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Left and Right Amygdala - Mediofrontal Cortical Functional Connectivity Is Differentially Modulated by Harm Avoidance  [PDF]
Chris Baeken, Daniele Marinazzo, Peter Van Schuerbeek, Guo-Rong Wu, Johan De Mey, Robert Luypaert, Rudi De Raedt
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0095740
Abstract: Background The left and right amygdalae are key regions distinctly involved in emotion-regulation processes. Individual differences, such as personality features, may affect the implicated neurocircuits. The lateralized amygdala affective processing linked with the temperament dimension Harm Avoidance (HA) remains poorly understood. Resting state functional connectivity imaging (rsFC) may provide more insight into these neuronal processes. Methods In 56 drug-naive healthy female subjects, we have examined the relationship between the personality dimension HA on lateralized amygdala rsFC. Results Across all subjects, left and right amygdalae were connected with distinct regions mainly within the ipsilateral hemisphere. Females scoring higher on HA displayed stronger left amygdala rsFC with ventromedial prefrontal cortical (vmPFC) regions involved in affective disturbances. In high HA scorers, we also observed stronger right amygdala rsFC with the dorsomedial prefrontal cortex (dmPFC), which is implicated in negative affect regulation. Conclusions In healthy females, left and right amygdalae seem implicated in distinct mPFC brain networks related to HA and may represent a vulnerability marker for sensitivity to stress and anxiety (disorders).
Women with Multiple Chemical Sensitivity Have Increased Harm Avoidance and Reduced 5-HT1A Receptor Binding Potential in the Anterior Cingulate and Amygdala  [PDF]
Lena Hillert, Hristina Jovanovic, Fredrik ?hs, Ivanka Savic
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0054781
Abstract: Multiple chemical sensitivity (MCS) is a common condition, characterized by somatic distress upon exposure to odors. As in other idiopathic environmental intolerances, the underlying mechanisms are unknown. Contrary to the expectations it was recently found that persons with MCS activate the odor-processing brain regions less than controls, while their activation of the anterior cingulate cortex (ACC) is increased. The present follow-up study was designed to test the hypotheses that MCS subjects have increased harm avoidance and deviations in the serotonin system, which could render them intolerant to environmental odors. Twelve MCS and 11 control subjects, age 22–44, all working or studying females, were included in a PET study where 5-HT1A receptor binding potential (BP) was assessed after bolus injection of [11C]WAY100635. Psychological profiles were assessed by the Temperament and Character Inventory and the Swedish universities Scales of Personality. All MCS and 12 control subjects were also tested for emotional startle modulation in an acoustic startle test. MCS subjects exhibited significantly increased harm avoidance, and anxiety compared to controls. They also had a reduced 5-HT1A receptor BP in amygdala (p = 0.029), ACC (p = 0.005) (planned comparisons, significance level 0.05), and insular cortex (p = 0.003; significance level p<0.005 with Bonferroni correction), and showed an inverse correlation between degree of anxiety and the BP in the amygdala (planned comparison). No group by emotional category difference was found in the startle test. Increased harm avoidance and the observed changes in the 5-HT1A receptor BP in the regions processing harm avoidance provides a plausible pathophysiological ground for the symptoms described in MCS, and yields valuable information for our general understanding of idiopathic environmental intolerances.
Response Properties of Human Amygdala Subregions: Evidence Based on Functional MRI Combined with Probabilistic Anatomical Maps  [PDF]
Tonio Ball, Benjamin Rahm, Simon B. Eickhoff, Andreas Schulze-Bonhage, Oliver Speck, Isabella Mutschler
PLOS ONE , 2007, DOI: 10.1371/journal.pone.0000307
Abstract: The human amygdala is thought to play a pivotal role in the processing of emotionally significant sensory information. The major subdivisions of the human amygdala—the laterobasal group (LB), the superficial group (SF), and the centromedial group (CM)—have been anatomically delineated, but the functional response properties of these amygdala subregions in humans are still unclear. We combined functional MRI with cyto-architectonically defined probabilistic maps to analyze the response characteristics of amygdala subregions in subjects presented with auditory stimuli. We found positive auditory stimulation-related signal changes predominantly in probabilistically defined LB, and negative responses predominantly in SF and CM. In the left amygdala, mean response magnitude in the core area of LB with 90–100% assignment probability was significantly larger than in the core areas of SF and CM. These differences were observed for pleasant and unpleasant stimuli. Our findings reveal that the probabilistically defined anatomical subregions of the human amygdala show distinctive fMRI response patterns. The stronger auditory responses in LB as compared with SF and CM may reflect a predominance of auditory inputs to human LB, similar to many animal species in which the majority of sensory, including auditory, afferents project to this subdivision of the amygdala. Our study indicates that the intrinsic functional differentiation of the human amygdala may be probed using fMRI combined with probabilistic anatomical maps.
Altered Effective Connectivity Network of the Amygdala in Social Anxiety Disorder: A Resting-State fMRI Study  [PDF]
Wei Liao,Changjian Qiu,Claudio Gentili,Martin Walter,Zhengyong Pan,Jurong Ding,Wei Zhang,Qiyong Gong,Huafu Chen
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015238
Abstract: The amygdala is often found to be abnormally recruited in social anxiety disorder (SAD) patients. The question whether amygdala activation is primarily abnormal and affects other brain systems or whether it responds “normally” to an abnormal pattern of information conveyed by other brain structures remained unanswered. To address this question, we investigated a network of effective connectivity associated with the amygdala using Granger causality analysis on resting-state functional MRI data of 22 SAD patients and 21 healthy controls (HC). Implications of abnormal effective connectivity and clinical severity were investigated using the Liebowitz Social Anxiety Scale (LSAS). Decreased influence from inferior temporal gyrus (ITG) to amygdala was found in SAD, while bidirectional influences between amygdala and visual cortices were increased compared to HCs. Clinical relevance of decreased effective connectivity from ITG to amygdala was suggested by a negative correlation of LSAS avoidance scores and the value of Granger causality. Our study is the first to reveal a network of abnormal effective connectivity of core structures in SAD. This is in support of a disregulation in predescribed modules involved in affect control. The amygdala is placed in a central position of dysfunction characterized both by decreased regulatory influence of orbitofrontal cortex and increased crosstalk with visual cortex. The model which is proposed based on our results lends neurobiological support towards cognitive models considering disinhibition and an attentional bias towards negative stimuli as a core feature of the disorder.
Resting-state connectivity of the amygdala is altered following Pavlovian fear conditioning  [PDF]
Douglas H. Schultz,Nicholas L. Balderston,Fred J. Helmstetter
Frontiers in Human Neuroscience , 2012, DOI: 10.3389/fnhum.2012.00242
Abstract: Neural plasticity in the amygdala is necessary for the acquisition and storage of memory in Pavlovian fear conditioning, but most neuroimaging studies have focused only on stimulus-evoked responses during the conditioning session. This study examined changes in the resting-state functional connectivity (RSFC) of the amygdala before and after Pavlovian fear conditioning, an emotional learning task. Behavioral results from the conditioning session revealed that participants learned normally and fMRI data recorded during learning identified a number of stimulus-evoked changes that were consistent with previous work. A direct comparison between the pre- and post-conditioning amygdala connectivity revealed a region of dorsal prefrontal cortex (PFC) in the superior frontal gyrus that showed a significant increase in connectivity following the conditioning session. A behavioral measure of explicit memory performance was positively correlated with the change in amygdala connectivity within a neighboring region in the superior frontal gyrus. Additionally, an implicit autonomic measure of conditioning was positively correlated with the change in connectivity between the amygdala and the anterior cingulate cortex (ACC). The resting-state data show that amygdala connectivity is altered following Pavlovian fear conditioning and that these changes are also related to behavioral outcomes. These alterations may reflect the operation of a consolidation process that strengthens neural connections to support memory after the learning event.
DARU : Journal of Pharmaceutical Sciences , 2000,
Abstract: The present study examined the significance of glucocorticoid receptors (GRs) in the basolateral amygdala (BLA) on place avoidance memory in male rats. Rats were trained to avoid footshock in a 60° segment while foraging for scattered food on a circular (80-cm diameter) arena. The rats were injected bilaterally in the BLA with the specific GR antagonist RU 38486 (3 ng dissolved in 1 ul 2% ethanol) before acquisition, after training or before retrieval of the place avoidance task. Control rats were injected with vehicle. The learning in a single 30-min session was assessed 24h later by a 30 min extinction trial in which the time to first entrance and the number of entrances to the shocked area measured the avoidance memory. Acquisition and consolidation were impaired when the drug was injected 10 min before training, immediately after training, or 60 min after training (P<0.01), but not 120 min after training. In contrast, injection of the antagonist before the retrieval test was ineffective (P>0.05). These findings indicate that glucocorticoids affect memory storage at least in part by binding directly to GR in the BLA and provide further evidences for the opinion that the BLA plays an important role in integrating hormonal and neurotransmitter influences on memory storage.
Sexually dimorphic effects of oxytocin receptor gene (OXTR ) variants on Harm Avoidance  [cached]
Stankova Trayana,Eichhammer Peter,Langguth Berthold,Sand Philipp G
Biology of Sex Differences , 2012, DOI: 10.1186/2042-6410-3-17
Abstract: Background Recent research has suggested that oxytocin receptor gene (OXTR) variants may account for individual differences in social behavior, the effects of stress and parenting styles. Little is known, however, on a putative role of the gene in heritable temperamental traits. Methods We addressed effects of two common OXTR variants, rs237900 and rs237902, on personality dimensions in 99 healthy subjects using the Temperament and Character Inventory. Results When sex was controlled for and an OXTR genotype*sex interaction term was included in the regression model, 11% of the variance in Harm Avoidance could be explained (uncorrected p ≤ 0.01). Female carriers of the minor alleles scored highest, and a novel A217T mutation emerged in the most harm avoidant male participant. Conclusions Findings lend support to a modulatory effect of common OXTR variants on Harm Avoidance in healthy caucasian women and invite resequencing of the gene in anxiety phenotypes to identify more explanatory functional variation.
Altered Amygdala Resting-State Functional Connectivity in Post-Traumatic Stress Disorder  [PDF]
Christine A. Rabinak,Robert C. Welsh,K. Luan Phan
Frontiers in Psychiatry , 2011, DOI: 10.3389/fpsyt.2011.00062
Abstract: Post-traumatic stress disorder (PTSD) is often characterized by aberrant amygdala activation and functional abnormalities in corticolimbic circuitry, as elucidated by functional neuroimaging. These “activation” studies have primarily relied on tasks designed to induce region-specific, and task-dependent brain responses in limbic (e.g., amygdala) and paralimbic brain areas through the use of aversive evocative probes. It remains unknown if these corticolimbic circuit abnormalities exist at baseline or “at rest,” in the absence of fear/anxiety-related provocation and outside the context of task demands. Therefore the primary aim of the present experiment was to investigate aberrant amygdala functional connectivity patterns in combat-related PTSD patients during resting-state. Seventeen Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans with combat-related PTSD (PTSD group) and 17 combat-exposed OEF/OIF veterans without PTSD [combat-exposed control (CEC) group] underwent an 8-min resting-state functional magnetic resonance imaging scan. Using an anatomically derived amygdala “seed” region we observed stronger functional coupling between the amygdala and insula in the PTSD group compared to the CEC group, but did not find group differences in amygdala–prefrontal connectivity. These findings suggest that the aberrant amygdala and insula activation to fear-evocative probes previously characterized in PTSD may be driven by an underlying enhanced connectivity between the amygdala, a region known for perceiving threat and generating fear responses, and the insula, a region known for processing the meaning and prediction of aversive bodily states. This enhanced amygdala–insula connectivity may reflect an exaggerated, pervasive state of arousal that exists outside the presence of an overt actual threat/danger. Studying amygdala functional connectivity “at rest” extends our understanding of the pathophysiology of PTSD.
5-HTTLPR Polymorphism Impacts Task-Evoked and Resting-State Activities of the Amygdala in Han Chinese  [PDF]
Sufang Li, Qihong Zou, Jun Li, Jin Li, Deyi Wang, Chaogan Yan, Qi Dong, Yu-Feng Zang
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0036513
Abstract: Background Prior research has shown that the amygdala of carriers of the short allele (s) of the serotonin transporter (5-HTT) gene (5-HTTLPR) have a larger response to negative emotional stimuli and higher spontaneous activity during the resting state than non-carriers. However, recent studies have suggested that the effects of 5-HTTLPR may be specific to different ethnic groups. Few studies have been conducted to address this issue. Methodology/Principal Findings Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) was conducted on thirty-eight healthy Han Chinese subjects (l/l group, n = 19; s/s group, n = 19) during the resting state and during an emotional processing task. Compared with the s/s group, the l/l group showed significantly increased regional homogeneity or local synchronization in the right amygdala during the resting state (|t|>2.028, p<0.05, corrected), but no significant difference was found in the bilateral amygdala in response to negative stimuli in the emotional processing task. Conclusions/Significance 5-HTTLPR can alter the spontaneous activity of the amygdala in Han Chinese. However, the effect of 5-HTTLPR on the amygdala both in task state and resting state in Asian population was no similar with Caucasians. They suggest that the effect of 5-HTTLPR on the amygdala may be modulated by ethnic differences.
Infusions of AP5 into the basolateral amygdala impair the formation, but not the expression, of step-down inhibitory avoidance
Roesler, R.;Vianna, M.R.M.;de-Paris, F.;Quevedo, J.;Walz, R.;Bianchin, M.;
Brazilian Journal of Medical and Biological Research , 2000, DOI: 10.1590/S0100-879X2000000700014
Abstract: we evaluated the effects of infusions of the nmda receptor antagonist d,l-2-amino-5-phosphonopentanoic acid (ap5) into the basolateral nucleus of the amygdala (bla) on the formation and expression of memory for inhibitory avoidance. adult male wistar rats (215-300 g) were implanted under thionembutal anesthesia (30 mg/kg, ip) with 9.0-mm guide cannulae aimed 1.0 mm above the bla. bilateral infusions of ap5 (5.0 μg) were given 10 min prior to training, immediately after training, or 10 min prior to testing in a step-down inhibitory avoidance task (0.3 ma footshock, 24-h interval between training and the retention test session). both pre- and post-training infusions of ap5 blocked retention test performance. when given prior to the test, ap5 did not affect retention. ap5 did not affect training performance, and a control experiment showed that the impairing effects were not due to alterations in footshock sensitivity. the results suggest that nmda receptor activation in the bla is involved in the formation, but not the expression, of memory for inhibitory avoidance in rats. however, the results do not necessarily imply that the role of nmda receptors in the bla is to mediate long-term storage of fear-motivated memory within the amygdala.
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