Neural correlates of trait anxiety in fear extinction

2010 ◽  
Vol 41 (4) ◽  
pp. 789-798 ◽  
Author(s):  
C. Sehlmeyer ◽  
U. Dannlowski ◽  
S. Schöning ◽  
H. Kugel ◽  
M. Pyka ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Trait Anxiety ◽  
Conditioned Fear ◽  
Neural Correlates ◽  
Fear Extinction ◽  
Anterior Cingulate ◽  
Dorsal Anterior Cingulate Cortex ◽  
Neural Structure ◽  
Amygdala Activation ◽  
Conditioned Responses

BackgroundFear conditioning involves the amygdala as the main neural structure for learning fear responses whereas fear extinction mainly activates the inhibitory prefrontal cortex (PFC). In this study we investigated whether individual differences in trait anxiety affect amygdala and dorsal anterior cingulate cortex (dACC) activation during fear conditioning and extinction.MethodThirty-two healthy subjects were investigated by functional magnetic resonance imaging (fMRI) at 3 T while performing a cued fear-conditioning task. All participants completed the trait version of the State-Trait Anxiety Inventory (STAI-T). Activations of the amygdala and the dACC were examined with respect to the effects of trait anxiety.ResultsAnalysis of the fMRI data demonstrated enhanced activation in fear-related brain areas, such as the insula and the ACC, during both fear conditioning and extinction. Activation of the amygdala appeared only during the late acquisition phase whereas deactivation was observed during extinction. Regression analyses revealed that highly trait-anxious subjects exhibited sustained amygdala activation and reduced dACC involvement during the extinction of conditioned responses.ConclusionsThis study reveals that high levels of trait anxiety are associated with both increased amygdala activation and reduced dACC recruitment during the extinction of conditioned fear. This hyper-responsitivity of the amygdala and the deficient cognitive control during the extinction of conditioned fear in anxious subjects reflect an increased resistance to extinct fear responses and may thereby enhance the vulnerability to developing anxiety disorders.

scholarly journals Regular Music Exposure in Juvenile Rats Facilitates Conditioned Fear Extinction and Reduces Anxiety after Foot Shock in Adulthood

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Si Chen ◽  
Tuo Liang ◽  
Fiona H. Zhou ◽  
Ye Cao ◽  
Chao Wang ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Conditioned Fear ◽  
Conditioning Session ◽  
Fear Extinction ◽  
Extinction Training ◽  
Anterior Cingulate ◽  
Stressful Event ◽  
Sprague Dawley ◽  
Positive Role ◽  
Juvenile Rats

Music exposure is known to play a positive role in learning and memory and can be a complementary treatment for anxiety and fear. However, whether juvenile music exposure affects adult behavior is not known. Two-week-old Sprague-Dawley rats were exposed to music for 2 hours daily or to background noise (controls) for a period of 3 weeks. At 60 days of age, rats were subjected to auditory fear conditioning, fear extinction training, and anxiety-like behavior assessments or to anterior cingulate cortex (ACC) brain-derived neurotrophic factor (BDNF) assays. We found that the music-exposed rats showed significantly less freezing behaviors during fear extinction training and spent more time in the open arm of the elevated plus maze after fear conditioning when compared with the control rats. Moreover, the BDNF levels in the ACC in the music group were significantly higher than those of the controls with the fear conditioning session. This result suggests that music exposure in juvenile rats decreases anxiety-like behaviors, facilitates fear extinction, and increases BDNF levels in the ACC in adulthood after a stressful event.

A neurobehavioral account for individual differences in resilience to chronic military stress

2014 ◽  
Vol 45 (5) ◽  
pp. 1011-1023 ◽  
Author(s):  
T. Lin ◽  
S. Vaisvaser ◽  
E. Fruchter ◽  
R. Admon ◽  
I. Wald ◽  
...  
Keyword(s):  
Trait Anxiety ◽  
Military Training ◽  
Anterior Cingulate ◽  
Trauma Symptoms ◽  
Brain Response ◽  
Threat Bias ◽  
Dorsal Anterior Cingulate Cortex ◽  
High Anxious ◽  
Hippocampal Activity ◽  
Military Stress

Background.Military training is a chronic stressful period that often induces stress-related psychopathology. Stress vulnerability and resilience depend on personality trait anxiety, attentional threat bias and prefrontal–limbic dysfunction. However, how these neurobehavioral elements interact with regard to the development of symptoms following stress remains unclear.Method.Fifty-five healthy combat soldiers undergoing intensive military training completed functional magnetic resonance imaging (fMRI) testing while performing the dot-probe task (DPT) composed of angry (threat) and neutral faces. Participants were then stratified according to their bias tendency to avoidance (n = 25) or vigilance (n = 30) groups, categorized as high or low trait anxiety and assessed for post-stress symptom severity.Results.Avoidance compared to vigilance tendency was associated with fewer post-trauma symptoms and increased hippocampal response to threat among high anxious but not low anxious individuals. Importantly, mediation analysis revealed that only among high anxious individuals did hippocampal activity lead to lower levels of symptoms through avoidance bias tendency. However, in the whole group, avoidance bias was modulated by the interplay between the hippocampus and the dorsal anterior cingulate cortex (dACC).Conclusions.Our results provide a neurobehavioral model to explain the resilience to post-trauma symptoms following chronic exposure. The model points to the importance of considering threat bias tendency in addition to personality traits when investigating the brain response and symptoms of trauma. Such a multi-parametric approach that accounts for individual behavioral sensitivities may also improve brain-driven treatments of anxiety, possibly by targeting the interplay between the hippocampus and the dACC.

scholarly journals Revisiting potential associations between brain morphology, fear acquisition and extinction through new data and a literature review

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mana R. Ehlers ◽  
Janne Nold ◽  
Manuel Kuhn ◽  
Maren Klingelhöfer-Jens ◽  
Tina B. Lonsdorf
Keyword(s):  
Individual Differences ◽  
Fear Conditioning ◽  
Cortical Thickness ◽  
Anterior Cingulate ◽  
Brain Morphology ◽  
Small Samples ◽  
Dorsal Anterior Cingulate Cortex ◽  
Defensive Responding ◽  
Brain Behavior ◽  
Subcortical Volume

AbstractInter-individual differences in defensive responding are widely established but their morphological correlates in humans have not been investigated exhaustively. Previous studies reported associations with cortical thickness of the dorsal anterior cingulate cortex, insula and medial orbitofrontal cortex as well as amygdala volume in fear conditioning studies. However, these associations are partly inconsistent and often derived from small samples. The current study aimed to replicate previously reported associations between physiological and subjective measures of fear acquisition and extinction and brain morphology. Structural magnetic resonance imaging was performed on 107 healthy adults who completed a differential cued fear conditioning paradigm with 24 h delayed extinction while skin conductance response (SCR) and fear ratings were recorded. Cortical thickness and subcortical volume were obtained using the software Freesurfer. Results obtained by traditional null hypothesis significance testing and Bayesians statistics do not support structural brain-behavior relationships: Neither differential SCR nor fear ratings during fear acquisition or extinction training could be predicted by cortical thickness or subcortical volume in regions previously reported. In summary, the current pre-registered study does not corroborate associations between brain morphology and inter-individual differences in defensive responding but differences in experimental design and analyses approaches compared to previous work should be acknowledged.

scholarly journals Medial Cortical Structures Mediate Implicit Trustworthiness Judgments about Kin Faces, but Not Familiar Faces: A Brief Report

Psych ◽  
2019 ◽  
Vol 1 (1) ◽  
pp. 482-490 ◽  
Author(s):  
Steven M. Platek ◽  
Judson C. Hendry
Keyword(s):  
Right Hemisphere ◽  
Kin Recognition ◽  
Insular Cortex ◽  
Neural Correlates ◽  
The Self ◽  
Anterior Cingulate ◽  
Dorsal Anterior Cingulate Cortex ◽  
Facial Stimuli ◽  
The Right ◽  
Processing Network

Human kin recognition activates substrates of the extended facial processing network, notably the right-hemisphere structures involved in self-face recognition and posterior medial cortical substrates. To understand the mechanisms underlying prosociality toward kin faces in comparison to other familiar faces, we investigated the neural correlates of implicit trustworthiness ratings to faces of actual kin and personal friends, controlling for activation to distracter faces. When controlling for activation associated with unknown faces, trustworthiness ratings of faces of kin, compared to friends, were associated with increased activation in the dorsal anterior cingulate cortex, posterior cingulate, and precuneous. On the other hand, trustworthiness ratings of friend faces, relative to kin faces, were associated with the lateral occipital gyrus and insular cortex. Trustworthiness ratings for unknown faces were only associated with activation in the fusiform gyrus. These findings suggest that we should employ medial cortical substrates known to be part of the self-other network when making implicit social judgements about kin, but not other classes of facial stimuli.

Neural correlates of trauma-unrelated emotional processing in war veterans with PTSD

2014 ◽  
Vol 45 (3) ◽  
pp. 575-587 ◽  
Author(s):  
S. J. H. van Rooij ◽  
A. R. Rademaker ◽  
M. Kennis ◽  
M. Vink ◽  
R. S. Kahn ◽  
...  
Keyword(s):  
Emotional Processing ◽  
Negative Contrast ◽  
Anterior Cingulate ◽  
Post Traumatic Stress ◽  
Dorsal Anterior Cingulate Cortex ◽  
Superior Frontal Gyrus ◽  
Amygdala Activation ◽  
Amygdala Response ◽  
Post Traumatic ◽  
Emotional Pictures

BackgroundPost-traumatic stress disorder (PTSD) is thought to be characterized by general heightened amygdala activation. However, this hypothesis is mainly based on specific studies presenting fear or trauma-related stimuli, hence, a thorough investigation of trauma-unrelated emotional processing in PTSD is needed.MethodsIn this study, 31 male medication-naive veterans with PTSD, 28 male control veterans (combat controls; CC) and 25 non-military men (healthy controls; HC) were included. Participants underwent functional MRI while trauma-unrelated neutral, negative and positive emotional pictures were presented. In addition to the group analyses, PTSD patients with and without major depressive disorder (MDD) were compared.ResultsAll groups showed an increased amygdala response to negative and positive contrasts, but amygdala activation did not differ between groups. However, a heightened dorsal anterior cingulate cortex (dACC) response for negative contrasts was observed in PTSD patients compared to HC. The medial superior frontal gyrus was deactivated in the negative contrast in HC, but not in veterans. PTSD+MDD patients showed decreased subgenual ACC (sgACC) activation to all pictures compared to PTSD–MDD.ConclusionOur findings do not support the hypothesis that increased amygdala activation in PTSD generalizes to trauma-unrelated emotional processing. Instead, the increased dACC response found in PTSD patients implicates an attentional bias that extends to trauma-unrelated negative stimuli. Only HC showed decreased medial superior frontal gyrus activation. Finally, decreased sgACC activation was related to MDD status within the PTSD group.

scholarly journals SUN-235 Deficient Fear Extinction in PRKAR1A-Defective Mice

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Margaret Keil ◽  
Enrica Paradiso ◽  
Rita S Keil ◽  
Maddalena Ugolini ◽  
Evan Harris ◽  
...  
Keyword(s):  
Gene Expression ◽  
Fear Conditioning ◽  
Conditioned Fear ◽  
Critical Role ◽  
Fear Memory ◽  
Brain Regions ◽  
Fear Extinction ◽  
Carney Complex ◽  
Bdnf Gene ◽  
Extinction Learning

Abstract Background: The role of the cAMP/PKA signaling in molecular pathways involved in fear memory is well established: PKA is required for fear memory formation and is a constraint for fear extinction. Previously we reported that a Prkar1a heterozygote (HZ) mouse that was developed in our lab to investigate Carney complex (CNC), the disease caused by PRKAR1A mutations, showed brain region-specific increased PKA activity that was associated with anxiety-like behavioral phenotype and threat bias (Keil, 2010, 2013). We hypothesized that Prkar1a+/- (HZ) mice would have deficits in fear extinction behavior. Brain derived neurotrophic factor (BDNF) has a critical role in formation of fear memory and its transcription is regulated by PKA/CREB. A mouse model with down regulation of PKA provides an opportunity for the first time to investigate the effect of altered PKA signaling on fear conditioning and extinction. Method: Fear conditioning, fear extinction learning, and fear extinction recall were tested in adult male HZ and wild-type (WT) mice as follows: fear conditioning training followed 24hr later by extinction training (new context), then 24hr later by extinction recall training. Percentage of time freezing was used to assess conditioned fear response. We measured BDNF gene expression in brain regions after completion of extinction recall training. Results: As expected, fear conditioning (learning) behavior was similar in HZ and WT mice. However, HZ mice showed a significant deficit in the early phase of fear extinction learning compared to WT. There was no difference in extinction recall between genotypes. Alterations in BDNF gene expression in the prefrontal cortex and amygdala was associated with deficit in fear extinction. Conclusion: Mice with a downregulation of Prkar1a gene demonstrate intact fear conditioning but impaired fear extinction learning, consistent with prior studies that report that PKA inhibition is necessary to facilitate extinction learning. Prkar1a+/- mice provide a valuable model to investigate impaired fear extinction to identify mechanisms for therapeutic targets for anxiety and trauma-related disorders.

scholarly journals Backtracking during navigation is correlated with enhanced anterior cingulate activity and suppression of alpha oscillations and the ‘default-mode’ network

2019 ◽  
Vol 286 (1908) ◽  
pp. 20191016 ◽  
Author(s):  
Amir-Homayoun Javadi ◽  
Eva Zita Patai ◽  
Eugenia Marin-Garcia ◽  
Aaron Margois ◽  
Heng-Ru M. Tan ◽  
...  
Keyword(s):  
Error Detection ◽  
Default Mode Network ◽  
Neural Correlates ◽  
Anterior Cingulate ◽  
Dorsal Anterior Cingulate Cortex ◽  
Default Mode ◽  
Current Path ◽  
Desert Island ◽  
Neural Underpinnings ◽  
The Brain

Successful navigation can require realizing the current path choice was a mistake and the best strategy is to retreat along the recent path: ‘back-track’. Despite the wealth of studies on the neural correlates of navigation little is known about backtracking. To explore the neural underpinnings of backtracking we tested humans during functional magnetic resonance imaging on their ability to navigate to a set of goal locations in a virtual desert island riven by lava which constrained the paths that could be taken. We found that on a subset of trials, participants spontaneously chose to backtrack and that the majority of these choices were optimal. During backtracking, activity increased in frontal regions and the dorsal anterior cingulate cortex, while activity was suppressed in regions associated with the core default-mode network. Using the same task, magnetoencephalography and a separate group of participants, we found that power in the alpha band was significantly decreased immediately prior to such backtracking events. These results highlight the importance for navigation of brain networks previously identified in processing internally-generated errors and that such error-detection responses may involve shifting the brain from default-mode states to aid successful spatial orientation.

An fMRI Study Examining Effects of Acute D-Cycloserine During Symptom Provocation in Spider Phobia

CNS Spectrums ◽  
2009 ◽  
Vol 14 (10) ◽  
pp. 556-571 ◽  
Author(s):  
Robin L. Aupperle ◽  
Lisa R. Hale ◽  
Rebecca J. Chambers ◽  
Sharon E. Cain ◽  
Frank X. Barth ◽  
...  
Keyword(s):  
Block Design ◽  
Fear Extinction ◽  
Anterior Cingulate ◽  
Acute Administration ◽  
Symptom Provocation ◽  
Treatment Groups ◽  
Amygdala Activation ◽  
Fmri Study ◽  
Design Paradigm ◽  
To Receive

ABSTRACTBackground: Exposure-based therapy for anxiety disorders is believed to operate on the basis of fear extinction. Studies have shown acute administration of D-cycloserine (DCS) enhances fear extinction in animals and facilitates exposure therapy in humans, but the neural mechanisms are not completely understood. To date, no study has examined neural effects of acute DCS in anxiety-disordered populations.Methods: Two hours prior to functional magnetic resonance imaging scanning, 23 spider-phobic and 23 non-phobic participants were randomized to receive DCS 100 mg or placebo. During scanning, participants viewed spider, butterfly, and Gaussian-blurred baseline images in a block-design paradigm. Diagnostic and treatment groups were compared regarding differential activations to spider versus butterfly stimuli.Results: In the phobic group, DCS enhanced prefrontal (PFC), dorsal anterior cingulate (ACC), and insula activations. For controls, DCS enhanced ventral ACC and caudate activations. There was a positive correlation between lateral PFC and amygdala activation for the placebo-phobic group. Reported distress during symptom provocation was correlated with amygdala activation in the placebo-phobic group and orbitofrontal cortex activation in the DCS-phobic group.Conclusions: Results suggest that during initial phobic symptom provocation DCS enhances activation in regions involved in cognitive control and interoceptive integration, including the PFC, ACC, and insular cortices for phobic participants.

scholarly journals MPP2 Interacts With SK2 Rescue The Excitability of Glutamatergic Neurons in The BLA and Facilitate The Extinction of Conditioned Fear in Mice

2021 ◽  
Author(s):  
Xiao-Han Peng ◽  
Pan-Pan Chen ◽  
Yang Zhang ◽  
Ke Wu ◽  
Ningning Ji ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Basolateral Amygdala ◽  
Conditioned Fear ◽  
Fear Memory ◽  
Fear Extinction ◽  
Definitive Evidence ◽  
Glutamatergic Neurons ◽  
Integral Role ◽  
Calcium Activated Potassium Channel ◽  
Increased Activity

Abstract Posttraumatic stress disorder (PTSD) and other anxiety disorders stem from dysregulated fear memory in which the basolateral amygdala (BLA) plays an integral role. The excitability of glutamatergic neurons in the BLA correlates with fear memory, and the afterhyperpolarization current (IAHP) mediated by small-conductance calcium-activated potassium channel subtype 2 (SK2) dominates the excitability of glutamatergic neurons. However, definitive evidence for the involvement of the SK2 channel in the BLA in fear extinction is lacking. Here, we discovered that fear conditioning decreased the levers of synaptic SK2 channels in the BLA, which were restored following fear extinction. Notably, reduced expression of synaptic SK2 channels in the BLA during fear conditioning was caused by the increased activity of protein kinase A (PKA), while increased levers of synaptic SK2 channels in the BLA during fear extinction were mediated by interactions with membrane palmitoylated protein 2 (MPP2). Collectively, our results revealed that MPP2 interacts with the SK2 channels and rescues the excitability of glutamatergic neurons by increasing the expression of synaptic SK2 channels in the BLA to promote the normalization of fear memory. These findings expand our understanding of the neurobiological mechanism of PTSD and provide a new direction for PTSD treatment.

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