scholarly journals Human fear conditioning depends on stimulus contingency instructions

2020 ◽  
Author(s):  
Gaëtan Mertens ◽  
Yannick Boddez ◽  
Angelos-Miltiadis Krypotos ◽  
Iris Engelhard
Keyword(s):  
Fear Conditioning ◽  
Conditioned Fear ◽  
Automatic Process ◽  
Conditioning Phase ◽  
Acquisition Rate ◽  
Stimulus Contingency ◽  
Verbal Instructions ◽  
Research Findings ◽  
Higher Cognitive Functions ◽  
Contingency Reversal

Human fear conditioning is often seen as the result of a highly automatic process that is independent of higher cognitive functions and verbal instructions. However, cumulative research findings call this view into question. In the current preregistered study (N = 102), we investigated whether the number of participants who successfully show conditioned fear acquisition depends on the instructions given to them before the fear conditioning phase. Particularly, one third of the participants were instructed about the precise contingency between the conditioned stimulus (CS) and unconditioned stimulus (US). Another third was merely instructed that there would be a contingency. The last third did not get any instructions about the CS-US contingency. We found facilitated fear acquisition rate in the first and second group compared to the third group. Furthermore, contingency reversal instructions following the acquisition phase reversed both conditioned skin conductance and startle responses. These results highlight that researchers should systematically report the instructions given to participants in human fear conditioning studies.

scholarly journals Fear-induced brain activations distinguish anxious and trauma-exposed brains

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Zhenfu Wen ◽  
Marie-France Marin ◽  
Jennifer Urbano Blackford ◽  
Zhe Sage Chen ◽  
Mohammed R. Milad
Keyword(s):  
Neural Network ◽  
Fear Conditioning ◽  
Psychiatric Diagnosis ◽  
Data Analytics ◽  
Conditioned Fear ◽  
Brain Regions ◽  
Brain Network ◽  
Neuroimaging Data ◽  
Task Irrelevant ◽  
Translational Models

AbstractTranslational models of fear conditioning and extinction have elucidated a core neural network involved in the learning, consolidation, and expression of conditioned fear and its extinction. Anxious or trauma-exposed brains are characterized by dysregulated neural activations within regions of this fear network. In this study, we examined how the functional MRI activations of 10 brain regions commonly activated during fear conditioning and extinction might distinguish anxious or trauma-exposed brains from controls. To achieve this, activations during four phases of a fear conditioning and extinction paradigm in 304 participants with or without a psychiatric diagnosis were studied. By training convolutional neural networks (CNNs) using task-specific brain activations, we reliably distinguished the anxious and trauma-exposed brains from controls. The performance of models decreased significantly when we trained our CNN using activations from task-irrelevant brain regions or from a brain network that is irrelevant to fear. Our results suggest that neuroimaging data analytics of task-induced brain activations within the fear network might provide novel prospects for development of brain-based psychiatric diagnosis.

scholarly journals Fear conditioning and stimulus generalization in association with age in children and adolescents

2021 ◽  
Author(s):  
Julia Reinhard ◽  
Anna Slyschak ◽  
Miriam A. Schiele ◽  
Marta Andreatta ◽  
Katharina Kneer ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Fear Conditioning ◽  
Repeated Measures ◽  
Conditioned Fear ◽  
Fear Learning ◽  
Stimulus Generalization ◽  
Healthy Children ◽  
Older Individuals ◽  
Age Related ◽  
Current Task

AbstractThe aim of the study was to investigate age-related differences in fear learning and generalization in healthy children and adolescents (n = 133), aged 8–17 years, using an aversive discriminative fear conditioning and generalization paradigm adapted from Lau et al. (2008). In the current task, participants underwent 24 trials of discriminative conditioning of two female faces with neutral facial expressions, with (CS+) or without (CS−) a 95-dB loud female scream, presented simultaneously with a fearful facial expression (US). The discriminative conditioning was followed by 72 generalization trials (12 CS+, 12 GS1, 12 GS2, 12 GS3, 12 GS4, and 12 CS−): four generalization stimuli depicting gradual morphs from CS+ to CS− in 20%-steps were created for the generalization phases. We hypothesized that generalization in children and adolescents is negatively correlated with age. The subjective ratings of valence, arousal, and US expectancy (the probability of an aversive noise following each stimulus), as well as skin conductance responses (SCRs) were measured. Repeated-measures ANOVAs on ratings and SCR amplitudes were calculated with the within-subject factors stimulus type (CS+, CS−, GS1-4) and phase (Pre-Acquisition, Acquisition 1, Acquisition 2, Generalization 1, Generalization 2). To analyze the modulatory role of age, we additionally calculated ANCOVAs considering age as covariate. Results indicated that (1) subjective and physiological responses were generally lower with increasing age irrespective to the stimulus quality, and (2) stimulus discrimination improved with increasing age paralleled by reduced overgeneralization in older individuals. Longitudinal follow-up studies are required to analyze fear generalization with regard to brain maturational aspects and clarify whether overgeneralization of conditioned fear promotes the development of anxiety disorders or vice versa.

scholarly journals Fear signaling in the prelimbic-amygdala circuit: a computational modeling and recording study

2013 ◽  
Vol 110 (4) ◽  
pp. 844-861 ◽  
Author(s):  
Sandeep Pendyam ◽  
Christian Bravo-Rivera ◽  
Anthony Burgos-Robles ◽  
Francisco Sotres-Bayon ◽  
Gregory J. Quirk ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Fear Conditioning ◽  
Large Scale ◽  
Conditioned Fear ◽  
Individual Variability ◽  
Biophysical Model ◽  
Human Homolog ◽  
Lateral Amygdala ◽  
Internal Inhibition ◽  
Β Blocker

The acquisition and expression of conditioned fear depends on prefrontal-amygdala circuits. Auditory fear conditioning increases the tone responses of lateral amygdala neurons, but the increase is transient, lasting only a few hundred milliseconds after tone onset. It was recently reported that that the prelimbic (PL) prefrontal cortex transforms transient lateral amygdala input into a sustained PL output, which could drive fear responses via projections to the lateral division of basal amygdala (BL). To explore the possible mechanisms involved in this transformation, we developed a large-scale biophysical model of the BL-PL network, consisting of 850 conductance-based Hodgkin-Huxley-type cells, calcium-based learning, and neuromodulator effects. The model predicts that sustained firing in PL can be derived from BL-induced release of dopamine and norepinephrine that is maintained by PL-BL interconnections. These predictions were confirmed with physiological recordings from PL neurons during fear conditioning with the selective β-blocker propranolol and by inactivation of BL with muscimol. Our model suggests that PL has a higher bandwidth than BL, due to PL's decreased internal inhibition and lower spiking thresholds. It also suggests that variations in specific microcircuits in the PL-BL interconnection can have a significant impact on the expression of fear, possibly explaining individual variability in fear responses. The human homolog of PL could thus be an effective target for anxiety disorders.

764 Neural activation accompanying fear conditioning and extinction in Generalized Anxiety Disorder with and without Insomnia Disorder

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A297-A298
Author(s):  
Jeehye Seo ◽  
Katelyn Oliver ◽  
Carolina Daffre ◽  
Natasha Lasko ◽  
Edward Pace-Schott
Keyword(s):  
Anxiety Disorder ◽  
Sleep Quality ◽  
Fear Conditioning ◽  
Generalized Anxiety Disorder ◽  
Conditioned Fear ◽  
Generalized Anxiety ◽  
Neural Activation ◽  
Extinction Learning ◽  
Regulatory Regions ◽  
Insomnia Disorder

Abstract Introduction We examined associations of sleep quality with neural responses to fear conditioning and extinction in individuals with Generalized Anxiety Disorder (GAD) with (INS) and without (NOI) Insomnia Disorder (ID). We hypothesized fear-related regions would show greater, and emotion-regulatory regions lesser activity in INS versus NOI and across both groups with decreasing sleep quality. Methods Participants were assigned to either an INS group with Insomnia Severity Index (ISI) ≥ 13 (N=21) or NOI with ISI ≤ 12 (N=14). Two weeks of actigraphy and sleep diaries were followed by a 2-session protocol with fMRI. During Session 1, mild electric shock produced conditioned fear to 2 different colors (CS+s) but not a third (CS-) (Fear Conditioning). Immediately afterward, one CS+ (CS+E) but not the other (CS+U) was extinguished (Extinction Learning). All 3 stimuli were presented 24h later (Extinction Recall). An acclimation/diagnostic ambulatory polysomnography (PSG) night was followed by PSGs before Session 1 and between Sessions 1 and 2. Using SPM8, t-tests compared groups, and multiple regressions predicted anterior cerebral activations (as a whole and as ROIs) using ISI, actigraph and diary sleep efficiency (SE) and latency (SOL), and sleep architecture. Results Beginning Fear Conditioning, differential activation to the reinforced stimulus (CS+>CS-) in the right insula was greater in INS than NOI, and greater actigraph SE predicted greater prefrontal activation. Change in activation to the CS+ across Extinction Learning (late CS+>early CS+) did not differentiate groups or correlate with sleep measures. During Extinction Recall, NOI versus INS showed less activation in bilateral amygdala ROIs (CS+E>CS-) but more activation in prefrontal regulatory regions (CS+U>CS-) and bilateral insula ROIs (both contrasts). Greater activation of prefrontal emotion-regulatory areas was associated with greater REM% (CS+E>CS+U and CS+E>CS-), lesser ISI (CS+E>CS- and CS+U>CS-), and greater actigraph SE (CS+U>CS). However for CS+E>CS+U, lesser diary SE and greater ISI were associated with greater prefrontal activity. Conclusion Results, on balance, suggest that persons with GAD and ID activated more fear-related and less prefrontal emotion-regulatory regions during fear conditioning and extinction recall than those with GAD alone. Across groups, greater REM% and sleep quality were associated with greater activity of emotion-regulatory areas. Support (if any) Funding: R21MH115279, R01MH109638

scholarly journals Human fear conditioning is moderated by stimulus contingency instructions

2021 ◽  
Vol 158 ◽  
pp. 107994
Author(s):  
Gaëtan Mertens ◽  
Yannick Boddez ◽  
Angelos-Miltiadis Krypotos ◽  
Iris M. Engelhard
Keyword(s):  
Fear Conditioning ◽  
Stimulus Contingency

scholarly journals A Biologically Realistic Network Model of Acquisition and Extinction of Conditioned Fear Associations in Lateral Amygdala Neurons

2009 ◽  
Vol 101 (3) ◽  
pp. 1629-1646 ◽  
Author(s):  
Guoshi Li ◽  
Satish S. Nair ◽  
Gregory J. Quirk
Keyword(s):  
Fear Conditioning ◽  
Network Model ◽  
Basolateral Amygdala ◽  
Conditioned Fear ◽  
Pyramidal Cells ◽  
Model Learning ◽  
Lateral Amygdala ◽  
Single Structure ◽  
Firing Properties

The basolateral amygdala plays an important role in the acquisition and expression of both fear conditioning and fear extinction. To understand how a single structure could encode these “opposite” memories, we developed a biophysical network model of the lateral amygdala (LA) neurons during auditory fear conditioning and extinction. Membrane channel properties were selected to match waveforms and firing properties of pyramidal cells and interneurons in LA, from published in vitro studies. Hebbian plasticity was implemented in excitatory AMPA and inhibitory GABAA receptor-mediated synapses to model learning. The occurrence of synaptic potentiation versus depression was determined by intracellular calcium levels, according to the calcium control hypothesis. The model was able to replicate conditioning- and extinction-induced changes in tone responses of LA neurons in behaving rats. Our main finding is that LA activity during both acquisition and extinction can be controlled by a balance between pyramidal cell and interneuron activations. Extinction training depressed conditioned synapses and also potentiated local interneurons, thereby inhibiting the responses of pyramidal cells to auditory input. Both long-term depression and potentiation of inhibition were required to initiate and maintain extinction. The model provides insights into the sites of plasticity in conditioning and extinction, the mechanism of spontaneous recovery, and the role of amygdala NMDA receptors in extinction learning.

scholarly journals Vagus Nerve Stimulation Enhances Extinction of Conditioned Fear in Rats and Modulates Arc Protein, CaMKII, and GluN2B-Containing NMDA Receptors in the Basolateral Amygdala

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Amanda C. Alvarez-Dieppa ◽  
Kimberly Griffin ◽  
Sheridan Cavalier ◽  
Christa K. McIntyre
Keyword(s):  
Synaptic Plasticity ◽  
Vagus Nerve ◽  
Nmda Receptors ◽  
Fear Conditioning ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Basolateral Amygdala ◽  
Conditioned Fear ◽  
Associated Proteins

Vagus nerve stimulation (VNS) enhances the consolidation of extinction of conditioned fear. High frequency stimulation of the infralimbic cortex (IL) produces long-term potentiation in the basolateral amygdala (BLA) in rats given VNS-paired extinction training, whereas the same stimulation produces long-term depression in sham-treated rats. The present study investigated the state of synaptic plasticity-associated proteins in the BLA that could be responsible for this shift. Male Sprague-Dawley rats were separated into 4 groups: auditory fear conditioning only (fear-conditioned); fear conditioning + 20 extinction trials (extended-extinction); fear conditioning + 4 extinction trials paired with sham stimulation (sham-extinction); fear conditioning + 4 extinction trials paired with VNS (VNS-extinction). Freezing was significantly reduced in extended-extinction and VNS-extinction rats. Western blots were used to quantify expression and phosphorylation state of synaptic plasticity-associated proteins such as Arc, CaMKII, ERK, PKA, and AMPA and NMDA receptors. Results show significant increases in GluN2B expression and phosphorylated CaMKII in BLA samples from VNS- and extended-extinction rats. Arc expression was significantly reduced in VNS-extinction rats compared to all groups. Administration of the GluN2B antagonist ifenprodil immediately after fear extinction training blocked consolidation of extinction learning. Results indicate a role for BLA CaMKII-induced GluN2B expression and reduced Arc protein in VNS-enhanced extinction.

scholarly journals Rule-based processes in generalisation and peak shift in human fear conditioning

2018 ◽  
Vol 72 (2) ◽  
pp. 118-131 ◽  
Author(s):  
Ola Ahmed ◽  
Peter F Lovibond
Keyword(s):  
Fear Conditioning ◽  
Electric Shock ◽  
Aversive Stimulus ◽  
Conditioned Fear ◽  
Peak Shift ◽  
Test Phase ◽  
Conditioned Stimuli ◽  
Rule Based ◽  
Extinction Testing

Two experiments explored the role of verbalisable rules in generalisation of human differential fear conditioning with electric shock as the aversive stimulus. Two circles of different sizes served as conditioned stimuli (CS+ and CS–), before testing with a range of circle sizes. In Experiment 1, shock expectancy ratings followed a peak-shifted unimodal gradient, with maximum ratings at a test value further along the dimension from CS+ in the opposite direction to CS–. However, differentiable gradients were observed when participants were divided on the basis of the rules they reported using during the task (linear and similarity). Experiment 2 was designed to counter the contradictory feedback arising from extinction testing by removing the shock electrodes during the test phase. A more linear overall gradient was observed, and sub-groups defined by self-reported rules showed distinct gradients that were congruent with their rules. These results indicate that rule-based processes are influential in generalisation of conditioned fear along simple stimulus dimensions, and may help explain generalisation phenomena that have traditionally been attributed to automatic, similarity-based processes.

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