Nevertheless, NMDA receptors in the right, but not the left lateral amygdala, mediate initiation of changes in startle. The data also suggest that the right amygdala action is "downstream" from the left

In vivo voltage-dependent influences on summation of synaptic potentials in neurons of the lateral nucleus of the amygdala

PubMed Central

Rosenkranz, J. Amiel

2012-01-01

The amygdala has a fundamental role in driving affective behaviors in response to sensory cues. To accomplish this, neurons of the lateral nucleus (LAT) must integrate a large number of synaptic inputs. A wide range of factors influence synaptic integration, including membrane potential, voltage-gated ion channels and GABAergic inhibition. However, little is known about how these factors modulate integration of synaptic inputs in LAT neurons in vivo. The purpose of this study was to determine the voltage-dependent factors that modify in vivo integration of synaptic inputs in the soma of LAT neurons. In vivo intracellular recordings from anesthetized rats were used to measure post-synaptic potentials (PSPs) and clusters of PSPs across a range of membrane potentials. These studies found that the relationship between membrane potential and PSP clusters was sublinear, due to a reduction of cluster amplitude and area at depolarized membrane potentials. In combination with intracellular delivery of pharmacological agents, it was found that the voltage-dependent suppression of PSP clusters was sensitive to tetraethylammonium (TEA), but not cesium or a blocker of fast GABAergic inhibition. These findings indicate that integration of PSPs in LAT neurons in vivo is strongly modified by somatic membrane potential, likely through voltage-dependent TEA-sensitive potassium channels. Conditions that lead to a shift in membrane potential, or a modulation of the number or function of these ion channels will lead to a more uniform capacity for integration across voltages, and perhaps greatly facilitate amygdala-dependent behaviors. PMID:22989917

Intergenerational transmission of emotional trauma through amygdala-dependent mother-to-infant transfer of specific fear

PubMed Central

Debiec, Jacek; Sullivan, Regina Marie

2014-01-01

Emotional trauma is transmitted across generations. For example, children witnessing their parent expressing fear to specific sounds or images begin to express fear to those cues. Within normal range, this is adaptive, although pathological fear, such as occurs in posttraumatic stress disorder or specific phobias, is also socially transmitted to children and is thus of clinical concern. Here, using a rodent model, we report a mother-to-infant transfer of fear to a novel peppermint odor, which is dependent on the mother expressing fear to that smell in pups’ presence. Examination of pups’ neural activity using c-Fos early gene expression and 14C 2-deoxyglucose autoradiography during mother-to-infant fear transmission revealed lateral and basal amygdala nuclei activity, with a causal role highlighted by pharmacological inactivation of pups’ amygdala preventing the fear transmission. Maternal presence was not needed for fear transmission, because an elevation of pups’ corticosterone induced by the odor of the frightened mother along with a novel peppermint odor was sufficient to produce pups’ subsequent aversion to that odor. Disruption of axonal tracts from the Grueneberg ganglion, a structure implicated in alarm chemosignaling, or blockade of pups’ alarm odor-induced corticosterone increase prevented transfer of fear. These memories are acquired at younger ages compared with amygdala-dependent odor-shock conditioning and are more enduring following minimal conditioning. Our results provide clues to understanding transmission of specific fears across generations and its dependence upon maternal induction of pups’ stress response paired with the cue to induce amygdala-dependent learning plasticity. Results are discussed within the context of caregiver emotional responses and adaptive vs. pathological fears social transmission. PMID:25071168

Chemosensory function of the amygdala.

PubMed

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.

Glutamate Receptor GluA1 Subunit Is Implicated in Capsaicin Induced Modulation of Amygdala LTP but Not LTD

ERIC Educational Resources Information Center

Gebhardt, Christine; Albrecht, Doris

2018-01-01

Capsaicin has been shown to modulate synaptic plasticity in various brain regions including the amygdala. Whereas in the lateral amygdala the modulatory effect of capsaicin on long-term potentiation (LA-LTP) is mediated by TRPV1 channels, we have recently shown that capsaicin-induced enhancement of long term depression (LA-LTD) is mediated by…

A case of hyperthymesia: Rethinking the role of the amygdala in autobiographical memory

PubMed Central

Ally, Brandon A.; Hussey, Erin P.; Donahue, Manus J.

2012-01-01

Much controversy has been focused on the extent to which the amygdala belongs to the autobiographical memory core network. Early evidence suggested the amygdala played a vital role in emotional processing, likely helping to encode emotionally charged stimuli. However, recent work has highlighted the amygdala’s role in social and self-referential processing, leading to speculation that the amygdala likely supports the encoding and retrieval of autobiographical memory. Here, cognitive as well as structural and functional magnetic resonance imaging data was collected from an extremely rare individual with near-perfect autobiographical memory, or hyperthymesia. Right amygdala hypertrophy (approximately 20%) and enhanced amygdala-to-hippocampus connectivity (> 10 standard deviations) was observed in this volunteer relative to controls. Based on these findings and previous literature, we speculate that the amygdala likely charges autobiographical memories with emotional, social, and self-relevance. In heightened memory, this system may be hyperactive, allowing for many types of autobiographical information, including emotionally benign, to be more efficiently processed as self-relevant for encoding and storage. PMID:22519463

Receptor-driven, multimodal mapping of the human amygdala.

PubMed

Kedo, Olga; Zilles, Karl; Palomero-Gallagher, Nicola; Schleicher, Axel; Mohlberg, Hartmut; Bludau, Sebastian; Amunts, Katrin

2018-05-01

The human amygdala consists of subdivisions contributing to various functions. However, principles of structural organization at the cellular and molecular level are not well understood. Thus, we re-analyzed the cytoarchitecture of the amygdala and generated cytoarchitectonic probabilistic maps of ten subdivisions in stereotaxic space based on novel workflows and mapping tools. This parcellation was then used as a basis for analyzing the receptor expression for 15 receptor types. Receptor fingerprints, i.e., the characteristic balance between densities of all receptor types, were generated in each subdivision to comprehensively visualize differences and similarities in receptor architecture between the subdivisions. Fingerprints of the central and medial nuclei and the anterior amygdaloid area were highly similar. Fingerprints of the lateral, basolateral and basomedial nuclei were also similar to each other, while those of the remaining nuclei were distinct in shape. Similarities were further investigated by a hierarchical cluster analysis: a two-cluster solution subdivided the phylogenetically older part (central, medial nuclei, anterior amygdaloid area) from the remaining parts of the amygdala. A more fine-grained three-cluster solution replicated our previous parcellation including a laterobasal, superficial and centromedial group. Furthermore, it helped to better characterize the paralaminar nucleus with a molecular organization in-between the laterobasal and the superficial group. The multimodal cyto- and receptor-architectonic analysis of the human amygdala provides new insights into its microstructural organization, intersubject variability, localization in stereotaxic space and principles of receptor-based neurochemical differences.

Getting Over It: Long-Lasting Effects of Emotion Regulation on Amygdala Response.

PubMed

Denny, Bryan T; Inhoff, Marika C; Zerubavel, Noam; Davachi, Lila; Ochsner, Kevin N

2015-09-01

Little is known about whether emotion regulation can have lasting effects on the ability of a stimulus to continue eliciting affective responses in the future. We addressed this issue in this study. Participants cognitively reappraised negative images once or four times, and then 1 week later, they passively viewed old and new images, so that we could identify lasting effects of prior reappraisal. As in prior work, active reappraisal increased prefrontal responses but decreased amygdala responses and self-reported emotion. At 1 week, amygdala responses remained attenuated for images that had been repeatedly reappraised compared with images that had been reappraised once, new control images, and control images that had been seen as many times as reappraised images but had never been reappraised. Prefrontal activation was not selectively elevated for repeatedly reappraised images and was not related to long-term attenuation of amygdala responses. These results suggest that reappraisal can exert long-lasting "dose-dependent" effects on amygdala response that may cause lasting changes in the neural representation of an unpleasant event's emotional value. © The Author(s) 2015.

Right away: A late, right-lateralized category effect complements an early, left-lateralized category effect in visual search.

PubMed

Constable, Merryn D; Becker, Stefanie I

2017-10-01

According to the Sapir-Whorf hypothesis, learned semantic categories can influence early perceptual processes. A central finding in support of this view is the lateralized category effect-namely, the finding that categorically different colors (e.g., blue and green hues) can be discriminated faster than colors within the same color category (e.g., different hues of green), especially when they are presented in the right visual field. Because the right visual field projects to the left hemisphere, this finding has been popularly couched in terms of the left-lateralization of language. However, other studies have reported bilateral category effects, which has led some researchers to question the linguistic origins of the effect. Here we examined the time course of lateralized and bilateral category effects in the classical visual search paradigm by means of eyetracking and RT distribution analyses. Our results show a bilateral category effect in the manual responses, which is combined of an early, left-lateralized category effect and a later, right-lateralized category effect. The newly discovered late, right-lateralized category effect occurred only when observers had difficulty locating the target, indicating a specialization of the right hemisphere to find categorically different targets after an initial error. The finding that early and late stages of visual search show different lateralized category effects can explain a wide range of previously discrepant findings.

Strychnine and Taurine Modulation of Amygdala-associated Anxiety-like Behavior is ‘State’ Dependent

PubMed Central

McCool, Brian A.; Chappell, Ann

2007-01-01

Strychnine-sensitive glycine receptors are expressed in many adult forebrain regions, yet the biological function of these receptors outside the spinal cord/brainstem is poorly understood. We have recently shown that rat lateral/basolateral amygdala neurons express strychnine-sensitive glycine-gated currents whose pharmacological and molecular characteristics are consistent with those established for classic ligand-gated chloride channels. The current studies were undertaken to establish the behavioral role, if any, of these strychnine-sensitive glycine receptors. Adult Long-Evans male rats were implanted with guide cannulae targeted at the lateral amygdala and were micro-injected with standard artificial cerebrospinal fluid with or without various doses of strychnine or taurine. Anxiety-like behaviors were assessed with the elevated plus-maze or the light/dark box. In the elevated plus maze, strychnine decreased closed-arm time and increased open-arm time, suggestive of an anxiolytic effect. Similarly, strychnine produced a modest anxiolytic effect in the light/dark box. Post-hoc analysis of ‘open-arm’ time and ‘light-side’ time indicated that aCSF-treated animals were distributed into two apparent groups that displayed either high or low amounts of anxiety-like behavior in a given apparatus. Surprisingly, the pharmacological effects of both strychnine and taurine in these assays were dependent upon a given animal’s behavioral phenotype. Together, these findings are significant because they suggest that the basal ‘emotional state’ of the animal could influence the behavioral outcome associated with drug application directly into the lateral/basolateral amygdala. Furthermore, our findings also suggest that compounds acting at amygdala strychnine-sensitive glycine receptors may actively modulate this basal anxiety-like state. PMID:17207866

Amygdala subsystems and control of feeding behavior by learned cues.

PubMed

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.

Prenatal stress alters amygdala functional connectivity in preterm neonates.

PubMed

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 < 0.05). Similarly, when compared to extremely preterm neonates without exposure to prenatal stress, extremely preterm neonates with exposure to prenatal stress show significantly less connectivity between the left amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p < 0.05). Exploratory analysis of the combined cohorts suggests additive effects of prenatal stress on alterations in 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

Re-valuing the amygdala.

PubMed

Morrison, Sara E; Salzman, C Daniel

2010-04-01

Recent advances indicate that the amygdala represents valence: a general appetitive/aversive affective characteristic that bears similarity to the neuroeconomic concept of value. Neurophysiological studies show that individual amygdala neurons respond differentially to a range of stimuli with positive or negative affective significance. Meanwhile, increasingly specific lesion/inactivation studies reveal that the amygdala is necessary for processes--for example, fear extinction and reinforcer devaluation--that involve updating representations of value. Furthermore, recent neuroimaging studies suggest that the human amygdala mediates performance on many reward-based decision-making tasks. The encoding of affective significance by the amygdala might be best described as a representation of state value-a representation that is useful for coordinating physiological, behavioral, and cognitive responses in an affective/emotional context. (c) 2010 Elsevier Ltd. All rights reserved.

Lidocaine attenuates anisomycin-induced amnesia and release of norepinephrine in the amygdala

PubMed Central

Sadowski, Renee N.; Canal, Clint E.; Gold, Paul E.

2011-01-01

When administered near the time of training, protein synthesis inhibitors such as anisomycin impair later memory. A common interpretation of these findings is that memory consolidation requires new protein synthesis initiated by training. However, recent findings support an alternative interpretation that abnormally large increases in neurotransmitter release after injections of anisomycin may be responsible for producing amnesia. In the present study, a local anesthetic was administered prior to anisomycin injections in an attempt to mitigate neurotransmitter actions and thereby attenuate the resulting amnesia. Rats received lidocaine and anisomycin injections into the amygdala 130 and 120 min, respectively, prior to inhibitory avoidance training. Memory tests 48 hr later revealed that lidocaine attenuated anisomycin-induced amnesia. In other rats, in vivo microdialysis was performed at the site of amygdala infusion of lidocaine and anisomycin. As seen previously, anisomycin injections produced large increases in release of norepinephrine in the amygdala. Lidocaine attenuated the anisomycin-induced increase in release of norepinephrine but did not reverse anisomycin inhibition of protein synthesis, as assessed by c-Fos immunohistochemistry. These findings are consistent with past evidence suggesting that anisomycin causes amnesia by initiating abnormal release of neurotransmitters in response to the inhibition of protein synthesis. PMID:21453778

Amygdala volumes in childhood absence epilepsy.

PubMed

Schreibman Cohen, Ayelet; Daley, Melita; Siddarth, Prabha; Levitt, Jennifer; Loesch, Ingrid K; Altshuler, Lori; Ly, Ronald; Shields, W Donald; Gurbani, Suresh; Caplan, Rochelle

2009-11-01

Abnormal amygdala volumes in pediatric mood-anxiety disorders and attention deficit hyperactivity disorder (ADHD), as well as high rates of these diagnoses in childhood absence epilepsy (CAE), prompted this study of amygdala volume in CAE. Twenty-six children with CAE and 23 normal children, aged 6.6-15.8 years, underwent MRI at 1.5 T. The tissue imaged with MRI was segmented, and amygdala volumes were obtained by manual tracings. There were no significant amygdala volume differences between the CAE and normal groups. Within the CAE group, however, the children with ADHD had significantly smaller amygdala volumes than the subjects with CAE with no psychopathology and those with mood/anxiety diagnoses. There was also a significant relationship between higher seizure frequency and greater amygdala asymmetry in the epilepsy group. Given ongoing development of the amygdala during late childhood and adolescence, despite the lack of significant group differences in amygdala volumes, the association of amygdala volume abnormalities with ADHD and seizure frequency implies a possible impact of the disorder on amygdala development and CAE-associated comorbidities, such as ADHD.

Basolateral amygdala volume and cell numbers in major depressive disorder: a postmortem stereological study.

PubMed

Rubinow, Marisa J; Mahajan, Gouri; May, Warren; Overholser, James C; Jurjus, George J; Dieter, Lesa; Herbst, Nicole; Steffens, David C; Miguel-Hidalgo, Jose J; Rajkowska, Grazyna; Stockmeier, Craig A

2016-01-01

Functional imaging studies consistently report abnormal amygdala activity in major depressive disorder (MDD). Neuroanatomical correlates are less clear: imaging studies have produced mixed results on amygdala volume, and postmortem neuroanatomic studies have only examined cell densities in portions of the amygdala or its subregions in MDD. Here, we present a stereological analysis of the volume of, and the total number of, neurons, glia, and neurovascular (pericyte and endothelial) cells in the basolateral amygdala in MDD. Postmortem tissues from 13 subjects with MDD and 10 controls were examined. Sections (~15/subject) taken throughout the rostral-caudal extent of the basolateral amygdala (BLA) were stained for Nissl substance and utilized for stereological estimation of volume and cell numbers. Results indicate that depressed subjects had a larger lateral nucleus than controls and a greater number of total BLA neurovascular cells than controls. There were no differences in the number or density of neurons or glia between depressed and control subjects. These findings present a more detailed picture of BLA cellular anatomy in depression than has previously been available. Further studies are needed to determine whether the greater number of neurovascular cells in depressed subjects may be related to increased amygdala activity in depression.

Connectivity between the superior colliculus and the amygdala in humans and macaque monkeys: virtual dissection with probabilistic DTI tractography

PubMed Central

Koller, Kristin; Bultitude, Janet H.; Mullins, Paul; Ward, Robert; Mitchell, Anna S.; Bell, Andrew H.

2015-01-01

It has been suggested that some cortically blind patients can process the emotional valence of visual stimuli via a fast, subcortical pathway from the superior colliculus (SC) that reaches the amygdala via the pulvinar. We provide in vivo evidence for connectivity between the SC and the amygdala via the pulvinar in both humans and rhesus macaques. Probabilistic diffusion tensor imaging tractography revealed a streamlined path that passes dorsolaterally through the pulvinar before arcing rostrally to traverse above the temporal horn of the lateral ventricle and connect to the lateral amygdala. To obviate artifactual connectivity with crossing fibers of the stria terminalis, the stria was also dissected. The putative streamline between the SC and amygdala traverses above the temporal horn dorsal to the stria terminalis and is positioned medial to it in humans and lateral to it in monkeys. The topography of the streamline was examined in relation to lesion anatomy in five patients who had previously participated in behavioral experiments studying the processing of emotionally valenced visual stimuli. The pulvinar lesion interrupted the streamline in two patients who had exhibited contralesional processing deficits and spared the streamline in three patients who had no deficit. Although not definitive, this evidence supports the existence of a subcortical pathway linking the SC with the amygdala in primates. It also provides a necessary bridge between behavioral data obtained in future studies of neurological patients, and any forthcoming evidence from more invasive techniques, such as anatomical tracing studies and electrophysiological investigations only possible in nonhuman species. PMID:26224780

Memory-influencing intra-basolateral amygdala drug infusions modulate expression of Arc protein in the hippocampus.

PubMed

McIntyre, Christa K; Miyashita, Teiko; Setlow, Barry; Marjon, Kristopher D; Steward, Oswald; Guzowski, John F; McGaugh, James L

2005-07-26

Activation of beta-adrenoceptors in the basolateral complex of the amygdala (BLA) modulates memory storage processes and long-term potentiation in downstream targets of BLA efferents, including the hippocampus. Here, we show that this activation also increases hippocampal levels of activity-regulated cytoskeletal protein (Arc), an immediate-early gene (also termed Arg 3.1) implicated in hippocampal synaptic plasticity and memory consolidation processes. Infusions of the beta-adrenoreceptor agonist, clenbuterol, into the BLA immediately after training on an inhibitory avoidance task enhanced memory tested 48 h later. The same dose of clenbuterol significantly increased Arc protein levels in the dorsal hippocampus. Additionally, posttraining intra-BLA infusions of a memory-impairing dose of lidocaine significantly reduced Arc protein levels in the dorsal hippocampus. Increases in Arc protein levels were not accompanied by increases in Arc mRNA, suggesting that amygdala modulation of Arc protein and synaptic plasticity in efferent brain regions occurs at a posttranscriptional level. Finally, infusions of Arc antisense oligodeoxynucleotides into the dorsal hippocampus impaired performance of an inhibitory avoidance task, indicating that the changes in Arc protein expression are related to the observed changes in memory performance.

Memory-influencing intra-basolateral amygdala drug infusions modulate expression of Arc protein in the hippocampus

PubMed Central

McIntyre, Christa K.; Miyashita, Teiko; Setlow, Barry; Marjon, Kristopher D.; Steward, Oswald; Guzowski, John F.; McGaugh, James L.

2005-01-01

Activation of β-adrenoceptors in the basolateral complex of the amygdala (BLA) modulates memory storage processes and long-term potentiation in downstream targets of BLA efferents, including the hippocampus. Here, we show that this activation also increases hippocampal levels of activity-regulated cytoskeletal protein (Arc), an immediate-early gene (also termed Arg 3.1) implicated in hippocampal synaptic plasticity and memory consolidation processes. Infusions of the β-adrenoreceptor agonist, clenbuterol, into the BLA immediately after training on an inhibitory avoidance task enhanced memory tested 48 h later. The same dose of clenbuterol significantly increased Arc protein levels in the dorsal hippocampus. Additionally, posttraining intra-BLA infusions of a memory-impairing dose of lidocaine significantly reduced Arc protein levels in the dorsal hippocampus. Increases in Arc protein levels were not accompanied by increases in Arc mRNA, suggesting that amygdala modulation of Arc protein and synaptic plasticity in efferent brain regions occurs at a posttranscriptional level. Finally, infusions of Arc antisense oligodeoxynucleotides into the dorsal hippocampus impaired performance of an inhibitory avoidance task, indicating that the changes in Arc protein expression are related to the observed changes in memory performance. PMID:16020527

Development of White Matter Microstructure and Intrinsic Functional Connectivity Between the Amygdala and Ventromedial Prefrontal Cortex: Associations With Anxiety and Depression.

PubMed

Jalbrzikowski, Maria; Larsen, Bart; Hallquist, Michael N; Foran, William; Calabro, Finnegan; Luna, Beatriz

2017-10-01

Connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) is compromised in multiple psychiatric disorders, many of which emerge during adolescence. To identify to what extent the deviations in amygdala-vmPFC maturation contribute to the onset of psychiatric disorders, it is essential to characterize amygdala-vmPFC connectivity changes during typical development. Using an accelerated cohort longitudinal design (1-3 time points, 10-25 years old, n = 246), we characterized developmental changes of the amygdala-vmPFC subregion functional and structural connectivity using resting-state functional magnetic resonance imaging and diffusion-weighted imaging. Functional connectivity between the centromedial amygdala and rostral anterior cingulate cortex (rACC), anterior vmPFC, and subgenual cingulate significantly decreased from late childhood to early adulthood in male and female subjects. Age-associated decreases were also observed between the basolateral amygdala and the rACC. Importantly, these findings were replicated in a separate cohort (10-22 years old, n = 327). Similarly, structural connectivity, as measured by quantitative anisotropy, significantly decreased with age in the same regions. Functional connectivity between the centromedial amygdala and the rACC was associated with structural connectivity in these same regions during early adulthood (22-25 years old). Finally, a novel time-varying coefficient analysis showed that increased centromedial amygdala-rACC functional connectivity was associated with greater anxiety and depression symptoms during early adulthood, while increased structural connectivity in centromedial amygdala-anterior vmPFC white matter was associated with greater anxiety/depression during late childhood. Specific developmental periods of functional and structural connectivity between the amygdala and the prefrontal systems may contribute to the emergence of anxiety and depressive symptoms and may play a critical role in

Cumulative activation during positive and negative events and state anxiety predicts subsequent inertia of amygdala reactivity

PubMed Central

Miendlarzewska, Ewa A.; Eryilmaz, Hamdi; Vuilleumier, Patrik

2015-01-01

Inertia, together with intensity and valence, is an important component of emotion. We tested whether positive and negative events generate lingering changes in subsequent brain responses to unrelated threat stimuli and investigated the impact of individual anxiety. We acquired fMRI data while participants watched positive or negative movie-clips and subsequently performed an unrelated task with fearful and neutral faces. We quantified changes in amygdala reactivity to fearful faces as a function of the valence of preceding movies and cumulative neural activity evoked during them. We demonstrate that amygdala responses to emotional movies spill over to subsequent processing of threat information in a valence-specific manner: negative movies enhance later amygdala activation whereas positive movies attenuate it. Critically, the magnitude of such changes is predicted by a measure of cumulative amygdala responses to the preceding positive or negative movies. These effects appear independent of overt attention, are regionally limited to amygdala, with no changes in functional connectivity. Finally, individuals with higher state anxiety displayed stronger modulation of amygdala reactivity by positive movies. These results suggest that intensity and valence of emotional events as well as anxiety levels promote local changes in amygdala sensitivity to threat, highlighting the importance of past experience in shaping future affective reactivity. PMID:24603023

Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later Health Outcomes

PubMed Central

Maniam, Jayanthi; Antoniadis, Christopher; Morris, Margaret J.

2014-01-01

Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early-life stress can impact on later health but less is known about how early-life stress impairs HPA axis activity, contributing to maladaptation of the stress–response system. Early-life stress exposure (either prenatally or in the early postnatal period) can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical, and experimental studies have demonstrated that early-life stress produces long term hyper-responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviors. Recently, evidence has emerged on early-life stress-induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early-life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1). We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early-life stress-induced maladaptation of the HPA axis, and its subsequent effects on energy utilization and expenditure. The effects of positive later environments as a means of ameliorating early-life stress-induced health deficits, and proposed mechanisms underpinning the interaction between early-life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early-life stress and later health outcomes will also be

Heightened amygdala responsiveness in s-carriers of 5-HTTLPR genetic polymorphism reflects enhanced cortical rather than subcortical inputs: An MEG study.

PubMed

Luo, Qian; Holroyd, Tom; Mitchell, Derek; Yu, Henry; Cheng, Xi; Hodgkinson, Colin; Chen, Gang; McCaffrey, Daniel; Goldman, David; Blair, R James

2017-09-01

Short allele carriers (S-carriers) of the serotonin transporter gene (5-HTTLPR) show an elevated amygdala response to emotional stimuli relative to long allele carriers (LL-homozygous). However, whether this reflects increased responsiveness of the amygdala generally or interactions between the amygdala and the specific input systems remains unknown. It is argued that the amygdala receives input via a quick subcortical and a slower cortical pathway. If the elevated amygdala response in S-carriers reflects generally increased amygdala responding, then group differences in amygdala should be seen across the amygdala response time course. However, if the difference is a secondary consequence of enhanced amygdala-cortical interactions, then group differences might only be present later in the amygdala response. Using magnetoencephalography (MEG), we found an enhanced amygdala response to fearful expressions starting 40-50 ms poststimulus. However, group differences in the amygdala were only seen 190-200 ms poststimulus, preceded by increased superior temporal sulcus (STS) responses in S-carriers from 130 to 140 ms poststimulus. An enhanced amygdala response to angry expressions started 260-270 ms poststimulus with group differences in the amygdala starting at 160-170 ms poststimulus onset, preceded by increased STS responses in S-carriers from 150 to 160 ms poststimulus. These suggest that enhanced amygdala responses in S-carriers might reflect enhanced STS-amygdala connectivity in S-carriers. Hum Brain Mapp 38:4313-4321, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

PubMed

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

The amygdala excitatory/inhibitory balance in a valproate-induced rat autism model.

PubMed

Lin, Hui-Ching; Gean, Po-Wu; Wang, Chao-Chuan; Chan, Yun-Han; Chen, Po See

2013-01-01

The amygdala is an important structure contributing to socio-emotional behavior. However, the role of the amygdala in autism remains inconclusive. In this study, we used the 28-35 days valproate (VPA)-induced rat model of autism to observe the autistic phenotypes and evaluate their synaptic characteristics in the lateral nucleus (LA) of the amygdala. The VPA-treated offspring demonstrated less social interaction, increased anxiety, enhanced fear learning and impaired fear memory extinction. Slice preparation and electrophysiological recordings of the amygdala showed significantly enhanced long-term potentiation (LTP) while stimulating the thalamic-amygdala pathway of the LA. In addition, the pair pulse facilitation (PPF) at 30- and 60-ms intervals decreased significantly. Whole-cell recordings of the LA pyramidal neurons showed an increased miniature excitatory postsynaptic current (EPSC) frequency and amplitude. The relative contributions of the AMPA receptor and NMDA receptor to the EPSCs did not differ significantly between groups. These results suggested that the enhancement of the presynaptic efficiency of excitatory synaptic transmission might be associated with hyperexcitibility and enhanced LTP in LA pyramidal neurons. Disruption of the synaptic excitatory/inhibitory (E/I) balance in the LA of VPA-treated rats might play certain roles in the development of behaviors in the rat that may be relevant to autism. Further experiments to demonstrate the direct link are warranted.

Evidence that the medial amygdala projects to the anterior/ventromedial hypothalamic nuclei to inhibit maternal behavior in rats.

PubMed

Sheehan, T; Paul, M; Amaral, E; Numan, M J; Numan, M

2001-01-01

The maternal behaviors shown by a rat that has given birth are not shown by a virgin female rat when she is first presented with young. This absence of maternal behavior in virgins has been attributed to the activity of a neural circuit that inhibits maternal behavior in nulliparae. The medial amygdala and regions of the medial hypothalamus such as the anterior and ventromedial hypothalamic nuclei have previously been shown to inhibit maternal behavior, in that lesions to these regions promote maternal responding. Furthermore, we have recently shown that these and other regions, such as the principal bed nucleus of the stria terminalis, the ventral lateral septum, and the dorsal premammillary nucleus, show higher pup-induced Fos-immunoreactivity in non-maternal rats exposed to pups than during the performance of maternal behavior, indicating that they too could be involved in preventing maternal responsiveness. The current study tested whether the medial amygdala projects to the anterior/ventromedial hypothalamic nuclei in a neural circuit that inhibits maternal behavior, as well as to see what other brain regions could participate in this circuit. Bilateral excitotoxic lesions of the medial amygdala, or of the anterior/ventromedial hypothalamic nuclei, promoted maternal behavior. Unilateral medial amygdala lesions caused a reduction of pup-induced Fos-immunoreactivity in the anterior/ventromedial hypothalamic nuclei in non-maternal rats ipsilateral to the lesion, as well as in the principal bed nucleus of the stria terminalis, ventral lateral septum, and dorsal premammillary nucleus. Finally, unilateral medial amygdala lesions paired with contralateral anterior/ventromedial hypothalamic nuclei lesions promoted maternal behavior, although ipsilateral lesion placements were also effective.Together, these results indicate that the medial amygdala projects to the anterior/ventromedial hypothalamic nuclei in a neural circuit that inhibits maternal behavior, and that

Kindling-Induced Changes in Plasticity of the Rat Amygdala and Hippocampus

ERIC Educational Resources Information Center

Schubert, Manja; Siegmund, Herbert; Pape, Hans-Christian; Albrecht, Doris

2005-01-01

Temporal lobe epilepsy (TLE) is often accompanied by interictal behavioral abnormalities, such as fear and memory impairment. To identify possible underlying substrates, we analyzed long-term synaptic plasticity in two relevant brain regions, the lateral amygdala (LA) and the CA1 region of the hippocampus, in the kindling model of epilepsy. Wistar…

Running exercise delays neurodegeneration in amygdala and hippocampus of Alzheimer's disease (APP/PS1) transgenic mice.

PubMed

Lin, Tzu-Wei; Shih, Yao-Hsiang; Chen, Shean-Jen; Lien, Chi-Hsiang; Chang, Chia-Yuan; Huang, Tung-Yi; Chen, Shun-Hua; Jen, Chauying J; Kuo, Yu-Min

2015-02-01

Alzheimer's disease (AD) is an age-related neurodegenerative disease. Post-mortem examination and brain imaging studies indicate that neurodegeneration is evident in the hippocampus and amygdala of very early stage AD patients. Exercise training is known to enhance hippocampus- and amygdala-associated neuronal function. Here, we investigated the effects of exercise (running) on the neuronal structure and function of the hippocampus and amygdala in APP/PS1 transgenic (Tg) mice. At 4-months-old, an age before amyloid deposition, the amygdala-associated, but not the hippocampus-associated, long-term memory was impaired in the Tg mice. The dendritic complexities of the amygdalar basolateral neurons, but not those in the hippocampal CA1 and CA3 neurons, were reduced. Furthermore, the levels of BDNF/TrkB signaling molecules (i.e. p-TrkB, p-Akt and p-PKC) were reduced in the amygdala, but not in the hippocampus of the 4-month-old Tg mice. The concentrations of Aβ40 and Aβ42 in the amygdala were higher than those in the hippocampus. Ten weeks of treadmill training (from 1.5- to 4-month-old) increased the hippocampus-associated memory and dendritic arbor of the CA1 and CA3 neurons, and also restored the amygdala-associated memory and the dendritic arbor of amygdalar basolateral neurons in the Tg mice. Similarly, exercise training also increased the levels of p-TrkB, p-AKT and p-PKC in the hippocampus and amygdala. Furthermore, exercise training reduced the levels of soluble Aβ in the amygdala and hippocampus. Exercise training did not change the levels of APP or RAGE, but significantly increased the levels of LRP-1 in both brain regions of the Tg mice. In conclusion, our results suggest that tests of amygdala function should be incorporated into subject selection for early prevention trials. Long-term exercise protects neurons in the amygdala and hippocampus against AD-related degeneration, probably via enhancements of BDNF signaling pathways and Aβ clearance. Physical

Lateral unicompartmental knee arthroplasty through a lateral parapatellar approach has high early survivorship.

PubMed

Berend, Keith R; Kolczun, Michael C; George, Joseph W; Lombardi, Adolph V

2012-01-01

The literature suggests lateral unicompartmental knee arthroplasties are associated with low revision rates. However, there are fewer reports describing techniques for lateral unicompartmental arthroplasty and whether technique influences ROM and function compared to reports for medial unicompartmental arthroplasty. We report our indications for lateral unicompartmental arthroplasty, how we perform this procedure, and the subsequent Knee Society scores, ROM, and revision and reoperation rates. From a retrospective review of electronic records from 2004 through 2008, we identified 93 patients who had 100 lateral unicompartmental arthroplasties. Indications were complete lateral bone-on-bone arthrosis with a correctible deformity and maintenance of the medial joint space on varus stress radiographs or isolated lateral disease by diagnostic arthroscopy. Average age was 68 years. Seventy percent of patients were women. At followup, we obtained Knee Society scores and ROM. Minimum followup was 24 months (average, 39 months; range, 24-81 months). At followup, Knee Society scores averaged 46 for pain, 94 for clinical, and 89 for function, and ROM averaged 124°. Three patients had reoperations: one an open reduction and internal fixation for fracture at 2 years postoperatively, one an arthroscopy for a medial meniscal tear, and one a revision for pain. Based on our observations, we believe complete cartilage loss laterally and correctible deformity with maintenance of the medial joint on varus stress radiographs are reasonable indications for lateral unicompartmental arthroplasty. We recommend a lateral parapatellar approach can be utilized. The early reoperation and revision rates were low.

Unconditioned stimulus pathways to the amygdala: effects of lesions of the posterior intralaminar thalamus on foot-shock-induced c-Fos expression in the subdivisions of the lateral amygdala.

PubMed

Lanuza, E; Moncho-Bogani, J; Ledoux, J E

2008-08-26

The lateral nucleus of the amygdala (LA) is a site of convergence for auditory (conditioned stimulus) and foot-shock (unconditioned stimulus) inputs during fear conditioning. The auditory pathways to LA are well characterized, but less is known about the pathways through which foot shock is transmitted. Anatomical tracing and physiological recording studies suggest that the posterior intralaminar thalamic nucleus, which projects to LA, receives both auditory and somatosensory inputs. In the present study we examined the expression of the immediate-early gene c-fos in the LA in rats in response to foot-shock stimulation. We then determined the effects of posterior intralaminar thalamic lesions on foot-shock-induced c-Fos expression in the LA. Foot-shock stimulation led to an increase in the density of c-Fos-positive cells in all LA subnuclei in comparison to controls exposed to the conditioning box but not shocked. However, some differences among the dorsolateral, ventrolateral and ventromedial subnuclei were observed. The ventrolateral subnucleus showed a homogeneous activation throughout its antero-posterior extension. In contrast, only the rostral aspect of the ventromedial subnucleus and the central aspect of the dorsolateral subnucleus showed a significant increment in c-Fos expression. The density of c-Fos-labeled cells in all LA subnuclei was also increased in animals placed in the box in comparison to untreated animals. Unilateral electrolytic lesions of the posterior intralaminar thalamic nucleus and the medial division of the medial geniculate body reduced foot-shock-induced c-Fos activation in the LA ipsilateral to the lesion. The number of c-Fos labeled cells on the lesioned side was reduced to the levels observed in the animals exposed only to the box. These results indicate that the LA is involved in processing information about the foot-shock unconditioned stimulus and receives this kind of somatosensory information from the posterior intralaminar

Qualitatively different effect of repeated stress during adolescence on principal neuron morphology across lateral and basal nuclei of the rat amygdala

PubMed Central

Padival, Mallika A.; Blume, Shannon R.; Vantrease, Jaime E.; Rosenkranz, J. Amiel

2015-01-01

Repeated stress can elicit symptoms of depression and anxiety. The amygdala is a significant contributor to the expression of emotion and the basolateral amygdala (BLA) is a major target for the effects of stress on emotion. The adolescent time period may be particularly susceptible to the effects of stress on emotion. While repeated stress has been demonstrated to modify the morphology of BLA neurons in adult rats, little is known about its effects on BLA neurons during adolescence. This study tests the effects of repeated stress during adolescence on BLA neuronal morphology, and whether these are similar to the effects of stress during adulthood. The BLA includes the basal (BA) and lateral (LAT) nuclei, which are differentially responsive to stress in adults. Therefore, effects of stress during adolescence were compared between the BA and LAT nuclei. Morphological features of reconstructed BLA neurons were examined using Golgi-Cox stained tissue from control or repeated restraint stress exposed rats. We found subtle dendritic growth coupled with loss of spines after repeated stress during adolescence. The magnitude and dendritic location of these differences varied between the BA and LAT nuclei in strong contrast to the stress-induced increases in spine number seen in adults. These results demonstrate that repeated stress during adolescence has markedly different effects on BLA neuronal morphology, and the extent of these changes are BLA nucleus-dependent. Moreover, altered neuroanatomy was associated with age-dependent effects of repeated stress on generalization of fear, and may point to the necessity for different approaches to target stress-induced changes in adolescents. PMID:25701125

Task-irrelevant fear enhances amygdala-FFG inhibition and decreases subsequent face processing.

PubMed

Schulte Holthausen, Barbara; Habel, Ute; Kellermann, Thilo; Schelenz, Patrick D; Schneider, Frank; Christopher Edgar, J; Turetsky, Bruce I; Regenbogen, Christina

2016-09-01

Facial threat is associated with changes in limbic activity as well as modifications in the cortical face-related N170. It remains unclear if task-irrelevant threat modulates the response to a subsequent facial stimulus, and whether the amygdala's role in early threat perception is independent and direct, or modulatory. In 19 participants, crowds of emotional faces were followed by target faces and a rating task while simultaneous EEG-fMRI were recorded. In addition to conventional analyses, fMRI-informed EEG analyses and fMRI dynamic causal modeling (DCM) were performed. Fearful crowds reduced EEG N170 target face amplitudes and increased responses in a fMRI network comprising insula, amygdala and inferior frontal cortex. Multimodal analyses showed that amygdala response was present ∼60 ms before the right fusiform gyrus-derived N170. DCM indicated inhibitory connections from amygdala to fusiform gyrus, strengthened when fearful crowds preceded a target face. Results demonstrated the suppressing influence of task-irrelevant fearful crowds on subsequent face processing. The amygdala may be sensitive to task-irrelevant fearful crowds and subsequently strengthen its inhibitory influence on face-responsive fusiform N170 generators. This provides spatiotemporal evidence for a feedback mechanism of the amygdala by narrowing attention in order to focus on potential threats. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Planning in Middle Childhood: Early Predictors and Later Outcomes

ERIC Educational Resources Information Center

Friedman, Sarah L.; Scholnick, Ellin K.; Bender, Randall H.; Vandergrift, Nathan; Spieker, Susan; Pasek, Kathy Hirsh; Keating, Daniel P.; Park, Yoonjung

2014-01-01

Data from 1,364 children and families who participated in the National Institute of Child Health and Human Development's Study of Early Child Care and Youth Development were analyzed to track the early correlates and later academic outcomes of planning during middle childhood. Maternal education, through its effect on parenting quality when…

Cumulative activation during positive and negative events and state anxiety predicts subsequent inertia of amygdala reactivity.

PubMed

Pichon, Swann; Miendlarzewska, Ewa A; Eryilmaz, Hamdi; Vuilleumier, Patrik

2015-02-01

Inertia, together with intensity and valence, is an important component of emotion. We tested whether positive and negative events generate lingering changes in subsequent brain responses to unrelated threat stimuli and investigated the impact of individual anxiety. We acquired fMRI data while participants watched positive or negative movie-clips and subsequently performed an unrelated task with fearful and neutral faces. We quantified changes in amygdala reactivity to fearful faces as a function of the valence of preceding movies and cumulative neural activity evoked during them. We demonstrate that amygdala responses to emotional movies spill over to subsequent processing of threat information in a valence-specific manner: negative movies enhance later amygdala activation whereas positive movies attenuate it. Critically, the magnitude of such changes is predicted by a measure of cumulative amygdala responses to the preceding positive or negative movies. These effects appear independent of overt attention, are regionally limited to amygdala, with no changes in functional connectivity. Finally, individuals with higher state anxiety displayed stronger modulation of amygdala reactivity by positive movies. These results suggest that intensity and valence of emotional events as well as anxiety levels promote local changes in amygdala sensitivity to threat, highlighting the importance of past experience in shaping future affective reactivity. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Early Adolescent Affect Predicts Later Life Outcomes.

PubMed

Kansky, Jessica; Allen, Joseph P; Diener, Ed

2016-07-01

Subjective well-being as a predictor for later behavior and health has highlighted its relationship to health, work performance, and social relationships. However, the majority of such studies neglect the developmental nature of well-being in contributing to important changes across the transition to adulthood. To examine the potential role of subjective well-being as a long-term predictor of critical life outcomes, we examined indicators of positive and negative affect at age 14 as predictors of relationship, adjustment, self-worth, and career outcomes a decade later at ages 23 to 25, controlling for family income and gender. We utilised multi-informant methods including reports from the target participant, close friends, and romantic partners in a demographically diverse community sample of 184 participants. Early adolescent positive affect predicted fewer relationship problems (less self-reported and partner-reported conflict, and greater friendship attachment as rated by close peers) and healthy adjustment to adulthood (lower levels of depression, anxiety, and loneliness). It also predicted positive work functioning (higher levels of career satisfaction and job competence) and increased self-worth. Negative affect did not significantly predict any of these important life outcomes. In addition to predicting desirable mean levels of later outcomes, early positive affect predicted beneficial changes across time in many outcomes. The findings extend early research on the beneficial outcomes of subjective well-being by having an earlier assessment of well-being, including informant reports in measuring a large variety of outcome variables, and by extending the findings to a lower socioeconomic group of a diverse and younger sample. The results highlight the importance of considering positive affect as an important component of subjective well-being distinct from negative affect. © 2016 The International Association of Applied Psychology.

Early Adolescent Affect Predicts Later Life Outcomes

PubMed Central

Kansky, Jessica; Allen, Joseph P.; Diener, Ed

2016-01-01

Background Subjective well-being as a predictor for later behavior and health has highlighted its relationship to health, work performance, and social relationships. However, the majority of such studies neglect the developmental nature of well-being in contributing to important changes across the transition to adulthood. Methods To examine the potential role of subjective well-being as a long-term predictor of critical life outcomes, we examined indicators of positive and negative affect at age 14 as a predictor of relationship, adjustment, self worth, and career outcomes a decade later at ages 23 to 25, controlling for family income and gender. We utilized multi-informant methods including reports from the target participant, close friends, and romantic partners in a demographically diverse community sample of 184 participants. Results Early adolescent positive affect predicted less relationship problems (less self-reported and partner-reported conflict, greater friendship attachment as rated by close peers), healthy adjustment to adulthood (lower levels of depression, anxiety, and loneliness). It also predicted positive work functioning (higher levels of career satisfaction and job competence) and increased self-worth. Negative affect did not significantly predict any of these important life outcomes. In addition to predicting desirable mean levels of later outcomes, early positive affect predicted beneficial changes across time in many outcomes. Conclusions The findings extend early research on the beneficial outcomes of subjective well-being by having an earlier assessment of well-being, including informant reports in measuring a large variety of outcome variables, and by extending the findings to a lower socioeconomic group of a diverse and younger sample. The results highlight the importance of considering positive affect as an important component of subjective well-being distinct from negative affect. PMID:27075545

Arp2/3 and VASP Are Essential for Fear Memory Formation in Lateral Amygdala.

PubMed

Basu, Sreetama; Kustanovich, Irina; Lamprecht, Raphael

2016-01-01

The actin cytoskeleton is involved in key neuronal functions such as synaptic transmission and morphogenesis. However, the roles and regulation of actin cytoskeleton in memory formation remain to be clarified. In this study, we unveil the mechanism whereby actin cytoskeleton is regulated to form memory by exploring the roles of the major actin-regulatory proteins Arp2/3, VASP, and formins in long-term memory formation. Inhibition of Arp2/3, involved in actin filament branching and neuronal morphogenesis, in lateral amygdala (LA) with the specific inhibitor CK-666 during fear conditioning impaired long-term, but not short-term, fear memory. The inactive isomer CK-689 had no effect on memory formation. We observed that Arp2/3 is colocalized with the actin-regulatory protein profilin in LA neurons of fear-conditioned rats. VASP binding to profilin is needed for profilin-mediated stabilization of actin cytoskeleton and dendritic spine morphology. Microinjection of poly-proline peptide [G(GP 5 ) 3 ] into LA, to interfere with VASP binding to profilin, impaired long-term but not short-term fear memory formation. Control peptide [G(GA 5 ) 3 ] had no effect. Inhibiting formins, which regulate linear actin elongation, in LA during fear conditioning by microinjecting the formin-specific inhibitor SMIFH2 into LA had no effect on long-term fear memory formation. We conclude that Arp2/3 and VASP, through the profilin binding site, are essential for the formation of long-term fear memory in LA and propose a model whereby these proteins subserve cellular events, leading to memory consolidation.

Conditioned Fear Inhibits c-fos mRNA Expression in the Central Extended Amygdala

PubMed Central

Day, Heidi E.W.; Kryskow, Elisa M.; Nyhuis, Tara J.; Herlihy, Lauren; Campeau, Serge

2008-01-01

We have shown previously that unconditioned stressors inhibit neurons of the lateral/capsular division of the central nucleus of the amygdala (CEAl/c) and oval division of the bed nucleus of the stria terminalis (BSTov), which form part of the central extended amygdala. The current study investigated whether conditioned fear inhibits c-fos mRNA expression in these regions. Male rats were trained either to associate a visual stimulus (light) with footshock or were exposed to the light alone. After training, animals were replaced in the apparatus, and 2 hours later injected remotely, via a catheter, with amphetamine (2 mg/kg i.p.), to induce c-fos mRNA and allow inhibition of expression to be measured. The rats were then presented with 15 visual stimuli over a 30 minute period. As expected, fear conditioned animals that were not injected with amphetamine, had extremely low levels of c-fos mRNA in the central extended amygdala. In contrast, animals that were trained with the light alone (no fear conditioning) and were injected with amphetamine had high levels of c-fos mRNA in the CEAl/c and BSTov. Animals that underwent fear-conditioning, and were re-exposed to the conditioned stimulus after amphetamine injection had significantly reduced levels of c-fos mRNA in both the BSTov and CEAl/c, compared to the non-conditioned animals. These data suggest that conditioned fear can inhibit neurons of the central extended amygdala. Because these neurons are GABAergic, and project to the medial CEA (an amygdaloid output region), this may be a novel mechanism whereby conditioned fear potentiates amygdaloid output. PMID:18634767

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

PubMed

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.

How Human Amygdala and Bed Nucleus of the Stria Terminalis May Drive Distinct Defensive Responses.

PubMed

Klumpers, Floris; Kroes, Marijn C W; Baas, Johanna M P; Fernández, Guillén

2017-10-04

The ability to adaptively regulate responses to the proximity of potential danger is critical to survival and imbalance in this system may contribute to psychopathology. The bed nucleus of the stria terminalis (BNST) is implicated in defensive responding during uncertain threat anticipation whereas the amygdala may drive responding upon more acute danger. This functional dissociation between the BNST and amygdala is however controversial, and human evidence scarce. Here we used data from two independent functional magnetic resonance imaging studies [ n = 108 males and n = 70 (45 females)] to probe how coordination between the BNST and amygdala may regulate responses during shock anticipation and actual shock confrontation. In a subset of participants from Sample 2 ( n = 48) we demonstrate that anticipation and confrontation evoke bradycardic and tachycardic responses, respectively. Further, we show that in each sample when going from shock anticipation to the moment of shock confrontation neural activity shifted from a region anatomically consistent with the BNST toward the amygdala. Comparisons of functional connectivity during threat processing showed overlapping yet also consistently divergent functional connectivity profiles for the BNST and amygdala. Finally, childhood maltreatment levels predicted amygdala, but not BNST, hyperactivity during shock anticipation. Our results support an evolutionary conserved, defensive distance-dependent dynamic balance between BNST and amygdala activity. Shifts in this balance may enable shifts in defensive reactions via the demonstrated differential functional connectivity. Our results indicate that early life stress may tip the neural balance toward acute threat responding and via that route predispose for affective disorder. SIGNIFICANCE STATEMENT Previously proposed differential contributions of the BNST and amygdala to fear and anxiety have been recently debated. Despite the significance of understanding their

The changing face of emotion: age-related patterns of amygdala activation to salient faces.

PubMed

Todd, Rebecca M; Evans, Jennifer W; Morris, Drew; Lewis, Marc D; Taylor, Margot J

2011-01-01

The present study investigated age-related differences in the amygdala and other nodes of face-processing networks in response to facial expression and familiarity. fMRI data were analyzed from 31 children (3.5-8.5 years) and 14 young adults (18-33 years) who viewed pictures of familiar (mothers) and unfamiliar emotional faces. Results showed that amygdala activation for faces over a scrambled image baseline increased with age. Children, but not adults, showed greater amygdala activation to happy than angry faces; in addition, amygdala activation for angry faces increased with age. In keeping with growing evidence of a positivity bias in young children, our data suggest that children find happy faces to be more salient or meaningful than angry faces. Both children and adults showed preferential activation to mothers' over strangers' faces in a region of rostral anterior cingulate cortex associated with self-evaluation, suggesting that some nodes in frontal evaluative networks are active early in development. This study presents novel data on neural correlates of face processing in childhood and indicates that preferential amygdala activation for emotional expressions changes with age.

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

PubMed

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.

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

PubMed

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.

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

PubMed

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.

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

PubMed

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.

A Developmental Shift from Positive to Negative Connectivity in Human Amygdala-Prefrontal Circuitry

PubMed Central

Gee, Dylan G.; Humphreys, Kathryn L.; Flannery, Jessica; Goff, Bonnie; Telzer, Eva H.; Shapiro, Mor; Hare, Todd A.; Bookheimer, Susan Y.; Tottenham, Nim

2013-01-01

Recent human imaging and animal studies highlight the importance of frontoamygdala circuitry in the regulation of emotional behavior and its disruption in anxiety-related disorders. While tracing studies have suggested changes in amygdala-cortical connectivity through the adolescent period in rodents, less is known about the reciprocal connections within this circuitry across human development, when these circuits are being fine-tuned and substantial changes in emotional control are observed. The present study examined developmental changes in amygdala-prefrontal circuitry across the ages of 4 to 22 years using task-based functional magnetic resonance imaging (fMRI). Results suggest positive amygdala-prefrontal connectivity in early childhood that switches to negative functional connectivity during the transition to adolescence. Amygdala-mPFC functional connectivity was significantly positive (greater than zero) among participants younger than ten, whereas functional connectivity was significantly negative (less than zero) among participants ten years and older, over and above the effect of amygdala reactivity. The developmental switch in functional connectivity was paralleled by a steady decline in amygdala reactivity. Moreover, the valence switch might explain age-related improvement in task performance and a developmentally normative decline in anxiety. Initial positive connectivity followed by a valence shift to negative connectivity provides a neurobiological basis for regulatory development and may present novel insight into a more general process of developing regulatory connections. PMID:23467374

Attentional bias towards and away from fearful faces is modulated by developmental amygdala damage.

PubMed

Pishnamazi, Morteza; Tafakhori, Abbas; Loloee, Sogol; Modabbernia, Amirhossein; Aghamollaii, Vajiheh; Bahrami, Bahador; Winston, Joel S

2016-08-01

The amygdala is believed to play a major role in orienting attention towards threat-related stimuli. However, behavioral studies on amygdala-damaged patients have given inconsistent results-variously reporting decreased, persisted, and increased attention towards threat. Here we aimed to characterize the impact of developmental amygdala damage on emotion perception and the nature and time-course of spatial attentional bias towards fearful faces. We investigated SF, a 14-year-old with selective bilateral amygdala damage due to Urbach-Wiethe disease (UWD), and ten healthy controls. Participants completed a fear sensitivity questionnaire, facial expression classification task, and dot-probe task with fearful or neutral faces for spatial cueing. Three cue durations were used to assess the time-course of attentional bias. SF expressed significantly lower fear sensitivity, and showed a selective impairment in classifying fearful facial expressions. Despite this impairment in fear recognition, very brief (100 msec) fearful cues could orient SF's spatial attention. In healthy controls, the attentional bias emerged later and persisted longer. SF's attentional bias was due solely to facilitated engagement to fear, while controls showed the typical phenomenon of difficulty in disengaging from fear. Our study is the first to demonstrate the separable effects of amygdala damage on engagement and disengagement of spatial attention. The findings indicate that multiple mechanisms contribute in biasing attention towards fear, which vary in their timing and dependence on amygdala integrity. It seems that the amygdala is not essential for rapid attention to emotion, but probably has a role in assessment of biological relevance. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The L-type voltage-gated calcium channel CaV1.2 mediates fear extinction and modulates synaptic tone in the lateral amygdala.

PubMed

Temme, Stephanie J; Murphy, Geoffrey G

2017-11-01

L-type voltage-gated calcium channels (LVGCCs) have been implicated in both the formation and the reduction of fear through Pavlovian fear conditioning and extinction. Despite the implication of LVGCCs in fear learning and extinction, studies of the individual LVGCC subtypes, Ca V 1.2 and Ca V 1.3, using transgenic mice have failed to find a role of either subtype in fear extinction. This discontinuity between the pharmacological studies of LVGCCs and the studies investigating individual subtype contributions could be due to the limited neuronal deletion pattern of the Ca V 1.2 conditional knockout mice previously studied to excitatory neurons in the forebrain. To investigate the effects of deletion of Ca V 1.2 in all neuronal populations, we generated Ca V 1.2 conditional knockout mice using the synapsin1 promoter to drive Cre recombinase expression. Pan-neuronal deletion of Ca V 1.2 did not alter basal anxiety or fear learning. However, pan-neuronal deletion of Ca V 1.2 resulted in a significant deficit in extinction of contextual fear, implicating LVGCCs, specifically Ca V 1.2, in extinction learning. Further exploration on the effects of deletion of Ca V 1.2 on inhibitory and excitatory input onto the principle neurons of the lateral amygdala revealed a significant shift in inhibitory/excitatory balance. Together these data illustrate an important role of Ca V 1.2 in fear extinction and the synaptic regulation of activity within the amygdala. © 2017 Temme and Murphy; Published by Cold Spring Harbor Laboratory Press.

Mood-congruent amygdala responses to subliminally presented facial expressions in major depression: associations with anhedonia

PubMed Central

Stuhrmann, Anja; Dohm, Katharina; Kugel, Harald; Zwanzger, Peter; Redlich, Ronny; Grotegerd, Dominik; Rauch, Astrid Veronika; Arolt, Volker; Heindel, Walter; Suslow, Thomas; Zwitserlood, Pienie; Dannlowski, Udo

2013-01-01

Background Anhedonia has long been recognized as a key feature of major depressive disorders, but little is known about the association between hedonic symptoms and neurobiological processes in depressed patients. We investigated whether amygdala mood-congruent responses to emotional stimuli in depressed patients are correlated with anhedonic symptoms at automatic levels of processing. Methods We measured amygdala responsiveness to subliminally presented sad and happy facial expressions in depressed patients and matched healthy controls using functional magnetic resonance imaging. Amygdala responsiveness was compared between patients and healthy controls within a 2 (group) × 2 (emotion) design. In addition, we correlated patients’ amygdala responsiveness to sad and happy facial stimuli with self-report questionnaire measures of anhedonia. Results We included 35 patients and 35 controls in our study. As in previous studies, we observed a strong emotion × group interaction in the bilateral amygdala: depressed patients showed greater amygdala responses to sad than happy faces, whereas healthy controls responded more strongly to happy than sad faces. The lack of automatic right amygdala responsiveness to happy faces in depressed patients was associated with higher physical anhedonia scores. Limitations Almost all depressed patients were taking antidepressant medications. Conclusion We replicated our previous finding of depressed patients showing automatic amygdala mood-congruent biases in terms of enhanced reactivity to negative emotional stimuli and reduced activity to positive emotional stimuli. The altered amygdala processing of positive stimuli in patients was associated with anhedonia scores. The results indicate that reduced amygdala responsiveness to positive stimuli may contribute to an-hedonic symptoms due to reduced/inappropriate salience attribution to positive information at very early processing levels. PMID:23171695

Measured Early Lateral Energy Fractions in Concert Halls and Opera Houses

NASA Astrophysics Data System (ADS)

BARRON, M.

2000-04-01

In the 30 years since early lateral reflections were first suggested as important for concert halls, spatial impression and source broadening have become almost universally accepted as essential characteristics of halls with good acoustics. Two objective measures of source broadening have been proposed. Measured values of the best defined of these measures, the early lateral energy fraction (LF), are considered here. Results from two independent measurement surveys are discussed. Comparisons of LF values by hall show a significant link between hall mean LF and hall width. There is however considerable overlap between measured LF values in different halls so the relevance of describing halls by their mean early lateral energy fraction values is questionable. The behaviour of LF values within auditoria is discussed for different concert hall plan forms and within opera houses. A measure of source broadening including sound level is proposed and results considered in the context of auditorium design.

Negative Urgency Mediates the Relationship between Amygdala and Orbitofrontal Cortex Activation to Negative Emotional Stimuli and General Risk-Taking

PubMed Central

Cyders, Melissa A.; Dzemidzic, Mario; Eiler, William J.; Coskunpinar, Ayca; Karyadi, Kenny A.; Kareken, David A.

2015-01-01

The tendency toward impulsive behavior under emotional duress (negative and positive urgency) predicts a wide range of maladaptive risk-taking and behavioral disorders. However, it remains unclear how urgency relates to limbic system activity as induced from emotional provocation. This study used functional magnetic resonance imaging to examine the relationship between brain responses to visual emotional stimuli and urgency traits. Twenty-seven social drinkers (mean age = 25.2, 14 males) viewed negative (Neg), neutral (Neu), and positive (Pos) images during 6 fMRI scans. Brain activation was extracted from a priori limbic regions previously identified in studies of emotional provocation. The right posterior orbitofrontal cortex (OFC) and left amygdala were activated in the [Neg>Neu] contrast, whereas the left posterior OFC was activated in the [Pos>Neu] contrast. Negative urgency was related to the right lateral OFC (r = 0.43, P = 0.03) and the left amygdala (r = 0.39, P = 0.04) [Neg>Neu] activation. Negative urgency also mediated the relationship between [Neg>Neu] activation and general risk-taking (regression weights = 3.42 for right OFC and 2.75 for the left amygdala). Emotional cue-induced activation in right lateral OFC and left amygdala might relate to emotion-based risk-taking through negative urgency. PMID:24904065

High-resolution magnetic resonance imaging reveals nuclei of the human amygdala: manual segmentation to automatic atlas.

PubMed

Saygin, Z M; Kliemann, D; Iglesias, J E; van der Kouwe, A J W; Boyd, E; Reuter, M; Stevens, A; Van Leemput, K; McKee, A; Frosch, M P; Fischl, B; Augustinack, J C

2017-07-15

The amygdala is composed of multiple nuclei with unique functions and connections in the limbic system and to the rest of the brain. However, standard in vivo neuroimaging tools to automatically delineate the amygdala into its multiple nuclei are still rare. By scanning postmortem specimens at high resolution (100-150µm) at 7T field strength (n = 10), we were able to visualize and label nine amygdala nuclei (anterior amygdaloid, cortico-amygdaloid transition area; basal, lateral, accessory basal, central, cortical medial, paralaminar nuclei). We created an atlas from these labels using a recently developed atlas building algorithm based on Bayesian inference. This atlas, which will be released as part of FreeSurfer, can be used to automatically segment nine amygdala nuclei from a standard resolution structural MR image. We applied this atlas to two publicly available datasets (ADNI and ABIDE) with standard resolution T1 data, used individual volumetric data of the amygdala nuclei as the measure and found that our atlas i) discriminates between Alzheimer's disease participants and age-matched control participants with 84% accuracy (AUC=0.915), and ii) discriminates between individuals with autism and age-, sex- and IQ-matched neurotypically developed control participants with 59.5% accuracy (AUC=0.59). For both datasets, the new ex vivo atlas significantly outperformed (all p < .05) estimations of the whole amygdala derived from the segmentation in FreeSurfer 5.1 (ADNI: 75%, ABIDE: 54% accuracy), as well as classification based on whole amygdala volume (using the sum of all amygdala nuclei volumes; ADNI: 81%, ABIDE: 55% accuracy). This new atlas and the segmentation tools that utilize it will provide neuroimaging researchers with the ability to explore the function and connectivity of the human amygdala nuclei with unprecedented detail in healthy adults as well as those with neurodevelopmental and neurodegenerative disorders. Copyright © 2017 Elsevier Inc. All

Characterization and reversal of synaptic defects in the amygdala in a mouse model of fragile X syndrome.

PubMed

Suvrathan, Aparna; Hoeffer, Charles A; Wong, Helen; Klann, Eric; Chattarji, Sumantra

2010-06-22

Fragile X syndrome (FXS), a common inherited form of mental impairment and autism, is caused by transcriptional silencing of the fragile X mental retardation 1 (FMR1) gene. Earlier studies have identified a role for aberrant synaptic plasticity mediated by the metabotropic glutamate receptors (mGluRs) in FXS. However, many of these observations are derived primarily from studies in the hippocampus. The strong emotional symptoms of FXS, on the other hand, are likely to involve the amygdala. Unfortunately, little is known about how exactly FXS affects synaptic function in the amygdala. Here, using whole-cell recordings in brain slices from adult Fmr1 knockout mice, we find mGluR-dependent long-term potentiation to be impaired at thalamic inputs to principal neurons in the lateral amygdala. Consistent with this long-term potentiation deficit, surface expression of the AMPA receptor subunit, GluR1, is reduced in the lateral amygdala of knockout mice. In addition to these postsynaptic deficits, lower presynaptic release was manifested by a decrease in the frequency of spontaneous miniature excitatory postsynaptic currents (mEPSCs), increased paired-pulse ratio, and slower use-dependent block of NMDA receptor currents. Strikingly, pharmacological inactivation of mGluR5 with 2-methyl-6-phenylethynyl-pyridine (MPEP) fails to rescue either the deficit in long-term potentiation or surface GluR1. However, the same acute MPEP treatment reverses the decrease in mEPSC frequency, a finding of potential therapeutic relevance. Therefore, our results suggest that synaptic defects in the amygdala of knockout mice are still amenable to pharmacological interventions against mGluR5, albeit in a manner not envisioned in the original hippocampal framework.

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

PubMed

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

Comparative Distribution of Relaxin-3 Inputs and Calcium-Binding Protein-Positive Neurons in Rat Amygdala

PubMed Central

Santos, Fabio N.; Pereira, Celia W.; Sánchez-Pérez, Ana M.; Otero-García, Marcos; Ma, Sherie; Gundlach, Andrew L.; Olucha-Bordonau, Francisco E.

2016-01-01

. In contrast, sparse anterogradely-labeled and relaxin-3-immunoreactive fibers were observed in other amygdala nuclei, including the lateral, central and basal nuclei, while the nucleus accumbens lacked any innervation. Using synaptophysin as a synaptic marker, we identified relaxin-3 positive synaptic terminals in the medial amygdala, BST and endopiriform nucleus of amygdala. Our findings demonstrate the existence of topographic NI and relaxin-3-containing projections to specific nuclei of the extended amygdala, consistent with a likely role for this putative integrative arousal system in the regulation of amygdala-dependent social and emotional behaviors. PMID:27092060

Comparative Distribution of Relaxin-3 Inputs and Calcium-Binding Protein-Positive Neurons in Rat Amygdala.

PubMed

Santos, Fabio N; Pereira, Celia W; Sánchez-Pérez, Ana M; Otero-García, Marcos; Ma, Sherie; Gundlach, Andrew L; Olucha-Bordonau, Francisco E

2016-01-01

contrast, sparse anterogradely-labeled and relaxin-3-immunoreactive fibers were observed in other amygdala nuclei, including the lateral, central and basal nuclei, while the nucleus accumbens lacked any innervation. Using synaptophysin as a synaptic marker, we identified relaxin-3 positive synaptic terminals in the medial amygdala, BST and endopiriform nucleus of amygdala. Our findings demonstrate the existence of topographic NI and relaxin-3-containing projections to specific nuclei of the extended amygdala, consistent with a likely role for this putative integrative arousal system in the regulation of amygdala-dependent social and emotional behaviors.

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

PubMed Central

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

DNA Methyltransferase Activity is Required for Memory- Related Neural Plasticity in the Lateral Amygdala

PubMed Central

Maddox, Stephanie A.; Watts, Casey S.; Schafe, Glenn E.

2014-01-01

We have previously shown that auditory Pavlovian fear conditioning is associated with an increase in DNA methyltransferase (DNMT) expression in the lateral amygdala (LA) and that intra-LA infusion or bath application of an inhibitor of DNMT activity impairs the consolidation of an auditory fear memory and long-term potentiation (LTP) at thalamic and cortical inputs to the LA, in vitro. In the present study, we use awake behaving neurophysiological techniques to examine the role of DNMT activity in memory-related neurophysiological changes accompanying fear memory consolidation and reconsolidation in the LA, in vivo. We show that auditory fear conditioning results in a training-related enhancement in the amplitude of short-latency auditory-evoked field potentials (AEFPs) in the LA. Intra-LA infusion of a DNMT inhibitor impairs both fear memory consolidation and, in parallel, the consolidation of training-related neural plasticity in the LA; that is, short-term memory (STM) and short-term training-related increases in AEFP amplitude in the LA are intact, while long-term memory (LTM) and long-term retention of training-related increases in AEFP amplitudes are impaired. In separate experiments, we show that intra-LA infusion of a DNMT inhibitor following retrieval of an auditory fear memory has no effect on post-retrieval STM or short-term retention of training-related changes in AEFP amplitude in the LA, but significantly impairs both post-retrieval LTM and long-term retention of AEFP amplitude changes in the LA. These findings are the first to demonstrate the necessity of DNMT activity in the consolidation and reconsolidation of memory-associated neural plasticity, in vivo. PMID:24291571

Prenatal Bisphenol A Exposure Alters Sex-Specific Estrogen Receptor Expression in the Neonatal Rat Hypothalamus and Amygdala

PubMed Central

Patisaul, Heather B.

2013-01-01

Bisphenol A (BPA) exposure is ubiquitous, and in laboratory animals, early-life BPA exposure has been shown to alter sex-specific neural organization, neuroendocrine physiology, and behavior. The specific mechanisms underlying these brain-related outcomes, however, remain largely unknown, constraining the capacity to ascertain the potential human relevance of neural effects observed in animal models. In the perinatal rat brain, estrogen is masculinizing, suggesting that BPA-induced perturbation of estrogen receptor (ESR) expression may underpin later in-life neuroendocrine effects. We hypothesized that prenatal BPA exposure alters sex-specific ESR1 (ERα) and ESR2 (ERβ) expression in postnatal limbic nuclei. Sprague Dawley rats were mated and gavaged on gestational days (GDs) 6–21 with vehicle, 2.5 or 25 μg/kg bw/day BPA, or 5 or 10 μg/kg bw/day ethinyl estradiol. An additional group was restrained but not gavaged (naïve control). Offspring were sacrificed the day after birth to quantify ESR gene expression throughout the hypothalamus and amygdala by in situ hybridization. Relative to the vehicle group, significant effects of BPA were observed on ESR1 and ESR2 expression throughout the mediobasal hypothalamus and amygdala in both sexes. Significant differences in ESR expression were also observed in the mediobasal hypothalamus and amygdala of the naïve control group compared with the vehicle group, highlighting the potential for gavage to influence gene expression in the developing brain. These results indicate that ESR expression in the neonatal brain of both sexes can be altered by low-dose prenatal BPA exposure. PMID:23457122

Developmental change in amygdala reactivity during adolescence: effects of family history of depression and stressful life events.

PubMed

Swartz, Johnna R; Williamson, Douglas E; Hariri, Ahmad R

2015-03-01

Although heightened amygdala reactivity is observed in patients with major depression, two critical gaps in our knowledge remain. First, it is unclear whether heightened amygdala reactivity is a premorbid vulnerability or a consequence of the disorder. Second, it is unknown how and when this neural phenotype develops. The authors sought to address these gaps by evaluating developmental change in threat-related amygdala reactivity in adolescents at high or low risk for depression based on family history, before onset of disorder. At baseline and again 2 years later, adolescents (initially 11-15 years of age) participated in a functional MRI paradigm that elicited threat-related amygdala reactivity. After quality control, data were available for 232 adolescents at wave 1 and 197 adolescents at wave 2; longitudinal data meeting quality control at both waves were available for 157 of these participants. Change in amygdala reactivity was assessed as a function of family history of depression and severity of stressful life events. Threat-related amygdala reactivity increased with age in participants with a positive family history regardless of the severity of life stress reported, and it increased in adolescents with a negative family history who reported relatively severe life stress. These changes in amygdala reactivity with age occurred in the absence of clinical disorder or increases in depressive symptoms. These results suggest that heightened amygdala reactivity emerges during adolescence, prior to the development of depression, as a function of familial risk or, in the absence of familial risk, stressful life events.

Enhanced noradrenergic activity in the amygdala contributes to hyperarousal in an animal model of PTSD.

PubMed

Ronzoni, Giacomo; Del Arco, Alberto; Mora, Francisco; Segovia, Gregorio

2016-08-01

Increased activity of the noradrenergic system in the amygdala has been suggested to contribute to the hyperarousal symptoms associated with post-traumatic stress disorder (PTSD). However, only two studies have examined the content of noradrenaline or its metabolites in the amygdala of rats previously exposed to traumatic stress showing inconsistent results. The aim of this study was to investigate the effects of an inescapable foot shock (IFS) procedure (1) on reactivity to novelty in an open-field (as an index of hyperarousal), and (2) on noradrenaline release in the amygdala during an acute stress. To test the role of noradrenaline in amygdala, we also investigated the effects of microinjections of propranolol, a β-adrenoreceptor antagonist, and clenbuterol, a β-adrenoreceptor agonist, into the amygdala of IFS and control animals. Finally, we evaluated the expression of mRNA levels of β-adrenoreceptors (β1 and β2) in the amygdala, the hippocampus and the prefrontal cortex. Male Wistar rats (3 months) were stereotaxically implanted with bilateral guide cannulae. After recovering from surgery, animals were exposed to IFS (10 shocks, 0.86mA, and 6s per shock) and seven days later either microdialysis or microinjections were performed in amygdala. Animals exposed to IFS showed a reduced locomotion compared to non-shocked animals during the first 5min in the open-field. In the amygdala, IFS animals showed an enhanced increase of noradrenaline induced by stress compared to control animals. Bilateral microinjections of propranolol (0.5μg) into the amygdala one hour before testing in the open-field normalized the decreased locomotion observed in IFS animals. On the other hand, bilateral microinjections of clenbuterol (30ng) into the amygdala of control animals did not change the exploratory activity induced by novelty in the open field. IFS modified the mRNA expression of β1 and β2 adrenoreceptors in the prefrontal cortex and the hippocampus. These results

Increases in extracellular zinc in the amygdala in acquisition and recall of fear experience and their roles in response to fear.

PubMed

Takeda, A; Tamano, H; Imano, S; Oku, N

2010-07-14

The amygdala is enriched with histochemically reactive zinc, which is dynamically coupled with neuronal activity and co-released with glutamate. The dynamics of the zinc in the amygdala was analyzed in rats, which were subjected to inescapable stress, to understand the role of the zinc in emotional behavior. In the communication box, two rats were subjected to foot shock stress and anxiety stress experiencing emotional responses of foot-shocked rat under amygdalar perfusion. Extracellular zinc was increased by foot shock stress, while decreased by anxiety stress, suggesting that the differential changes in extracellular zinc are associated with emotional behavior. In rats conditioned with foot shock, furthermore, extracellular zinc was increased again in the recall of fear (foot shock) in the same box without foot shock. When this recall was performed under perfusion with CaEDTA, a membrane-impermeable zinc chelator, to examine the role of the increase in extracellular zinc, the time of freezing behavior was more increased, suggesting that zinc released in the lateral amygdala during the recall of fear participates in freezing behavior. To examine the role of the increase in extracellular zinc during fear conditioning, fear conditioning was also performed under perfusion with CaEDTA. The time of freezing behavior was more increased in the contextual recall, suggesting that zinc released in the lateral nucleus during fear conditioning also participates in freezing behavior in the recall. In brain slice experiment, CaEDTA enhanced presynaptic activity (exocytosis) in the lateral nucleus after activation of the entorhinal cortex. The present paper demonstrates that zinc released in the lateral amygdala may participate in emotional behavior in response to fear. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

The changing face of emotion: age-related patterns of amygdala activation to salient faces

PubMed Central

Evans, Jennifer W.; Morris, Drew; Lewis, Marc D.; Taylor, Margot J.

2011-01-01

The present study investigated age-related differences in the amygdala and other nodes of face-processing networks in response to facial expression and familiarity. fMRI data were analyzed from 31 children (3.5–8.5 years) and 14 young adults (18–33 years) who viewed pictures of familiar (mothers) and unfamiliar emotional faces. Results showed that amygdala activation for faces over a scrambled image baseline increased with age. Children, but not adults, showed greater amygdala activation to happy than angry faces; in addition, amygdala activation for angry faces increased with age. In keeping with growing evidence of a positivity bias in young children, our data suggest that children find happy faces to be more salient or meaningful than angry faces. Both children and adults showed preferential activation to mothers’ over strangers’ faces in a region of rostral anterior cingulate cortex associated with self-evaluation, suggesting that some nodes in frontal evaluative networks are active early in development. This study presents novel data on neural correlates of face processing in childhood and indicates that preferential amygdala activation for emotional expressions changes with age. PMID:20194512

Amygdala response to faces parallels social behavior in Williams syndrome

PubMed Central

Snyder, Abraham Z.; Haist, Frank; Raichle, Marcus E.; Bellugi, Ursula; Stiles, Joan

2009-01-01

Individuals with Williams syndrome (WS), a genetically determined disorder, show relatively strong face-processing abilities despite poor visuospatial skills and depressed intellectual function. Interestingly, beginning early in childhood they also show an unusually high level of interest in face-to-face social interaction. We employed functional magnetic resonance imaging (fMRI) to investigate physiological responses in face-sensitive brain regions, including ventral occipito-temporal cortex and the amygdala, in this unique genetic disorder. Participants included 17 individuals with WS, 17 age- and gender-matched healthy adults (chronological age-matched controls, CA) and 17 typically developing 8- to 9-year-old children (developmental age controls, DA). While engaged in a face discrimination task, WS participants failed to recruit the amygdala, unlike both CA and DA controls. WS fMRI responses in ventral occipito-temporal cortex, however, were comparable to those of DA controls. Given the integral role of the amygdala in social behavior, the failure of WS participants to recruit this region during face processing may be a neural correlate of the abnormally high sociability that characterizes this disorder. PMID:19633063

The effects of neonatal amygdala or hippocampus lesions on adult social behavior.

PubMed

Bliss-Moreau, Eliza; Moadab, Gilda; Santistevan, Anthony; Amaral, David G

2017-03-30

The present report details the final phase of a longitudinal evaluation of the social behavior in a cohort of adult rhesus monkeys that received bilateral neurotoxic lesions of the amygdala or hippocampus, or sham operations at 2 weeks of age. Results were compared to previous studies in which adult animals received amygdala lesions and were tested in a similar fashion. Social testing with four novel interaction partners occurred when the animals were between 7 and 8 years of age. Experimental animals interacted with two male and two female partners in two conditions - one in which physical access was restricted (the constrained social access condition) and a second in which physical access was unrestricted (the unconstrained social access condition). Across conditions and interaction partners, there were no significant effects of lesion condition on the frequency or duration of social interactions. As a group, the hippocampus-lesioned animals generated the greatest number of communicative signals during the constrained social access condition. Amygdala-lesioned animals generated more frequent stress-related behaviors and were less exploratory. Amygdala and hippocampus-lesioned animals demonstrated greater numbers of stereotypies than control animals. Subtle, lesion-based differences in the sequencing of behaviors were observed. These findings suggest that alterations of adult social behavior are much less prominent when damage to the amygdala occurs early in life rather than in adulthood. Copyright © 2016 Elsevier B.V. All rights reserved.

Patterns of Neural Connectivity during an Attention Bias Task Moderate Associations between Early Childhood Temperament and Internalizing Symptoms in Young Adulthood

PubMed Central

Hardee, Jillian E.; Benson, Brenda E.; Bar-Haim, Yair; Mogg, Karin; Bradley, Brendan P; Chen, Gang; Britton, Jennifer C.; Ernst, Monique; Fox, Nathan A.; Pine, Daniel S.; Pérez-Edgar, Koraly

2013-01-01

Background Biased attention to threat is found in both individuals with anxiety symptoms and children with the childhood temperament of behavioral inhibition (BI). Although perturbed fronto-amygdala function is implicated in biased attention among anxious individuals, no work has examined the neural correlates of attention biases in BI. Work in this area may clarify underlying mechanisms for anxiety in a sample at risk for internalizing disorders. We examined the relations among early childhood BI, fronto-amygdala connectivity during an attention bias task in young adulthood, and internalizing symptoms, assessed in young adulthood. Methods Children were assessed for BI at multiple age points from infancy through age seven. Based on a composite of observational and maternal report data, we selected 21 young adults classified as having a history of BI and 23 classified as non-BI for this study (N=44). Participants completed an event-related fMRI attention-bias task involving threat (angry faces) and neutral trials. Internalizing symptoms were assessed by self-report and diagnostic interviews. Results The young adults characterized in childhood with BI exhibited greater strength in threat-related connectivity than non-behaviorally inhibited young adults. Between-group differences manifested in connections between the amygdala and two frontal regions: dorsolateral prefrontal cortex and anterior insula. Amygdala-insula connectivity also interacted with childhood BI to predict young adult internalizing symptoms. Conclusions BI during early childhood predicts differences as young adults in threat and attention-related fronto-amygdala connectivity. Connectivity strength, in turn, moderated the relations between early BI and later psychopathology. PMID:23489415

Optogenetic Examination of Prefrontal-Amygdala Synaptic Development.

PubMed

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.

Disruption of amygdala-entorhinal-hippocampal network in late-life depression.

PubMed

Leal, Stephanie L; Noche, Jessica A; Murray, Elizabeth A; Yassa, Michael A

2017-04-01

Episodic memory deficits are evident in late-life depression (LLD) and are associated with subtle synaptic and neurochemical changes in the medial temporal lobes (MTL). However, the particular mechanisms by which memory impairment occurs in LLD are currently unknown. We tested older adults with (DS+) and without (DS-) depressive symptoms using high-resolution fMRI that is capable of discerning signals in hippocampal subfields and amygdala nuclei. Scanning was conducted during performance of an emotional discrimination task used previously to examine the relationship between depressive symptoms and amygdala-mediated emotional modulation of hippocampal pattern separation in young adults. We found that hippocampal dentate gyrus (DG)/CA3 activity was reduced during correct discrimination of negative stimuli and increased during correct discrimination of neutral items in DS+ compared to DS- adults. The extent of the latter increase was correlated with symptom severity. Furthermore, DG/CA3 and basolateral amygdala (BLA) activity predicted discrimination performance on negative trials, a relationship that depended on symptom severity. The impact of the BLA on depressive symptom severity was mediated by the DG/CA3 during discrimination of neutral items, and by the lateral entorhinal cortex (LEC) during false recognition of positive items. These results shed light on a novel mechanistic account for amygdala-hippocampal network changes and concurrent alterations in emotional episodic memory in LLD. The BLA-LEC-DG/CA3 network, which comprises a key pathway by which emotion modulates memory, is specifically implicated in LLD. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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

ERIC Educational Resources Information Center

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…

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

PubMed

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

Sociability Deficits and Altered Amygdala Circuits in Mice Lacking Pcdh10, an Autism Associated Gene.

PubMed

Schoch, Hannah; Kreibich, Arati S; Ferri, Sarah L; White, Rachel S; Bohorquez, Dominique; Banerjee, Anamika; Port, Russell G; Dow, Holly C; Cordero, Lucero; Pallathra, Ashley A; Kim, Hyong; Li, Hongzhe; Bilker, Warren B; Hirano, Shinji; Schultz, Robert T; Borgmann-Winter, Karin; Hahn, Chang-Gyu; Feldmeyer, Dirk; Carlson, Gregory C; Abel, Ted; Brodkin, Edward S

2017-02-01

Behavioral symptoms in individuals with autism spectrum disorder (ASD) have been attributed to abnormal neuronal connectivity, but the molecular bases of these behavioral and brain phenotypes are largely unknown. Human genetic studies have implicated PCDH10, a member of the δ2 subfamily of nonclustered protocadherin genes, in ASD. PCDH10 expression is enriched in the basolateral amygdala, a brain region implicated in the social deficits of ASD. Previous reports indicate that Pcdh10 plays a role in axon outgrowth and glutamatergic synapse elimination, but its roles in social behaviors and amygdala neuronal connectivity are unknown. We hypothesized that haploinsufficiency of Pcdh10 would reduce social approach behavior and alter the structure and function of amygdala circuits. Mice lacking one copy of Pcdh10 (Pcdh10 +/- ) and wild-type littermates were assessed for social approach and other behaviors. The lateral/basolateral amygdala was assessed for dendritic spine number and morphology, and amygdala circuit function was studied using voltage-sensitive dye imaging. Expression of Pcdh10 and N-methyl-D-aspartate receptor (NMDAR) subunits was assessed in postsynaptic density fractions of the amygdala. Male Pcdh10 +/- mice have reduced social approach behavior, as well as impaired gamma synchronization, abnormal spine morphology, and reduced levels of NMDAR subunits in the amygdala. Social approach deficits in Pcdh10 +/- male mice were rescued with acute treatment with the NMDAR partial agonist d-cycloserine. Our studies reveal that male Pcdh10 +/- mice have synaptic and behavioral deficits, and establish Pcdh10 +/- mice as a novel genetic model for investigating neural circuitry and behavioral changes relevant to ASD. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Sequence of information processing for emotions based on the anatomic dialogue between prefrontal cortex and amygdala.

PubMed

Ghashghaei, H T; Hilgetag, C C; Barbas, H

2007-02-01

The prefrontal cortex and the amygdala have synergistic roles in regulating purposive behavior, effected through bidirectional pathways. Here we investigated the largely unknown extent and laminar relationship of prefrontal input-output zones linked with the amygdala using neural tracers injected in the amygdala in rhesus monkeys. Prefrontal areas varied vastly in their connections with the amygdala, with the densest connections found in posterior orbitofrontal and posterior medial cortices, and the sparsest in anterior lateral prefrontal areas, especially area 10. Prefrontal projection neurons directed to the amygdala originated in layer 5, but significant numbers were also found in layers 2 and 3 in posterior medial and orbitofrontal cortices. Amygdalar axonal terminations in prefrontal cortex were most frequently distributed in bilaminar bands in the superficial and deep layers, by columns spanning the entire cortical depth, and less frequently as small patches centered in the superficial or deep layers. Heavy terminations in layers 1-2 overlapped with calbindin-positive inhibitory neurons. A comparison of the relationship of input to output projections revealed that among the most heavily connected cortices, cingulate areas 25 and 24 issued comparatively more projections to the amygdala than they received, whereas caudal orbitofrontal areas were more receivers than senders. Further, there was a significant relationship between the proportion of 'feedforward' cortical projections from layers 2-3 to 'feedback' terminations innervating the superficial layers of prefrontal cortices. These findings indicate that the connections between prefrontal cortices and the amygdala follow similar patterns as corticocortical connections, and by analogy suggest pathways underlying the sequence of information processing for emotions.

Amygdala volume mediates the relationship between externalizing symptoms and daily smoking in adolescence: A prospective study.

PubMed

Cheetham, Ali; Allen, Nicholas B; Whittle, Sarah; Simmons, Julian; Yücel, Murat; Lubman, Dan I

2018-06-30

The current study examined amygdala and orbitofrontal cortex (OFC) volumes as mediators of the relationship between externalizing symptoms and daily smoking in adolescence. Externalizing behaviors are among the most robust predictors of adolescent smoking, and there is emerging evidence that volume reductions in the amygdala and OFC are associated with risk for substance misuse as well as aggressive, impulsive, and disinhibited tendencies. Using a prospective longitudinal design, we recruited 109 adolescents who provided data on brain volume and externalizing behaviors at age 12, and on smoking at age 18. Daily smoking at age 18 (n = 27) was predicted by externalizing behaviors (measured by the self-report Child Behavior Checklist, CBCL) as well as smaller right amygdala volumes. Right amygdala volumes mediated the relationship between externalizing symptoms and later smoking. These findings provide important insight into the neurobiological risk factors associated with adolescent smoking, and, more generally, into factors that may be associated with vulnerability to substance use disorders and related psychopathology. Copyright © 2018 Elsevier B.V. All rights reserved.

Sex Differences and Laterality in Astrocyte Number and Complexity in the Adult Rat Medial Amygdala

PubMed Central

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

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

ERIC Educational Resources Information Center

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…

Medial Amygdala Lesions Selectively Block Aversive Pavlovian–Instrumental Transfer in Rats

PubMed Central

McCue, Margaret G.; LeDoux, Joseph E.; Cain, Christopher K.

2014-01-01

Pavlovian conditioned stimuli (CSs) play an important role in the reinforcement and motivation of instrumental active avoidance (AA). Conditioned threats can also invigorate ongoing AA responding [aversive Pavlovian–instrumental transfer (PIT)]. The neural circuits mediating AA are poorly understood, although lesion studies suggest that lateral, basal, and central amygdala nuclei, as well as infralimbic prefrontal cortex, make key, and sometimes opposing, contributions. We recently completed an extensive analysis of brain c-Fos expression in good vs. poor avoiders following an AA test (Martinez et al., 2013, Learning and Memory). This analysis identified medial amygdala (MeA) as a potentially important region for Pavlovian motivation of instrumental actions. MeA is known to mediate defensive responding to innate threats as well as social behaviors, but its role in mediating aversive Pavlovian–instrumental interactions is unknown. We evaluated the effect of MeA lesions on Pavlovian conditioning, Sidman two-way AA conditioning (shuttling) and aversive PIT in rats. Mild footshocks served as the unconditioned stimulus in all conditioning phases. MeA lesions had no effect on AA but blocked the expression of aversive PIT and 22 kHz ultrasonic vocalizations in the AA context. Interestingly, MeA lesions failed to affect Pavlovian freezing to discrete threats but reduced freezing to contextual threats when assessed outside of the AA chamber. These findings differentiate MeA from lateral and central amygdala, as lesions of these nuclei disrupt Pavlovian freezing and aversive PIT, but have opposite effects on AA performance. Taken together, these results suggest that MeA plays a selective role in the motivation of instrumental avoidance by general or uncertain Pavlovian threats. PMID:25278858

Subpopulations of neurokinin 1 receptor-expressing neurons in the rat lateral amygdala display a differential pattern of innervation from distinct glutamatergic afferents

PubMed Central

Sreepathi, H.K.; Ferraguti, F.

2012-01-01

Substance P by acting on its preferred receptor neurokinin 1 (NK1) in the amygdala appears to be critically involved in the modulation of fear and anxiety. The present study was undertaken to identify neurochemically specific subpopulations of neuron expressing NK1 receptors in the lateral amygdaloid nucleus (LA), a key site for regulating these behaviors. We also analyzed the sources of glutamatergic inputs to these neurons. Immunofluorescence analysis of the co-expression of NK1 with calcium binding proteins in LA revealed that ∼35% of NK1-containing neurons co-expressed parvalbumin (PV), whereas no co-localization was detected in the basal amygdaloid nucleus. We also show that neurons expressing NK1 receptors in LA did not contain detectable levels of calcium/calmodulin kinase IIα, thus suggesting that NK1 receptors are expressed by interneurons. By using a dual immunoperoxidase/immunogold-silver procedure at the ultrastructural level, we found that in LA ∼75% of glutamatergic synapses onto NK1-expressing neurons were labeled for the vesicular glutamate transporter 1 indicating that they most likely are of cortical, hippocampal, or intrinsic origin. The remaining ∼25% were immunoreactive for the vesicular glutamate transporter 2 (VGluT2), and may then originate from subcortical areas. On the other hand, we could not detect VGluT2-containing inputs onto NK1/PV immunopositive neurons. Our data add to previous localization studies by describing an unexpected variation between LA and basal nucleus of the amygdala (BA) in the neurochemical phenotype of NK1-expressing neurons and reveal the relative source of glutamatergic inputs that may activate these neurons, which in turn regulate fear and anxiety responses. PMID:22210508

Exogenous determinants of early-life conditions, and mortality later in life.

PubMed

van den Berg, Gerard J; Doblhammer, Gabriele; Christensen, Kaare

2009-05-01

We analyze causal effects of conditions early in life on the individual mortality rate later in life. Conditions early in life are captured by transitory features of the macro-environment around birth, notably the state of the business cycle around birth, but also food price deviations, weather indicators, and demographic indicators. We argue that these features can only affect high-age mortality by way of the individual early-life conditions. Moreover, they are exogenous from the individual point of view, which is a methodological advantage compared to the use of unique characteristics of the newborn individual or his or her family or household as early-life indicators. We collected national annual time-series data on the above-mentioned indicators, and we combine these to the individual data records from the Danish Twin Registry covering births in 1873-1906. The empirical analyses (mostly based on the estimation of duration models) indicate a significant negative causal effect of economic conditions early in life on individual mortality rates at higher ages. If the national economic performance in the year of birth exceeds its trend value (i.e., if the business cycle is favorable) then the mortality rate later in life is lower. The implied effect on the median lifetime of those who survive until age 35 is about 10 months. A systematic empirical exploration of all macro-indicators reveals that economic conditions in the first years after birth also affect mortality rates later in life.

Executive Function Buffers the Association between Early Math and Later Academic Skills.

PubMed

Ribner, Andrew D; Willoughby, Michael T; Blair, Clancy B

2017-01-01

Extensive evidence has suggested that early academic skills are a robust indicator of later academic achievement; however, there is mixed evidence of the effectiveness of intervention on academic skills in early years to improve later outcomes. As such, it is clear there are other contributing factors to the development of academic skills. The present study tests the role of executive function (EF) (a construct made up of skills complicit in the achievement of goal-directed tasks) in predicting 5th grade math and reading ability above and beyond math and reading ability prior to school entry, and net of other cognitive covariates including processing speed, vocabulary, and IQ. Using a longitudinal dataset of N = 1292 participants representative of rural areas in two distinctive geographical parts of the United States, the present investigation finds EF at age 5 strongly predicts 5th grade academic skills, as do cognitive covariates. Additionally, investigation of an interaction between early math ability and EF reveals the magnitude of the association between early math and later math varies as a function of early EF, such that participants who have high levels of EF can "catch up" to peers who perform better on assessments of early math ability. These results suggest EF is pivotal to the development of academic skills throughout elementary school. Implications for further research and practice are discussed.

The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity

PubMed Central

Kraehenmann, Rainer; Schmidt, André; Friston, Karl; Preller, Katrin H.; Seifritz, Erich; Vollenweider, Franz X.

2015-01-01

Stimulation of serotonergic neurotransmission by psilocybin has been shown to shift emotional biases away from negative towards positive stimuli. We have recently shown that reduced amygdala activity during threat processing might underlie psilocybin's effect on emotional processing. However, it is still not known whether psilocybin modulates bottom-up or top-down connectivity within the visual-limbic-prefrontal network underlying threat processing. We therefore analyzed our previous fMRI data using dynamic causal modeling and used Bayesian model selection to infer how psilocybin modulated effective connectivity within the visual–limbic–prefrontal network during threat processing. First, both placebo and psilocybin data were best explained by a model in which threat affect modulated bidirectional connections between the primary visual cortex, amygdala, and lateral prefrontal cortex. Second, psilocybin decreased the threat-induced modulation of top-down connectivity from the amygdala to primary visual cortex, speaking to a neural mechanism that might underlie putative shifts towards positive affect states after psilocybin administration. These findings may have important implications for the treatment of mood and anxiety disorders. PMID:26909323

The mixed serotonin receptor agonist psilocybin reduces threat-induced modulation of amygdala connectivity.

PubMed

Kraehenmann, Rainer; Schmidt, André; Friston, Karl; Preller, Katrin H; Seifritz, Erich; Vollenweider, Franz X

2016-01-01

Stimulation of serotonergic neurotransmission by psilocybin has been shown to shift emotional biases away from negative towards positive stimuli. We have recently shown that reduced amygdala activity during threat processing might underlie psilocybin's effect on emotional processing. However, it is still not known whether psilocybin modulates bottom-up or top-down connectivity within the visual-limbic-prefrontal network underlying threat processing. We therefore analyzed our previous fMRI data using dynamic causal modeling and used Bayesian model selection to infer how psilocybin modulated effective connectivity within the visual-limbic-prefrontal network during threat processing. First, both placebo and psilocybin data were best explained by a model in which threat affect modulated bidirectional connections between the primary visual cortex, amygdala, and lateral prefrontal cortex. Second, psilocybin decreased the threat-induced modulation of top-down connectivity from the amygdala to primary visual cortex, speaking to a neural mechanism that might underlie putative shifts towards positive affect states after psilocybin administration. These findings may have important implications for the treatment of mood and anxiety disorders.

Early-life disruption of amphibian microbiota decreases later-life resistance to parasites.

PubMed

Knutie, Sarah A; Wilkinson, Christina L; Kohl, Kevin D; Rohr, Jason R

2017-07-20

Changes in the early-life microbiota of hosts might affect infectious disease risk throughout life, if such disruptions during formative times alter immune system development. Here, we test whether an early-life disruption of host-associated microbiota affects later-life resistance to infections by manipulating the microbiota of tadpoles and challenging them with parasitic gut worms as adults. We find that tadpole bacterial diversity is negatively correlated with parasite establishment in adult frogs: adult frogs that had reduced bacterial diversity as tadpoles have three times more worms than adults without their microbiota manipulated as tadpoles. In contrast, adult bacterial diversity during parasite exposure is not correlated with parasite establishment in adult frogs. Thus, in this experimental setup, an early-life disruption of the microbiota has lasting reductions on host resistance to infections, which is possibly mediated by its effects on immune system development. Our results support the idea that preventing early-life disruption of host-associated microbiota might confer protection against diseases later in life.Early-life microbiota alterations can affect infection susceptibility later in life, in animal models. Here, Knutie et al. show that manipulating the microbiota of tadpoles leads to increased susceptibility to parasitic infection in adult frogs, in the absence of substantial changes in the adults' microbiota.

Two consecutive pregnancies in early and late stage of amyotrophic lateral sclerosis.

PubMed

Sarafov, Stayko; Doitchinova, Maryana; Karagiozova, Zhvka; Slancheva, Boriana; Dengler, Reinhard; Petri, Susanne; Kollewe, Katja

2009-01-01

There are few reports on pregnancies in sporadic and familial amyotrophic lateral sclerosis (ALS). We report on a young woman with sporadic ALS who gave birth twice during the course of her disease. The first pregnancy occurred 13 months after the onset of symptoms, and one month after diagnosis. The pregnancy was uncomplicated and resulted in vaginal delivery of a healthy boy. Fifteen months later, when she was already bed-ridden, she became pregnant again. She received a percutaneous endoscopic gastrostomy in the 21st gestational week and underwent early Caesarean section in the 34th week of gestation. The child was ventilated for 72 h in a neonatological unit. The patient was tracheotomized and ventilated two months later, i.e. 47 months after symptom onset, and died nine months later from gastrointestinal haemorrhage. Her two children have developed without abnormalities to date. This case confirms that pregnancies in early-stage ALS can develop normally and may result in uncomplicated vaginal delivery. Pregnancies in late stages may be critical for mother and child, and early delivery by Caesarean section may become necessary although neonatal outcome can be good.

Maladaptive social information processing in childhood predicts young men’s atypical amygdala reactivity to threat

PubMed Central

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

2014-01-01

Background 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. Methods A cohort of 310 boys participated in an ongoing longitudinal study and completed questionnaires and laboratory tasks assessing their social and cognitive characteristics between 10- and 12-years-old. 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. Results 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. Conclusions Childhood social information processing and IQ predicted young men’s amygdala response to threat a decade later, which suggests that

Mandibular Symmetrical Bilateral Canine-Lateral Incisors Transposition: Its Early Diagnosis and Treatment Considerations.

PubMed

Shapira, Yehoshua; Finkelstein, Tamar; Kadry, Rana; Schonberger, Shirley; Shpack, Nir

2016-01-01

Bilateral mandibular tooth transposition is a relatively rare dental anomaly caused by distal migration of the mandibular lateral incisors and can be detected in the early mixed dentition by radiographic examination. Early diagnosis and interceptive intervention may reduce the risk of possible transposition between the mandibular canine and lateral incisor. This report illustrates the orthodontic management of bilateral mandibular canine-lateral incisor transposition. Correct positioning of the affected teeth was achieved on the left side while teeth on the right side were aligned in their transposed position. It demonstrates the outcome of good alignment of the teeth in the dental arch.

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

PubMed

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

From circuits to behaviour in the amygdala

PubMed Central

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

Framing effect following bilateral amygdala lesion.

PubMed

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.

Peripuberty stress leads to abnormal aggression, altered amygdala and orbitofrontal reactivity and increased prefrontal MAOA gene expression

PubMed Central

Márquez, C; Poirier, G L; Cordero, M I; Larsen, M H; Groner, A; Marquis, J; Magistretti, P J; Trono, D; Sandi, C

2013-01-01

Although adverse early life experiences have been found to increase lifetime risk to develop violent behaviors, the neurobiological mechanisms underlying these long-term effects remain unclear. We present a novel animal model for pathological aggression induced by peripubertal exposure to stress with face, construct and predictive validity. We show that male rats submitted to fear-induction experiences during the peripubertal period exhibit high and sustained rates of increased aggression at adulthood, even against unthreatening individuals, and increased testosterone/corticosterone ratio. They also exhibit hyperactivity in the amygdala under both basal conditions (evaluated by 2-deoxy-glucose autoradiography) and after a resident–intruder (RI) test (evaluated by c-Fos immunohistochemistry), and hypoactivation of the medial orbitofrontal (MO) cortex after the social challenge. Alterations in the connectivity between the orbitofrontal cortex and the amygdala were linked to the aggressive phenotype. Increased and sustained expression levels of the monoamine oxidase A (MAOA) gene were found in the prefrontal cortex but not in the amygdala of peripubertally stressed animals. They were accompanied by increased activatory acetylation of histone H3, but not H4, at the promoter of the MAOA gene. Treatment with an MAOA inhibitor during adulthood reversed the peripuberty stress-induced antisocial behaviors. Beyond the characterization and validation of the model, we present novel data highlighting changes in the serotonergic system in the prefrontal cortex—and pointing at epigenetic control of the MAOA gene—in the establishment of the link between peripubertal stress and later pathological aggression. Our data emphasize the impact of biological factors triggered by peripubertal adverse experiences on the emergence of violent behaviors. PMID:23321813

Peripuberty stress leads to abnormal aggression, altered amygdala and orbitofrontal reactivity and increased prefrontal MAOA gene expression.

PubMed

Márquez, C; Poirier, G L; Cordero, M I; Larsen, M H; Groner, A; Marquis, J; Magistretti, P J; Trono, D; Sandi, C

2013-01-15

Although adverse early life experiences have been found to increase lifetime risk to develop violent behaviors, the neurobiological mechanisms underlying these long-term effects remain unclear. We present a novel animal model for pathological aggression induced by peripubertal exposure to stress with face, construct and predictive validity. We show that male rats submitted to fear-induction experiences during the peripubertal period exhibit high and sustained rates of increased aggression at adulthood, even against unthreatening individuals, and increased testosterone/corticosterone ratio. They also exhibit hyperactivity in the amygdala under both basal conditions (evaluated by 2-deoxy-glucose autoradiography) and after a resident-intruder (RI) test (evaluated by c-Fos immunohistochemistry), and hypoactivation of the medial orbitofrontal (MO) cortex after the social challenge. Alterations in the connectivity between the orbitofrontal cortex and the amygdala were linked to the aggressive phenotype. Increased and sustained expression levels of the monoamine oxidase A (MAOA) gene were found in the prefrontal cortex but not in the amygdala of peripubertally stressed animals. They were accompanied by increased activatory acetylation of histone H3, but not H4, at the promoter of the MAOA gene. Treatment with an MAOA inhibitor during adulthood reversed the peripuberty stress-induced antisocial behaviors. Beyond the characterization and validation of the model, we present novel data highlighting changes in the serotonergic system in the prefrontal cortex-and pointing at epigenetic control of the MAOA gene-in the establishment of the link between peripubertal stress and later pathological aggression. Our data emphasize the impact of biological factors triggered by peripubertal adverse experiences on the emergence of violent behaviors.

Contribution of amygdala CRF neurons to chronic pain.

PubMed

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

Patterns of neural connectivity during an attention bias task moderate associations between early childhood temperament and internalizing symptoms in young adulthood.

PubMed

Hardee, Jillian E; Benson, Brenda E; Bar-Haim, Yair; Mogg, Karin; Bradley, Brendan P; Chen, Gang; Britton, Jennifer C; Ernst, Monique; Fox, Nathan A; Pine, Daniel S; Pérez-Edgar, Koraly

2013-08-15

Biased attention to threat is found in both individuals with anxiety symptoms and children with the childhood temperament of behavioral inhibition (BI). Although perturbed fronto-amygdala function is implicated in biased attention among anxious individuals, no work has examined the neural correlates of attention biases in BI. Work in this area might clarify underlying mechanisms for anxiety in a sample at risk for internalizing disorders. We examined the relations among early childhood BI, fronto-amygdala connectivity during an attention bias task in young adulthood, and internalizing symptoms, assessed in young adulthood. Children were assessed for BI at multiple age points from infancy through age seven. On the basis of a composite of observational and maternal report data, we selected 21 young adults classified as having a history of BI and 23 classified as non-BI for this study (n = 44). Participants completed an event-related functional magnetic resonance imaging attention-bias task involving threat (angry faces) and neutral trials. Internalizing symptoms were assessed by self-report and diagnostic interviews. The young adults characterized in childhood with BI exhibited greater strength in threat-related connectivity than non-behaviorally inhibited young adults. Between-group differences manifested in connections between the amygdala and two frontal regions: dorsolateral prefrontal cortex and anterior insula. Amygdala-insula connectivity also interacted with childhood BI to predict young adult internalizing symptoms. Behavioral inhibition during early childhood predicts differences as young adults in threat and attention-related fronto-amygdala connectivity. Connectivity strength, in turn, moderated the relations between early BI and later psychopathology. Copyright © 2013 Society of Biological Psychiatry. All rights reserved.

Early mathematical competencies and later achievement: insights from the Longitudinal Study of Australian Children

NASA Astrophysics Data System (ADS)

MacDonald, Amy; Carmichael, Colin

2017-11-01

International research suggests that early mathematical competence predicts later mathematical achievement. In this article, we explore the relationship between mathematical competencies at 4-5 years, as measured by teacher ratings, and later results on Years 3, 5, 7 and 9 National Assessment Program - Literacy and Numeracy (NAPLAN) numeracy tests. Data from a nationally representative sample of 2343 children participating in the Longitudinal Study of Australian Children (LSAC) are examined. In line with international studies, we report moderate correlations between preschool-entry mathematics and later NAPLAN numeracy test results. However, analysis of individual growth trajectories indicates that early mathematics predicts the initial (Year 3) level, but not subsequent growth. This suggests that early mathematical competencies are important for enhancing achievement in early schooling, but that the quality of mathematics education provided in the schooling years is critical for future development.

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

PubMed Central

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. PMID:23087626

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

PubMed

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.

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

PubMed

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 (p<0.05, corrected). In addition, rsFC between the amygdala and left middle frontal cortex was significantly decreased in depressive and manic state participants of the BD group when compared with the HC group (p<0.05, corrected). Our findings suggest that mood state during the first episodes of BD may be related to abnormality in hemispheric lateralization. The abnormalities in amygdala- 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.

Subpopulations of neurokinin 1 receptor-expressing neurons in the rat lateral amygdala display a differential pattern of innervation from distinct glutamatergic afferents.

PubMed

Sreepathi, H K; Ferraguti, F

2012-02-17

Substance P by acting on its preferred receptor neurokinin 1 (NK1) in the amygdala appears to be critically involved in the modulation of fear and anxiety. The present study was undertaken to identify neurochemically specific subpopulations of neuron expressing NK1 receptors in the lateral amygdaloid nucleus (LA), a key site for regulating these behaviors. We also analyzed the sources of glutamatergic inputs to these neurons. Immunofluorescence analysis of the co-expression of NK1 with calcium binding proteins in LA revealed that ~35% of NK1-containing neurons co-expressed parvalbumin (PV), whereas no co-localization was detected in the basal amygdaloid nucleus. We also show that neurons expressing NK1 receptors in LA did not contain detectable levels of calcium/calmodulin kinase IIα, thus suggesting that NK1 receptors are expressed by interneurons. By using a dual immunoperoxidase/immunogold-silver procedure at the ultrastructural level, we found that in LA ~75% of glutamatergic synapses onto NK1-expressing neurons were labeled for the vesicular glutamate transporter 1 indicating that they most likely are of cortical, hippocampal, or intrinsic origin. The remaining ~25% were immunoreactive for the vesicular glutamate transporter 2 (VGluT2), and may then originate from subcortical areas. On the other hand, we could not detect VGluT2-containing inputs onto NK1/PV immunopositive neurons. Our data add to previous localization studies by describing an unexpected variation between LA and basal nucleus of the amygdala (BA) in the neurochemical phenotype of NK1-expressing neurons and reveal the relative source of glutamatergic inputs that may activate these neurons, which in turn regulate fear and anxiety responses. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Disorganized Amygdala Networks in Conduct-Disordered Juvenile Offenders With Callous-Unemotional Traits.

PubMed

Aghajani, Moji; Klapwijk, Eduard T; van der Wee, Nic J; Veer, Ilya M; Rombouts, Serge A R B; Boon, Albert E; van Beelen, Peter; Popma, Arne; Vermeiren, Robert R J M; Colins, Olivier F

2017-08-15

The developmental trajectory of psychopathy seemingly begins early in life and includes the presence of callous-unemotional (CU) traits (e.g., deficient emotional reactivity, callousness) in conduct-disordered (CD) youth. Though subregion-specific anomalies in amygdala function have been suggested in CU pathophysiology among antisocial populations, system-level studies of CU traits have typically examined the amygdala as a unitary structure. Hence, nothing is yet known of how amygdala subregional network function may contribute to callous-unemotionality in severely antisocial people. We addressed this important issue by uniquely examining the intrinsic functional connectivity of basolateral amygdala (BLA) and centromedial amygdala (CMA) networks across three matched groups of juveniles: CD offenders with CU traits (CD/CU+; n = 25), CD offenders without CU traits (CD/CU-; n = 25), and healthy control subjects (n = 24). We additionally examined whether perturbed amygdala subregional connectivity coincides with altered volume and shape of the amygdaloid complex. Relative to CD/CU- and healthy control youths, CD/CU+ youths showed abnormally increased BLA connectivity with a cluster that included both dorsal and ventral portions of the anterior cingulate and medial prefrontal cortices, along with posterior cingulate, sensory associative, and striatal regions. In contrast, compared with CD/CU- and healthy control youths, CD/CU+ youths showed diminished CMA connectivity with ventromedial/orbitofrontal regions. Critically, these connectivity changes coincided with local hypotrophy of BLA and CMA subregions (without being statistically correlated) and were associated to more severe CU symptoms. These findings provide unique insights into a putative mechanism for perturbed attention-emotion interactions, which could bias salience processing and associative learning in youth with CD/CU+. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights

School Age Outcomes of Children Diagnosed Early and Later with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Clark, Megan Louise Erin; Vinen, Zoe; Barbaro, Josephine; Dissanayake, Cheryl

2018-01-01

Early diagnosis of Autism Spectrum Disorder is considered best practice, increasing access to early intervention. Yet, many children are diagnosed after 3-years. The current study investigated the school age outcomes of children who received an early and later diagnosis of ASD. The cognitive and behavioural outcomes of children diagnosed early (n…

Preschool Anxiety Disorders Predict Different Patterns of Amygdala-Prefrontal Connectivity at School-Age

PubMed Central

Carpenter, Kimberly L. H.; Angold, Adrian; Chen, Nan-Kuei; Copeland, William E.; Gaur, Pooja; Pelphrey, Kevin; Song, Allen W.; Egger, Helen L.

2015-01-01

Objective In this prospective, longitudinal study of young children, we examined whether a history of preschool generalized anxiety, separation anxiety, and/or social phobia is associated with amygdala-prefrontal dysregulation at school-age. As an exploratory analysis, we investigated whether distinct anxiety disorders differ in the patterns of this amygdala-prefrontal dysregulation. Methods Participants were children taking part in a 5-year study of early childhood brain development and anxiety disorders. Preschool symptoms of generalized anxiety, separation anxiety, and social phobia were assessed with the Preschool Age Psychiatric Assessment (PAPA) in the first wave of the study when the children were between 2 and 5 years old. The PAPA was repeated at age 6. We conducted functional MRIs when the children were 5.5 to 9.5 year old to assess neural responses to viewing of angry and fearful faces. Results A history of preschool social phobia predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces. Preschool generalized anxiety predicted less functional connectivity between the amygdala and dorsal prefrontal cortices in response to fearful faces. Finally, a history of preschool separation anxiety predicted less school-age functional connectivity between the amygdala and the ventral prefrontal cortices to angry faces and greater school-age functional connectivity between the amygdala and dorsal prefrontal cortices to angry faces. Conclusions Our results suggest that there are enduring neurobiological effects associated with a history of preschool anxiety, which occur over-and-above the effect of subsequent emotional symptoms. Our results also provide preliminary evidence for the neurobiological differentiation of specific preschool anxiety disorders. PMID:25625285

Lateralization of ERPs to speech and handedness in the early development of Autism Spectrum Disorder.

PubMed

Finch, Kayla H; Seery, Anne M; Talbott, Meagan R; Nelson, Charles A; Tager-Flusberg, Helen

2017-01-01

Language is a highly lateralized function, with typically developing individuals showing left hemispheric specialization. Individuals with autism spectrum disorder (ASD) often show reduced or reversed hemispheric lateralization in response to language. However, it is unclear when this difference emerges and whether or not it can serve as an early ASD biomarker. Additionally, atypical language lateralization is not specific to ASD as it is also seen more frequently in individuals with mixed- and left-handedness. Here, we examined early asymmetry patterns measured through neural responses to speech sounds at 12 months and behavioral observations of handedness at 36 months in children with and without ASD. Three different groups of children participated in the study: low-risk controls (LRC), high risk for ASD (HRA; infants with older sibling with ASD) without ASD, and HRA infants who later receive a diagnosis of ASD (ASD). Event-related potentials (ERPs) to speech sounds were recorded at 12 months. Utilizing a novel observational approach, handedness was measured by hand preference on a variety of behaviors at 36 months. At 12 months, lateralization patterns of ERPs to speech stimuli differed across the groups with the ASD group showing reversed lateralization compared to the LRC group. At 36 months, factor analysis of behavioral observations of hand preferences indicated a one-factor model with medium to high factor loadings. A composite handedness score was derived; no group differences were observed. There was no association between lateralization to speech at 12 months and handedness at 36 months in the LRC and HRA groups. However, children with ASD did show an association such that infants with lateralization patterns more similar to the LRC group at 12 months were stronger right-handers at 36 months. These results highlight early developmental patterns that might be specific to ASD, including a potential early biomarker of reversed lateralization to

How Important Is Where You Start? Early Mathematics Knowledge and Later School Success

ERIC Educational Resources Information Center

Claessens, Amy; Engel, Mimi

2013-01-01

Background: Children's early skills are essential for their later success in school. Recent evidence highlights the importance of early mathematics, relative to reading and socioemotional skills, for elementary school achievement. Key advocacy groups for both early childhood and mathematics education have issued position statements on the…

Predictors of Early versus Later Spelling Development in Danish

ERIC Educational Resources Information Center

Nielsen, Anne-Mette Veber; Juul, Holger

2016-01-01

The present study examined phoneme awareness, phonological short term memory, letter knowledge, rapid automatized naming (RAN), and visual-verbal paired associate learning (PAL) as longitudinal predictors of spelling skills in an early phase (Grade 2) and a later phase (Grade 5) of development in a sample of 140 children learning to spell in the…

Genetic identification of the central nucleus and other components of the central extended amygdala in chicken during development

PubMed Central

Vicario, Alba; Abellán, Antonio; Desfilis, Ester; Medina, Loreta

2014-01-01

In mammals, the central extended amygdala shows a highly complex organization, and is essential for animal survival due to its implication in fear responses. However, many aspects of its evolution are still unknown, and this structure is especially poorly understood in birds. The aim of this study was to define the central extended amygdala in chicken, by means of a battery of region-specific transcription factors (Pax6, Islet1, Nkx2.1) and phenotypic markers that characterize these different subdivisions in mammals. Our results allowed the identification of at least six distinct subdivisions in the lateral part of the avian central extended amygdala: (1) capsular central subdivision; (2) a group of intercalated-like cell patches; (3) oval central nucleus; (4) peri-intrapeduncular (peri-INP) island field; (5) perioval zone; and (6) a rostral part of the subpallial extended amygdala. In addition, we identified three subdivisions of the laterodorsal bed nucleus of the stria terminalis (BSTLd) belonging to the medial region of the chicken central extended amygdala complex. Based on their genetic profile, cellular composition and apparent embryonic origin of the cells, we discuss the similarity of these different subdivisions of chicken with different parts of the mouse central amygdala and surrounding cell masses, including the intercalated amygdalar masses and the sublenticular part of the central extended amygdala. Most of the subdivisions include various subpopulations of cells that apparently originate in the dorsal striatal, ventral striatal, pallidal, and preoptic embryonic domains, reaching their final location by either radial or tangential migrations. Similarly to mammals, the central amygdala and BSTLd of chicken project to the hypothalamus, and include different neurons expressing proenkephalin, corticotropin-releasing factor, somatostatin or tyrosine hydroxylase, which may be involved in the control of different aspects of fear/anxiety-related behavior

Angiotensin-(1-7)-Induced Plasticity Changes in the Lateral Amygdala Are Mediated by COX-2 and NO

ERIC Educational Resources Information Center

Albrecht, Doris

2007-01-01

It is known from studies outside the brain that upon binding to its receptor, angiotensin-(1-7) elicits the release of prostanoids and nitric oxide (NO). Cyclooxygenase (COX) is a key enzyme that converts arachidonic acid to prostaglandins. Since there are no data available so far on the role of COX-2 in the amygdala, in a first step we…

Abnormal Amygdala and Prefrontal Cortex Activation to Facial Expressions in Pediatric Bipolar Disorder

ERIC Educational Resources Information Center

Garrett, Amy S.; Reiss, Allan L.; Howe, Meghan E.; Kelley, Ryan G.; Singh, Manpreet K.; Adleman, Nancy E.; Karchemskiy, Asya; Chang, Kiki D.

2012-01-01

Objective: Previous functional magnetic resonance imaging (fMRI) studies in pediatric bipolar disorder (BD) have reported greater amygdala and less dorsolateral prefrontal cortex (DLPFC) activation to facial expressions compared to healthy controls. The current study investigates whether these differences are associated with the early or late…

Acute in utero exposure to lipopolysaccharide induces inflammation in the pre- and postnatal brain and alters the glial cytoarchitecture in the developing amygdala.

PubMed

O'Loughlin, Elaine; Pakan, Janelle M P; Yilmazer-Hanke, Deniz; McDermott, Kieran W

2017-11-02

Maternal immune activation (MIA) is a risk factor for neurodevelopmental disorders such as autism and schizophrenia, as well as seizure development. The amygdala is a brain region involved in the regulation of emotions, and amygdalar maldevelopment due to infection-induced MIA may lead to amygdala-related disorders. MIA priming of glial cells during development has been linked to abnormalities seen in later life; however, little is known about its effects on amygdalar biochemical and cytoarchitecture integrity. Time-mated C57BL6J mice were administered a single intraperitoneal injection of 50 μg/kg lipopolysaccharide (LPS) on embryonic day 12 (E12), and the effects of MIA were examined at prenatal, neonatal, and postnatal developmental stages using immunohistochemistry, real-time quantitative PCR, and stereological quantification of cytoarchitecture changes. Fetal brain expression of pro-inflammatory cytokines (IL-1β, TNFα, and IL-6) was significantly upregulated at 4 h postinjection (E12) and remained elevated until the day of birth (P0). In offspring from LPS-treated dams, amygdalar expression of pro-inflammatory cytokines was also increased on day 7 (P7) and expression was sustained on day 40 (P40). Toll-like receptor (TLR-2, TLR-4) expression was also upregulated in fetal brains and in the postnatal amygdala in LPS-injected animals. Morphological examination of cells expressing ionized calcium-binding adaptor molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) suggested long-term microglial activation and astrogliosis in postnatal amygdalar regions. Our results showed that LPS-induced MIA at E12 induces a pro-inflammatory cytokine profile in the developing fetal brain that continues up to early adulthood in the amygdala. Inflammation elicited by MIA may activate cells in the fetal brain and lead to alterations in glial (microglia and astrocyte) cells observed in the postnatal amygdala. Moreover, increased pro-inflammatory cytokines and their

Contributions of the Central Extended Amygdala to Fear and Anxiety

PubMed Central

2016-01-01

It is widely thought that phasic and sustained responses to threat reflect dissociable circuits centered on the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST), the two major subdivisions of the central extended amygdala. Early versions of this hypothesis remain highly influential and have been incorporated into the National Institute of Mental Health Research Research Domain Criteria framework. However, new observations encourage a different perspective. Anatomical studies show that the Ce and BST form a tightly interconnected unit, where different kinds of threat-relevant information can be integrated and used to assemble states of fear and anxiety. Imaging studies in humans and monkeys show that the Ce and BST exhibit similar functional profiles. Both regions are sensitive to a range of aversive challenges, including uncertain or temporally remote threat; both covary with concurrent signs and symptoms of fear and anxiety; both show phasic responses to short-lived threat; and both show heightened activity during sustained exposure to diffusely threatening contexts. Mechanistic studies demonstrate that both regions can control the expression of fear and anxiety during sustained exposure to diffuse threat. These observations compel a reconsideration of the central extended amygdala's contributions to fear and anxiety and its role in neuropsychiatric disease. PMID:27488625

ADRA2B genotype differentially modulates stress-induced neural activity in the amygdala and hippocampus during emotional memory retrieval.

PubMed

Li, Shijia; Weerda, Riklef; Milde, Christopher; Wolf, Oliver T; Thiel, Christiane M

2015-02-01

Noradrenaline interacts with stress hormones in the amygdala and hippocampus to enhance emotional memory consolidation, but the noradrenergic-glucocorticoid interaction at retrieval, where stress impairs memory, is less understood. We used a genetic neuroimaging approach to investigate whether a genetic variation of the noradrenergic system impacts stress-induced neural activity in amygdala and hippocampus during recognition of emotional memory. This study is based on genotype-dependent reanalysis of data from our previous publication (Li et al. Brain Imaging Behav 2014). Twenty-two healthy male volunteers were genotyped for the ADRA2B gene encoding the α2B-adrenergic receptor. Ten deletion carriers and 12 noncarriers performed an emotional face recognition task, while their brain activity was measured with fMRI. During encoding, 50 fearful and 50 neutral faces were presented. One hour later, they underwent either an acute stress (Trier Social Stress Test) or a control procedure which was followed immediately by the retrieval session, where participants had to discriminate between 100 old and 50 new faces. A genotype-dependent modulation of neural activity at retrieval was found in the bilateral amygdala and right hippocampus. Deletion carriers showed decreased neural activity in the amygdala when recognizing emotional faces in control condition and increased amygdala activity under stress. Noncarriers showed no differences in emotional modulated amygdala activation under stress or control. Instead, stress-induced increases during recognition of emotional faces were present in the right hippocampus. The genotype-dependent effects of acute stress on neural activity in amygdala and hippocampus provide evidence for noradrenergic-glucocorticoid interaction in emotional memory retrieval.

Larger amygdala but no change in hippocampal volume in 10-year-old children exposed to maternal depressive symptomatology since birth

PubMed Central

Lupien, Sonia J.; Parent, Sophie; Evans, Alan C.; Tremblay, Richard E.; Zelazo, Philip David; Corbo, Vincent; Pruessner, Jens C.; Séguin, Jean R.

2011-01-01

Maternal separation and poor maternal care in animals have been shown to have important effects on the developing hippocampus and amygdala. In humans, children exposed to abuse/maltreatment or orphanage rearing do not present changes in hippocampal volumes. However, children reared in orphanages present enlarged amygdala volumes, suggesting that the amygdala may be particularly sensitive to severely disturbed (i.e., discontinous, neglectful) care in infancy. Maternal depressive symptomatology has been associated with reductions in overall sensitivity to the infant, and with an increased rate of withdrawn, disengaged behaviors. To determine if poor maternal care associated with maternal depressive symptomatology has a similar pattern of association to the volumes of the hippocampus and amygdala in children, as is the case for severely disturbed infant care (orphanage rearing), we measured hippocampal and amygdala volumes as well as stress hormone (glucocorticoid) levels in children exposed (n = 17) or not (n = 21) to maternal depressive symptomatology since birth. Results revealed no group difference in hippocampal volumes, but larger left and right amygdala volumes and increased levels of glucocorticoids in the children of mothers presenting depressive symptomatology since birth. Moreover, a significant positive correlation was observed between mothers' mean depressive scores and amygdala volumes in their children. The results of this study suggest that amygdala volume in human children may represent an early marker of biological sensitivity to quality of maternal care. PMID:21844357

Amygdala Volumetry in Patients with Temporal Lobe Epilepsy and Normal Magnetic Resonance Imaging

PubMed Central

Singh, Paramdeep; Kaur, Rupinderjeet; Saggar, Kavita; Singh, Gagandeep; Aggarwal, Simmi

2016-01-01

Summary Background It has been suggested that the pathophysiology of temporal lobe epilepsy may relate to abnormalities in various brain structures, including the amygdala. Patients with mesial temporal lobe epilepsy (MTLE) without MRI abnormalities (MTLE-NMRI) represent a challenge for diagnosis of the underlying abnormality and for presurgical evaluation. To date, however, only few studies have used quantitative structural Magnetic Resonance Imaging-based techniques to examine amygdalar pathology in these patients. Material/Methods Based on clinical examination, 24-hour video EEG recordings and MRI findings, 50 patients with EEG lateralized TLE and normal structural Magnetic Resonance Imaging results were included in this study. Volumetric magnetic resonance imaging (MRI) studies of the amygdalas and hippocampi were conducted in 50 non-epileptic controls (age 7–79 years) and 50 patients with MTLE with normal MRI on a 1.5-Tesla scanner. Visual assessment and amygdalar volumetry were performed on oblique coronal T2W and T1W MP-RAGE images respectively. The T2 relaxation times were measured using the 16-echo Carr-Purcell-Meiboom-Gill sequence (TE, 22–352). Volumetric data were normalized for variation in head size between individuals. Results were assessed by SSPS statistic program. Results Individual manual volumetric analysis confirmed statistically significant amygdala enlargement (AE) in eight (16%) patients. Overall, among all patients with AE and a defined epileptic focus, 7 had predominant increased volume ipsilateral to the epileptic focus. The T2 relaxometry demonstrated no hyperintense signal of the amygdala in any patient with significant AE. Conclusions This paper presented AE in a few patients with TLE and normal MRI. These findings support the hypothesis that there might be a subgroup of patients with MTLE-NMRI in which the enlarged amygdala could be related to the epileptogenic process. PMID:27231493

Unseen fearful faces promote amygdala guidance of attention.

PubMed

Troiani, Vanessa; Price, Elinora T; Schultz, Robert T

2014-02-01

Little is known about the network of brain regions activated prior to explicit awareness of emotionally salient social stimuli. We investigated this in a functional magnetic resonance imaging study using a technique that combined elements of binocular rivalry and motion flash suppression in order to prevent awareness of fearful faces and houses. We found increased left amygdala and fusiform gyrus activation for fearful faces compared to houses, despite suppression from awareness. Psychophysiological interaction analyses showed that amygdala activation was associated with task-specific (fearful faces greater than houses) modulation of an attention network, including bilateral pulvinar, bilateral insula, left frontal eye fields, left intraparietal sulcus and early visual cortex. Furthermore, we report an unexpected main effect of increased left parietal cortex activation associated with suppressed fearful faces compared to suppressed houses. This parietal finding is the first report of increased dorsal stream activation for a social object despite suppression, which suggests that information can reach parietal cortex for a class of emotionally salient social objects, even in the absence of awareness.

Individualized Functional Parcellation of the Human Amygdala Using a Semi-supervised Clustering Method: A 7T Resting State fMRI Study.

PubMed

Zhang, Xianchang; Cheng, Hewei; Zuo, Zhentao; Zhou, Ke; Cong, Fei; Wang, Bo; Zhuo, Yan; Chen, Lin; Xue, Rong; Fan, Yong

2018-01-01

The amygdala plays an important role in emotional functions and its dysfunction is considered to be associated with multiple psychiatric disorders in humans. Cytoarchitectonic mapping has demonstrated that the human amygdala complex comprises several subregions. However, it's difficult to delineate boundaries of these subregions in vivo even if using state of the art high resolution structural MRI. Previous attempts to parcellate this small structure using unsupervised clustering methods based on resting state fMRI data suffered from the low spatial resolution of typical fMRI data, and it remains challenging for the unsupervised methods to define subregions of the amygdala in vivo . In this study, we developed a novel brain parcellation method to segment the human amygdala into spatially contiguous subregions based on 7T high resolution fMRI data. The parcellation was implemented using a semi-supervised spectral clustering (SSC) algorithm at an individual subject level. Under guidance of prior information derived from the Julich cytoarchitectonic atlas, our method clustered voxels of the amygdala into subregions according to similarity measures of their functional signals. As a result, three distinct amygdala subregions can be obtained in each hemisphere for every individual subject. Compared with the cytoarchitectonic atlas, our method achieved better performance in terms of subregional functional homogeneity. Validation experiments have also demonstrated that the amygdala subregions obtained by our method have distinctive, lateralized functional connectivity (FC) patterns. Our study has demonstrated that the semi-supervised brain parcellation method is a powerful tool for exploring amygdala subregional functions.

Enhanced prefrontal-amygdala connectivity following childhood adversity as a protective mechanism against internalizing in adolescence.

PubMed

Herringa, Ryan J; Burghy, Cory A; Stodola, Diane E; Fox, Michelle E; Davidson, Richard J; Essex, Marilyn J

2016-07-01

Much research has focused on the deleterious neurobiological effects of childhood adversity that may underlie internalizing disorders. While most youth show emotional adaptation following adversity, the corresponding neural mechanisms remain poorly understood. In this longitudinal community study, we examined the associations among childhood family adversity, adolescent internalizing symptoms, and their interaction on regional brain activation and amygdala/hippocampus functional connectivity during emotion processing in 132 adolescents. Consistent with prior work, childhood adversity predicted heightened amygdala reactivity to negative, but not positive, images in adolescence. However, amygdala reactivity was not related to internalizing symptoms. Furthermore, childhood adversity predicted increased fronto-amygdala connectivity to negative, but not positive, images, yet only in lower internalizing adolescents. Childhood adversity also predicted increased fronto-hippocampal connectivity to negative images, but was not moderated by internalizing. These findings were unrelated to adolescence adversity or externalizing symptoms, suggesting specificity to childhood adversity and adolescent internalizing. Together, these findings suggest that adaptation to childhood adversity is associated with augmentation of fronto-subcortical circuits specifically for negative emotional stimuli. Conversely, insufficient enhancement of fronto-amygdala connectivity, with increasing amygdala reactivity, may represent a neural signature of vulnerability for internalizing by late adolescence. These findings implicate early childhood as a critical period in determining the brain's adaptation to adversity, and suggest that even normative adverse experiences can have significant impact on neurodevelopment and functioning. These results offer potential neural mechanisms of adaptation and vulnerability which could be used in the prediction of risk for psychopathology following childhood

Previous Institutionalization Is Followed by Broader Amygdala-Hippocampal-PFC Network Connectivity during Aversive Learning in Human Development.

PubMed

Silvers, Jennifer A; Lumian, Daniel S; Gabard-Durnam, Laurel; Gee, Dylan G; Goff, Bonnie; Fareri, Dominic S; Caldera, Christina; Flannery, Jessica; Telzer, Eva H; Humphreys, Kathryn L; Tottenham, Nim

2016-06-15

Early institutional care can be profoundly stressful for the human infant, and, as such, can lead to significant alterations in brain development. In animal models, similar variants of early adversity have been shown to modify amygdala-hippocampal-prefrontal cortex development and associated aversive learning. The current study examined this rearing aberration in human development. Eighty-nine children and adolescents who were either previously institutionalized (PI youth; N = 46; 33 females and 13 males; age range, 7-16 years) or were raised by their biological parents from birth (N = 43; 22 females and 21 males; age range, 7-16 years) completed an aversive-learning paradigm while undergoing functional neuroimaging, wherein visual cues were paired with either an aversive sound (CS+) or no sound (CS-). For the PI youth, better aversive learning was associated with higher concurrent trait anxiety. Both groups showed robust learning and amygdala activation for CS+ versus CS- trials. However, PI youth also exhibited broader recruitment of several regions and increased hippocampal connectivity with prefrontal cortex. Stronger connectivity between the hippocampus and ventromedial PFC predicted significant improvements in future anxiety (measured 2 years later), and this was particularly true within the PI group. These results suggest that for humans as well as for other species, early adversity alters the neurobiology of aversive learning by engaging a broader prefrontal-subcortical circuit than same-aged peers. These differences are interpreted as ontogenetic adaptations and potential sources of resilience. Prior institutionalization is a significant form of early adversity. While nonhuman animal research suggests that early adversity alters aversive learning and associated neurocircuitry, no prior work has examined this in humans. Here, we show that youth who experienced prior institutionalization, but not comparison youth, recruit the hippocampus during aversive

Lifespan anxiety is reflected in human amygdala cortical connectivity

PubMed Central

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

Subcortical afferent connections of the amygdala in the monkey

NASA Technical Reports Server (NTRS)

Mehler, W. R.

1980-01-01

The cells of origin of the afferent connections of the amygdala in the rhesus and squirrel monkeys are determined according to the retrograde axonal transport of the enzyme horseradish peroxidase injected into various quadrants of the amygdala. Analysis of the distribution of enzyme-labeled cells reveals afferent amygdalar connections with the ipsilateral halves of the midline nucleus paraventricularis thalami and both the parvo- and magnocellular parts of the nucleus subparafascicularis in the dorsal thalamus, all the subdivisions of the midline nucleus centralis complex, the nucleus reuniens ventralis and the nucleus interventralis. The largest populations of enzyme-labeled cells in the hypothalamus are found to lie in the middle and posterior parts of the ipsilateral, lateral hypothalamus and the ventromedial hypothalamic nucleus, with scattered cells in the supramammillary and dorsomedial nuclei and the posterior hypothalamic area, Tsai's ventral tegmental area, the rostral and caudal subdivisions of the nucleus linearis in the midbrain and the dorsal raphe nucleus. The most conspicuous subdiencephalic source of amygdalar afferent connections is observed to be the pars lateralis of the nucleus parabrachialis in the dorsolateral pontine tegmentum, with a few labeled cells differentiated from pigmented cells in the locus coeruleus.

A model of differential amygdala activation in psychopathy.

PubMed

Moul, Caroline; Killcross, Simon; Dadds, Mark R

2012-10-01

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 passive avoidance, and response-reversal learning tasks. Evidence for amygdala dysfunction in psychopathy is considered with regard to these deficits; however, the idea of unified amygdala function is untenable. A model of differential amygdala activation in which the basolateral amygdala (BLA) is underactive while the activity of the central amygdala (CeA) is of average to above average levels is proposed to provide a more accurate and up-to-date account for the specific cognitive and emotional deficits found in psychopathy. In addition, the model provides a mechanism by which attentional-based models and emotion-based models of psychopathy can coexist. Data to support the differential amygdala activation model are provided from studies from both human and animal research. Supporting evidence concerning some of the neurochemicals implicated in psychopathy is then reviewed. Implications of the model and areas of future research are discussed. PsycINFO Database Record (c) 2012 APA, all rights reserved.

Context conditioning and extinction in humans: differential contribution of the hippocampus, amygdala and prefrontal cortex

PubMed Central

Lang, Simone; Kroll, Alexander; Lipinski, Slawomira J; Wessa, Michèle; Ridder, Stephanie; Christmann, Christoph; Schad, Lothar R; Flor, Herta

2009-01-01

Functional magnetic resonance imaging was used to investigate the role of the hippocampus, amygdala and medial prefrontal cortex (mPFC) in a contextual conditioning and extinction paradigm provoking anxiety. Twenty-one healthy persons participated in a differential context conditioning procedure with two different background colours as contexts. During acquisition increased activity to the conditioned stimulus (CS+) relative to the CS− was found in the left hippocampus and anterior cingulate cortex (ACC). The amygdala, insula and inferior frontal cortex were differentially active during late acquisition. Extinction was accompanied by enhanced activation to CS+ vs. CS− in the dorsal anterior cingulate cortex (dACC). The results are in accordance with animal studies and provide evidence for the important role of the hippocampus in contextual learning in humans. Connectivity analyses revealed correlated activity between the left posterior hippocampus and dACC (BA32) during early acquisition and the dACC, left posterior hippocampus and right amygdala during extinction. These data are consistent with theoretical models that propose an inhibitory effect of the mPFC on the amygdala. The interaction of the mPFC with the hippocampus may reflect the context-specificity of extinction learning. PMID:19200075

Early-Onset LMNA-Associated Muscular Dystrophy with Later Involvement of Contracture.

PubMed

Lee, Younggun; Lee, Jung Hwan; Park, Hyung Jun; Choi, Young Chul

2017-10-01

The early diagnosis of LMNA-associated muscular dystrophy is important for preventing sudden arrest related to cardiac conduction block. However, diagnosing early-onset Emery-Dreifuss muscular dystrophy (EDMD) with later involvement of contracture and limb-girdle muscular dystrophy type 1B is often delayed due to heterogeneous clinical presentations. We aimed to determine the clinical features that contribute to a delayed diagnosis. We reviewed four patients who were recently diagnosed with LMNA-associated muscular dystrophy by targeted exome sequencing and who were initially diagnosed with nonspecific or other types of muscular dystrophy. Certain clinical features such as delayed contracture involvement and calf hypertrophy were found to contribute to a delayed diagnosis. Muscle biopsies were not informative for the diagnosis in these patients. Genetic testing of single or multiple genes is useful for confirming a diagnosis of LMNA-associated muscular dystrophy. Even EDMD patients could experience the later involvement of contracture, so clinicians should consider early genetic testing for patients with undiagnosed muscular dystrophy or laminopathy. Copyright © 2017 Korean Neurological Association

In monkeys making value-based decisions, amygdala neurons are sensitive to cue value as distinct from cue salience.

PubMed

Leathers, Marvin L; Olson, Carl R

2017-04-01

Neurons in the lateral intraparietal (LIP) area of macaque monkey parietal cortex respond to cues predicting rewards and penalties of variable size in a manner that depends on the motivational salience of the predicted outcome (strong for both large reward and large penalty) rather than on its value (positive for large reward and negative for large penalty). This finding suggests that LIP mediates the capture of attention by salient events and does not encode value in the service of value-based decision making. It leaves open the question whether neurons elsewhere in the brain encode value in the identical task. To resolve this issue, we recorded neuronal activity in the amygdala in the context of the task employed in the LIP study. We found that responses to reward-predicting cues were similar between areas, with the majority of reward-sensitive neurons responding more strongly to cues that predicted large reward than to those that predicted small reward. Responses to penalty-predicting cues were, however, markedly different. In the amygdala, unlike LIP, few neurons were sensitive to penalty size, few penalty-sensitive neurons favored large over small penalty, and the dependence of firing rate on penalty size was negatively correlated with its dependence on reward size. These results indicate that amygdala neurons encoded cue value under circumstances in which LIP neurons exhibited sensitivity to motivational salience. However, the representation of negative value, as reflected in sensitivity to penalty size, was weaker than the representation of positive value, as reflected in sensitivity to reward size. NEW & NOTEWORTHY This is the first study to characterize amygdala neuronal responses to cues predicting rewards and penalties of variable size in monkeys making value-based choices. Manipulating reward and penalty size allowed distinguishing activity dependent on motivational salience from activity dependent on value. This approach revealed in a previous study

Amygdala subnuclei connectivity in response to violence reveals unique influences of individual differences in psychopathic traits in a nonforensic sample.

PubMed

Yoder, Keith J; Porges, Eric C; Decety, Jean

2015-04-01

Atypical amygdala function and connectivity have reliably been associated with psychopathy. However, the amygdala is not a unitary structure. To examine how psychopathic traits in a nonforensic sample are linked to amygdala response to violence, this study used probabilistic tractography to classify amygdala subnuclei based on anatomical projections to and from amygdala subnuclei in a group of 43 male participants. The segmentation identified the basolateral complex (BLA; lateral, basal, and accessory basal subnuclei) and the central subnucleus (CE), which were used as seeds in a functional connectivity analysis to identify differences in neuronal coupling specific to observed violence. While a full amygdala seed showed significant connectivity only to right middle occipital gyrus, subnuclei seeds revealed unique connectivity patterns. BLA showed enhanced coupling with anterior cingulate and prefrontal regions, while CE showed increased connectivity with the brainstem, but reduced connectivity with superior parietal and precentral gyrus. Further, psychopathic personality factors were related to specific patterns of connectivity. Fearless Dominance scores on the psychopathic personality inventory predicted increased coupling between the BLA seed and sensory integration cortices, and increased connectivity between the CE seed and posterior insula. Conversely, Self-Centered Impulsivity scores were negatively correlated with coupling between BLA and ventrolateral prefrontal cortex, and Coldheartedness scores predicted increased functional connectivity between BLA and dorsal anterior cingulate cortex. Taken together, these findings demonstrate how subnuclei segmentations reveal important functional connectivity differences that are otherwise inaccessible. Such an approach yields a better understanding of amygdala dysfunction in psychopathy. © 2014 Wiley Periodicals, Inc.

p300/CBP Histone Acetyltransferase Activity Is Required for Newly Acquired and Reactivated Fear Memories in the Lateral Amygdala

ERIC Educational Resources Information Center

Maddox, Stephanie A.; Watts, Casey S.; Schafe, Glenn E.

2013-01-01

Modifications in chromatin structure have been widely implicated in memory and cognition, most notably using hippocampal-dependent memory paradigms including object recognition, spatial memory, and contextual fear memory. Relatively little is known, however, about the role of chromatin-modifying enzymes in amygdala-dependent memory formation.…

The Central Nucleus of the Amygdala and Corticotropin-Releasing Factor: Insights into Contextual Fear Memory

PubMed Central

Pitts, Matthew W.; Todorovic, Cedomir; Blank, Thomas; Takahashi, Lorey K.

2009-01-01

The central nucleus of the amygdala (CeA) has been traditionally viewed in fear conditioning to serve as an output neural center that transfers conditioned information formed in the basolateral amygdala to brain structures that generate emotional responses. Recent studies suggest that the CeA may also be involved in fear memory consolidation. In addition, corticotropin-releasing factor systems were shown to facilitate memory consolidation in the amygdala, which contains a high density of CRF immunoreactive cell bodies and fibers in the lateral part of the CeA (CeAl). However, the involvement of CeA CRF in contextual fear conditioning remains poorly understood. Therefore, we first conducted a series of studies using fiber-sparing lesion and reversible inactivation methods to assess the general role of the CeA in contextual fear. We then used identical training and testing procedures to compare and evaluate the specific function of CeA CRF using CRF antisense oligonucleotides (CRF ASO). Rats microinjected with ibotenic acid, muscimol, or a CRF ASO into the CeA prior to contextual fear conditioning showed typical levels of freezing during acquisition training but exhibited significant reductions in contextual freezing in a retention test 48 h later. Furthermore, CeA inactivation induced by either muscimol or CRF ASO administration immediately prior to retention testing did not impair freezing, suggesting that the previously observed retention deficits were due to inhibition of consolidation rather than fear expression. Collectively, our results suggest CeA involvement in the consolidation of contextual fear memory and specifically implicate CeA CRF as an important mediator. PMID:19494159

Basolateral amygdala response to food cues in the absence of hunger is associated with weight gain susceptibility.

PubMed

Sun, Xue; Kroemer, Nils B; Veldhuizen, Maria G; Babbs, Amanda E; de Araujo, Ivan E; Gitelman, Darren R; Sherwin, Robert S; Sinha, Rajita; Small, Dana M

2015-05-20

In rodents, food-predictive cues elicit eating in the absence of hunger (Weingarten, 1983). This behavior is disrupted by the disconnection of amygdala pathways to the lateral hypothalamus (Petrovich et al., 2002). Whether this circuit contributes to long-term weight gain is unknown. Using fMRI in 32 healthy individuals, we demonstrate here that the amygdala response to the taste of a milkshake when sated but not hungry positively predicts weight change. This effect is independent of sex, initial BMI, and total circulating ghrelin levels, but it is only present in individuals who do not carry a copy of the A1 allele of the Taq1A polymorphism. In contrast, A1 allele carriers, who have decreased D2 receptor density (Blum et al., 1996), show a positive association between caudate response and weight change. Regardless of genotype, however, dynamic causal modeling supports unidirectional gustatory input from basolateral amygdala (BLA) to hypothalamus in sated subjects. This finding suggests that, as in rodents, external cues gain access to the homeostatic control circuits of the human hypothalamus via the amygdala. In contrast, during hunger, gustatory inputs enter the hypothalamus and drive bidirectional connectivity with the amygdala. These findings implicate the BLA-hypothalamic circuit in long-term weight change related to nonhomeostatic eating and provide compelling evidence that distinct brain mechanisms confer susceptibility to weight gain depending upon individual differences in dopamine signaling. Copyright © 2015 the authors 0270-6474/15/357964-13$15.00/0.

Basolateral Amygdala Response to Food Cues in the Absence of Hunger Is Associated with Weight Gain Susceptibility

PubMed Central

Kroemer, Nils B.; Veldhuizen, Maria G.; Babbs, Amanda E.; de Araujo, Ivan E.; Gitelman, Darren R.; Sherwin, Robert S.; Sinha, Rajita

2015-01-01

In rodents, food-predictive cues elicit eating in the absence of hunger (Weingarten, 1983). This behavior is disrupted by the disconnection of amygdala pathways to the lateral hypothalamus (Petrovich et al., 2002). Whether this circuit contributes to long-term weight gain is unknown. Using fMRI in 32 healthy individuals, we demonstrate here that the amygdala response to the taste of a milkshake when sated but not hungry positively predicts weight change. This effect is independent of sex, initial BMI, and total circulating ghrelin levels, but it is only present in individuals who do not carry a copy of the A1 allele of the Taq1A polymorphism. In contrast, A1 allele carriers, who have decreased D2 receptor density (Blum et al., 1996), show a positive association between caudate response and weight change. Regardless of genotype, however, dynamic causal modeling supports unidirectional gustatory input from basolateral amygdala (BLA) to hypothalamus in sated subjects. This finding suggests that, as in rodents, external cues gain access to the homeostatic control circuits of the human hypothalamus via the amygdala. In contrast, during hunger, gustatory inputs enter the hypothalamus and drive bidirectional connectivity with the amygdala. These findings implicate the BLA–hypothalamic circuit in long-term weight change related to nonhomeostatic eating and provide compelling evidence that distinct brain mechanisms confer susceptibility to weight gain depending upon individual differences in dopamine signaling. PMID:25995480

Uncovering Camouflage: Amygdala Activation Predicts Long-Term Memory of Induced Perceptual Insight

PubMed Central

Ludmer, Rachel; Dudai, Yadin; Rubin, Nava

2012-01-01

What brain mechanisms underlie learning of new knowledge from single events? We studied encoding in long-term memory of a unique type of one-shot experience, induced perceptual insight. While undergoing an fMRI brain scan, participants viewed degraded images of real-world pictures where the underlying objects were hard to recognize (‘camouflage’), followed by brief exposures to the original images (‘solution’), which led to induced insight (“Aha!”). A week later, participants’ memory was tested; a solution image was classified as ‘remembered’ if detailed perceptual knowledge was elicited from the camouflage image alone. During encoding, subsequently remembered images enjoyed higher activity in mid-level visual cortex and medial frontal cortex, but most pronouncedly in the amygdala, whose activity could be used to predict which solutions will remain in long-term memory. Our findings extend the known roles of amygdala in memory to include promoting of long-term memory of the sudden reorganization of internal representations. PMID:21382558

Links between inflammation, amygdala reactivity, and social support in breast cancer survivors

PubMed Central

Muscatell, Keely A.; Eisenberger, Naomi I.; Dutcher, Janine M.; Cole, Steven W.; Bower, Julienne E.

2017-01-01

Psychosocial stress can affect inflammatory processes that have important consequences for cancer outcomes and the behavioral side effects of cancer treatment. To date, however, little is known about the upstream neural processes that may link psychosocial stressors and inflammation in cancer patients and survivors. To address this issue, 15 women who had been diagnosed with early-stage breast cancer and completed cancer treatment and 15 age- and ethnicity-matched women with no cancer history were recruited for a neuroimaging study. Participants provided a blood sample for levels of circulating inflammatory markers (CRP and IL-6), underwent an fMRI scan in which they completed a threat reactivity task designed to elicit activity in the amygdala, and reported their levels of perceived social attachment/ support. There were no significant differences between cancer survivors and controls in levels of CRP or IL-6, in amygdala reactivity to the socially threatening images, or in levels of perceived social support. However, results showed a strong, positive correlation between CRP concentration and left amygdala reactivity in the survivor group that was not apparent in controls. Higher levels of social support in the survivor group were also associated with reduced amygdala reactivity and CRP. These data suggest the possibility of a stronger “neural-immune pipeline” among breast cancer survivors, such that peripheral inflammation is more strongly associated with neural activity in threat-related brain regions. PMID:26384778

MRI Amygdala Volume in Williams Syndrome

ERIC Educational Resources Information Center

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…

Neonatal Amygdala Lesions Alter Mother–Infant Interactions in Rhesus Monkeys Living in a Species-Typical Social Environment

PubMed Central

Stephens, Shannon B.Z.; Sanchez, Mar; Bachevalier, Jocelyne; Wallen, Kim

2015-01-01

The current study examined the effects of neonatal amygdala lesions on mother–infant interactions in rhesus monkeys reared in large species-typical social groups. Focal observations of mother–infant interactions were collected in their social group for the first 12 months postpartum on infants that had received amygdala lesions (Neo-A) at 24–25 days of age and control infants. Early amygdala lesions resulted in subtle behavioral alterations. Neo-A females exhibited earlier emergence of independence from the mother than did control females, spending more time away from their mother, whereas Neo-A males did not. Also, a set of behaviors, including coo vocalizations, time in contact, and time away from the mother, accurately discriminated Neo-A females from control females, but not Neo-A and control males. Data suggest that neonatal amygdalectomy either reduced fear, therefore increasing exploration in females, or reduced the positive reward value of maternal contact. Unlike females, neonatal amygdala lesions had little measurable effects on male mother–infant interactions. The source of this sex difference is unknown. PMID:24986273

The caudo-ventral pallium is a novel pallial domain expressing Gdf10 and generating Ebf3-positive neurons of the medial amygdala.

PubMed

Ruiz-Reig, Nuria; Andres, Belen; Lamonerie, Thomas; Theil, Thomas; Fairén, Alfonso; Studer, Michèle

2018-06-04

In rodents, the medial nucleus of the amygdala receives direct inputs from the accessory olfactory bulbs and is mainly implicated in pheromone-mediated reproductive and defensive behaviors. The principal neurons of the medial amygdala are GABAergic neurons generated principally in the caudo-ventral medial ganglionic eminence and preoptic area. Beside GABAergic neurons, the medial amygdala also contains glutamatergic Otp-expressing neurons cells generated in the lateral hypothalamic neuroepithelium and a non-well characterized Pax6-positive population. In the present work, we describe a novel glutamatergic Ebf3-expressing neuronal subpopulation distributed within the periphery of the postero-ventral medial amygdala. These neurons are generated in a pallial domain characterized by high expression of Gdf10. This territory is topologically the most caudal tier of the ventral pallium and accordingly, we named it Caudo-Ventral Pallium (CVP). In the absence of Pax6, the CVP is disrupted and Ebf3-expressing neurons fail to be generated. Overall, this work proposes a novel model of the neuronal composition of the medial amygdala and unravels for the first time a new novel pallial subpopulation originating from the CVP and expressing the transcription factor Ebf3.

Learning from other people’s fear: amygdala-based social reference learning in social anxiety disorder

PubMed Central

Blair, K. S.; Otero, M.; Teng, C.; Geraci, M.; Lewis, E.; Hollon, N.; Blair, R. J. R.; Ernst, Monique; Grillon, C.; Pine, D. S.

2016-01-01

Background Social anxiety disorder involves fear of social objects or situations. Social referencing may play an important role in the acquisition of this fear and could be a key determinant in future biomarkers and treatment pathways. However, the neural underpinnings mediating such learning in social anxiety are unknown. Using event-related functional magnetic resonance imaging, we examined social reference learning in social anxiety disorder. Specifically, would patients with the disorder show increased amygdala activity during social reference learning, and further, following social reference learning, show particularly increased response to objects associated with other people’s negative reactions? Method A total of 32 unmedicated patients with social anxiety disorder and 22 age-, intelligence quotient- and gender-matched healthy individuals responded to objects that had become associated with others’ fearful, angry, happy or neutral reactions. Results During the social reference learning phase, a significant group × social context interaction revealed that, relative to the comparison group, the social anxiety group showed a significantly greater response in the amygdala, as well as rostral, dorsomedial and lateral frontal and parietal cortices during the social, relative to non-social, referencing trials. In addition, during the object test phase, relative to the comparison group, the social anxiety group showed increased bilateral amygdala activation to objects associated with others’ fearful reactions, and a trend towards decreased amygdala activation to objects associated with others’ happy and neutral reactions. Conclusions These results suggest perturbed observational learning in social anxiety disorder. In addition, they further implicate the amygdala and dorsomedial prefrontal cortex in the disorder, and underscore their importance in future biomarker developments. PMID:27476529

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

PubMed Central

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

2017-01-01

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. PMID:28220796

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

PubMed

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.

Contributions of the Central Extended Amygdala to Fear and Anxiety.

PubMed

Shackman, Alexander J; Fox, Andrew S

2016-08-03

It is widely thought that phasic and sustained responses to threat reflect dissociable circuits centered on the central nucleus of the amygdala (Ce) and the bed nucleus of the stria terminalis (BST), the two major subdivisions of the central extended amygdala. Early versions of this hypothesis remain highly influential and have been incorporated into the National Institute of Mental Health Research Research Domain Criteria framework. However, new observations encourage a different perspective. Anatomical studies show that the Ce and BST form a tightly interconnected unit, where different kinds of threat-relevant information can be integrated and used to assemble states of fear and anxiety. Imaging studies in humans and monkeys show that the Ce and BST exhibit similar functional profiles. Both regions are sensitive to a range of aversive challenges, including uncertain or temporally remote threat; both covary with concurrent signs and symptoms of fear and anxiety; both show phasic responses to short-lived threat; and both show heightened activity during sustained exposure to diffusely threatening contexts. Mechanistic studies demonstrate that both regions can control the expression of fear and anxiety during sustained exposure to diffuse threat. These observations compel a reconsideration of the central extended amygdala's contributions to fear and anxiety and its role in neuropsychiatric disease. Copyright © 2016 the authors 0270-6474/16/368050-14$15.00/0.

Amygdala lesions in rhesus macaques decrease attention to threat

PubMed Central

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

Amygdala Hyperactivity at Rest in Paranoid Individuals With Schizophrenia.

PubMed

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.

The role of the amygdala and the basal ganglia in visual processing of central vs. peripheral emotional content.

PubMed

Almeida, Inês; van Asselen, Marieke; Castelo-Branco, Miguel

2013-09-01

In human cognition, most relevant stimuli, such as faces, are processed in central vision. However, it is widely believed that recognition of relevant stimuli (e.g. threatening animal faces) at peripheral locations is also important due to their survival value. Moreover, task instructions have been shown to modulate brain regions involved in threat recognition (e.g. the amygdala). In this respect it is also controversial whether tasks requiring explicit focus on stimulus threat content vs. implicit processing differently engage primitive subcortical structures involved in emotional appraisal. Here we have addressed the role of central vs. peripheral processing in the human amygdala using animal threatening vs. non-threatening face stimuli. First, a simple animal face recognition task with threatening and non-threatening animal faces, as well as non-face control stimuli, was employed in naïve subjects (implicit task). A subsequent task was then performed with the same stimulus categories (but different stimuli) in which subjects were told to explicitly detect threat signals. We found lateralized amygdala responses both to the spatial location of stimuli and to the threatening content of faces depending on the task performed: the right amygdala showed increased responses to central compared to left presented stimuli specifically during the threat detection task, while the left amygdala was better prone to discriminate threatening faces from non-facial displays during the animal face recognition task. Additionally, the right amygdala responded to faces during the threat detection task but only when centrally presented. Moreover, we have found no evidence for superior responses of the amygdala to peripheral stimuli. Importantly, we have found that striatal regions activate differentially depending on peripheral vs. central processing of threatening faces. Accordingly, peripheral processing of these stimuli activated more strongly the putaminal region, while central

Amygdala reactivity to fearful faces correlates positively with impulsive aggression.

PubMed

da Cunha-Bang, Sofi; Fisher, Patrick M; Hjordt, Liv V; Holst, Klaus; Knudsen, Gitte M

2018-01-07

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 whether it is associated with amygdala reactivity to angry and fearful faces. We estimated amygdala reactivity with functional magnetic resonance imaging in 47 men with varying degree of aggressive traits (19 incarcerated violent offenders and 28 healthy controls). We modeled a composite "impulsive aggression" trait construct (LV agg ) using a linear structural equation model, with a single latent variable capturing the shared correlation between five self-report measures of trait aggression, anger and impulsivity. We tested for associations between amygdala reactivity and the LV agg , adjusting for age and group. The LV agg was significantly positively associated with amygdala reactivity to fearful (p = 0.001), but not angry faces (p = 0.9). We found no group difference in amygdala reactivity to fearful or angry faces. The findings suggest that that amygdala reactivity to fearful faces is represented by a composite index of impulsive aggression and provide evidence that impulsive aggression is associated with amygdala reactivity in response to submissive cues, i.e., fearful faces.

Early life adversity potentiates the effects of later life stress on cumulative physiological dysregulation.

PubMed

Dich, Nadya; Hansen, Åse Marie; Avlund, Kirsten; Lund, Rikke; Mortensen, Erik Lykke; Bruunsgaard, Helle; Rod, Naja Hulvej

2015-01-01

Previous research indicates that early life adversity may heighten stress reactivity and impair mechanisms for adaptive coping, suggesting that experience of stress in early life may also potentiate adults' physiological vulnerability to stress in later life. The study tested this hypothesis by investigating whether the experience of stressful events and circumstances (SEC) in childhood or adolescence amplified the effect of adulthood SEC on physiological dysregulation (allostatic load, AL) in later midlife. Observational data were used in the present study. Physiological functioning was measured in later midlife (participants' age ranged from 49 to 63 years). Both childhood/adolescence and adulthood SEC were reported retrospectively on the same occasion. Participants were 5309 Danish men and women from Copenhagen Aging and Midlife Biobank (CAMB). SEC included socioeconomic and family factors. The AL index was based on nine cardiovascular, metabolic, and immune biomarkers. Experience of SEC in both early life and adulthood independently predicted higher AL. In men, experience of SEC in early life also potentiated the effect of SEC in adulthood on AL. The results provide further insight into the mechanisms behind the "biological embedding" of childhood stress.

Amygdala, Hippocampal and Corpus Callosum Size Following Severe Early Institutional Deprivation: The English and Romanian Adoptees Study Pilot

ERIC Educational Resources Information Center

Mehta, Mitul A.; Golembo, Nicole I.; Nosarti, Chiara; Colvert, Emma; Mota, Ashley; Williams, Steven C. R.; Rutter, Michael; Sonuga-Barke, Edmund J. S.

2009-01-01

The adoption into the UK of children who have been reared in severely deprived conditions provides an opportunity to study possible association between very early negative experiences and subsequent brain development. This cross-sectional study was a pilot for a planned larger study quantifying the effects of early deprivation on later brain…

Amygdala subnuclei connectivity in response to violence reveals unique influences of individual differences in psychopathic traits in a non-forensic sample

PubMed Central

Yoder, Keith J.; Porges, Eric C.; Decety, Jean

2016-01-01

Atypical amygdala function and connectivity have reliably been associated with psychopathy. However, the amygdala is not a unitary structure. To examine how psychopathic traits in a non-forensic sample are linked to amygdala response to violence, the current study used probabilistic tractography to classify amygdala subnuclei based on anatomical projections to and from amygdala subnuclei in a group of 43 male participants. The segmentation identified the basolateral complex (BLA; lateral, basal, and accessory basal subnuclei) and the central subnucleus (CE), which were used as seeds in a functional connectivity analysis to identify differences in neuronal coupling specific to observed violence. While a full amygdala seed showed significant connectivity only to right middle occipital gyrus, subnuclei seeds revealed unique connectivity patterns. BLA showed enhanced coupling with anterior cingulate and prefrontal regions, while CE showed increased connectivity with the brainstem, but reduced connectivity with superior parietal and precentral gyrus. Further, psychopathic personality factors were related to specific patterns of connectivity. Fearless Dominance scores on the psychopathic personality inventory predicted increased coupling between the BLA seed and sensory integration cortices, and increased connectivity between the CE seed and posterior insula. Conversely, Self-Centered Impulsivity scores were negatively correlated with coupling between BLA and ventrolateral prefrontal cortex, and Coldheartedness scores predicted increased functional connectivity between BLA and dorsal anterior cingulate cortex. Taken together, these findings demonstrate how subnuclei segmentations reveal important functional connectivity differences that are otherwise inaccessible. Such an approach yields a better understanding of amygdala dysfunction in psychopathy. PMID:25557777

Moderate Alcohol Drinking and the Amygdala Proteome: Identification and Validation of Calcium/Calmodulin Dependent Kinase II and AMPA Receptor Activity as Novel Molecular Mechanisms of the Positive Reinforcing Effects of Alcohol

PubMed Central

Salling, Michael C.; Faccidomo, Sara P.; Li, Chia; Psilos, Kelly; Galunas, Christina; Spanos, Marina; Agoglia, Abigail E.; Kash, Thomas L.; Hodge, Clyde W.

2015-01-01

BACKGROUND Despite worldwide consumption of moderate amounts of alcohol, the neural mechanisms that mediate the transition from use to abuse are not fully understood. METHODS Here, we conducted a high-through put screen of the amygdala proteome in mice after moderate alcohol drinking (n = 12/group) followed by behavioral studies (n = 6–8/group) to uncover novel molecular mechanisms of the positive reinforcing properties of alcohol that strongly influence the development of addiction. RESULTS Two-dimensional difference in-gel electrophoresis with matrix assisted laser desorption ionization tandem time-of-flight identified 29 differentially expressed proteins in the amygdala of nondependent C57BL/6J mice following 24 days of alcohol drinking. Alcohol-sensitive proteins included calcium/calmodulin-dependent protein kinase II alpha (CaMKIIα) and a network of functionally linked proteins that regulate neural plasticity and glutamate-mediated synaptic activity. Accordingly, alcohol drinking increased α-amino-3-hydroxy-5-methyl-4-isooxazole receptor (AMPAR) in central amygdala (CeA) and phosphorylation of AMPAR GluA1 subunit at a CaMKII locus (GluA1-Ser831) in CeA and lateral amygdala. Further, CaMKIIα-Thr286 and GluA1-Ser831 phosphorylation was increased in CeA and lateral amygdala of mice that lever-pressed for alcohol versus the nondrug reinforcer sucrose. Mechanistic studies showed that targeted pharmacologic inhibition of amygdala CaMKII or AMPAR activity specifically inhibited the positive reinforcing properties of alcohol but not sucrose. CONCLUSIONS Moderate alcohol drinking increases the activity and function of plasticity-linked protein networks in the amygdala that regulate the positive reinforcing effects of the drug. Given the prominence of positive reinforcement in the etiology of addiction, we propose that alcohol-induced adaptations in CaMKIIα and AMPAR signaling in the amygdala may serve as a molecular gateway from use to abuse. PMID:25579851

Generous economic investments after basolateral amygdala damage.

PubMed

van Honk, Jack; Eisenegger, Christoph; Terburg, David; Stein, Dan J; Morgan, Barak

2013-02-12

Contemporary economic models hold that instrumental and impulsive behaviors underlie human social decision making. The amygdala is assumed to be involved in social-economic behavior, but its role in human behavior is poorly understood. Rodent research suggests that the basolateral amygdala (BLA) subserves instrumental behaviors and regulates the central-medial amygdala, which subserves impulsive behaviors. The human amygdala, however, typically is investigated as a single unit. If these rodent data could be translated to humans, selective dysfunction of the human BLA might constrain instrumental social-economic decisions and result in more impulsive social-economic choice behavior. Here we show that humans with selective BLA damage and a functional central-medial amygdala invest nearly 100% more money in unfamiliar others in a trust game than do healthy controls. We furthermore show that this generosity is not caused by risk-taking deviations in nonsocial contexts. Moreover, these BLA-damaged subjects do not expect higher returns or perceive people as more trustworthy, implying that their generous investments are not instrumental in nature. These findings suggest that the human BLA is essential for instrumental behaviors in social-economic interactions.

Early Developmental Conditioning of Later Health and Disease: Physiology or Pathophysiology?

PubMed Central

Hanson, M. A.; Gluckman, P. D.

2014-01-01

Extensive experimental animal studies and epidemiological observations have shown that environmental influences during early development affect the risk of later pathophysiological processes associated with chronic, especially noncommunicable, disease (NCD). This field is recognized as the developmental origins of health and disease (DOHaD). We discuss the extent to which DOHaD represents the result of the physiological processes of developmental plasticity, which may have potential adverse consequences in terms of NCD risk later, or whether it is the manifestation of pathophysiological processes acting in early life but only becoming apparent as disease later. We argue that the evidence suggests the former, through the operation of conditioning processes induced across the normal range of developmental environments, and we summarize current knowledge of the physiological processes involved. The adaptive pathway to later risk accords with current concepts in evolutionary developmental biology, especially those concerning parental effects. Outside the normal range, effects on development can result in nonadaptive processes, and we review their underlying mechanisms and consequences. New concepts concerning the underlying epigenetic and other mechanisms involved in both disruptive and nondisruptive pathways to disease are reviewed, including the evidence for transgenerational passage of risk from both maternal and paternal lines. These concepts have wider implications for understanding the causes and possible prevention of NCDs such as type 2 diabetes and cardiovascular disease, for broader social policy and for the increasing attention paid in public health to the lifecourse approach to NCD prevention. PMID:25287859

Functional somato-dendritic α7-containing nicotinic acetylcholine receptors in the rat basolateral amygdala complex

PubMed Central

Klein, Rebecca C; Yakel, Jerrel L

2006-01-01

Multiple subtypes of nicotinic acetylcholine receptors (nAChRs) are expressed in the CNS. The amygdala complex, the limbic structure important for emotional memory formation, receives cholinergic innervation from the basal forebrain. Although cholinergic drugs have been shown to regulate passive avoidance performance via the amygdala, the neuronal subtypes and circuits involved in this regulation are unknown. In the present study, whole-cell patch-clamp electrophysiological techniques were used to identify and characterize the presence of functional somato-dendritic nAChRs within the basolateral complex of the amygdala. Pressure-application of acetylcholine (ACh; 2 mm) evoked inward current responses in a subset of neurons from both the lateral (49%) and basolateral nuclei (72%). All responses displayed rapid activation kinetics, and were blocked by the α7-selective antagonist methyllycaconitine. In addition, the α7-selective agonist choline induced inward current responses that were similar to ACh-evoked responses. Spiking patterns were consistent with pyramidal class I neurons (the major neuronal type in the basolateral complex); however, there was no correlation between firing frequency and the response to ACh. The local photolysis of caged carbachol demonstrated that the functional expression of nAChRs is located both on the soma and dendrites. This is the first report demonstrating the presence of functional nAChR-mediated current responses from rat amygdala slices, where they may be playing a significant role in fear and aversively motivated memory. PMID:16931547

Amygdala reactivity is inversely related to level of cannabis use in individuals with comorbid cannabis dependence and major depression.

PubMed

Cornelius, Jack R; Aizenstein, Howard J; Hariri, Ahmad R

2010-06-01

Phan et al. (2008) recently reported that an acute dose of oral THC is associated with a decrease in threat-related amygdala reactivity during a social threat stimulus task. However, to date, those findings have not been replicated, and have not been extended to clinical studies involving smoked rather than oral cannabis. In this study, we hypothesized that level of cannabis smoked by participants in our treatment study would be inversely related to the level of threat-related amygdala reactivity. Subjects were recruited from among participants in our double-blind, placebo-controlled trial of fluoxetine in comorbid youth with cannabis dependence/major depression. The threat-related amygdala reactivity task used by Hariri et al. (2009) was completed during BOLD fMRI scans at study baseline and then again 12 weeks later at the end of the trial. Data are available from six subjects with pre-and post-treatment fMRI data. During the course of the study, five of the six subjects demonstrated a decrease in their level of cannabis use, with a mean decrease of 64%, and those persons all demonstrated an increase in their level of amygdala reactivity. One subject demonstrated an increase in their level of cannabis use (a 79% increase) during the treatment trial, and that person demonstrated a decrease in their level of amygdala reactivity. Thus, a higher level of cannabis use was consistently associated with a lower level of amygdala reactivity across all subjects (matched pairs t = 2.70, df = 5, p < 0.05, two-tailed). These findings are consistent with the reports by Phan et al. (2008) and Hariri et al. (2009) suggesting that cannabinoids have an inhibitory effect on threat-related amygdala reactivity. Copyright 2010 Elsevier Ltd. All rights reserved.

Resilience and amygdala function in older healthy and depressed adults.

PubMed

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

2018-09-01

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.

Hippocampus and amygdala volumes in patients with vaginismus.

PubMed

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.

Early-Life State-of-Residence Characteristics and Later Life Hypertension, Diabetes, and Ischemic Heart Disease.

PubMed

Rehkopf, David H; Eisen, Ellen A; Modrek, Sepideh; Mokyr Horner, Elizabeth; Goldstein, Benjamin; Costello, Sadie; Cantley, Linda F; Slade, Martin D; Cullen, Mark R

2015-08-01

We examined how state characteristics in early life are associated with individual chronic disease later in life. We assessed early-life state of residence using the first 3 digits of social security numbers from blue- and white-collar workers from a US manufacturing company. Longitudinal data were available from 1997 to 2012, with 305 936 person-years of observation. Disease was assessed using medical claims. We modeled associations using pooled logistic regression with inverse probability of censoring weights. We found small but statistically significant associations between early-state-of-residence characteristics and later life hypertension, diabetes, and ischemic heart disease. The most consistent associations were with income inequality, percentage non-White, and education. These associations were similar after statistically controlling for individual socioeconomic and demographic characteristics and current state characteristics. Characteristics of the state in which an individual lives early in life are associated with prevalence of chronic disease later in life, with a strength of association equivalent to genetic associations found for these same health outcomes.

Heightened extended amygdala metabolism following threat characterizes the early phenotypic risk to develop anxiety-related psychopathology

PubMed Central

Shackman, Alexander J.; Fox, Andrew S.; Oler, Jonathan A.; Shelton, Steven E.; Oakes, Terrence R.; Davidson, Richard J.; Kalin, Ned H.

2016-01-01

Children with an anxious temperament (AT) are prone to heightened shyness and behavioral inhibition (BI). When chronic and extreme, this anxious, inhibited phenotype is an important early-life risk factor for the development of anxiety disorders, depression, and co-morbid substance abuse. Individuals with extreme AT often show persistent distress in the absence of immediate threat and this contextually inappropriate anxiety predicts future symptom development. Despite its clear clinical relevance, the neural circuitry governing the maladaptive persistence of anxiety remains unknown. Here, we used a well-established nonhuman primate model of childhood temperament and high-resolution 18fluorodeoxyglucose positron emission tomography (FDG-PET) imaging to understand the neural systems governing persistent anxiety and clarify their relevance to early-life phenotypic risk. We focused on BI, a core component of anxious temperament, because it affords the moment-by-moment temporal resolution needed to assess contextually appropriate and inappropriate anxiety. From a pool of 109 peri-adolescent rhesus monkeys, we formed groups characterized by high or low levels of BI, as indexed by freezing in response to an unfamiliar human intruder’s profile. The High-BI group showed consistently elevated signs of anxiety and wariness across more than 2 years of assessments. At the time of brain imaging, 1.5 years after initial phenotyping, the High-BI group showed persistently elevated freezing during a 30-min ‘recovery’ period following an encounter with the intruder — more than an order of magnitude greater than the Low-BI group — and this was associated with increased metabolism in the bed nucleus of the stria terminalis, a key component of the central extended amygdala. These observations provide a neurobiological framework for understanding the early phenotypic risk to develop anxiety-related psychopathology, for accelerating the development of improved interventions, and

Limbic Justice—Amygdala Involvement in Immediate Rejection in the Ultimatum Game

PubMed Central

Fransson, Peter; Petrovic, Predrag; Johannesson, Magnus; Ingvar, Martin

2011-01-01

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. PMID:21559322

Local amygdala structural differences with 3T MRI in patients with Alzheimer disease

PubMed Central

Cavedo, E.; Boccardi, M.; Ganzola, R.; Canu, E.; Beltramello, A.; Caltagirone, C.; Thompson, P.M.

2011-01-01

Objective: Histologic studies show that the amygdala is affected by Alzheimer disease (AD) pathology, and its medial aspect is the most involved. We aimed to assess in vivo local structural differences in the amygdala of patients with AD using high-field MRI. Methods: A total of 19 patients with AD (mean age 76, SD 6 years, mean Mini-Mental State Examination score [MMSE] 13, SD 4) and 19 healthy elderly controls (age 74, SD 5, MMSE 29, SD 1) were enrolled. The radial atrophy mapping technique was used to reconstruct the 3-dimensional surface of the amygdala. Maps of surface tissue loss in patients with AD vs controls were computed and statistically tested with permutation tests thresholded at p < 0.05, to correct for multiple comparisons. A digital atlas of the amygdalar nuclei was used to infer which nuclei were involved. Results: Both amygdalar volumes were significantly smaller in patients with AD (right 1,508 mm3, SD 418; left 1,646, SD 419) than controls (right 2,129 mm3, SD 316; left 2,077, SD 376; p < 0.002). In the dorsomedial part, significant local tissue loss (20%–30%) was mapped in the medial and central nuclei. Ventrally, the lateral nucleus (La) and the basolateral ventral medial nucleus (BLVM) were also involved (20%–30% loss). Conclusions: We found in vivo local structural differences in the amygdala of patients with AD. The nuclei involved have known connections to the hippocampus (BLVM, La) and olfactory system (medial nucleus) and with cholinergic pathways (central nucleus). This pattern is consistent with the known pathophysiology of neural systems affected by AD. PMID:21339500

Amygdala hyperactivation to angry faces in intermittent explosive disorder.

PubMed

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.

Early experience of a novel-environment in isolation primes a fearful phenotype characterized by persistent amygdala activation.

PubMed

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

Cholinergic signaling controls conditioned-fear behaviors and enhances plasticity of cortical-amygdala circuits

PubMed Central

Jiang, Li; Kundu, Srikanya; Lederman, James D.; López-Hernández, Gretchen Y.; Ballinger, Elizabeth C.; Wang, Shaohua; Talmage, David A.; Role, Lorna W.

2016-01-01

Summary We examined the contribution of endogenous cholinergic signaling to the acquisition and extinction of fear- related memory by optogenetic regulation of cholinergic input to the basal lateral amygdala (BLA). Stimulation of cholinergic terminal fields within the BLA in awake-behaving mice during training in a cued fear-conditioning paradigm slowed the extinction of learned fear as assayed by multi-day retention of extinction learning. Inhibition of cholinergic activity during training reduced the acquisition of learned fear behaviors. Circuit mechanisms underlying the behavioral effects of cholinergic signaling in the BLA were assessed by in vivo and ex vivo electrophysiological recording. Photo-stimulation of endogenous cholinergic input: (1) enhances firing of putative BLA principal neurons through activation of acetylcholine receptors (AChRs); (2) enhances glutamatergic synaptic transmission in the BLA and (3) induces LTP of cortical-amygdala circuits. These studies support an essential role of cholinergic modulation of BLA circuits in the inscription and retention of fear memories. PMID:27161525

Effects of early-life adversity on immune function are mediated by prenatal environment: Role of prenatal alcohol exposure.

PubMed

Raineki, Charlis; Bodnar, Tamara S; Holman, Parker J; Baglot, Samantha L; Lan, Ni; Weinberg, Joanne

2017-11-01

The contribution of the early postnatal environment to the pervasive effects of prenatal alcohol exposure (PAE) is poorly understood. Moreover, PAE often carries increased risk of exposure to adversity/stress during early life. Dysregulation of immune function may play a role in how pre- and/or postnatal adversity/stress alters brain development. Here, we combine two animal models to examine whether PAE differentially increases vulnerability to immune dysregulation in response to early-life adversity. PAE and control litters were exposed to either limited bedding (postnatal day [PN] 8-12) to model early-life adversity or normal bedding, and maternal behavior and pup vocalizations were recorded. Peripheral (serum) and central (amygdala) immune (cytokines and C-reactive protein - CRP) responses of PAE animals to early-life adversity were evaluated at PN12. Insufficient bedding increased negative maternal behavior in both groups. Early-life adversity increased vocalization in all animals; however, PAE pups vocalized less than controls. Early-life adversity reduced serum TNF-α, KC/GRO, and IL-10 levels in control but not PAE animals. PAE increased serum CRP, and levels were even higher in pups exposed to adversity. Finally, PAE reduced KC/GRO and increased IL-10 levels in the amygdala. Our results indicate that PAE alters immune system development and both behavioral and immune responses to early-life adversity, which could have subsequent consequences for brain development and later life health. Copyright © 2017 Elsevier Inc. All rights reserved.

4 Hz oscillations synchronize prefrontal-amygdala circuits during fear behaviour

PubMed Central

Karalis, Nikolaos; Dejean, Cyril; Chaudun, Fabrice; Khoder, Suzana; Rozeske, Robert R.; Wurtz, Hélène; Bagur, Sophie; Benchenane, Karim; Sirota, Anton; Courtin, Julien; Herry, Cyril

2016-01-01

Fear expression relies on the coordinated activity of prefrontal and amygdala circuits, yet the mechanisms allowing long-range network synchronization during fear remain unknown. Using a combination of extracellular recordings, pharmacological, and optogenetic manipulations we report that freezing, a behavioural expression of fear, temporally coincides with the development of sustained, internally generated 4 Hz oscillations within prefrontal-amygdala circuits. 4 Hz oscillations predict freezing onset and offset and synchronize prefrontal-amygdala circuits. Optogenetic induction of prefrontal 4 Hz oscillations coordinates prefrontal-amygdala activity and elicits fear behaviour. These results unravel a novel sustained oscillatory mechanism mediating prefrontal-amygdala coupling during fear behaviour. PMID:26878674

Hippocampus and amygdala volumes in patients with vaginismus

PubMed Central

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

2016-01-01

AIM: To compare hippocampus and amygdala volumes of patients with vaginismus with those of healthy control subjects. METHODS: 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. RESULTS: 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. CONCLUSION: 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. PMID:27354964

Amygdala habituation and prefrontal functional connectivity in youth with autism spectrum disorders.

PubMed

Swartz, Johnna R; Wiggins, Jillian Lee; Carrasco, Melisa; Lord, Catherine; Monk, Christopher S

2013-01-01

Amygdala habituation, the rapid decrease in amygdala responsiveness to the repeated presentation of stimuli, is fundamental to the nervous system. Habituation is important for maintaining adaptive levels of arousal to predictable social stimuli and decreased habituation is associated with heightened anxiety. Input from the ventromedial prefrontal cortex (vmPFC) regulates amygdala activity. Although previous research has shown abnormal amygdala function in youth with autism spectrum disorders (ASD), no study has examined amygdala habituation in a young sample or whether habituation is related to amygdala connectivity with the vmPFC. Data were analyzed from 32 children and adolescents with ASD and 56 typically developing controls who underwent functional magnetic resonance imaging while performing a gender identification task for faces that were fearful, happy, sad, or neutral. Habituation was tested by comparing amygdala activation to faces during the first half versus the second half of the session. VmPFC-amygdala connectivity was examined through psychophysiologic interaction analysis. Youth with ASD had decreased amygdala habituation to sad and neutral faces compared with controls. Moreover, decreased amygdala habituation correlated with autism severity as measured by the Social Responsiveness Scale. There was a group difference in vmPFC-amygdala connectivity while viewing sad faces, and connectivity predicted amygdala habituation to sad faces in controls. Sustained amygdala activation to faces suggests that repeated face presentations are processed differently in individuals with ASD, which could contribute to social impairments. Abnormal modulation of the amygdala by the vmPFC may play a role in decreased habituation. Copyright © 2013 American Academy of Child & Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.

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

PubMed

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.

Genoarchitecture of the extended amygdala in zebra finch, and expression of FoxP2 in cell corridors of different genetic profile.

PubMed

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.

Relation between early motor delay and later communication delay in infants at risk for autism.

PubMed

Bhat, A N; Galloway, J C; Landa, R J

2012-12-01

Motor delays have been reported in retrospective studies of young infants who later develop Autism Spectrum Disorders (ASDs). In this study, we prospectively compared the gross motor development of a cohort at risk for ASDs; infant siblings of children with ASDs (AU sibs) to low risk typically developing (LR) infants. 24 AU sibs and 24 LR infants were observed at 3 and 6 months using a standardized motor measure, the Alberta Infant Motor Scale (AIMS). In addition, as part of a larger study, the AU sibs also received a follow-up assessment to determine motor and communication performance at 18 months using the Mullen Scales of Early Learning. Significantly more AU sibs showed motor delays at 3 and 6 months than LR infants. The majority of the AU sibs showed both early motor delays and later communication delays. Small sample size and limited follow-up. Early motor delays are more common in AU sibs than LR infants. Communication delays later emerged in 67-73% of the AU sibs who had presented with early motor delays. Overall, early motor delays may be predictive of future communication delays in children at risk for autism. Copyright © 2012 Elsevier Inc. All rights reserved.

Relationship between early motor delay and later communication delay in infants at risk for autism

PubMed Central

Bhat, A. N.; Galloway, J. C.; Landa, R. J.

2012-01-01

Background Motor delays have been reported in retrospective studies of young infants who later develop Autism Spectrum Disorders (ASDs). Objective In this study, we prospectively compared the gross motor development of a cohort at risk for ASDs; infant siblings of children with ASDs (AU sibs) to low risk typically developing (LR) infants. Methods 24 AU sibs and 24 LR infants were observed at 3 and 6 months using a standardized motor measure, the Alberta Infant Motor Scale (AIMS). In addition, as part of a larger study, the AU sibs also received a follow-up assessment to determine motor and communication performance at 18 months using the Mullen Scales of Early Learning. Results Significantly more AU sibs showed motor delays at 3 and 6 months than LR infants. The majority of the AU sibs showed both early motor delays and later communication delays. Limitations Small sample size and limited follow-up. Conclusions Early motor delays are more common in infant AU sibs than LR infants. Communication delays later emerged in 67–73% of the AU sibs who had presented with early motor delays. Overall, early motor delays may be predictive of future communication delays in children at risk for autism. PMID:22982285

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

PubMed

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.

The minimal local-asperity hypothesis of early retinal lateral inhibition.

PubMed

Balboa, R M; Grzywacz, N M

2000-07-01

Recently we found that the theories related to information theory existent in the literature cannot explain the behavior of the extent of the lateral inhibition mediated by retinal horizontal cells as a function of background light intensity. These theories can explain the fall of the extent from intermediate to high intensities, but not its rise from dim to intermediate intensities. We propose an alternate hypothesis that accounts for the extent's bell-shape behavior. This hypothesis proposes that the lateral-inhibition adaptation in the early retina is part of a system to extract several image attributes, such as occlusion borders and contrast. To do so, this system would use prior probabilistic knowledge about the biological processing and relevant statistics in natural images. A key novel statistic used here is the probability of the presence of an occlusion border as a function of local contrast. Using this probabilistic knowledge, the retina would optimize the spatial profile of lateral inhibition to minimize attribute-extraction error. The two significant errors that this minimization process must reduce are due to the quantal noise in photoreceptors and the straddling of occlusion borders by lateral inhibition.

Relation between Amygdala Structure and Function in Adolescents with Bipolar Disorder

ERIC Educational Resources Information Center

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.

White matter integrity deficits in prefrontal-amygdala pathways in Williams syndrome.

PubMed

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.

Maternal depression in childhood and aggression in young adulthood: evidence for mediation by offspring amygdala-hippocampal volume ratio.

PubMed

Gilliam, Mary; Forbes, Erika E; Gianaros, Peter J; Erickson, Kirk I; Brennan, Lauretta M; Shaw, Daniel S

2015-10-01

There is abundant evidence that offspring of depressed mothers are at increased risk for persistent behavior problems related to emotion regulation, but the mechanisms by which offspring incur this risk are not entirely clear. Early adverse caregiving experiences have been associated with structural alterations in the amygdala and hippocampus, which parallel findings of cortical regions altered in adults with behavior problems related to emotion regulation. This study examined whether exposure to maternal depression during childhood might predict increased aggression and/or depression in early adulthood, and whether offspring amygdala:hippocampal volume ratio might mediate this relationship. Participants were 258 mothers and sons at socioeconomic risk for behavior problems. Sons' trajectories of exposure to maternal depression were generated from eight reports collected prospectively from offspring ages 18 months to 10 years. Offspring brain structure, aggression, and depression were assessed at age 20 (n = 170). Persistent, moderately high trajectories of maternal depression during childhood predicted increased aggression in adult offspring. In contrast, stable and very elevated trajectories of maternal depression during childhood predicted depression in adult offspring. Increased amygdala: hippocampal volume ratios at age 20 were significantly associated with concurrently increased aggression, but not depression, in adult offspring. Offspring amygdala: hippocampal volume ratio mediated the relationship found between trajectories of moderately elevated maternal depression during childhood and aggression in adult offspring. Alterations in the relative size of brain structures implicated in emotion regulation may be one mechanism by which offspring of depressed mothers incur increased risk for the development of aggression. © 2014 Association for Child and Adolescent Mental Health.

Activation of Basolateral Amygdala in Juvenile C57BL/6J Mice During Social Approach Behavior

PubMed Central

Ferri, Sarah L.; Kreibich, Arati S.; Torre, Matthew; Piccoli, Cara T.; Dow, Holly; Pallathra, Ashley A.; Li, Hongzhe; Bilker, Warren B.; Gur, Ruben C.; Abel, Ted; Brodkin, Edward S.

2016-01-01

There is a strong need to better understand the neurobiology of juvenile sociability (tendency to seek social interaction), a phenotype of central relevance to autism spectrum disorders (ASD). Although numerous genetic mouse models of ASD showing reduced sociability have been reported, and certain brain regions, such as the amygdala, have been implicated in sociability, there has been little emphasis on delineating brain structures and circuits activated during social interactions in the critical juvenile period of the mouse strain that serves as the most common genetic background for these models—the highly sociable C57BL/6J (B6) strain. We measured expression of the immediate early genes Fos and Egr-1 to map activation of brain regions following the Social Approach Test (SAT) in juvenile male B6 mice. We hypothesized that juvenile B6 mice would show activation of the amygdala during social interactions. The basoloateral amygdala (BLA) was activated by social exposure in highly sociable, 4-week-old B6 mice. In light of these data, and the many lines of evidence indicating alteration of amygdala circuits in human ASD, future studies are warranted to assess structural and functional alterations in the BLA, particularly at BLA synapses, in various mouse models of ASD. PMID:27520082

Contribution of amygdala pathology to comorbid emotional disturbances in temporal lobe epilepsy.

PubMed

Yilmazer-Hanke, Deniz; O'Loughlin, Elaine; McDermott, Kieran

2016-06-01

The amygdala contributes to the generation and propagation of epileptiform activity in temporal lobe epilepsy (TLE). Ictal symptoms such as fear, dreamy states (déjà vu, memory flashbacks, experiential hallucinations), epigastric auras, or sympathetic outflow with cardiovascular changes are often linked to a seizure focus in the amygdala. However, the amygdala may also play a role in comorbid anxiety, depression, and other psychiatric symptoms experienced in the interictal phase, especially in pharmacoresistant TLE. The few studies available on TLE-related alterations in surgical amygdala specimens indicate loss of both excitatory spiny projection neurons as well as interneurons in nuclei with a cortex-like architecture, which may influence mechanisms of feedforward and feedback inhibition. Studies of the human amygdala indicate global alterations in the density of AMPA/kainate, metabotropic glutamate, γ-aminobutyric acid type A (GABAA ), muscarinic M2 and M3, serotonergic 5-HT1A, and adrenergic α1 receptors. Also, amygdala GABAergic and neuropeptide Y (NPY) systems affected in human TLE are both involved in antiepileptic and anxiolytic effects. Experimental and human positron emission tomography studies indicate changes in amygdala serotonergic, NPY Y1 receptor, neurokinin, and opioid systems in emotional disturbances in TLE. Of particular interest is the reduction in amygdala volume in conjunction with ictal fear, seizure focus in the amygdala, and amygdala and hippocampal sclerosis in TLE patients. In contrast, patients with interictal depression often have an intact or even enlarged amygdala and a negative MRI associated with amygdala hypometabolism, which can be associated with limbic autoimmune encephalitis. These findings suggest a differential role of TLE-related amygdala changes in ictal and interictal emotional disturbances. © 2015 Wiley Periodicals, Inc.

Opposing Amygdala and Ventral Striatum Connectivity During Emotion Identification

PubMed Central

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 a well-characterized emotion identification task. As expected, the amygdala responded to THREAT (angry or fearful) faces more than NON-THREAT (sad or happy) faces. A functional connectivity analysis of the time series from an anatomically defined amygdala seed revealed a strong anti-correlation between the amygdala and the ventral striatum /ventral pallidum, consistent with an opposing role for these regions in during emotion identification. A second functional connectivity analysis (psychophysiological interaction) investigating relative connectivity on THREAT vs. NON-THREAT trials demonstrated that the amygdala had increased connectivity with the orbitofrontal cortex during THREAT trials, whereas the ventral striatum demonstrated increased connectivity with the posterior hippocampus on NON-THREAT trials. These results indicate that activity in the amygdala and ventral striatum may be inversely related, and that both regions may provide opposing affective bias signals during emotion identification. PMID:21600684

Neural mechanisms of social decision-making in the primate amygdala.

PubMed

Chang, Steve W C; Fagan, Nicholas A; Toda, Koji; Utevsky, Amanda V; Pearson, John M; Platt, Michael L

2015-12-29

Social decisions require evaluation of costs and benefits to oneself and others. Long associated with emotion and vigilance, the amygdala has recently been implicated in both decision-making and social behavior. The amygdala signals reward and punishment, as well as facial expressions and the gaze of others. Amygdala damage impairs social interactions, and the social neuropeptide oxytocin (OT) influences human social decisions, in part, by altering amygdala function. Here we show in monkeys playing a modified dictator game, in which one individual can donate or withhold rewards from another, that basolateral amygdala (BLA) neurons signaled social preferences both across trials and across days. BLA neurons mirrored the value of rewards delivered to self and others when monkeys were free to choose but not when the computer made choices for them. We also found that focal infusion of OT unilaterally into BLA weakly but significantly increased both the frequency of prosocial decisions and attention to recipients for context-specific prosocial decisions, endorsing the hypothesis that OT regulates social behavior, in part, via amygdala neuromodulation. Our findings demonstrate both neurophysiological and neuroendocrinological connections between primate amygdala and social decisions.

Neural mechanisms of social decision-making in the primate amygdala

PubMed Central

Chang, Steve W. C.; Fagan, Nicholas A.; Toda, Koji; Utevsky, Amanda V.; Pearson, John M.; Platt, Michael L.

2015-01-01

Social decisions require evaluation of costs and benefits to oneself and others. Long associated with emotion and vigilance, the amygdala has recently been implicated in both decision-making and social behavior. The amygdala signals reward and punishment, as well as facial expressions and the gaze of others. Amygdala damage impairs social interactions, and the social neuropeptide oxytocin (OT) influences human social decisions, in part, by altering amygdala function. Here we show in monkeys playing a modified dictator game, in which one individual can donate or withhold rewards from another, that basolateral amygdala (BLA) neurons signaled social preferences both across trials and across days. BLA neurons mirrored the value of rewards delivered to self and others when monkeys were free to choose but not when the computer made choices for them. We also found that focal infusion of OT unilaterally into BLA weakly but significantly increased both the frequency of prosocial decisions and attention to recipients for context-specific prosocial decisions, endorsing the hypothesis that OT regulates social behavior, in part, via amygdala neuromodulation. Our findings demonstrate both neurophysiological and neuroendocrinological connections between primate amygdala and social decisions. PMID:26668400

NADPH oxidase and redox status in amygdala, hippocampus and cortex of male Wistar rats in an animal model of post-traumatic stress disorder.

PubMed

Petrovic, Romana; Puskas, Laslo; Jevtic Dozudic, Gordana; Stojkovic, Tihomir; Velimirovic, Milica; Nikolic, Tatjana; Zivkovic, Milica; Djorovic, Djordje J; Nenadovic, Milutin; Petronijevic, Natasa

2018-05-26

Post-traumatic stress disorder (PTSD) is a highly prevalent and impairing disorder. Oxidative stress is implicated in its pathogenesis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of free radicals. The aim of the study was to assess oxidative stress parameters, activities of respiratory chain enzymes, and the expression of NADPH oxidase subunits (gp91phox, p22phox, and p67phox) in the single prolonged stress (SPS) animal model of PTSD. Twenty-four (12 controls; 12 subjected to SPS), 9-week-old, male Wistar rats were used. SPS included physical restraint, forced swimming, and ether exposure. The rats were euthanized seven days later. Cortex, hippocampus, amygdala, and thalamus were dissected. Malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT), Complex I, and cytochrome C oxidase were measured using spectrophotometric methods, while the expression of NADPH oxidase subunits was determined by Western blot. Increased MDA and decreased GSH concentrations were found in the amygdala and hippocampus of the SPS rats. SOD activity was decreased in amygdala and GPx was decreased in hippocampus. Increased expression of the NADPH oxidase subunits was seen in amygdala, while mitochondrial respiratory chain enzyme expression was unchanged both in amygdala and hippocampus. In the cortex concentrations of MDA and GSH were unchanged despite increased Complex I and decreased GPx, while in the thalamus no change of any parameter was noticed. We conclude that oxidative stress is present in hippocampus and amygdala seven days after the SPS procedure. NADPH oxidase seems to be a main source of free radicals in the amygdala.

The effect of increased genetic risk for Alzheimer’s disease on hippocampal and amygdala volume

PubMed Central

Lupton, Michelle K.; Strike, Lachlan; Hansell, Narelle K.; Wen, Wei; Mather, Karen A.; Armstrong, Nicola J.; Thalamuthu, Anbupalam; McMahon, Katie L.; de Zubicaray, Greig I.; Assareh, Amelia A.; Simmons, Andrew; Proitsi, Petroula; Powell, John F.; Montgomery, Grant W.; Hibar, Derrek P.; Westman, Eric; Tsolaki, Magda; Kloszewska, Iwona; Soininen, Hilkka; Mecocci, Patrizia; Velas, Bruno; Lovestone, Simon; Brodaty, Henry; Ames, David; Trollor, Julian N.; Martin, Nicholas G.; Thompson, Paul M.; Sachdev, Perminder S.; Wright, Margaret J.

2016-01-01

Reduction in hippocampal and amygdala volume measured via structural magnetic resonance imaging is an early marker of Alzheimer’s disease (AD). Whether genetic risk factors for AD exert an effect on these subcortical structures independent of clinical status has not been fully investigated. We examine whether increased genetic risk for AD influences hippocampal and amygdala volumes in case-control and population cohorts at different ages, in 1674 older (aged >53 years; 17% AD, 39% mild cognitive impairment [MCI]) and 467 young (16–30 years) adults. An AD polygenic risk score combining common risk variants excluding apolipoprotein E (APOE), and a single nucleotide polymorphism in TREM2, were both associated with reduced hippocampal volume in healthy older adults and those with MCI. APOE ɛ4 was associated with hippocampal and amygdala volume in those with AD and MCI but was not associated in healthy older adults. No associations were found in young adults. Genetic risk for AD affects the hippocampus before the clinical symptoms of AD, reflecting a neurodegenerative effect before clinical manifestations in older adults. PMID:26973105

Amygdala reactivity to negative stimuli is influenced by oral contraceptive use.

PubMed

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.

Increased expression of c-fos in the medial preoptic area after mating in male rats: role of afferent inputs from the medial amygdala and midbrain central tegmental field.

PubMed

Baum, M J; Everitt, B J

1992-10-01

Immunocytochemical methods were used to localize the protein product of the immediate-early gene, c-fos, in male rats after exposure to, or direct physical interaction with, oestrous females. Increasing amounts of physical contact with a female, with resultant olfactory-vomeronasal and/or genital-somatosensory inputs, caused corresponding increments in c-fos expression in the medial preoptic area, the caudal part of the bed nucleus of the stria terminalis, the medial amygdala, and the midbrain central tegmental field. Males bearing unilateral electrothermal lesions of the olfactory peduncle showed a significant reduction in c-fos expression in the ipsilateral medial amygdala, but not in other structures, provided their coital interaction with oestrous females was restricted to mount-thrust and occasional intromissive patterns due to repeated application of lidocaine anaesthetic to the penis. No such lateralization of c-fos expression occurred in other males with unilateral olfactory lesions which were allowed to intromit and ejaculate with a female. These results suggest that olfactory inputs, possibly of vomeronasal origin, contribute to the activation of c-fos in the medial amygdala. However, lesion-induced deficits in this type of afferent input to the nervous system appear to be readily compensated for by the genital somatosensory input derived from repeated intromissions. Unilateral excitotoxic lesions of the medial preoptic area, made by infusing quinolinic acid, failed to reduce c-fos expression in the ipsilateral or contralateral medial amygdala or central tegmental field following ejaculation. By contrast, combined, unilateral excitotoxic lesions of the medial amygdala and the central tegmental field significantly reduced c-fos expression in the ipsilateral bed nucleus of the stria terminalis and medial preoptic area after mating; no such asymmetry in c-fos expression occurred when lesions were restricted to either the medial amygdala or central tegmental

Altered amygdala-prefrontal connectivity during emotion perception in schizophrenia.

PubMed

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.

Neurons in the human amygdala selective for perceived emotion

PubMed Central

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

Temporal Sequence of Ictal discharges Propagation in the Corticolimbic Basal Ganglia System during Amygdala Kindled Seizures in Freely Moving Rats

PubMed Central

Shi, Li-Hong; Luo, Fei; Woodward, Donald J.; McIntyre, Dan C.; Chang, Jing-Yu

2007-01-01

We used a multiple channel, single unit recording technique to investigate the neural activity in different corticolimbic and basal ganglia regions in freely moving rats before and during generalized amygdala kindled seizures. Neural activity was recorded simultaneously in the sensorimotor cortex (Ctx), hippocampus, amygdala, substantia nigra pars reticulata (SNr) and the subthalamic nucleus (STN). We observed massive synchronized activity among neurons of different brain regions during seizure episodes. Neurons in the kindled amygdala led other regions in synchronized firing, revealed by time lags of neurons in other regions in crosscorrelogram analysis. While there was no obvious time lag between Ctx and SNr, the STN and hippocampus did lag behind the Ctx and SNr in correlated firing. Activity in the amygdala and SNr contralateral to the kindling stimulation site lagged behind their ipsilateral counterparts. However no time lag was found between the kindling and contralateral sides of Ctx, hippocampus and STN. Our data confirm that the amygdala is an epileptic focus that emits ictal discharges to other brain regions. The observed temporal pattern indicates that ictal discharges from the amygdala arrive first at Ctx and SNr, and then spread to the hippocampus and STN. The simultaneous activation of both sides of the Ctx suggests that the neocortex participates in kindled seizures as a unisonant entity to provoke the clonic motor seizures. Early activation of the SNr (before the STN and hippocampus) points to an important role of the SNr in amygdala kindled seizures and supports the view that different SNr manipulations may be effective ways to control seizures. PMID:17049434

Reduced amygdala response in youths with disruptive behavior disorders and psychopathic traits: decreased emotional response versus increased top-down attention to nonemotional features.

PubMed

White, Stuart F; Marsh, Abigail A; Fowler, Katherine A; Schechter, Julia C; Adalio, Christopher; Pope, Kayla; Sinclair, Stephen; Pine, Daniel S; Blair, R James R

2012-07-01

Amygdala dysfunction has been reported to exist in youths and adults with psychopathic traits. However, there has been disagreement as to whether this dysfunction reflects a primary emotional deficit or is secondary to atypical attentional control. The authors examined the validity of the contrasting predictions. Participants were 15 children and adolescents (ages 10–17 years) with both disruptive behavior disorders and psychopathic traits and 17 healthy comparison youths. Functional MRI was used to assess the response of the amygdala and regions implicated in top-down attentional control (the dorsomedial and lateral frontal cortices) to emotional expression under conditions of high and low attentional load. Relative to youths with disruptive behavior disorders and psychopathic traits, healthy comparison subjects showed a significantly greater increase in the typical amygdala response to fearful expressions under low relative to high attentional load conditions. There was also a selective inverse relationship between the response to fearful expressions under low attentional load and the callous-unemotional component (but not the narcissism or impulsivity component) of psychopathic traits. In contrast, the two groups did not differ in the significant recruitment of the dorsomedial and lateral frontal cortices as a function of attentional load. Youths with disruptive behavior disorders and psychopathic traits showed reduced amygdala responses to fearful expressions under low attentional load but no indications of increased recruitment of regions implicated in top-down attentional control. These findings suggest that the emotional deficit observed in youths with disruptive behavior disorders and psychopathic traits is primary and not secondary to increased top-down attention to nonemotional stimulus features.

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

PubMed

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.

Early mathematics development and later achievement: Further evidence

NASA Astrophysics Data System (ADS)

Aubrey, Carol; Godfrey, Ray; Dahl, Sarah

2006-05-01

There is a growing international recognition of the importance of the early years of schooling as well as an interest being shown in the relationship of early education to later achievement. This article focuses on a cohort of English pupils who have been tracked through primary school during the first five years of the new National Numeracy Strategy. It reports a limited longitudinal study of young children's early mathematical development, initially within three testing cycles: at the mid-point and towards the end of their reception year (at five years-of-age) and again at the mid-point of Year 1 (at six years-ofage). These cycles were located within the broader context of progress through to the end of Key Stage 1 (at seven years) and Key Stage 2 (at eleven years) on the basis of national standardised assessment tests (SATs). Results showed that children who bring into school early mathematical knowledge do appear to be advantaged in terms of their mathematical progress through primary school. Numerical attainment increases in importance across the primary years and practical problem solving remains an important element of this. This finding is significant given the current emphasis on numerical calculation in the English curriculum. It is concluded that without active intervention, it is likely that children with little mathematical knowledge at the beginning of formal schooling will remain low achievers throughout their primary years and, probably, beyond.

Activation of Group II Metabotropic Glutamate Receptors Induces Depotentiation in Amygdala Slices and Reduces Fear-Potentiated Startle in Rats

ERIC Educational Resources Information Center

Lin, Chia-Ho; Lee, Chia-Ching; Huang, Ya-Chun; Wang, Su-Jane; Gean, Po-Wu

2005-01-01

There is a close correlation between long-term potentiation (LTP) in the synapses of lateral amygdala (LA) and fear conditioning in animals. We predict that reversal of LTP (depotentiation) in this area of the brain may ameliorate conditioned fear. Activation of group II metabotropic glutamate receptors (mGluR II) with DCG-IV induces…

Stimulus-Elicited Connectivity Influences Resting-State Connectivity Years Later in Human Development: A Prospective Study.

PubMed

Gabard-Durnam, Laurel Joy; Gee, Dylan Grace; Goff, Bonnie; Flannery, Jessica; Telzer, Eva; Humphreys, Kathryn Leigh; Lumian, Daniel Stephen; Fareri, Dominic Stephen; Caldera, Christina; Tottenham, Nim

2016-04-27

Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is currently known about the mechanisms through which these networks assemble into stable mature patterns. The current study posits and tests the long-term phasic molding hypothesis that resting-state networks are gradually shaped by recurring stimulus-elicited connectivity across development by examining how both stimulus-elicited and resting-state functional connections of the human brain emerge over development at the systems level. Using a sequential design following 4- to 18-year-olds over a 2 year period, we examined the predictive associations between stimulus-elicited and resting-state connectivity in amygdala-cortical circuitry as an exemplar case (given this network's protracted development across these ages). Age-related changes in amygdala functional connectivity converged on the same regions of medial prefrontal cortex (mPFC) and inferior frontal gyrus when elicited by emotional stimuli and when measured at rest. Consistent with the long-term phasic molding hypothesis, prospective analyses for both connections showed that the magnitude of an individual's stimulus-elicited connectivity unidirectionally predicted resting-state functional connectivity 2 years later. For the amygdala-mPFC connection, only stimulus-elicited connectivity during childhood and the transition to adolescence shaped future resting-state connectivity, consistent with a sensitive period ending with adolescence for the amygdala-mPFC circuit. Together, these findings suggest that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited by environmental stimuli over the course of development on the order of years. A fundamental issue in understanding the ontogeny of brain function is how resting-state (intrinsic) functional networks emerge and relate to stimulus-elicited functional connectivity. Here, we posit and test the long

Stimulus-Elicited Connectivity Influences Resting-State Connectivity Years Later in Human Development: A Prospective Study

PubMed Central

Gee, Dylan Grace; Goff, Bonnie; Flannery, Jessica; Telzer, Eva; Humphreys, Kathryn Leigh; Lumian, Daniel Stephen; Fareri, Dominic Stephen; Caldera, Christina; Tottenham, Nim

2016-01-01

Although the functional architecture of the brain is indexed by resting-state connectivity networks, little is currently known about the mechanisms through which these networks assemble into stable mature patterns. The current study posits and tests the long-term phasic molding hypothesis that resting-state networks are gradually shaped by recurring stimulus-elicited connectivity across development by examining how both stimulus-elicited and resting-state functional connections of the human brain emerge over development at the systems level. Using a sequential design following 4- to 18-year-olds over a 2 year period, we examined the predictive associations between stimulus-elicited and resting-state connectivity in amygdala-cortical circuitry as an exemplar case (given this network's protracted development across these ages). Age-related changes in amygdala functional connectivity converged on the same regions of medial prefrontal cortex (mPFC) and inferior frontal gyrus when elicited by emotional stimuli and when measured at rest. Consistent with the long-term phasic molding hypothesis, prospective analyses for both connections showed that the magnitude of an individual's stimulus-elicited connectivity unidirectionally predicted resting-state functional connectivity 2 years later. For the amygdala-mPFC connection, only stimulus-elicited connectivity during childhood and the transition to adolescence shaped future resting-state connectivity, consistent with a sensitive period ending with adolescence for the amygdala-mPFC circuit. Together, these findings suggest that resting-state functional architecture may arise from phasic patterns of functional connectivity elicited by environmental stimuli over the course of development on the order of years. SIGNIFICANCE STATEMENT A fundamental issue in understanding the ontogeny of brain function is how resting-state (intrinsic) functional networks emerge and relate to stimulus-elicited functional connectivity. Here, we

Differential activation of amygdala, dorsal and ventral hippocampus following an exposure to a reminder of underwater trauma

PubMed Central

Ritov, Gilad; Ardi, Ziv; Richter-Levin, Gal

2014-01-01

Recollection of emotional memories is attributed in part to the activation of the amygdala and the hippocampus. Recent hypothesis suggests a pivotal role for the ventral hippocampus (VH) in traumatic stress processing and emotional memory retrieval. Persistent re-experiencing and intrusive recollections are core symptoms in acute and posttraumatic stress disorders (ASD; PTSD). Such intrusive recollections are often triggered by reminders associated with the trauma. We examined the impact of exposure to a trauma reminder (under water trauma (UWT)) on the activation of the basolateral amygdala (BLA), dorsal and VH. Rats were exposed to UWT and 24 h later were re-exposed to the context of the trauma. Phosphorylation of the extracellular signal-regulated kinase (ERK) was used as a marker for level of activation of these regions. Significant increase in ERK activation was found in the VH and BLA. Such pattern of activation was not found in animals exposed only to the trauma or in animals exposed only to the trauma reminder. Additionally, the dissociative pattern of activation of the VH sub-regions positively correlated with the activation of the BLA. Our findings suggest a specific pattern of neural activation during recollection of a trauma reminder, with a unique contribution of the VH. Measured 24 h after the exposure to the traumatic experience, the current findings relate to relatively early stages of traumatic memory consolidation. Understanding the neural mechanisms underlying these initial stages may contribute to developing intervention strategies that could reduce the risk of eventually developing PTSD. PMID:24523683

Inhibition of the amygdala central nucleus by stimulation of cerebellar output in rats: a putative mechanism for extinction of the conditioned fear response.

PubMed

Magal, Ari; Mintz, Matti

2014-11-01

The amygdala and the cerebellum serve two distinctively different functions. The amygdala plays a role in the expression of emotional information, whereas the cerebellum is involved in the timing of discrete motor responses. Interaction between these two systems is the basis of the two-stage theory of learning, according to which an encounter with a challenging event triggers fast classical conditioning of fear-conditioned responses in the amygdala and slow conditioning of motor-conditioned responses in the cerebellum. A third stage was hypothesised when an apparent interaction between amygdala and cerebellar associative plasticity was observed: an adaptive rate of cerebellum-dependent motor-conditioned responses was associated with a decrease in amygdala-dependent fear-conditioned responses, and was interpreted as extinction of amygdala-related fear-conditioned responses by the cerebellar output. To explore this hypothesis, we mimicked some components of classical eyeblink conditioning in anesthetised rats by applying an aversive periorbital pulse as an unconditioned stimulus and a train of pulses to the cerebellar output nuclei as a cerebellar neuronal-conditioned response. The central amygdala multiple unit response to the periorbital pulse was measured with or without a preceding train to the cerebellar output nuclei. The results showed that activation of the cerebellar output nuclei prior to periorbital stimulation produced diverse patterns of inhibition of the amygdala response to the periorbital aversive stimulus, depending upon the nucleus stimulated, the laterality of the nucleus stimulated, and the stimulus interval used. These results provide a putative extinction mechanism of learned fear behavior, and could have implications for the treatment of pathologies involving abnormal fear responses by using motor training as therapy. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Sex- and Estrus-Dependent Differences in Rat Basolateral Amygdala

PubMed Central

Blume, Shannon R.; Freedberg, Mari; Vantrease, Jaime E.; Chan, Ronny; Padival, Mallika; Record, Matthew J.; DeJoseph, M. Regina; Urban, Janice H.

2017-01-01

Depression and anxiety are diagnosed almost twice as often in women, and the symptomology differs in men and women and is sensitive to sex hormones. The basolateral amygdala (BLA) contributes to emotion-related behaviors that differ between males and females and across the reproductive cycle. This hints at sex- or estrus-dependent features of BLA function, about which very little is known. The purpose of this study was to test whether there are sex differences or estrous cyclicity in rat BLA physiology and to determine their mechanistic correlates. We found substantial sex differences in the activity of neurons in lateral nuclei (LAT) and basal nuclei (BA) of the BLA that were associated with greater excitatory synaptic input in females. We also found strong differences in the activity of LAT and BA neurons across the estrous cycle. These differences were associated with a shift in the inhibition–excitation balance such that LAT had relatively greater inhibition during proestrus which paralleled more rapid cued fear extinction. In contrast, BA had relatively greater inhibition during diestrus that paralleled more rapid contextual fear extinction. These results are the first to demonstrate sex differences in BLA neuronal activity and the impact of estrous cyclicity on these measures. The shift between LAT and BA predominance across the estrous cycle provides a simple construct for understanding the effects of the estrous cycle on BLA-dependent behaviors. These results provide a novel framework to understand the cyclicity of emotional memory and highlight the importance of considering ovarian cycle when studying the BLA of females. SIGNIFICANCE STATEMENT There are differences in emotional responses and many psychiatric symptoms between males and females. This may point to sex differences in limbic brain regions. Here we demonstrate sex differences in neuronal activity in one key limbic region, the basolateral amygdala (BLA), whose activity fluctuates across the

Multi-modal neuroimaging of adolescents with non-suicidal self-injury: Amygdala functional connectivity.

PubMed

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.

Early father's and mother's involvement and child's later educational outcomes.

PubMed

Flouri, Eirini; Buchanan, Ann

2004-06-01

Few studies have investigated the individual long-term contributions that mothers and fathers make to their children's schooling. (1) To explore the role of early father involvement in children's later educational attainment independently of the role of early mother involvement and other confounds, (2) to investigate whether gender and family structure moderate the relationship between father's and mother's involvement and child's educational attainment, and (3) to explore whether the impact of father's involvement depends on the level of mother's involvement. The study used longitudinal data from the National Child Development Study. The initial sample were those 7,259 cohort members with valid data on mother involvement at age 7, father involvement at age 7, and school-leaving qualification by age 20. Of those, 3,303 were included in the final analysis. The measures were control variables, structural factors (family structure, sibship size and residential mobility), child factors (emotional/behavioural problems, cognitive ability and academic motivation), and father's and mother's involvement. Father involvement and mother involvement at age 7 independently predicted educational attainment by age 20. The association between parents' involvement and educational attainment was not stronger for sons than for daughters. Father involvement was not more important for educational attainment when mother involvement was low rather than high. Not growing up in intact two-parent family did not weaken the association between father's or mother's involvement and educational outcomes. Early father involvement can be another protective factor in counteracting risk conditions that might lead to later low attainment levels.

Short-term SSRI treatment normalises amygdala hyperactivity in depressed patients.

PubMed

Godlewska, B R; Norbury, R; Selvaraj, S; Cowen, P J; Harmer, C J

2012-12-01

Antidepressant drugs such as selective serotonin re-uptake inhibitors (SSRIs) remediate negative biases in emotional processing in depressed patients in both behavioural and neural outcome measures. However, it is not clear if these effects occur before, or as a consequence of, changes in clinical state. In the present study, we investigated the effects of short-term SSRI treatment in depressed patients on the neural response to fearful faces prior to clinical improvement in mood. Altogether, 42 unmedicated depressed patients received SSRI treatment (10 mg escitalopram daily) or placebo in a randomised, parallel-group design. The neural response to fearful and happy faces was measured on day 7 of treatment using functional magnetic resonance imaging. A group of healthy controls was imaged in the same way. Amygdala responses to fearful facial expressions were significantly greater in depressed patients compared to healthy controls. However, this response was normalised in patients receiving 7 days treatment with escitalopram. There was no significant difference in clinical depression ratings at 7 days between the escitalopram and placebo-treated patients. Our results suggest that short-term SSRI treatment in depressed patients remediates amygdala hyperactivity in response to negative emotional stimuli prior to clinical improvement in depressed mood. This supports the hypothesis that the clinical effects of antidepressant treatment may be mediated in part through early changes in emotional processing. Further studies will be needed to show if these early effects of antidepressant medication predict eventual clinical outcome.

The Central Amygdala Nucleus is Critical for Incubation of Methamphetamine Craving

PubMed Central

Li, Xuan; Zeric, Tamara; Kambhampati, Sarita; Bossert, Jennifer M; Shaham, Yavin

2015-01-01

Cue-induced methamphetamine seeking progressively increases after withdrawal but mechanisms underlying this ‘incubation of methamphetamine craving' are unknown. Here we studied the role of central amygdala (CeA), ventral medial prefrontal cortex (vmPFC), and orbitofrontal cortex (OFC), brain regions implicated in incubation of cocaine and heroin craving, in incubation of methamphetamine craving. We also assessed the role of basolateral amygdala (BLA) and dorsal medial prefrontal cortex (dmPFC). We trained rats to self-administer methamphetamine (10 days; 9 h/day, 0.1 mg/kg/infusion) and tested them for cue-induced methamphetamine seeking under extinction conditions during early (2 days) or late (4–5 weeks) withdrawal. We first confirmed that ‘incubation of methamphetamine craving' occurs under our experimental conditions. Next, we assessed the effect of reversible inactivation of CeA or BLA by GABAA+GABAB receptor agonists (muscimol+baclofen, 0.03+0.3 nmol) on cue-induced methamphetamine seeking during early and late withdrawal. We also assessed the effect of muscimol+baclofen reversible inactivation of vmPFC, dmPFC, and OFC on ‘incubated' cue-induced methamphetamine seeking during late withdrawal. Lever presses in the cue-induced methamphetamine extinction tests were higher during late withdrawal than during early withdrawal (incubation of methamphetamine craving). Muscimol+baclofen injections into CeA but not BLA decreased cue-induced methamphetamine seeking during late but not early withdrawal. Muscimol+baclofen injections into dmPFC, vmPFC, or OFC during late withdrawal had no effect on incubated cue-induced methamphetamine seeking. Together with previous studies, results indicate that the CeA has a critical role in incubation of both drug and non-drug reward craving and demonstrate an unexpected dissociation in mechanisms of incubation of methamphetamine vs cocaine craving. PMID:25475163

Tracking the fear memory engram: discrete populations of neurons within amygdala, hypothalamus, and lateral septum are specifically activated by auditory fear conditioning

PubMed Central

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

Face value: amygdala response reflects the validity of first impressions.

PubMed

Rule, Nicholas O; Moran, Joseph M; Freeman, Jonathan B; Whitfield-Gabrieli, Susan; Gabrieli, John D E; Ambady, Nalini

2011-01-01

The human amygdala responds to first impressions of people as judged from their faces, such as normative judgments about the trustworthiness of strangers. It is unknown, however, whether amygdala responses to first impressions can be validated by objective criteria. Here, we examined amygdala responses to faces of Chief Executive Officers (CEOs) where real-world outcomes could be measured objectively by the amounts of profits made by each CEO's company. During fMRI scanning, participants made incidental judgments about the symmetry of each CEO's face. After scanning, participants rated each CEO's face on leadership ability. Parametric analyses showed that greater left amygdala response to the CEOs' faces was associated with higher post-scan ratings of the CEOs' leadership ability. In addition, greater left amygdala response was also associated with greater profits made by the CEOs' companies and this relationship was statistically mediated by external raters' perceptions of arousal. Thus, amygdala response reflected both subjective judgments and objective measures of leadership ability based on first impressions. Copyright © 2010 Elsevier Inc. All rights reserved.

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

PubMed Central

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

The Impact of Early and Late Damage to the Human Amygdala on "Theory of Mind" Reasoning

ERIC Educational Resources Information Center

Shaw, P.; Lawrence, E. J.; Radbourne, C.; Bramham, J.; Polkey, C. E.; David, A. S.

2004-01-01

There is a burgeoning interest in the neural basis of the ability to attribute mental states to others; a capacity referred to as "theory of mind" (ToM). We examined the effects of lesions of the amygdala which arise at different stages of development on this key aspect of social cognition. Tests of ToM, executive and general neuropsychological…

Early versus later response to treatment in patients with community-acquired pneumonia: analysis of the REACH study.

PubMed

Blasi, Francesco; Ostermann, Helmut; Racketa, Jill; Medina, Jesús; McBride, Kyle; Garau, Javier

2014-01-22

Key goals in the treatment of CAP include early response to treatment and achievement of clinical stability. The US FDA recommends early response endpoints (72 hours after initiation of treatment) in clinical trials for the treatment of community-acquired bacterial pneumonia. REACH (REtrospective Study to Assess the Clinical Management of Patients With Moderate-to-Severe Complicated Skin and Soft Tissue Infections [cSSTI] or CAP in the Hospital Setting) was a retrospective observational study, providing current data on the clinical management and resource burden of CAP in real-life settings in European hospitals. This analysis reviews the characteristics and outcomes of patients showing early positive response to treatment (time to clinical stability [TCS] ≤4 days, as assessed by Halm's criteria) compared with patients with later positive response (TCS >4 days). Patients were adults, hospitalized with CAP (2010-2011) and requiring in-hospital treatment with intravenous antibiotics. Of the 2039 patients included in REACH, 585 (28.7%) had TCS assessed by Halm's criteria: 332 (56.8%) showed early response (median 3.0 days), and 253 (43.2%) showed later response to treatment (median 7.0 days). Use of Halm's criteria varied across participating countries, ranging from 0% (Belgium) to 49.1% (UK). Patient characteristics and relevant medical history were similar between the two groups. There were no notable differences in initial antibiotic therapy between groups, except that more early responders had been treated with amoxicillin-clavulanate and amoxicillin monotherapy (22.6%; 7.5%, respectively) than later responders (5.9%; 1.2%, respectively). Initial treatment modification and re-infection or recurrences were less frequent in early responders compared with later responders (14.2% and 3.3% vs. 34.8% and 5.9%, respectively). Early responders had a shorter duration of hospitalization (mean 9.4 ± SD 7.0; median 8.0 days vs. mean 15.6 ± SD 10.5; median 12

Early Life Conditions, Adverse Life Events, and Chewing Ability at Middle and Later Adulthood

PubMed Central

Watt, Richard G.; Tsakos, Georgios

2014-01-01

Objectives. We sought to determine the extent to which early life conditions and adverse life events impact chewing ability in middle and later adulthood. Methods. Secondary analyses were conducted based on data from waves 2 and 3 of the Survey of Health, Ageing, and Retirement in Europe (SHARE), collected in the years 2006 to 2009 and encompassing information on current chewing ability and the life history of persons aged 50 years or older from 13 European countries. Logistic regression models were estimated with sequential inclusion of explanatory variables representing living conditions in childhood and adverse life events. Results. After controlling for current determinants of chewing ability at age 50 years or older, certain childhood and later life course socioeconomic, behavioral, and cognitive factors became evident as correlates of chewing ability at age 50 years or older. Specifically, childhood financial hardship was identified as an early life predictor of chewing ability at age 50 years or older (odds ratio = 1.58; 95% confidence interval = 1.22, 2.06). Conclusions. Findings suggest a potential enduring impact of early life conditions and adverse life events on oral health in middle and later adulthood and are relevant for public health decision-makers who design strategies for optimal oral health. PMID:24625140

Does early-life family income influence later dental pain experience? A prospective 14-year study.

PubMed

Ghorbani, Z; Peres, M A; Liu, P; Mejia, G C; Armfield, J M; Peres, K G

2017-12-01

The aim of this study was to investigate the association between early-life family income and dental pain experience from childhood to early adulthood. Data came from a 14-year prospective study (1991/1992-2005/2006) carried out in South Australia, which included children and adolescents aged 4-17 years (N = 9875) at baseline. The outcome was dental pain experience obtained at baseline, 14 years later in adulthood and at a middle point of time. The main explanatory variable was early-life family income collected at baseline. The prevalence of dental pain was 22.8% at baseline, 19.3% at 'middle time' and 39.3% at follow up. The proportion of people classified as 'poor' at baseline was 27.7%. Being poor early in life was significantly associated with dental pain at 14-year follow up (odds ratio = 1.45; 95% confidence interval = 1.27-1.66). Early-life relative poverty is associated with more frequent dental pain across the 14-year follow up and may be a key exposure variable for later dental conditions. © 2017 Australian Dental Association.

Activation of basolateral amygdala in juvenile C57BL/6J mice during social approach behavior.

PubMed

Ferri, Sarah L; Kreibich, Arati S; Torre, Matthew; Piccoli, Cara T; Dow, Holly; Pallathra, Ashley A; Li, Hongzhe; Bilker, Warren B; Gur, Ruben C; Abel, Ted; Brodkin, Edward S

2016-10-29

There is a strong need to better understand the neurobiology of juvenile sociability (tendency to seek social interaction), a phenotype of central relevance to autism spectrum disorders (ASD). Although numerous genetic mouse models of ASD showing reduced sociability have been reported, and certain brain regions, such as the amygdala, have been implicated in sociability, there has been little emphasis on delineating brain structures and circuits activated during social interactions in the critical juvenile period of the mouse strain that serves as the most common genetic background for these models-the highly sociable C57BL/6J (B6) strain. We measured expression of the immediate early genes Fos and Egr-1 to map activation of brain regions following the Social Approach Test (SAT) in juvenile male B6 mice. We hypothesized that juvenile B6 mice would show activation of the amygdala during social interactions. The basolateral amygdala (BLA) was activated by social exposure in highly sociable, 4-week-old B6 mice. In light of these data, and the many lines of evidence indicating alteration of amygdala circuits in human ASD, future studies are warranted to assess structural and functional alterations in the BLA, particularly at BLA synapses, in various mouse models of ASD. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Basolateral amygdala lesions abolish mutual reward preferences in rats.

PubMed

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.

Early and Later Maternal-Infant Interactions in Adolescent Mothers: A Comparison Study.

ERIC Educational Resources Information Center

Penny, Judith M.; And Others

This study examined differences between the positive mother-infant interactions of adolescents and those of young adult mothers, both before and after controlling for socioeconomic status (SES) and educational level. The study also investigated factors related to adolescents' early and later maternal-infant interaction patterns. Subjects were 100…

Human Amygdala Represents the Complete Spectrum of Subjective Valence

PubMed Central

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

Tracking the fear memory engram: discrete populations of neurons within amygdala, hypothalamus, and lateral septum are specifically activated by auditory fear conditioning.

PubMed

Butler, Christopher W; Wilson, Yvette M; Gunnersen, Jenny M; Murphy, Mark

2015-08-01

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. © 2015 Butler et al.; Published by Cold Spring Harbor Laboratory Press.

Retrieval of Inhibitory Avoidance Memory Induces Differential Transcription of arc in Striatum, Hippocampus, and Amygdala.

PubMed

González-Salinas, Sofía; Medina, Andrea C; Alvarado-Ortiz, Eduardo; Antaramian, Anaid; Quirarte, Gina L; Prado-Alcalá, Roberto A

2018-07-01

Similar to the hippocampus and amygdala, the dorsal striatum is involved in memory retrieval of inhibitory avoidance, a task commonly used to study memory processes. It has been reported that memory retrieval of fear conditioning regulates gene expression of arc and zif268 in the amygdala and the hippocampus, and it is surprising that only limited effort has been made to study the molecular events caused by retrieval in the striatum. To further explore the involvement of immediate early genes in retrieval, we used real-time PCR to analyze arc and zif268 transcription in dorsal striatum, dorsal hippocampus, and amygdala at different time intervals after retrieval of step-through inhibitory avoidance memory. We found that arc expression in the striatum increased 30 min after retrieval while no changes were observed in zif268 in this region. Expression of arc and zif268 also increased in the dorsal hippocampus but the changes were attributed to context re-exposure. Control procedures indicated that in the amygdala, arc and zif268 expression was not dependent on retrieval. Our data indicate that memory retrieval of inhibitory avoidance induces arc gene expression in the dorsal striatum, caused, very likely, by the instrumental component of the task. Striatal arc expression after retrieval may induce structural and functional changes in the neurons involved in this process. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Absence of gender effect on amygdala volume in temporal lobe epilepsy.

PubMed

Silva, Ivaldo; Lin, Katia; Jackowski, Andrea P; Centeno, Ricardo da Silva; Pinto, Magali L; Carrete, Henrique; Yacubian, Elza M; Amado, Débora

2010-11-01

Sexual dimorphism has already been described in temporal lobe epilepsy with mesial temporal sclerosis (TLE-MTS). This study evaluated the effect of gender on amygdala volume in patients with TLE-MTS. One hundred twenty-four patients with refractory unilateral or bilateral TLE-MTS who were being considered for epilepsy surgery underwent a comprehensive presurgical evaluation and MRI. Amygdalas of 67 women (27 with right; 32 with left, and 8 with bilateral TLE) and 57 men (22 with right, 30 with left, and 5 with bilateral TLE) were manually segmented. Significant ipsilateral amygdala volume reduction was observed for patients with right and left TLE. No gender effect on amygdala volume was observed. Contralateral amygdalar asymmetry was observed for patients with right and left TLE. Although no gender effect was observed on amygdala volume, ipsilateral amygdala volume reductions in patients with TLE might be related to differential rates of cerebral maturation between hemispheres. Copyright © 2010 Elsevier Inc. All rights reserved.

Extraversion and neuroticism related to the resting-state effective connectivity of amygdala

PubMed Central

Pang, Yajing; Cui, Qian; Wang, Yifeng; Chen, Yuyan; Wang, Xiaona; Han, Shaoqiang; Zhang, Zhiqiang; Lu, Guangming; Chen, Huafu

2016-01-01

The amygdala plays a key role in emotion processing. Its functional connectivity with other brain regions has been extensively demonstrated to be associated with extraversion and neuroticism. However, how the amygdala affects other regions and is affected by others within these connectivity patterns associated with extraversion and neuroticism remains unclear. To address this issue, we investigated the effective connectivity of the amygdala using Granger causality analysis on the resting-state functional magnetic resonance imaging data of 70 participants. Results showed that extraversion was positively correlated with the influence from the right inferior occipital gyrus (IOG) to the left amygdala, and from the bilateral IOG to the right amygdala; such result may represent the neural correlates of social interactions in extraverts. Conversely, neuroticism was associated with an increased influence from right amygdala to right middle frontal gyrus and a decreased influence from right precuneus to right amygdala. This influence might affect the modulations of cognitive regulation function and self-referential processes in neurotic individuals. These findings highlight the importance of the causal influences of amygdala in explaining the individual differences in extraversion and neuroticism, and offer further insights into the specific neural networks underlying personality. PMID:27765947

Odour discrimination learning in the Indian greater short-nosed fruit bat (Cynopterus sphinx): differential expression of Egr-1, C-fos and PP-1 in the olfactory bulb, amygdala and hippocampus.

PubMed

Mukilan, Murugan; Bogdanowicz, Wieslaw; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel

2018-06-15

Activity-dependent expression of immediate-early genes (IEGs) is induced by exposure to odour. The present study was designed to investigate whether there is differential expression of IEGs ( Egr-1 , C-fos ) in the brain region mediating olfactory memory in the Indian greater short-nosed fruit bat, Cynopterus sphinx We assumed that differential expression of IEGs in different brain regions may orchestrate a preference odour (PO) and aversive odour (AO) memory in C. sphinx We used preferred (0.8% w/w cinnamon powder) and aversive (0.4% w/v citral) odour substances, with freshly prepared chopped apple, to assess the behavioural response and induction of IEGs in the olfactory bulb, hippocampus and amygdala. After experiencing PO and AO, the bats initially responded to both, later only engaging in feeding bouts in response to the PO food. The expression pattern of EGR-1 and c-Fos in the olfactory bulb, hippocampus and amygdala was similar at different time points (15, 30 and 60 min) following the response to PO, but was different for AO. The response to AO elevated the level of c-Fos expression within 30 min and reduced it at 60 min in both the olfactory bulb and the hippocampus, as opposed to the continuous increase noted in the amygdala. In addition, we tested whether an epigenetic mechanism involving protein phosphatase-1 (PP-1) acts on IEG expression. The observed PP-1 expression and the level of unmethylated/methylated promoter revealed that C-fos expression is possibly controlled by odour-mediated regulation of PP-1. These results in turn imply that the differential expression of C-fos in the hippocampus and amygdala may contribute to olfactory learning and memory in C. sphinx . © 2018. Published by The Company of Biologists Ltd.

Intranasal Oxytocin Affects Amygdala Functional Connectivity after Trauma Script-Driven Imagery in Distressed Recently Trauma-Exposed Individuals.

PubMed

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

2016-04-01

Approximately 10% of trauma-exposed individuals go on to develop post-traumatic stress disorder (PTSD). Neural emotion regulation may be etiologically involved in PTSD development. Oxytocin administration early post-trauma may be a promising avenue for PTSD prevention, as intranasal oxytocin has previously been found to affect emotion regulation networks in healthy individuals and psychiatric patients. In a randomized double-blind placebo-controlled between-subjects functional magnetic resonance (fMRI) study, we assessed the effects of a single intranasal oxytocin administration (40 IU) on seed-based amygdala resting-state FC with emotion regulation areas (ventromedial prefrontal cortex (vmPFC), ventrolateral prefrontal cortex (vlPFC)), and salience processing areas (insula, dorsal anterior cingulate cortex (dACC)) in 37 individuals within 11 days post trauma. Two resting-state scans were acquired; one after neutral- and one after trauma-script-driven imagery. We found that oxytocin administration reduced amygdala-left vlPFC FC after trauma script-driven imagery, compared with neutral script-driven imagery, whereas in PL-treated participants enhanced amygdala-left vlPFC FC was observed following trauma script-driven imagery. Irrespective of script condition, oxytocin increased amygdala-insula FC and decreased amygdala-vmPFC FC. These neural effects were accompanied by lower levels of sleepiness and higher flashback intensity in the oxytocin group after the trauma script. Together, our findings show that oxytocin administration may impede emotion regulation network functioning in response to trauma reminders in recently trauma-exposed individuals. Therefore, caution may be warranted in administering oxytocin to prevent PTSD in distressed, recently trauma-exposed individuals.

Context-Dependent Encoding of Fear and Extinction Memories in a Large-Scale Network Model of the Basal Amygdala

PubMed Central

Vlachos, Ioannis; Herry, Cyril; Lüthi, Andreas; Aertsen, Ad; Kumar, Arvind

2011-01-01

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. PMID:21437238

Calcitonin gene-related peptide erases the fear memory and facilitates long-term potentiation in the central nucleus of the amygdala in rats.

PubMed

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

Evidence for Metabolic Hypothalamo-Amygdala Dysfunction in Narcolepsy

PubMed Central

Poryazova, Rositsa; Schnepf, Betina; Werth, Esther; Khatami, Ramin; Dydak, Ulrike; Meier, Dieter; Boesiger, Peter; Bassetti, Claudio L.

2009-01-01

Study Objectives: Proton resonance spectroscopy (1H-MRS) allows noninvasive chemical tissue analysis in the living brain. As neuronal loss and gliosis have been described in narcolepsy, metabolites of primary interest are N-acetylaspartate (NAA), a marker of neuronal integrity and myo-Inositol (mI), a glial marker and second messenger involved in the regulation of intracellular calcium. One 1H-MRS study in narcolepsy found no metabolic changes in the pontomedullary junction. Another study showed a reduction in NAA/creatine-phosphocreatine (Cr) in the hypothalamus of narcolepsy patients with cataplexy. We aimed to test for metabolic changes in specific brain areas, “regions of interest,” thought to be involved in emotional processing, sleep regulation and pathophysiology of narcolepsy: hypothalamus, pontomesencephalic junction and both amygdalae. Design: We performed 1H-MRS using a 3T Philips Achieva whole body MR scanner. Single-voxel proton MR spectra were acquired and quantified with LCModel to determine metabolite concentration ratios. Setting: The participants in the study were recruited at the outpatient clinic for sleep medicine, Department of Neurology and magnetic resonance spectroscopy was performed at the MRI facility, University Hospital Zurich. Participants: 1H-MRS was performed in fourteen narcolepsy patients with cataplexy, CSF hypocretin deficiency (10/10) and HLA-DQB1*0602 positivity (14/14) and 14 age, gender and body mass index matched controls. Patients were treatment naïve or off therapy for at least 14 days before scanning. Measurements and Results: No differences were observed in the regions of interest for (total NAA)/Cr ratios. Myo-Inositol (mI)/Cr was significantly lower in the right amygdala of the patients, compared to controls (P < 0.042). Significant negative correlations only in the patients group were found between (total NAA)/Cr in hypothalamus and mI/Cr in the right amygdala (r = −0.89, P < 0.001), between mI/Cr in

Early fathering as a predictor of later psychosocial functioning among preschool children with behavior problems.

PubMed

Herbert, Sharonne D; Harvey, Elizabeth A; Lugo-Candelas, Claudia I; Breaux, Rosanna P

2013-07-01

The present study examined the role of early fathering in subsequent trajectories of social emotional and academic functioning of preschool children with behavior problems. Participants were 128 preschool-aged children (73 boys, 55 girls) with behavior problems whose biological fathers took part in a longitudinal study. Children were 3 years of age at the beginning of the study and were assessed annually for 3 years. Early paternal depressive symptoms predicted many aspects of children's outcome 3 years later, including externalizing and internalizing problems, social skills deficits, and lower cognitive and academic functioning, and predicted changes in children's externalizing, internalizing, and social problems across the preschool years. Paternal socioeconomic status (SES) also consistently predicted children's later functioning across these domains. Furthermore, self-reported paternal attention-deficit hyperactivity disorder (ADHD) symptoms and laxness, as well as observed frequent commands were associated with later externalizing problems in children. Paternal depressive symptoms and laxness mediated the relation between paternal ADHD symptoms and child functioning. Results suggest that aspects of early father functioning play an important role in the psychosocial, cognitive, and academic development of preschool-aged children with behavior problems.

Early Fathering as a Predictor of Later Psychosocial Functioning Among Preschool Children with Behavior Problems

PubMed Central

Herbert, Sharonne D.; Harvey, Elizabeth A.; Lugo-Candelas, Claudia I.; Breaux, Rosanna P.

2015-01-01

Objective The present study examined the role of early fathering in subsequent trajectories of social emotional and academic functioning of preschool children with behavior problems. Method Participants were 128 preschool-aged children (73 boys, 55 girls) with behavior problems whose biological fathers took part in a longitudinal study. Children were 3 years of age at the beginning of the study and were assessed annually for 3 years. Results Early paternal depressive symptoms predicted many aspects of children’s outcome 3 years later, including externalizing and internalizing problems, social skills deficits, and lower cognitive and academic functioning, and predicted changes in children’s externalizing, internalizing, and social problems across the preschool years. Paternal socioeconomic status (SES) also consistently predicted children’s later functioning across these domains. Furthermore, self-reported paternal attention deficit hyperactivity disorder (ADHD) symptoms and laxness, as well as observed frequent commands were associated with later externalizing problems in children. Paternal depressive symptoms and laxness mediated the relation between paternal ADHD symptoms and child functioning. Conclusions Results suggest that aspects of early father functioning play an important role in the psychosocial, cognitive, and academic development of preschool-aged children with behavior problems. PMID:23269560

Amygdala activity and prefrontal cortex-amygdala effective connectivity to emerging emotional faces distinguish remitted and depressed mood states in bipolar disorder.

PubMed

Perlman, Susan B; Almeida, Jorge R C; Kronhaus, Dina M; Versace, Amelia; Labarbara, Edmund J; Klein, Crystal R; Phillips, Mary L

2012-03-01

Few studies have employed effective connectivity (EC) to examine the functional integrity of neural circuitry supporting abnormal emotion processing in bipolar disorder (BD), a key feature of the illness. We used Granger Causality Mapping (GCM) to map EC between the prefrontal cortex (PFC) and bilateral amygdala and a novel paradigm to assess emotion processing in adults with BD. Thirty-one remitted adults with BD [(remitted BD), mean age = 32 years], 21 adults with BD in a depressed episode [(depressed BD), mean age = 33 years], and 25 healthy control participants [(HC), mean age = 31 years] performed a block-design emotion processing task requiring color-labeling of a color flash superimposed on a task-irrelevant face morphing from neutral to emotional (happy, sad, angry, or fearful). GCM measured EC preceding (top-down) and following (bottom-up) activity between the PFC and the left and right amygdalae. Our findings indicated patterns of abnormally elevated bilateral amygdala activity in response to emerging fearful, sad, and angry facial expressions in remitted-BD subjects versus HC, and abnormally elevated right amygdala activity to emerging fearful faces in depressed-BD subjects versus HC. We also showed distinguishable patterns of abnormal EC between the amygdala and dorsomedial and ventrolateral PFC, especially to emerging happy and sad facial expressions in remitted-BD and depressed-BD subjects. EC measures of neural system level functioning can further understanding of neural mechanisms associated with abnormal emotion processing and regulation in BD. Our findings suggest major differences in recruitment of amygdala-PFC circuitry, supporting implicit emotion processing between remitted-BD and depressed-BD subjects, which may underlie changes from remission to depression in BD. © 2012 John Wiley and Sons A/S.

Voluntary Ethanol Consumption Reduces GABAergic Neuroactive Steroid (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP) in the Amygdala of the Cynomolgus Monkey

PubMed Central

Beattie, Matthew C.; Maldonado-Devincci, Antoniette M.; Porcu, Patrizia; O’Buckley, Todd K.; Daunais, James B.; Grant, Kathleen A.; Morrow, A. Leslie

2016-01-01

Neuroactive steroids such as (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone) enhance the GABAergic effects of ethanol and modulate excessive drinking in rodents. Moreover, chronic ethanol consumption reduces 3α,5α-THP levels in human plasma, rat hippocampus, and mouse limbic regions. We explored the relationship between 3α,5α-THP levels in limbic brain areas and voluntary ethanol consumption in the cynomolgus monkey following daily self-administration of ethanol for 12 months and further examined the relationship to HPA axis function prior to ethanol exposure. Monkeys were subjected to scheduled induction of ethanol consumption followed by free access to ethanol or water for 22 hours/day over twelve months. Immunohistochemistry was performed using an anti-3α,5α-THP antibody. Prolonged voluntary drinking resulted in individual differences in ethanol consumption that ranged from 1.2 – 4.2 g/kg/day over 12 months. Prolonged ethanol consumption reduced cellular 3α,5α-THP immunoreactivity by 13±2% (p<0.05) in the lateral amygdala and 17±2% (p<0.05) in the basolateral amygdala. The effect of ethanol was most pronounced in heavy drinkers that consumed ≥3 g/kg≥20% of days. Consequently, 3α,5α-THP immunoreactivity in both the lateral and basolateral amygdala was inversely correlated with average daily ethanol intake (Spearman r = −0.87 and −0.72, respectively, p<0.05). However, no effect of ethanol and no correlation between drinking and 3α,5α-THP immunoreactivity was observed in the basomedial amygdala. 3α,5α-THP immunoreactivity following ethanol exposure was also correlated with HPA axis function prior to ethanol exposure. These data indicate that voluntary ethanol drinking reduces amygdala levels of 3α,5α-THP in nonhuman primates and that amygdala 3α,5α-THP levels may be linked to HPA axis function. PMID:26625954

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

PubMed

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.

Amygdala and Ventral Striatum Make Distinct Contributions to Reinforcement Learning.

PubMed

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

2016-10-19

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 an 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 trade-off 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. Published by Elsevier Inc.

Amygdala and ventral striatum make distinct contributions to reinforcement learning

PubMed Central

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

Deformations of amygdala morphology in familial pediatric bipolar disorder.

PubMed

Kelley, Ryan; Chang, Kiki D; Garrett, Amy; Alegría, Dylan; Thompson, Paul; Howe, Meghan; L Reiss, Allan

2013-11-01

Smaller amygdalar volumes have been consistently observed in pediatric bipolar disorder subjects compared to healthy control subjects. Whether smaller amygdalar volume is a consequence or antecedent of the first episode of mania is not known. Additionally, smaller volume has not been localized to specific amygdala subregions. We compared surface contour maps of the amygdala between 22 youths at high risk for bipolar disorder, 26 youths meeting full diagnostic criteria for pediatric familial bipolar disorder, and 24 healthy control subjects matched for age, gender, and intelligence quotient. Amygdalae were manually delineated on three-dimensional spoiled gradient echo images by a blinded rater using established tracing protocols. Statistical surface mesh modeling algorithms supported by permutation statistics were used to identify regional surface differences between the groups. When compared to high-risk subjects and controls, youth with bipolar disorder showed surface deformations in specific amygdalar subregions, suggesting smaller volume of the basolateral nuclei. The high-risk subjects did not differ from controls in any subregion. These findings support previous reports of smaller amygdala volume in pediatric bipolar disorder and map the location of abnormality to specific amygdala subregions. These subregions have been associated with fear conditioning and emotion-enhanced memory. The absence of amygdala size abnormalities in youth at high risk for bipolar disorder suggests that reductions might occur after the onset of mania. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Amygdala and Hippocampus Enlargement during Adolescence in Autism

ERIC Educational Resources Information Center

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.…

Brain-derived neurotrophic factor Val66Met genotype modulates amygdala habituation.

PubMed

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.

Meditation-induced neuroplastic changes in amygdala activity during negative affective processing.

PubMed

Leung, Mei-Kei; Lau, Way K W; Chan, Chetwyn C H; Wong, Samuel S Y; Fung, Annis L C; Lee, Tatia M C

2018-06-01

Recent evidence suggests that the effects of meditation practice on affective processing and resilience have the potential to induce neuroplastic changes within the amygdala. Notably, literature speculates that meditation training may reduce amygdala activity during negative affective processing. Nonetheless, studies have thus far not verified this speculation. In this longitudinal study, participants (N = 21, 9 men) were trained in awareness-based compassion meditation (ABCM) or matched relaxation training. The effects of meditation training on amygdala activity were examined during passive viewing of affective and neutral stimuli in a non-meditative state. We found that the ABCM group exhibited significantly reduced anxiety and right amygdala activity during negative emotion processing than the relaxation group. Furthermore, ABCM participants who performed more compassion practice had stronger right amygdala activity reduction during negative emotion processing. The lower right amygdala activity after ABCM training may be associated with a general reduction in reactivity and distress. As all participants performed the emotion processing task in a non-meditative state, it appears likely that the changes in right amygdala activity are carried over from the meditation practice into the non-meditative state. These findings suggest that the distress-reducing effects of meditation practice on affective processing may transfer to ordinary states, which have important implications on stress management.

“The Cooties Effect”: Amygdala Reactivity to Opposite-versus Same-sex Faces Declines from Childhood to Adolescence

PubMed Central

Telzer, Eva H.; Flannery, Jessica; Humphreys, Kathryn L.; Goff, Bonnie; Gabard-Durman, Laurel; Gee, Dylan G.; Tottenham, Nim

2017-01-01

One of the most important social identities that children learn to define themselves and others by is sex, becoming a salient social category by early childhood. Although older children begin to show greater flexibility in their gendered behaviors and attitudes, gender rigidity intensifies again around the time of puberty. In the current study, we assessed behavioral and neural biases to sex across a wide age group. Ninety-three youth (ages 7–17 years) provided behavioral rating of same- and opposite-sex attitudes, and 52 youth (ages 4–18 years) underwent an fMRI scan as they matched the emotion of same- and opposite-sex faces. We demonstrate significant age-related behavioral biases of sex that are mediated by differential amygdala response to opposite-sex relative to same-sex faces in children, an effect that completely attenuates by the teenage years. Moreover, we find a second peak in amygdala sensitivity to opposite-sex faces around the time of puberty. Thus, the amygdala codes for developmentally dependent and motivationally relevant social identification across development. PMID:25848681

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

PubMed

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.

Genetic variations in the serotonergic system contribute to amygdala volume in humans.

PubMed

Li, Jin; Chen, Chunhui; Wu, Karen; Zhang, Mingxia; Zhu, Bi; Chen, Chuansheng; Moyzis, Robert K; Dong, Qi

2015-01-01

The amygdala plays a critical role in emotion processing and psychiatric disorders associated with emotion dysfunction. Accumulating evidence suggests that amygdala structure is modulated by serotonin-related genes. However, there is a gap between the small contributions of single loci (less than 1%) and the reported 63-65% heritability of amygdala structure. To understand the "missing heritability," we systematically explored the contribution of serotonin genes on amygdala structure at the gene set level. The present study of 417 healthy Chinese volunteers examined 129 representative polymorphisms in genes from multiple biological mechanisms in the regulation of serotonin neurotransmission. A system-level approach using multiple regression analyses identified that nine SNPs collectively accounted for approximately 8% of the variance in amygdala volume. Permutation analyses showed that the probability of obtaining these findings by chance was low (p = 0.043, permuted for 1000 times). Findings showed that serotonin genes contribute moderately to individual differences in amygdala volume in a healthy Chinese sample. These results indicate that the system-level approach can help us to understand the genetic basis of a complex trait such as amygdala structure.

Acute food deprivation enhances fear extinction but inhibits long-term depression in the lateral amygdala via ghrelin signaling.

PubMed

Huang, Chiung-Chun; Chou, Dylan; Yeh, Che-Ming; Hsu, Kuei-Sen

2016-02-01

Fear memory-encoding thalamic input synapses to the lateral amygdala (T-LA) exhibit dynamic efficacy changes that are tightly correlated with fear memory strength. Previous studies have shown that auditory fear conditioning involves strengthening of synaptic strength, and conversely, fear extinction training leads to T-LA synaptic weakening and occlusion of long-term depression (LTD) induction. These findings suggest that the mechanisms governing LTD at T-LA synapses may determine the behavioral outcomes of extinction training. Here, we explored this hypothesis by implementing food deprivation (FD) stress in mice to determine its effects on fear extinction and LTD induction at T-LA synapses. We found that FD increased plasma acylated ghrelin levels and enhanced fear extinction and its retention. Augmentation of fear extinction by FD was blocked by pretreatment with growth hormone secretagogue receptor type-1a antagonist D-Lys(3)-GHRP-6, suggesting an involvement of ghrelin signaling. Confirming previous findings, two distinct forms of LTD coexist at thalamic inputs to LA pyramidal neurons that can be induced by low-frequency stimulation (LFS) or paired-pulse LFS (PP-LFS) paired with postsynaptic depolarization, respectively. Unexpectedly, we found that FD impaired the induction of PP-LFS- and group I metabotropic glutamate receptor agonist (S)-3,5-dihydroxyphenylglycine (DHPG)-induced LTD, but not LFS-induced LTD. Ghrelin mimicked the effects of FD to impair the induction of PP-LFS- and DHPG-induced LTD at T-LA synapses, which were blocked by co-application of D-Lys(3)-GHRP-6. The sensitivity of synaptic transmission to 1-naphthyl acetyl spermine was not altered by either FD or ghrelin treatment. These results highlight distinct features of fear extinction and LTD at T-LA synapses. Copyright © 2015 Elsevier Ltd. All rights reserved.

Anticipatory activation in the amygdala and anterior cingulate in generalized anxiety disorder and prediction of treatment response.

PubMed

Nitschke, Jack B; Sarinopoulos, Issidoros; Oathes, Desmond J; Johnstone, Tom; Whalen, Paul J; Davidson, Richard J; Kalin, Ned H

2009-03-01

The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response. Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine. Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms. These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder.

Anticipatory Activation in the Amygdala and Anterior Cingulate in Generalized Anxiety Disorder and Prediction of Treatment Response

PubMed Central

Nitschke, Jack B.; Sarinopoulos, Issidoros; Oathes, Desmond J.; Johnstone, Tom; Whalen, Paul J.; Davidson, Richard J.; Kalin, Ned H.

2009-01-01

Objective The anticipation of adverse outcomes, or worry, is a cardinal symptom of generalized anxiety disorder. Prior work with healthy subjects has shown that anticipating aversive events recruits a network of brain regions, including the amygdala and anterior cingulate cortex. This study tested whether patients with generalized anxiety disorder have alterations in anticipatory amygdala function and whether anticipatory activity in the anterior cingulate cortex predicts treatment response. Method Functional magnetic resonance imaging (fMRI) was employed with 14 generalized anxiety disorder patients and 12 healthy comparison subjects matched for age, sex, and education. The event-related fMRI paradigm was composed of one warning cue that preceded aversive pictures and a second cue that preceded neutral pictures. Following the fMRI session, patients received 8 weeks of treatment with extended-release venlafaxine. Results Patients with generalized anxiety disorder showed greater anticipatory activity than healthy comparison subjects in the bilateral dorsal amygdala preceding both aversive and neutral pictures. Building on prior reports of pretreatment anterior cingulate cortex activity predicting treatment response, anticipatory activity in that area was associated with clinical outcome 8 weeks later following treatment with venlafaxine. Higher levels of pretreatment anterior cingulate cortex activity in anticipation of both aversive and neutral pictures were associated with greater reductions in anxiety and worry symptoms. Conclusions These findings of heightened and indiscriminate amygdala responses to anticipatory signals in generalized anxiety disorder and of anterior cingulate cortex associations with treatment response provide neurobiological support for the role of anticipatory processes in the pathophysiology of generalized anxiety disorder. PMID:19122007

Effectiveness of oxfendazole against early and later 4th-stage Strongylus vulgaris in ponies.

PubMed

Slocombe, J O; McCraw, B M; Pennock, P; Ducharme, N G; Baird, J D

1986-03-01

Twenty pony foals (reared worm free), 6.5 to 10 weeks of age, were inoculated with Strongylus vulgaris and allocated to 5 groups, each with 4 foals. One week after inoculation, 1 group of 4 foals was given oxfendazole (OFZ) at a dosage rate of 10 mg/kg of body weight, another group was given 2 such treatments 48 hours apart, and a 3rd group was given a placebo. All treatments were administered by stomach tube. Three weeks later, foals were euthanatized and necropsied in a test for efficacy against early 4th-stage larvae. Oxfendazole was 80% and 94.9% effective against early 4th-stage S vulgaris with 1 and 2 doses, respectively. A 4th group of 4 foals was given 2 treatments of OFZ, 48 hours apart, about 8 weeks after inoculation, and a 5th group was given a placebo. These foals were euthanatized and necropsied 5 weeks after treatment in a test for efficacy against later 4th-stage larvae. Two doses of OFZ were 96.6% effective against later 4th-stage larvae.

Bi-Directional Tuning of Amygdala Sensitivity in Combat Veterans Investigated with fMRI

PubMed Central

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

Associative Learning during Early Adulthood Enhances Later Memory Retention in Honeybees

PubMed Central

Arenas, Andrés; Fernández, Vanesa M.; Farina, Walter M.

2009-01-01

Background Cognitive experiences during the early stages of life play an important role in shaping the future behavior in mammals but also in insects, in which precocious learning can directly modify behaviors later in life depending on both the timing and the rearing environment. However, whether olfactory associative learning acquired early in the adult stage of insects affect memorizing of new learning events has not been studied yet. Methodology Groups of adult honeybee workers that experienced an odor paired with a sucrose solution 5 to 8 days or 9 to 12 days after emergence were previously exposed to (i) a rewarded experience through the offering of scented food, or (ii) a non-rewarded experience with a pure volatile compound in the rearing environment. Principal Findings Early rewarded experiences (either at 1–4 or 5–8 days of adult age) enhanced retention performance in 9–12-day-conditioned bees when they were tested at 17 days of age. The highest retention levels at this age, which could not be improved with prior rewarded experiences, were found for memories established at 5–8 days of adult age. Associative memories acquired at 9–12 days of age showed a weak effect on retention for some pure pre-exposed volatile compounds; whereas the sole exposure of an odor at any younger age did not promote long-term effects on learning performance. Conclusions The associative learning events that occurred a few days after adult emergence improved memorizing in middle-aged bees. In addition, both the timing and the nature of early sensory inputs interact to enhance retention of new learning events acquired later in life, an important matter in the social life of honeybees. PMID:19956575

Amygdala α-Synuclein Pathology in the Population-Based Vantaa 85+ Study.

PubMed

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.

Sex differences in the correlation of emotional control and amygdala volumes in adolescents.

PubMed

Blanton, Rebecca E; Chaplin, Tara M; Sinha, Rajita

2010-10-06

We examined male and female adolescents (8-18 years of age) that were scanned with structural brain MRI and looked for a correlation between volume of the right or the left amygdala and parent-reported ability of emotional control. A sex difference was found in the correlation between emotional control and the corrected volume of the left amygdala (that is the amygdala volume adjusted for total cranial volume). In girls, smaller left amygdala volumes were associated with better emotional control. In boys, larger left amygdala volumes were associated with better emotional control. These findings suggest that healthy girls and boys show a difference in the correlation between parental reports of emotional control and the left amygdala volume.

Preferential amygdala reactivity to the negative assessment of neutral faces.

PubMed

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.

Preferential Amygdala Reactivity to the Negative Assessment of Neutral Faces

PubMed Central

Blasi, Giuseppe; Hariri, Ahmad R.; Alce, Guilna; Taurisano, Paolo; Sambataro, Fabio; Das, Saumitra; Bertolino, Alessandro; Weinberger, Daniel R.; Mattay, Venkata S.

2010-01-01

Background 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. Methods 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. Results 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. Conclusions 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. PMID:19709644

Amygdala Volume in Offspring from Multiplex for Alcohol Dependence Families: The Moderating Influence of Childhood Environment and 5-HTTLPR Variation.

PubMed

Hill, Shirley Y; Wang, Shuhui; Carter, Howard; McDermott, Michael D; Zezza, Nicholas; Stiffler, Scott

2013-12-12

The increased susceptibility for developing alcohol dependence seen in offspring from families with alcohol dependence may be related to structural and functional differences in brain circuits that influence emotional processing. Early childhood environment, genetic variation in the serotonin transporter-linked polymorphic region (5-HTTLPR) of the SLCA4 gene and allelic variation in the Brain Derived Neurotrophic Factor (BDNF) gene have each been reported to be related to volumetric differences in the temporal lobe especially the amygdala. Magnetic resonance imaging was used to obtain amygdala volumes for 129 adolescent/young adult individuals who were either High-Risk (HR) offspring from families with multiple cases of alcohol dependence (N=71) or Low-Risk (LR) controls (N=58). Childhood family environment was measured prospectively using age-appropriate versions of the Family Environment Scale during a longitudinal follow-up study. The subjects were genotyped for Brain-Derived Neurotrophic Factor (BDNF) Val66Met and the serotonin transporter polymorphism (5-HTTLPR). Two family environment scale scores (Cohesion and Conflict), genotypic variation, and their interaction were tested for their association with amygdala volumes. Personal and prenatal exposure to alcohol and drugs were considered in statistical analyses in order to more accurately determine the effects of familial risk group differences. Amygdala volume was reduced in offspring from families with multiple alcohol dependent members in comparison to offspring from control families. High-Risk offspring who were carriers of the S variant of the 5-HTTLPR polymorphism had reduced amygdala volume in comparison to those with an LL genotype. Larger amygdala volume was associated with greater family cohesion but only in Low-Risk control offspring. Familial risk for alcohol dependence is an important predictor of amygdala volume even when removing cases with significant personal exposure and covarying for

Pathophysiological Alterations In The Basolateral Amygdala And Neurodegeneration Of Limbic Structures During Epileptogenesis Induced By Status Epilepticus

DTIC Science & Technology

2009-02-05

Crestani F, Martin JR, Möhler H, and Rudolph U (2000) Mechanism of action of the hypnotic zolpidem in vivo. Br J Pharmacol 131:1251–56...epilepsy laterality and reproductive hormone levels in women. Epilepsy Behav 4:407-13. Houser CR (1990) Granule cell dispersion in the dentate gyrus of...cortex from epileptic patients. Neurobiol Dis 8:459- 68. Kostarczyk EM (1986) The amygdala and male reproductive functions. I. Anatomical and

Early play may predict later dominance relationships in yellow-bellied marmots (Marmota flaviventris).

PubMed

Blumstein, Daniel T; Chung, Lawrance K; Smith, Jennifer E

2013-05-22

Play has been defined as apparently functionless behaviour, yet since play is costly, models of adaptive evolution predict that it should have some beneficial function (or functions) that outweigh its costs. We provide strong evidence for a long-standing, but poorly supported hypothesis: that early social play is practice for later dominance relationships. We calculated the relative dominance rank by observing the directional outcome of playful interactions in juvenile and yearling yellow-bellied marmots (Marmota flaviventris) and found that these rank relationships were correlated with later dominance ranks calculated from agonistic interactions, however, the strength of this relationship attenuated over time. While play may have multiple functions, one of them may be to establish later dominance relationships in a minimally costly way.

Early play may predict later dominance relationships in yellow-bellied marmots (Marmota flaviventris)

PubMed Central

Blumstein, Daniel T.; Chung, Lawrance K.; Smith, Jennifer E.

2013-01-01

Play has been defined as apparently functionless behaviour, yet since play is costly, models of adaptive evolution predict that it should have some beneficial function (or functions) that outweigh its costs. We provide strong evidence for a long-standing, but poorly supported hypothesis: that early social play is practice for later dominance relationships. We calculated the relative dominance rank by observing the directional outcome of playful interactions in juvenile and yearling yellow-bellied marmots (Marmota flaviventris) and found that these rank relationships were correlated with later dominance ranks calculated from agonistic interactions, however, the strength of this relationship attenuated over time. While play may have multiple functions, one of them may be to establish later dominance relationships in a minimally costly way. PMID:23536602

Insensitive parenting may accelerate the development of the amygdala-medial prefrontal cortex circuit.

PubMed

Thijssen, Sandra; Muetzel, Ryan L; Bakermans-Kranenburg, Marian J; Jaddoe, Vincent W V; Tiemeier, Henning; Verhulst, Frank C; White, Tonya; Van Ijzendoorn, Marinus H

2017-05-01

This study examined whether the association between age and amygdala-medial prefrontal cortex (mPFC) connectivity in typically developing 6- to 10-year-old children is correlated with parental care. Resting-state functional magnetic resonance imaging scans were acquired from 124 children of the Generation R Study who at 4 years old had been observed interacting with their parents to assess maternal and paternal sensitivity. Amygdala functional connectivity was assessed using a general linear model with the amygdalae time series as explanatory variables. Higher level analyses assessing Sensitivity × Age as well as exploratory Sensitivity × Age × Gender interaction effects were performed restricted to voxels in the mPFC. We found significant Sensitivity × Age interaction effects on amygdala-mPFC connectivity. Age was related to stronger amygdala-mPFC connectivity in children with a lower combined parental sensitivity score (b = 0.11, p = .004, b = 0.06, p = .06, right and left amygdala, respectively), but not in children with a higher parental sensitivity score, (b = -0.07, p = .12, b = -0.06, p = .12, right and left amygdala, respectively). A similar effect was found for maternal sensitivity, with stronger amygdala-mPFC connectivity in children with less sensitive mothers. Exploratory (parental, maternal, paternal) Sensitivity × Age × Gender interaction analyses suggested that this effect was especially pronounced in girls. Amygdala-mPFC resting-state functional connectivity has been shown to increase from age 10.5 years onward, implying that the positive association between age and amygdala-mPFC connectivity in 6- to 10-year-old children of less sensitive parents represents accelerated development of the amygdala-mPFC circuit.

Hippocampus and amygdala volumes in children and young adults at high-risk of schizophrenia: research synthesis.

PubMed

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.

Amygdala damage eliminates monetary loss aversion

PubMed Central

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

2010-01-01

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. PMID:20142490

Early Attachment-Figure Separation and Increased Risk for Later Depression: Potential Mediation by Proinflammatory Processes

PubMed Central

Hennessy, Michael B.; Deak, Terrence; Schiml-Webb, Patricia A.

2009-01-01

Early maternal separation and other disruptions of attachment relations are known to increase risk for the later onset of depressive illness in vulnerable individuals. It is suggested here that sensitization involving proinflammatory processes may contribute to this effect. This argument is based on: (1) current notions of the role of proinflammatory cytokines in depressive illness; (2) evidence that proinflammatory cytokines mediate depressive-like behavior during separation in a rodent model of infant attachment; and (3) comparisons of the effects of early proinflammatory activation versus maternal separation on later proinflammatory activity and biobehavioral processes related to depression. The possible interaction of proinflammatory processes and corticotropin-releasing factor in the sensitization process is discussed. PMID:20359585

Genetic variations in the serotonergic system contribute to amygdala volume in humans

PubMed Central

Li, Jin; Chen, Chunhui; Wu, Karen; Zhang, Mingxia; Zhu, Bi; Chen, Chuansheng; Moyzis, Robert K.; Dong, Qi

2015-01-01

The amygdala plays a critical role in emotion processing and psychiatric disorders associated with emotion dysfunction. Accumulating evidence suggests that amygdala structure is modulated by serotonin-related genes. However, there is a gap between the small contributions of single loci (less than 1%) and the reported 63–65% heritability of amygdala structure. To understand the “missing heritability,” we systematically explored the contribution of serotonin genes on amygdala structure at the gene set level. The present study of 417 healthy Chinese volunteers examined 129 representative polymorphisms in genes from multiple biological mechanisms in the regulation of serotonin neurotransmission. A system-level approach using multiple regression analyses identified that nine SNPs collectively accounted for approximately 8% of the variance in amygdala volume. Permutation analyses showed that the probability of obtaining these findings by chance was low (p = 0.043, permuted for 1000 times). Findings showed that serotonin genes contribute moderately to individual differences in amygdala volume in a healthy Chinese sample. These results indicate that the system-level approach can help us to understand the genetic basis of a complex trait such as amygdala structure. PMID:26500508

Cortex and amygdala morphology in psychopathy.

PubMed

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 p<0.001 bilaterally). Up to 30% tissue reduction in the basolateral nucleus, and 10-30% enlargement effects in the central and lateral nuclei indicated abnormal structure of the amygdala (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.

Perfusion MRI in Early Stage of Legg-Calvé-Perthes Disease to Predict Lateral Pillar Involvement: A Preliminary Study.

PubMed

Kim, Harry K W; Wiesman, Kathryn D; Kulkarni, Vedant; Burgess, Jamie; Chen, Elena; Brabham, Case; Ikram, Haseeb; Du, Jerry; Lu, Amanda; Kulkarni, Ashok V; Dempsey, Molly; Herring, J Anthony

2014-07-16

Current radiographic classifications for Legg-Calvé-Perthes disease cannot be applied at the early stages of the disease. The purpose of this study was to quantify the perfusion of the femoral epiphysis in the early stages of Legg-Calvé-Perthes disease with use of perfusion magnetic resonance imaging (MRI) and to determine if the extent of epiphyseal perfusion can predict the lateral pillar involvement at the mid-fragmentation stage. Twenty-nine patients had gadolinium-enhanced perfusion MRI at the initial stage or early fragmentation stage of Legg-Calvé-Perthes disease and were followed prospectively. The percent perfusion of the whole epiphysis and its lateral third was measured by four independent observers using image analysis software. The radiographs obtained at the mid-fragmentation stage were used for the lateral pillar classification. Intraclass correlation coefficient (ICC) and logistic regression analyses were performed. The mean age (and standard deviation) at diagnosis was 7.7 ± 1.7 years (range, 5.3 to 11.3 years). The mean interval between the MRI and the time of maximum fragmentation was 8.2 ± 5.5 months. The interobserver ICC for the percent perfusion of the lateral third of the epiphysis was 0.90 (95% confidence interval [CI]: 0.83 to 0.95). The mean percent perfusion of the lateral third of the epiphysis was 92% ± 2%, 68% ± 18%, and 46% ± 12% for the hips in which the lateral pillar was later classified as A, B, and C, respectively (p = 0.001). When the perfusion level was ≥90% in the lateral third of the epiphysis, the odds ratio of the lateral pillar being later classified as group A, as opposed to B or C, was 72.0 (CI: 3.5 to 1476). With a perfusion level of ≤55% in the lateral third of the epiphysis, the odds ratio of the lateral pillar being later classified as group C, as opposed to A or B, was 33.3 (CI: 2.8 to 392). Similar results were obtained for the whole epiphysis. Perfusion MRI measurements of the total epiphysis and its

Biological profiling of prospective antidepressant response in major depressive disorder: Associations with (neuro)inflammation, fatty acid metabolism, and amygdala-reactivity.

PubMed

Mocking, R J T; Nap, T S; Westerink, A M; Assies, J; Vaz, F M; Koeter, M W J; Ruhé, H G; Schene, A H

2017-05-01

A better understanding of factors underlying antidepressant non-response may improve the prediction of which patients will respond to what treatment. Major depressive disorder (MDD) is associated with alterations in fatty acid metabolism, (neuro)inflammation and amygdala-reactivity. However, their mutual relations, and the extent to which they are associated with prospective antidepressant-response, remain unknown. To test (I) alterations in (neuro)inflammation and its associations with fatty acid metabolism and amygdala-reactivity in MDD-patients compared to controls, and (II) whether these alterations are associated with prospective paroxetine response. We compared 70 unmedicated MDD-patients with 51 matched healthy controls at baseline, regarding erythrocyte membrane omega-6 arachidonic acid (AA), inflammation [serum (high-sensitivity) C-reactive protein (CRP)], and in a subgroup amygdala-reactivity to emotional faces using functional magnetic resonance imaging (fMRI) (N=42). Subsequently, we treated patients with 12 weeks paroxetine, and repeated baseline measures after 6 and 12 weeks to compare non-responders, early-responders (response at 6 weeks), and late-responders (response at 12 weeks). Compared to controls, MDD-patients showed higher CRP (p=0.016) and AA (p=0.019) after adjustment for confounders at baseline. AA and CRP were mutually correlated (p=0.043). In addition, patients showed a more negative relation between AA and left amygdala-reactivity (p=0.014). Moreover, AA and CRP were associated with antidepressant-response: early responders showed lower AA (p=0.018) and higher CRP-concentrations (p=0.008) than non-responders throughout the study. Higher observed CRP and AA, their mutual association, and relation with amygdala-reactivity, are corroborative with a role for (neuro)inflammation in MDD. In addition, observed associations of these factors with prospective antidepressant-response suggest a potential role as biomarkers. Future studies in

Threat of Punishment Motivates Memory Encoding via Amygdala, Not Midbrain, Interactions with the Medial Temporal Lobe

PubMed Central

Murty, Vishnu P.; LaBar, Kevin S.; Adcock, R. Alison

2012-01-01

Neural circuits associated with motivated declarative encoding and active threat avoidance have both been described, but the relative contribution of these systems to punishment-motivated encoding remains unknown. The current study used functional magnetic resonance imaging in humans to examine mechanisms of declarative memory enhancement when subjects were motivated to avoid punishments that were contingent on forgetting. A motivational cue on each trial informed participants whether they would be punished or not for forgetting an upcoming scene image. Items associated with the threat of shock were better recognized 24 h later. Punishment-motivated enhancements in subsequent memory were associated with anticipatory activation of right amygdala and increases in its functional connectivity with parahippocampal and orbitofrontal cortices. On a trial-by-trial basis, right amygdala activation during the motivational cue predicted hippocampal activation during encoding of the subsequent scene; across participants, the strength of this interaction predicted memory advantages due to motivation. Of note, punishment-motivated learning was not associated with activation of dopaminergic midbrain, as would be predicted by valence-independent models of motivation to learn. These data are consistent with the view that motivation by punishment activates the amygdala, which in turn prepares the medial temporal lobe for memory formation. The findings further suggest a brain system for declarative learning motivated by punishment that is distinct from that for learning motivated by reward. PMID:22745496

Threat of punishment motivates memory encoding via amygdala, not midbrain, interactions with the medial temporal lobe.

PubMed

Murty, Vishnu P; Labar, Kevin S; Adcock, R Alison

2012-06-27

Neural circuits associated with motivated declarative encoding and active threat avoidance have both been described, but the relative contribution of these systems to punishment-motivated encoding remains unknown. The current study used functional magnetic resonance imaging in humans to examine mechanisms of declarative memory enhancement when subjects were motivated to avoid punishments that were contingent on forgetting. A motivational cue on each trial informed participants whether they would be punished or not for forgetting an upcoming scene image. Items associated with the threat of shock were better recognized 24 h later. Punishment-motivated enhancements in subsequent memory were associated with anticipatory activation of right amygdala and increases in its functional connectivity with parahippocampal and orbitofrontal cortices. On a trial-by-trial basis, right amygdala activation during the motivational cue predicted hippocampal activation during encoding of the subsequent scene; across participants, the strength of this interaction predicted memory advantages due to motivation. Of note, punishment-motivated learning was not associated with activation of dopaminergic midbrain, as would be predicted by valence-independent models of motivation to learn. These data are consistent with the view that motivation by punishment activates the amygdala, which in turn prepares the medial temporal lobe for memory formation. The findings further suggest a brain system for declarative learning motivated by punishment that is distinct from that for learning motivated by reward.

Meta-Analysis of Amygdala Volumes in Children and Adolescents with Bipolar Disorder

ERIC Educational Resources Information Center

Pfeifer, Jonathan C.; Welge, Jeffrey; Strakowski. Stephen M.; Adler, Caleb M.; Delbello, Melissa P.

2008-01-01

The size of amygdala of bipolar youths and adults is investigated using neuroimaging studies. Findings showed that smaller volumes of amygdala were observed in youths with bipolar youths compared with children and adolescents without bipolar disorder. The structural amygdala abnormalities in bipolar youths are examined further.

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

PubMed

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.

Primate amygdala neurons evaluate the progress of self-defined economic choice sequences.

PubMed

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.

Preferential attention to animals and people is independent of the amygdala

PubMed Central

Tsuchiya, Naotsugu; New, Joshua; Hurlemann, Rene; Adolphs, Ralph

2015-01-01

The amygdala is thought to play a critical role in detecting salient stimuli. Several studies have taken ecological approaches to investigating such saliency, and argue for domain-specific effects for processing certain natural stimulus categories, in particular faces and animals. Linking this to the amygdala, neurons in the human amygdala have been found to respond strongly to faces and also to animals. However, the amygdala’s necessary role for such category-specific effects at the behavioral level remains untested. Here we tested four rare patients with bilateral amygdala lesions on an established change-detection protocol. Consistent with prior published studies, healthy controls showed reliably faster and more accurate detection of people and animals, as compared with artifacts and plants. So did all four amygdala patients: there were no differences in phenomenal change blindness, in behavioral reaction time to detect changes or in eye-tracking measures. The findings provide decisive evidence against a critical participation of the amygdala in rapid initial processing of attention to animate stimuli, suggesting that the necessary neural substrates for this phenomenon arise either in other subcortical structures (such as the pulvinar) or within the cortex itself. PMID:24795434

Histological study on hippocampus, amygdala and cerebellum following low lead exposure during prenatal and postnatal brain development in rats.

PubMed

Barkur, Rajashekar Rao; Bairy, Laxminarayana K

2016-06-01

Neuropsychological studies in children who are exposed to lead during their early brain development have shown to develop behavioural and cognitive deficit. The aim of the present study was to assess the cellular damage in hippocampus, amygdala and cerebellum of rat pups exposed to lead during different periods of early brain development. Five groups of rat pups were investigated. (a) Control group (n = 8) (mothers of these rats were given normal drinking water throughout gestation and lactation), (b) pregestation lead-exposed group (n = 8) (mothers of these rats were exposed to 0.2% lead acetate in the drinking water for one month before conception), (c) gestation lead-exposed group (n = 8) (exposed to 0.2% lead acetate in the drinking water through the mother throughout gestation [gestation day 01 to day 21]), (d) lactation lead-exposed group (n = 8) (exposed to 0.2% lead acetate in the drinking water through the mother throughout lactation [postnatal day 01 to day 21]) and (e) gestation and lactation lead-exposed group (n = 8) (exposed to 0.2% lead acetate throughout gestation and lactation). On postnatal day 30, rat pups of all the groups were killed. Numbers of surviving neurons in the hippocampus, amygdala and cerebellum regions were counted using cresyl violet staining technique. Histological data indicate that lead exposure caused significant damage to neurons of hippocampus, amygdala and cerebellum regions in all lead-exposed groups except lactation lead-exposed group. The extent of damage to neurons of hippocampus, amygdala and cerebellum regions in lactation lead-exposed group was comparable to gestation and lactation groups even though the duration of lead exposure was much less in lactation lead-exposed group. To conclude, the postnatal period of brain development seems to be more vulnerable to lead neurotoxicity compared to prenatal period of brain development. © The Author(s) 2014.

Parametric modulation of reward sequences during a reversal task in ACC and VMPFC but not amygdala and striatum.

PubMed

Becker, Michael P I; Nitsch, Alexander M; Hewig, Johannes; Miltner, Wolfgang H R; Straube, Thomas

2016-12-01

Several regions of the frontal cortex interact with striatal and amygdala regions to mediate the evaluation of reward-related information and subsequent adjustment of response choices. Recent theories discuss the particular relevance of dorsal anterior cingulate cortex (dACC) for switching behavior; consecutively, ventromedial prefrontal cortex (VMPFC) is involved in mediating exploitative behaviors by tracking reward values unfolding after the behavioral switch. Amygdala, on the other hand, has been implied in coding the valence of stimulus-outcome associations and the ventral striatum (VS) has consistently been shown to code a reward prediction error (RPE). Here, we used fMRI data acquired in humans during a reversal task to parametrically model different sequences of positive feedback in order to unravel differential contributions of these brain regions to the tracking and exploitation of rewards. Parameters from an Optimal Bayesian Learner accurately predicted the divergent involvement of dACC and VMPFC during feedback processing: dACC signaled the first, but not later, presentations of positive feedback, while VMPFC coded trial-by-trial accumulations in reward value. Our results confirm that dACC carries a prominent confirmatory signal during processing of first positive feedback. Amygdala coded positive feedbacks more uniformly, while striatal regions were associated with RPE. Copyright © 2016 Elsevier Inc. All rights reserved.

Amygdala c-Fos induction corresponds to unconditioned and conditioned aversive stimuli but not to freezing.

PubMed

Holahan, Matthew R; White, Norman M

2004-06-04

These experiments examined the relationship between freezing and c-Fos expression in the amygdala. In Experiment 1 freezing was elevated during a period immediately following shock in rats that remained in the shock context, but not in rats that were moved to a different, neutral context. The two groups showed equally elevated c-Fos levels in both the central (CeA) and lateral (LA) nuclei. In Experiment 2 rats were shocked in one compartment (paired) and not shocked in another, distinct compartment (unpaired). Rats re-exposed to the paired compartment 24h later froze more than rats exposed to the unpaired compartment, and rats in both groups froze more than un-shocked rats. c-Fos protein expression in CeA, LA and basolateral (BLA) nucleus was elevated in the rats exposed to the paired compartment but not in rats exposed to the unpaired compartment. Thus, c-Fos expression was induced by exposure to both unconditioned and conditioned stimuli, although it is unclear if the same cell population was activated in both cases. Neither case of c-Fos expression coincided with the occurrence of freezing. c-Fos expression may represent neural activity in LA and CeA produced by exposure to unconditioned cues and activity in BLA, LA and CeA produced by conditioned cues. This activity may contribute to an aversive affective state (or "fear"). Behaviors promoted by this state, such as freezing, may be mediated in other brain areas, or by other neurons in the amygdala.

Using novel control groups to dissect the amygdala's role in Williams syndrome.

PubMed

Thornton-Wells, Tricia A; Avery, Suzanne N; Blackford, Jennifer Urbano

2011-07-01

Williams syndrome is a neurodevelopmental disorder with an intriguing behavioral phenotype-hypersociability combined with significant non-social fears. Previous studies have demonstrated abnormalities in amygdala function in individuals with Williams syndrome compared to typically-developing controls. However, it remains unclear whether the findings are related to the atypical neurodevelopment of Williams syndrome, or are also associated with behavioral traits at the extreme end of a normal continuum. We used functional magnetic resonance imaging (fMRI) to compare amygdala blood-oxygenation-level-dependent (BOLD) responses to non-social and social images in individuals with Williams syndrome compared to either individuals with inhibited temperament (high non-social fear) or individuals with uninhibited temperament (high sociability). Individuals with Williams syndrome had larger amygdala BOLD responses when viewing the non-social fear images than the inhibited temperament control group. In contrast, when viewing both fear and neutral social images, individuals with Williams syndrome did not show smaller amygdala BOLD responses relative to the uninhibited temperament control group, but instead had amygdala responses proportionate to their sociability. These results suggest heightened amygdala response to non-social fear images is characteristic of WS, whereas, variability in amygdala response to social fear images is proportionate to, and might be explained by, levels of trait sociability.

Age-related reduced prefrontal-amygdala structural connectivity is associated with lower trait anxiety

PubMed Central

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

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

PubMed

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.

Intrinsic Amygdala-Cortical Functional Connectivity Predicts Social Network Size in Humans

PubMed Central

Bickart, Kevin C.; Hollenbeck, Mark C.; Barrett, Lisa Feldman; Dickerson, Bradford C.

2012-01-01

Using resting-state functional MRI data from two independent samples of healthy adults, we parsed the amygdala’s intrinsic connectivity into three partially-distinct large-scale networks that strongly resemble the known anatomical organization of amygdala connectivity in rodents and monkeys. Moreover, in a third independent sample, we discovered that people who fostered and maintained larger and more complex social networks not only had larger amygdala volumes, but also amygdalae with stronger intrinsic connectivity within two of these networks, one putatively subserving perceptual abilities and one subserving affiliative behaviors. Our findings were anatomically specific to amygdalar circuitry in that individual differences in social network size and complexity could not be explained by the strength of intrinsic connectivity between nodes within two networks that do not typically involve the amygdala (i.e., the mentalizing and mirror networks), and were behaviorally specific in that amygdala connectivity did not correlate with other self-report measures of sociality. PMID:23077058

Task modulated brain connectivity of the amygdala: a meta-analysis of psychophysiological interactions.

PubMed

Di, Xin; Huang, Jia; Biswal, Bharat B

2017-01-01

Understanding functional connectivity of the amygdala with other brain regions, especially task modulated connectivity, is a critical step toward understanding the role of the amygdala in emotional processes and the interactions between emotion and cognition. The present study performed coordinate-based meta-analysis on studies of task modulated connectivity of the amygdala which used psychophysiological interaction (PPI) analysis. We first analyzed 49 PPI studies on different types of tasks using activation likelihood estimation (ALE) meta-analysis. Widespread cortical and subcortical regions showed consistent task modulated connectivity with the amygdala, including the medial frontal cortex, bilateral insula, anterior cingulate, fusiform gyrus, parahippocampal gyrus, thalamus, and basal ganglia. These regions were in general overlapped with those showed coactivations with the amygdala, suggesting that these regions and amygdala are not only activated together, but also show different levels of interactions during tasks. Further analyses with subsets of PPI studies revealed task specific functional connectivities with the amygdala that were modulated by fear processing, face processing, and emotion regulation. These results suggest a dynamic modulation of connectivity upon task demands, and provide new insights on the functions of the amygdala in different affective and cognitive processes. The meta-analytic approach on PPI studies may offer a framework toward systematical examinations of task modulated connectivity.

Relationships between Early Gestures and Later Language in Children with Fragile X Syndrome

ERIC Educational Resources Information Center

Flenthrope, Jennifer L.; Brady, Nancy C.

2010-01-01

Purpose: The authors hypothesized that significant positive relationships would exist between early gesture use and later language attainments in children with fragile X syndrome (FXS), as has been reported in studies with other populations. Method: Participants were young children with FXS and limited expressive language (21 boys, 4 girls),…

Amygdala Response to Emotional Stimuli without Awareness: Facts and Interpretations

PubMed Central

Diano, Matteo; Celeghin, Alessia; Bagnis, Arianna; Tamietto, Marco

2017-01-01

Over the past two decades, evidence has accumulated that the human amygdala exerts some of its functions also when the observer is not aware of the content, or even presence, of the triggering emotional stimulus. Nevertheless, there is as of yet no consensus on the limits and conditions that affect the extent of amygdala’s response without focused attention or awareness. Here we review past and recent studies on this subject, examining neuroimaging literature on healthy participants as well as brain-damaged patients, and we comment on their strengths and limits. We propose a theoretical distinction between processes involved in attentional unawareness, wherein the stimulus is potentially accessible to enter visual awareness but fails to do so because attention is diverted, and in sensory unawareness, wherein the stimulus fails to enter awareness because its normal processing in the visual cortex is suppressed. We argue this distinction, along with data sampling amygdala responses with high temporal resolution, helps to appreciate the multiplicity of functional and anatomical mechanisms centered on the amygdala and supporting its role in non-conscious emotion processing. Separate, but interacting, networks relay visual information to the amygdala exploiting different computational properties of subcortical and cortical routes, thereby supporting amygdala functions at different stages of emotion processing. This view reconciles some apparent contradictions in the literature, as well as seemingly contrasting proposals, such as the dual stage and the dual route model. We conclude that evidence in favor of the amygdala response without awareness is solid, albeit this response originates from different functional mechanisms and is driven by more complex neural networks than commonly assumed. Acknowledging the complexity of such mechanisms can foster new insights on the varieties of amygdala functions without awareness and their impact on human behavior. PMID:28119645

Amygdala and hippocampus volumetry and diffusivity in relation to dreaming.

PubMed

De Gennaro, Luigi; Cipolli, Carlo; Cherubini, Andrea; Assogna, Francesca; Cacciari, Claudia; Marzano, Cristina; Curcio, Giuseppe; Ferrara, Michele; Caltagirone, Carlo; Spalletta, Gianfranco

2011-09-01

Microstructural analyses by MRI brain scans and by DTI analysis of MR images were used to investigate the possible relationship between deep gray matter structures (amygdala and hippocampus) and dreaming in healthy subjects. Thirty-four subjects ranging in age 20s to 70s underwent to a MRI protocol for the assessment of volume and mean diffusivity (MD) in the amygdala and hippocampus and were asked to fill out a dream diary via audiotape recording upon morning awakening for two weeks. Multiple regression analyses evaluated the relationships between anatomical measures and quantitative and qualitative measures of the reported dreams. The main result points to a dissociation between some quantitative and qualitative aspects of dream reports. While the mean number of dreams recalled per day did not show any significant relationship with the neuroanatomical measures, significant associations with some qualitative features of the recalled dreams (emotional load, bizarreness, and vividness) and, to some extent, with the length of dream reports were observed. Particularly, a higher MD of the left amygdala, reflecting a decreased microstructural integrity, was associated with shorter dream reports and lower scores on emotional load. Bizarreness of dream reports was negatively correlated with the left amygdala volume and positively correlated with the right amygdala MD. Some specific, although weaker, relationships were also found between bizarreness and hippocampal measures. These findings indicate some direct relationships between volumetric and ultrastructural measures of the hippocampus-amygdala complex and specific qualitative features of dreaming. Copyright © 2010 Wiley-Liss, Inc.

Ephrin-B3 coordinates timed axon targeting and amygdala spinogenesis for innate fear behaviour

PubMed Central

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

2016-01-01

Innate emotion response to environmental stimuli is a fundamental brain function that is controlled by specific neural circuits. Dysfunction of early emotional circuits may lead to neurodevelopmental disorders such as autism and schizophrenia. However, how the functional circuits are formed to prime initial emotional behaviours remain elusive. We reveal here using gene-targeted mutations an essential role for ephrin-B3 ligand-like activity in the development of innate fear in the neonatal brain. We further demonstrate that ephrin-B3 controls axon targeting and coordinates spinogenesis and neuronal activity within the amygdala. The morphological and behavioural abnormalities in ephrin-B3 mutant mice are rescued by conditional knock-in of wild-type ephrin-B3 during the critical period when axon targeting and fear responses are initiated. Our results thus define a key axonal molecule that participates in the wiring of amygdala circuits and helps bring about fear emotion during the important adolescence period. PMID:27008987

Ephrin-B3 coordinates timed axon targeting and amygdala spinogenesis for innate fear behaviour.

PubMed

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

2016-03-24

Innate emotion response to environmental stimuli is a fundamental brain function that is controlled by specific neural circuits. Dysfunction of early emotional circuits may lead to neurodevelopmental disorders such as autism and schizophrenia. However, how the functional circuits are formed to prime initial emotional behaviours remain elusive. We reveal here using gene-targeted mutations an essential role for ephrin-B3 ligand-like activity in the development of innate fear in the neonatal brain. We further demonstrate that ephrin-B3 controls axon targeting and coordinates spinogenesis and neuronal activity within the amygdala. The morphological and behavioural abnormalities in ephrin-B3 mutant mice are rescued by conditional knock-in of wild-type ephrin-B3 during the critical period when axon targeting and fear responses are initiated. Our results thus define a key axonal molecule that participates in the wiring of amygdala circuits and helps bring about fear emotion during the important adolescence period.

Anxiety and social deficits have distinct relationships with amygdala function in autism spectrum disorder

PubMed Central

Miller, Judith S.; Pandey, Juhi; Schultz, Robert T.

2016-01-01

Current neural models of autism spectrum disorder (ASD) and anxiety disorders suggest hyperactivation of amygdala in anxiety, but hypoactivation of amygdala in ASD. The objectives of this study were to (i) test the hypothesis that amygdala activity measured by functional magnetic resonance imaging (fMRI) represents a hybrid signal of opposing social functions and anxiety symptoms, and (ii) determine whether longstanding findings of decreased amygdala activation in ASD apply only to those individuals with ASD and low levels of anxiety. During fMRI scanning, 81 youth with ASD and 67 non-ASD control participants completed a face recognition paradigm that elicits robust amygdala activation. Only individuals with ASD and low anxiety levels (a subsample of 28 participants) showed decreased amygdala activation relative to controls. In the ASD group, anxiety symptoms were positively correlated with amygdala activity across the full ASD group, whereas core ASD symptoms (including social deficits) were negatively correlated. Results indicate that hypoactivation of amygdala in ASD, a suggestive finding first reported nearly 20 years ago, can be masked by comorbid anxiety—thus bringing enhanced clarity to this line of work. Amygdala activity represents a hybrid signal of emotion and social processes that cannot be reduced to either alone. PMID:26865425

Bidirectional Control of Social Behavior by Activity within Basolateral and Central Amygdala of Primates.

PubMed

Wellman, Laurie L; Forcelli, Patrick A; Aguilar, Brittany L; Malkova, Ludise

2016-08-17

Both hypoactivity and hyperactivity in the amygdala are associated with perturbations in social behavior. While >60 years of experimental manipulations of the amygdala in animal models have shown that amygdala is critical for social behavior, many of these studies contradict one another. Moreover, several questions remain unaddressed. (1) What effect does activation of amygdala have on social behavior? (2) What is the effect of transient silencing, rather than permanent damage? (3) Is there a dissociation between the roles of the central (CeA) and basolateral amygdala (BLA) in regulating social behavior? (4) Can the prosocial effects of amygdala manipulations be explained by anxiolytic effects? We focally manipulated activity within the CeA or BLA in macaques by intracerebral microinjection of muscimol (to inactivate) or bicuculline (to activate) to these amygdaloid subregions. Social interactions were observed in pairs of highly familiar monkeys. We compared these effects to those achieved with systemic diazepam. Activation of the BLA but not CeA suppressed social behavior. Inhibition of either structure increased social behavior, although the effect was greater following inhibition of the BLA. Systemic diazepam was without effect. These studies, which are the first to bidirectionally manipulate the primate amygdala for effects on social behavior, revealed that (1) the amygdala, as a critical regulator of the social network, is bidirectionally sensitive to perturbations in activity, and (2) increased sociability after amygdala inactivation cannot be solely explained by decreased fear. Many previous studies reported loss of social interactions following permanent damage to the amygdala in nonhuman primates. In contrast, we report that transient inhibition of the basolateral amygdala triggered a profound increase in social interactions in dyads of monkeys highly familiar with each other. We compared these effects to those of systemic diazepam, which failed to

Primate amygdala neurons evaluate the progress of self-defined economic choice sequences

PubMed Central

Grabenhorst, Fabian; Hernadi, Istvan; Schultz, Wolfram

2016-01-01

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. DOI: http://dx.doi.org/10.7554/eLife.18731.001 PMID:27731795

Functionally distinct amygdala subregions identified using DTI and high-resolution fMRI

PubMed Central

Balderston, Nicholas L.; Schultz, Douglas H.; Hopkins, Lauren

2015-01-01

Although the amygdala is often directly linked with fear and emotion, amygdala neurons are activated by a wide variety of emotional and non-emotional stimuli. Different subregions within the amygdala may be engaged preferentially by different aspects of emotional and non-emotional tasks. To test this hypothesis, we measured and compared the effects of novelty and fear on amygdala activity. We used high-resolution blood oxygenation level-dependent (BOLD) imaging and streamline tractography to subdivide the amygdala into three distinct functional subunits. We identified a laterobasal subregion connected with the visual cortex that responds generally to visual stimuli, a non-projecting region that responds to salient visual stimuli, and a centromedial subregion connected with the diencephalon that responds only when a visual stimulus predicts an aversive outcome. We provide anatomical and functional support for a model of amygdala function where information enters through the laterobasal subregion, is processed by intrinsic circuits in the interspersed tissue, and is then passed to the centromedial subregion, where activation leads to behavioral output. PMID:25969533

Deconstructing white matter connectivity of human amygdala nuclei with thalamus and cortex subdivisions in vivo.

PubMed

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.

Deconstructing white matter connectivity of human amygdala nuclei with thalamus and cortex subdivisions in vivo

PubMed Central

2017-01-01

Abstract 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. PMID:28512761

Correlation between amygdala BOLD activity and frontal EEG asymmetry during real-time fMRI neurofeedback training in patients with depression

PubMed Central

Zotev, Vadim; Yuan, Han; Misaki, Masaya; Phillips, Raquel; Young, Kymberly D.; Feldner, Matthew T.; Bodurka, Jerzy

2016-01-01

Real-time fMRI neurofeedback (rtfMRI-nf) is an emerging approach for studies and novel treatments of major depressive disorder (MDD). EEG performed simultaneously with an rtfMRI-nf procedure allows an independent evaluation of rtfMRI-nf brain modulation effects. Frontal EEG asymmetry in the alpha band is a widely used measure of emotion and motivation that shows profound changes in depression. However, it has never been directly related to simultaneously acquired fMRI data. We report the first study investigating electrophysiological correlates of the rtfMRI-nf procedure, by combining the rtfMRI-nf with simultaneous and passive EEG recordings. In this pilot study, MDD patients in the experimental group (n = 13) learned to upregulate BOLD activity of the left amygdala using an rtfMRI-nf during a happy emotion induction task. MDD patients in the control group (n = 11) were provided with a sham rtfMRI-nf. Correlations between frontal EEG asymmetry in the upper alpha band and BOLD activity across the brain were examined. Average individual changes in frontal EEG asymmetry during the rtfMRI-nf task for the experimental group showed a significant positive correlation with the MDD patients' depression severity ratings, consistent with an inverse correlation between the depression severity and frontal EEG asymmetry at rest. The average asymmetry changes also significantly correlated with the amygdala BOLD laterality. Temporal correlations between frontal EEG asymmetry and BOLD activity were significantly enhanced, during the rtfMRI-nf task, for the amygdala and many regions associated with emotion regulation. Our findings demonstrate an important link between amygdala BOLD activity and frontal EEG asymmetry during emotion regulation. Our EEG asymmetry results indicate that the rtfMRI-nf training targeting the amygdala is beneficial to MDD patients. They further suggest that EEG-nf based on frontal EEG asymmetry in the alpha band would be compatible with the amygdala

Early math matters: kindergarten number competence and later mathematics outcomes.

PubMed

Jordan, Nancy C; Kaplan, David; Ramineni, Chaitanya; Locuniak, Maria N

2009-05-01

Children's number competencies over 6 time points, from the beginning of kindergarten to the middle of 1st grade, were examined in relation to their mathematics achievement over 5 later time points, from the end of 1st grade to the end of 3rd grade. The relation between early number competence and mathematics achievement was strong and significant throughout the study period. A sequential process growth curve model showed that kindergarten number competence predicted rate of growth in mathematics achievement between 1st and 3rd grades as well as achievement level through 3rd grade. Further, rate of growth in early number competence predicted mathematics performance level in 3rd grade. Although low-income children performed more poorly than their middle-income counterparts in mathematics achievement and progressed at a slower rate, their performance and growth were mediated through relatively weak kindergarten number competence. Similarly, the better performance and faster growth of children who entered kindergarten at an older age were explained by kindergarten number competence. The findings show the importance of early number competence for setting children's learning trajectories in elementary school mathematics. Copyright 2009 APA, all rights reserved

Early Math Matters: Kindergarten Number Competence and Later Mathematics Outcomes

PubMed Central

Jordan, Nancy C.; Kaplan, David; Ramineni, Chaitanya; Locuniak, Maria N.

2009-01-01

Children’s number competencies over 6 time points, from the beginning of kindergarten to the middle of 1st grade, were examined in relation to their mathematics achievement over 5 later time points, from the end of 1st grade to the end of 3rd grade. The relation between early number competence and mathematics achievement was strong and significant throughout the study period. A sequential process growth curve model showed that kindergarten number competence predicted rate of growth in mathematics achievement between 1st and 3rd grades as well as achievement level through 3rd grade. Further, rate of growth in early number competence predicted mathematics performance level in 3rd grade. Although low-income children performed more poorly than their middle-income counterparts in mathematics achievement and progressed at a slower rate, their performance and growth were mediated through relatively weak kindergarten number competence. Similarly, the better performance and faster growth of children who entered kindergarten at an older age were explained by kindergarten number competence. The findings show the importance of early number competence for setting children’s learning trajectories in elementary school mathematics. PMID:19413436

Dexamethasone Treatment Leads to Enhanced Fear Extinction and Dynamic Fkbp5 Regulation in Amygdala

PubMed Central

Sawamura, Takehito; Klengel, Torsten; Armario, Antonio; Jovanovic, Tanja; Norrholm, Seth D; Ressler, Kerry J; Andero, Raül

2016-01-01

Posttraumatic stress disorder (PTSD) is both a prevalent and debilitating trauma-related disorder associated with dysregulated fear learning at the core of many of its signs and symptoms. Improvements in the currently available psychological and pharmacological treatments are needed in order to improve PTSD treatment outcomes and to prevent symptom relapse. In the present study, we used a putative animal model of PTSD that included presentation of immobilization stress (IMO) followed by fear conditioning (FC) a week later. We then investigated the acute effects of GR receptor activation on the extinction (EXT) of conditioned freezing, using dexamethasone administered systemically which is known to result in suppression of the HPA axis. In our previous work, IMO followed by tone-shock-mediated FC was associated with impaired fear EXT. In this study, we administered dexamethasone 4 h before EXT training and then examined EXT retention (RET) 24 h later to determine whether dexamethasone suppression rescued EXT deficits. Dexamethasone treatment produced dose-dependent enhancement of both EXT and RET. Dexamethasone was also associated with reduced amygdala Fkbp5 mRNA expression following EXT and after RET. Moreover, DNA methylation of the Fkbp5 gene occurred in a dose-dependent and time course-dependent manner within the amygdala. Additionally, we found dynamic changes in epigenetic regulation, including Dnmt and Tet gene pathways, as a function of both fear EXT and dexamethasone suppression of the HPA axis. Together, these data suggest that dexamethasone may serve to enhance EXT by altering Fkbp5-mediated glucocorticoid sensitivity via epigenetic regulation of Fkbp5 expression. PMID:26174596

Dexamethasone Treatment Leads to Enhanced Fear Extinction and Dynamic Fkbp5 Regulation in Amygdala.

PubMed

Sawamura, Takehito; Klengel, Torsten; Armario, Antonio; Jovanovic, Tanja; Norrholm, Seth D; Ressler, Kerry J; Andero, Raül

2016-02-01

Posttraumatic stress disorder (PTSD) is both a prevalent and debilitating trauma-related disorder associated with dysregulated fear learning at the core of many of its signs and symptoms. Improvements in the currently available psychological and pharmacological treatments are needed in order to improve PTSD treatment outcomes and to prevent symptom relapse. In the present study, we used a putative animal model of PTSD that included presentation of immobilization stress (IMO) followed by fear conditioning (FC) a week later. We then investigated the acute effects of GR receptor activation on the extinction (EXT) of conditioned freezing, using dexamethasone administered systemically which is known to result in suppression of the HPA axis. In our previous work, IMO followed by tone-shock-mediated FC was associated with impaired fear EXT. In this study, we administered dexamethasone 4 h before EXT training and then examined EXT retention (RET) 24 h later to determine whether dexamethasone suppression rescued EXT deficits. Dexamethasone treatment produced dose-dependent enhancement of both EXT and RET. Dexamethasone was also associated with reduced amygdala Fkbp5 mRNA expression following EXT and after RET. Moreover, DNA methylation of the Fkbp5 gene occurred in a dose-dependent and time course-dependent manner within the amygdala. Additionally, we found dynamic changes in epigenetic regulation, including Dnmt and Tet gene pathways, as a function of both fear EXT and dexamethasone suppression of the HPA axis. Together, these data suggest that dexamethasone may serve to enhance EXT by altering Fkbp5-mediated glucocorticoid sensitivity via epigenetic regulation of Fkbp5 expression.

Catechol-O-methyltransferase gene variation: impact on amygdala response to aversive stimuli.

PubMed

Domschke, Katharina; Baune, Bernhard T; Havlik, Linda; Stuhrmann, Anja; Suslow, Thomas; Kugel, Harald; Zwanzger, Peter; Grotegerd, Dominik; Sehlmeyer, Christina; Arolt, Volker; Dannlowski, Udo

2012-05-01

The functional catechol-O-methyltransferase (COMT) val158met polymorphism has been found to be associated with anxiety disorders and depression as well as with neural correlates of emotional processing, with, however, contradictory results. Thus, the aim of the present study was to re-evaluate the impact of the COMT val158met variant on neural activation correlates of emotional face processing in a sample of healthy probands. In 85 healthy subjects genotyped for the COMT val158met polymorphism, amygdala responses were assessed by means of fMRI. Participants were presented with anger- and fear-relevant faces in a robust emotion-processing paradigm. For exploratory reasons, a supplementary whole-brain analysis of the allele-dose model and a gender-stratified analysis were conducted. The COMT 158val allele showed an allele-dose effect on increased predominantly left-sided amygdala activity in response to fearful/angry facial stimuli (p(uncorrected)=.00004). This effect was independent from the distribution of the frequently studied 5-HTTLPR polymorphism for which a linear effect of S-alleles on amygdala responsiveness was replicated. The influence of COMT 158val alleles was only discerned in the female subgroup of probands. The whole-brain analysis suggested associations of the COMT 158val allele with increased activity in areas of the ventral visual stream and the lateral prefrontal cortex. The present results provide further support for a-potentially female-specific-role of the COMT val158met polymorphism in the genetic and neural underpinnings of anxiety- and depression-related intermediate phenotypes and may aid in further clarifying the differential role of COMT genotype driven dopaminergic tonus in the processing of emotionally salient stimuli. Copyright © 2012 Elsevier Inc. All rights reserved.

Expectancy, ambiguity, and behavioral flexibility: separable and complementary roles of the orbital frontal cortex and amygdala in processing reward expectancies.

PubMed

Pauli, Wolfgang M; Hazy, Thomas E; O'Reilly, Randall C

2012-02-01

Appetitive goal-directed behavior can be associated with a cue-triggered expectancy that it will lead to a particular reward, a process thought to depend on the OFC and basolateral amygdala complex. We developed a biologically informed neural network model of this system to investigate the separable and complementary roles of these areas as the main components of a flexible expectancy system. These areas of interest are part of a neural network with additional subcortical areas, including the central nucleus of amygdala, ventral (limbic) and dorsomedial (associative) striatum. Our simulations are consistent with the view that the amygdala maintains Pavlovian associations through incremental updating of synaptic strength and that the OFC supports flexibility by maintaining an activation-based working memory of the recent reward history. Our model provides a mechanistic explanation for electrophysiological evidence that cue-related firing in OFC neurons is nonselectively early after a contingency change and why this nonselective firing is critical for promoting plasticity in the amygdala. This ambiguous activation results from the simultaneous maintenance of recent outcomes and obsolete Pavlovian contingencies in working memory. Furthermore, at the beginning of reversal, the OFC is critical for supporting responses that are no longer inappropriate. This result is inconsistent with an exclusive inhibitory account of OFC function.

The risk variant in ODZ4 for bipolar disorder impacts on amygdala activation during reward processing.

PubMed

Heinrich, Angela; Lourdusamy, Anbarasu; Tzschoppe, Jelka; Vollstädt-Klein, Sabine; Bühler, Mira; Steiner, Sabina; Bach, Christiane; Poustka, Luise; Banaschewski, Tobias; Barker, Gareth; Büchel, Christian; Conrod, Patricia; Garavan, Hugh; Gallinat, Jürgen; Heinz, Andreas; Ittermann, Bernd; Loth, Eva; Mann, Karl; Martinot, Jean-Luc; Paus, Tomáš; Pausova, Zdenka; Smolka, Michael; Ströhle, Andreas; Struve, Maren; Witt, Stephanie; Flor, Herta; Schumann, Gunter; Rietschel, Marcella; Nees, Frauke

2013-06-01

Bipolar disorder is a severe mood disorder, which normally begins during adolescence or early adulthood and has a heritability of up to 80%. The largest genome-wide association analysis of bipolar disorder recently identified a new genome-wide associated variant in OZD4 (rs12576775). The aim of the present study was to further elucidate the role of this risk variant in the disease process using an imaging genetics approach. As increased amygdala and striatal responses during the processing of reward and emotion are characteristic for bipolar disorder patients, it was tested whether the risk variant has an influence on this endophenotype in healthy adolescents. We examined the impact of the risk variant rs12576775 on functional magnetic resonance imaging data in an adolescent sample (N = 485). Differential activation between carriers of the risk allele (G-allele) and homozygous A-allele carriers in the amygdala and the striatum during a modification of the monetary incentive delay task (examining reward) and a face task (examining emotion) was analyzed. Carriers of the risk allele showed an increased blood oxygen level-dependent response in the amygdala during reward sensitivity (p = 0.05) and reward expectation (p < 0.05) but not during the face task. No significant group differences were found in the striatum during both reward and emotion processing. Our results indicate that the ODZ4 risk variant influences reward processing in the amygdala. Alterations in the processing of emotion may have different underlying mechanisms and need to be further examined. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Voluntary ethanol consumption reduces GABAergic neuroactive steroid (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP) in the amygdala of the cynomolgus monkey.

PubMed

Beattie, Matthew C; Maldonado-Devincci, Antoniette M; Porcu, Patrizia; O'Buckley, Todd K; Daunais, James B; Grant, Kathleen A; Morrow, A Leslie

2017-03-01

Neuroactive steroids such as (3α,5α)3-hydroxypregnan-20-one (3α,5α-THP, allopregnanolone) enhance the gamma-aminobutyric acid (GABA)-ergic effects of ethanol and modulate excessive drinking in rodents. Moreover, chronic ethanol consumption reduces 3α,5α-THP levels in human plasma, rat hippocampus and mouse limbic regions. We explored the relationship between 3α,5α-THP levels in limbic brain areas and voluntary ethanol consumption in the cynomolgus monkey following daily self-administration of ethanol for 12 months and further examined the relationship to hypothalamic-pituitary-adrenal (HPA) axis function prior to ethanol exposure. Monkeys were subjected to scheduled induction of ethanol consumption followed by free access to ethanol or water for 22 h/day over 12 months. Immunohistochemistry was performed using an anti-3α,5α-THP antibody. Prolonged voluntary drinking resulted in individual differences in ethanol consumption that ranged from 1.2 to 4.2 g/kg/day over 12 months. Prolonged ethanol consumption reduced cellular 3α,5α-THP immunoreactivity by 13 ± 2 percent (P < 0.05) in the lateral amygdala and 17 ± 2 percent (P < 0.05) in the basolateral amygdala. The effect of ethanol was most pronounced in heavy drinkers that consumed ≥3 g/kg ≥ 20 percent of days. Consequently, 3α,5α-THP immunoreactivity in both the lateral and basolateral amygdala was inversely correlated with average daily ethanol intake (Spearman r = -0.87 and -0.72, respectively, P < 0.05). However, no effect of ethanol and no correlation between drinking and 3α,5α-THP immunoreactivity were observed in the basomedial amygdala. 3α,5α-THP immunoreactivity following ethanol exposure was also correlated with HPA axis function prior to ethanol exposure. These data indicate that voluntary ethanol drinking reduces amygdala levels of 3α,5α-THP in non-human primates and that amygdala 3α,5α-THP levels may be linked to HPA axis function. �

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

PubMed

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.

Sex hormones in early infancy seem to predict aspects of later language development.

PubMed

Schaadt, Gesa; Hesse, Volker; Friederici, Angela D

2015-02-01

Sex differences in the development of cognitive behavior such as language have long been of great research interest. Lately, researchers have started to associate language function and brain differences with diverse sex hormones (e.g., testosterone/estradiol). However, results concerning the impact of early postnatal sex hormone concentration on the child's later language development are rare. Here, we analyze the impact of testosterone and estradiol in girls and boys as well as their neurophysiological phonemic discrimination at age 5months on language development at age 4years. Interestingly, we found strong positive estradiol and negative testosterone impact on later language performance at age 4years, which was true for both girls and boys. These results demonstrate that postnatal sex hormone surge might be viewed as one factor determining later language development, independent of gender. Copyright © 2014 Elsevier Inc. All rights reserved.

Limbic grey matter changes in early Parkinson's disease.

PubMed

Li, Xingfeng; Xing, Yue; Schwarz, Stefan T; Auer, Dorothee P

2017-05-02

The purpose of this study was to investigate local and network-related changes of limbic grey matter in early Parkinson's disease (PD) and their inter-relation with non-motor symptom severity. We applied voxel-based morphometric methods in 538 T1 MRI images retrieved from the Parkinson's Progression Markers Initiative website. Grey matter densities and cross-sectional estimates of age-related grey matter change were compared between subjects with early PD (n = 366) and age-matched healthy controls (n = 172) within a regression model, and associations of grey matter density with symptoms were investigated. Structural brain networks were obtained using covariance analysis seeded in regions showing grey matter abnormalities in PD subject group. Patients displayed focally reduced grey matter density in the right amygdala, which was present from the earliest stages of the disease without further advance in mild-moderate disease stages. Right amygdala grey matter density showed negative correlation with autonomic dysfunction and positive with cognitive performance in patients, but no significant interrelations were found with anxiety scores. Patients with PD also demonstrated right amygdala structural disconnection with less structural connectivity of the right amygdala with the cerebellum and thalamus but increased covariance with bilateral temporal cortices compared with controls. Age-related grey matter change was also increased in PD preferentially in the limbic system. In conclusion, detailed brain morphometry in a large group of early PD highlights predominant limbic grey matter deficits with stronger age associations compared with controls and associated altered structural connectivity pattern. This provides in vivo evidence for early limbic grey matter pathology and structural network changes that may reflect extranigral disease spread in PD. Hum Brain Mapp, 2017. © 2017 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2017 The

Amygdala-prefrontal connectivity during appraisal of symptom-related stimuli in obsessive-compulsive disorder.

PubMed

Paul, Sandra; Beucke, Jan C; Kaufmann, Christian; Mersov, Anna; Heinzel, Stephan; Kathmann, Norbert; Simon, Daniela

2018-04-06

Cognitive models of obsessive-compulsive disorder (OCD) posit dysfunctional appraisal of disorder-relevant stimuli in patients, suggesting disturbances in the processes relying on amygdala-prefrontal connectivity. Recent neuroanatomical models add to the traditional view of dysfunction in corticostriatal circuits by proposing alterations in an affective circuit including amygdala-prefrontal connections. However, abnormalities in amygdala-prefrontal coupling during symptom provocation, and particularly during conditions that require stimulus appraisal, remain to be demonstrated directly. Amygdala-prefrontal connectivity was examined in unmedicated OCD patients during appraisal (v. distraction) of symptom-provoking stimuli compared with an emotional control condition. Subsequent analyses tested whether hypothesized connectivity alterations could be also identified during passive viewing and the resting state in two independent samples. During symptom provocation, reductions in positive coupling between amygdala and orbitofrontal cortex were observed in OCD patients relative to healthy control participants during appraisal and passive viewing of OCD-relevant stimuli, whereas abnormally high amygdala-ventromedial prefrontal cortex coupling was found when appraisal was distracted by a secondary task. In contrast, there were no group differences in amygdala connectivity at rest. Our finding of abnormal amygdala-prefrontal connectivity during appraisal of symptom-related (relative to generally aversive) stimuli is consistent with the involvement of affective circuits in the functional neuroanatomy of OCD. Aberrant connectivity can be assumed to impact stimulus appraisal and emotion regulation, but might also relate to fear extinction deficits, which have recently been described in OCD. Taken together, we propose to integrate abnormalities in amygdala-prefrontal coupling in affective models of OCD.

Understanding amygdala responsiveness to fearful expressions through the lens of psychopathy and altruism.

PubMed

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.

The amygdala and temporal lobe simple partial seizures: a prospective and quantitative MRI study.

PubMed

Van Paesschen, W; King, M D; Duncan, J S; Connelly, A

2001-07-01

To determine whether specific temporal lobe simple partial seizures (SPSs) are associated with an abnormal amygdala T2 (AT2) ipsilateral to the seizure focus in patients with intractable unilateral temporal lobe epilepsy (TLE). AT2 relaxation time mapping is a sensitive method for the detection of abnormal tissue in the amygdala in patients with refractory TLE. The relation between an abnormal AT2 in the epileptic temporal lobe and amygdala seizure onset has not been established. Fifty patients with intractable unilateral TLE and concordant data during presurgical evaluation were included. Patients with a foreign-tissue lesion on standard magnetic resonance imaging (MRI) were excluded. All had AT2 mapping. Fifteen types of SPSs were ascertained prospectively, systematically, and blinded to the results of AT2 mapping. The SPSs of patients with a normal AT2 (n = 25) were compared with those of patients with an abnormal AT2 ipsilateral to the seizure focus (n = 25). The group of patients with an abnormal AT2 reported a median of six types of SPSs (range 1-11), in comparison with a median of three types of SPSs (range, 0-7) for the group with a normal AT2 (p<0.01). Déjà vu, a warm sensation, an indescribable strange sensation, a cephalic sensation, and fear were associated with an abnormal AT2. The combination of déjà vu, a cephalic sensation, a warm sensation, a gustatory hallucination, and an indescribable strange sensation discriminated best between the 25 patients with a normal and the 25 patients with an abnormal AT2. A high number and the types of different SPSs provide clinical evidence for early involvement of the amygdala during seizures in patients with refractory unilateral TLE and an abnormal AT2 in the epileptic temporal lobe

Rewarding brain stimulation reverses the disruptive effect of amygdala damage on emotional learning.

PubMed

Kádár, Elisabet; Ramoneda, Marc; Aldavert-Vera, Laura; Huguet, Gemma; Morgado-Bernal, Ignacio; Segura-Torres, Pilar

2014-11-01

Intracranial self-stimulation (SS) in the lateral hypothalamus, a rewarding deep-brain stimulation, is able to improve acquisition and retention of implicit and explicit memory tasks in rats. SS treatment is also able to reverse cognitive deficits associated with aging or with experimental brain injuries and evaluated in a two-way active avoidance (2wAA) task. The main objective of the present study was to explore the potential of the SS treatment to reverse the complete learning and memory impairment caused by bilateral lesion in the lateral amygdala (LA). The effects of post-training SS, administered after each acquisition session, were evaluated on distributed 2wAA acquisition and 10-day retention in rats with electrolytic bilateral LA lesions. SS effect in acetylcholinestaresase (AchE) activity was evaluated by immunohistochemistry in LA-preserved and Central nuclei (Ce) of the amygdala of LA-damaged rats. Results showed that LA lesion over 40% completely impeded 2wAA acquisition and retention. Post-training SS in the LA-lesioned rats improved conditioning and retention compared with both the lesioned but non-SS treated and the non-lesioned control rats. SS treatment also seemed to induce a decrease in AchE activity in the LA-preserved area of the lesioned rats, but no effects were observed in the Ce. This empirical evidence supports the idea that self-administered rewarding stimulation is able to completely counteract the 2wAA acquisition and retention deficits induced by LA lesion. Cholinergic mechanisms in preserved LA and the contribution of other brain memory-related areas activated by SS could mediate the compensatory effect observed. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of relevance on amygdala activation and association with the ventral striatum.

PubMed

Ousdal, Olga Therese; Reckless, Greg E; Server, Andres; Andreassen, Ole A; Jensen, Jimmy

2012-08-01

While the amygdala historically has been implicated in emotional stimuli processing, recent data suggest a general role in parceling out the relevance of stimuli, regardless of their emotional properties. Using functional magnetic resonance imaging, we tested the relevance hypothesis by investigating human amygdala responses to emotionally neutral stimuli while manipulating their relevance. The task was operationalized as highly relevant if a subsequent opportunity to respond for a reward depended on response accuracy of the task, and less relevant if the reward opportunity was independent of task performance. A region of interest analysis revealed bilateral amygdala activations in response to the high relevance condition compared to the low relevance condition. An exploratory whole-brain analysis yielded robust similar results in bilateral ventral striatum. A subsequent functional connectivity analysis demonstrated increased connectivity between amygdala and ventral striatum for the highly relevant stimuli compared to the less relevant stimuli. These findings suggest that the amygdala's processing profile goes beyond detection of emotions per se, and directly support the proposed role in relevance detection. In addition, the findings suggest a close relationship between amygdala and ventral striatal activity when processing relevant stimuli. Thus, the results may indicate that human amygdala modulates ventral striatum activity and subsequent behaviors beyond that observed for emotional cues, to encompass a broader range of relevant stimuli. Copyright © 2012 Elsevier Inc. All rights reserved.

Fear conditioning leads to alteration in specific genes expression in cortical and thalamic neurons that project to the lateral amygdala.

PubMed

Katz, Ira K; Lamprecht, Raphael

2015-02-01

RNA transcription is needed for memory formation. However, the ability to identify genes whose expression is altered by learning is greatly impaired because of methodological difficulties in profiling gene expression in specific neurons involved in memory formation. Here, we report a novel approach to monitor the expression of genes after learning in neurons in specific brain pathways needed for memory formation. In this study, we aimed to monitor gene expression after fear learning. We retrogradely labeled discrete thalamic neurons that project to the lateral amygdala (LA) of rats. The labeled neurons were dissected, using laser microdissection microscopy, after fear conditioning learning or unpaired training. The RNAs from the dissected neurons were subjected to microarray analysis. The levels of selected RNAs detected by the microarray analysis to be altered by fear conditioning were also assessed by nanostring analysis. We observed that the expression of genes involved in the regulation of translation, maturation and degradation of proteins was increased 6 h after fear conditioning compared to unpaired or naïve trained rats. These genes were not expressed 24 h after training or in cortical neurons that project to the LA. The expression of genes involved in transcription regulation and neuronal development was altered after fear conditioning learning in the cortical-LA pathway. The present study provides key information on the identity of genes expressed in discrete thalamic and cortical neurons that project to the LA after fear conditioning. Such an approach could also serve to identify gene products as targets for the development of a new generation of therapeutic agents that could be aimed to functionally identified brain circuits to treat memory-related disorders. © 2014 International Society for Neurochemistry.

Impaired threat prioritisation after selective bilateral amygdala lesions

PubMed Central

Bach, Dominik R.; Hurlemann, Rene; Dolan, Raymond J.

2015-01-01

The amygdala is proposed to process threat-related information in non-human animals. In humans, empirical evidence from lesion studies has provided the strongest evidence for a role in emotional face recognition and social judgement. Here we use a face-in-the-crowd (FITC) task which in healthy control individuals reveals prioritised threat processing, evident in faster serial search for angry compared to happy target faces. We investigate AM and BG, two individuals with bilateral amygdala lesions due to Urbach–Wiethe syndrome, and 16 control individuals. In lesion patients we show a reversal of a threat detection advantage indicating a profound impairment in prioritising threat information. This is the first direct demonstration that human amygdala lesions impair prioritisation of threatening faces, providing evidence that this structure has a causal role in responding to imminent danger. PMID:25282058