Cued Fear Research Articles

Fear learning alterations after traumatic brain injury and their role in development of posttraumatic stress symptoms

It is unknown how traumatic brain injury (TBI) increases risk for posttraumatic stress disorder (PTSD). One potential mechanism is via alteration of fear-learning processes that could affect responses to trauma memories and cues. We utilized a prospective, longitudinal design to determine if TBI is associated with altered fear learning and extinction, and if fear processing mediates effects of TBI on PTSD symptom change. Eight hundred fifty two active-duty Marines and Navy Corpsmen were assessed before and after deployment. Assessments included TBI history, PTSD symptoms, combat trauma and deployment stress, and a fear-potentiated startle task of fear acquisition and extinction. Startle response and self-reported expectancy and anxiety served as measures of fear conditioning, and PTSD symptoms were measured with the Clinician-Administered PTSD Scale. Individuals endorsing "multiple hit" exposure (both deployment TBI and a prior TBI) showed the strongest fear acquisition and highest fear expression compared to groups without multiple hits. Extinction did not differ across groups. Endorsing a deployment TBI was associated with higher anxiety to the fear cue compared to those without deployment TBI. The association of deployment TBI with increased postdeployment PTSD symptoms was mediated by postdeployment fear expression when recent prior-TBI exposure was included as a moderator. TBI associations with increased response to threat cues and PTSD symptoms remained when controlling for deployment trauma and postdeployment PTSD diagnosis. Deployment TBI, and multiple-hit TBI in particular, are associated with increases in conditioned fear learning and expression that may contribute to risk for developing PTSD symptoms.

GIRK2 splice variants and neuronal G protein-gated K+ channels: implications for channel function and behavior

Many neurotransmitters directly inhibit neurons by activating G protein-gated inwardly rectifying K+ (GIRK) channels, thereby moderating the influence of excitatory input on neuronal excitability. While most neuronal GIRK channels are formed by GIRK1 and GIRK2 subunits, distinct GIRK2 isoforms generated by alternative splicing have been identified. Here, we compared the trafficking and function of two isoforms (GIRK2a and GIRK2c) expressed individually in hippocampal pyramidal neurons lacking GIRK2. GIRK2a and GIRK2c supported comparable somato-dendritic GIRK currents in Girk2−/− pyramidal neurons, although GIRK2c achieved a more uniform subcellular distribution in pyramidal neurons and supported inhibitory postsynaptic currents in distal dendrites better than GIRK2a. While over-expression of either isoform in dorsal CA1 pyramidal neurons restored contextual fear learning in a conditional Girk2−/− mouse line, GIRK2a also enhanced cue fear learning. Collectively, these data indicate that GIRK2 isoform balance within a neuron can impact the processing of afferent inhibitory input and associated behavior.

Oxytocin differentially modulates pavlovian cue and context fear acquisition.

Fear acquisition and extinction have been demonstrated as core mechanisms for the development and maintenance of mental disorders, with different contributions of processing cues vs contexts. The hypothalamic peptide oxytocin (OXT) may have a prominent role in this context, as it has been shown to affect fear learning. However, investigations have focused on cue conditioning, and fear extinction. Its differential role for cue and context fear acquisition is still not known. In a randomized, double-blind, placebo (PLC)-controlled design, we administered an intranasal dose of OXT or PLC before the acquisition of cue and context fear conditioning in healthy individuals (n = 52), and assessed brain responses, skin conductance responses and self-reports (valence/arousal/contingency). OXT compared with PLC significantly induced decreased responses in the nucleus accumbens during early cue and context acquisition, and decreased responses of the anterior cingulate cortex and insula during early as well as increased hippocampal response during late context, but not cue acquisition. The OXT group additionally showed significantly higher arousal in late cue and context acquisition. OXT modulates various aspects of cue and context conditioning, which is relevant from a mechanism-based perspective and might have implications for the treatment of fear and anxiety.

Manipulating fear associations via optogenetic modulation of amygdala inputs to prefrontal cortex.

Fear-related disorders are thought to reflect strong and persistent fear memories. The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) form strong reciprocal synaptic connections that play a key role in acquisition and extinction of fear memories. While synaptic contacts of BLA cells onto mPFC neurons are likely to play a crucial role in this process, the BLA connects with several additional nuclei within the fear circuit that could relay fear-associated information to the mPFC, and the contribution of direct monosynaptic BLA-mPFC inputs is not yet clear. Here we establish an optogenetic stimulation protocol that induces synaptic depression in BLA-mPFC synapses. In behaving mice, optogenetic high-frequency stimulation of BLA inputs to mPFC interfered with retention of cued associations, attenuated previously acquired cue-associated responses in mPFC neurons and facilitated extinction. Our findings demonstrate the contribution of BLA inputs to mPFC in forming and maintaining cued fear associations.

Cystathionine-β-synthase-derived hydrogen sulfide is required for amygdalar long-term potentiation and cued fear memory in rats

Hydrogen sulfide (H2S) is an endogenous gaseous molecule that functions as a neuromodulator in the brain. We previously reported that H2S regulated amygdalar synaptic plasticity and cued fear memory in rats. However, whether endogenous H2S is required for amygdalar long-term potentiation (LTP) induction and cued fear memory formation remains unclear. Here, we show that cystathionine-β-synthase (CBS), the predominant H2S-producing enzyme in the brain, was highly expressed in the amygdala of rats. Suppressing CBS activity by inhibitor prevented activity-triggered generation of H2S in the lateral amygdala (LA) region. Incubating brain slices with CBS inhibitor significantly prevented the induction of NMDA receptors (NMDARs)-dependent LTP in the thalamo-LA pathway, and intra-LA infusion of CBS inhibitor impaired cued fear memory in rats. Notably, treatment with H2S donor, but not CBS activator, significantly reversed the impairments of LTP and fear memory caused by CBS inhibition. Mechanismly, inhibition of CBS activity led to a reduction in NMDAR-mediated synaptic response in the thalamo-LA pathway, and treatment with H2S donor restored the function of NMDARs. Collectively, these results indicate that CBS-derived H2S is required for amygdalar synaptic plasticity and cued fear memory in rats, and the effects of endogenous H2S might involve the regulation of NMDAR function.

Interactions of emotion and anxiety on visual working memory performance.

It is a widely observed finding that emotion and anxiety interact; highly stressed or anxious individuals show robust attentional biases towards external negative information. More generally, research has suggested that exposure to threatening stimuli, as well as the experience of acute stress, also may impair top-down attentional control and working memory. In the current study, we investigated how the influence of emotion and anxiety may interact to influenceworking memory performance. Participants were required to encode the orientation of four simple shapes, eight, or four shapes while filtering out four other irrelevant shapes from memory. Before memory displays, an irrelevant neutral or fearful face cue also was presented. Memory performance was found to interact with self-reported state anxiety and cue valence; on neutral cue trials, state anxiety was negatively correlated with performance. This effect was absent following a fear cue. In addition, filtering efficiency was negatively associated with state anxiety solely following a fear cue. Our findings suggest that state anxiety's influence to visual working memory can be strongly modulated by external signals to threat. Most crucially, rather than anxious individuals having greater difficulty rejecting external threatening information, we observed that external threat may in its own right generally impair filtering efficiency in anxious individuals.

Sex-Specific Effects of Childhood Poverty on Neurocircuitry of Processing of Emotional Cues: A Neuroimaging Study.

Background: There is accumulating evidence on the negative impacts of childhood poverty on physical and mental health. Previous work has suggested hyperactive neural response to social fear cues, as well as impairment in neural regulatory functions. However, despite differences found between males and females in stress-related and anxiety disorders, possible sex-specific effects of poverty on emotional processing have not been explored. Methods: We analyzed data from three previously reported experiments of childhood poverty effects on emotional processing and regulation, for sex-specific effects. Participants were 52 healthy Caucasian males and females, from a longitudinal cohort of poverty development study, who were recruited for examining the long-term effects of childhood poverty and stress. The three functional MRI studies included emotion regulation task, emotional face assessment task, and shifted attention emotion appraisal task. Brain activations that associated with childhood poverty previously were entered into a regression analysis with interaction of gender by childhood income-to-need ratio as the independent variable, and age and current income-to-need ratio as variables of no interest, separately for males and females. Results: Amygdala reactivity to implicitly processed fearful faces was positively correlated with childhood income-to-need in adult females but not males. On the other hand, activation in dorsolateral and ventrolateral prefrontal regions during emotion regulation by reappraisal was positively correlated with childhood income-to-need in males. Conclusion: Childhood poverty may exert sex-specific effects in adulthood as presented by hypersensitive emotional reactivity of the amygdala in females, and impaired emotion regulatory function of the prefrontal cortex in males. Results suggest further focus on sex-specific effects of childhood poverty.

"Incidental fear cues increase monetary loss aversion": Correction to Schulreich, Gerhardt, and Heekeren (2016).

Reports an error in "Incidental fear cues increase monetary loss aversion" by Stefan Schulreich, Holger Gerhardt and Hauke R. Heekeren (Emotion, 2016[Apr], Vol 16[3], 402-412). In the current article, there was an error in the Study 2 portion of the article. The fourth paragraph of the Results section should read as follows: Performing the same analyses as in Study 1, we found an effect of incidental fear cues on decision behavior. Participants accepted fewer gambles in the fearful-face condition (32.77%) than in the neutral-face condition (33.96%), with Z = -2.187, p = .027, d = -0.998 in the Wilcoxon signed-ranks test and β = 0.012, SE = 0.0053, F(1, 21) = 4.434, p = .047, partial η² = .174 in the linear regression. This suggests increased risk aversion in the fearful-face condition. Concerning personality, however, there were no significant between-subjects effects or between-within interaction effects (all ps = .349). (The following abstract of the original article appeared in record 2015-52358-001.) In many everyday decisions, people exhibit loss aversion-a greater sensitivity to losses relative to gains of equal size. Loss aversion is thought to be (at least partly) mediated by emotional-in particular, fear-related-processes. Decision research has shown that even incidental emotions, which are unrelated to the decision at hand, can influence decision making. The effect of incidental fear on loss aversion, however, is thus far unclear. In two studies, we experimentally investigated how incidental fear cues, presented during (Study 1) or before (Study 2) choices to accept or reject mixed gambles over real monetary stakes, influence monetary loss aversion. We find that the presentation of fearful faces, relative to the presentation of neutral faces, increased risk aversion-an effect that could be attributed to increased loss aversion. The size of this effect was moderated by psychopathic personality: Fearless dominance, in particular its interpersonal facet, but not self-centered impulsivity, attenuated the effect of incidental fear cues on loss aversion, consistent with reduced fear reactivity. Together, these results highlight the sensitivity of loss aversion to the affective context. (PsycINFO Database Record

GABAergic Synapses at the Axon Initial Segment of Basolateral Amygdala Projection Neurons Modulate Fear Extinction

Inhibitory synaptic transmission in the amygdala has a pivotal role in fear learning and its extinction. However, the local circuits formed by GABAergic inhibitory interneurons within the amygdala and their detailed function in shaping these behaviors are not well understood. Here we used lentiviral-mediated knockdown of the cell adhesion molecule neurofascin in the basolateral amygdala (BLA) to specifically remove inhibitory synapses at the axon initial segment (AIS) of BLA projection neurons. Quantitative analysis of GABAergic synapse markers and measurement of miniature inhibitory postsynaptic currents in BLA projection neurons after neurofascin knockdown ex vivo confirmed the loss of GABAergic input. We then studied the impact of this manipulation on anxiety-like behavior and auditory cued fear conditioning and its extinction as BLA related behavioral paradigms, as well as on long-term potentiation (LTP) in the ventral subiculum–BLA pathway in vivo. BLA knockdown of neurofascin impaired ventral subiculum–BLA–LTP. While this manipulation did not affect anxiety-like behavior and fear memory acquisition and consolidation, it specifically impaired extinction. Our findings indicate that modification of inhibitory synapses at the AIS of BLA projection neurons is sufficient to selectively impair extinction behavior. A better understanding of the role of distinct GABAergic synapses may provide novel and more specific targets for therapeutic interventions in extinction-based therapies.

Relevant and Irrelevant Fear in Flooding – A Crossover Study of Phobic Patients – Republished Article

This study investigated the role of relevant vs irrelevant fear cues in the flooding of phobic patients. Six specific phobics and 10 agoraphobics were treated in a balanced crossover design. Eight patients had eight sessions of imaginal flooding concerned with their phobias followed by eight imaginal sessions concerned with situations which are normally frightening to anybody. Another eight patients had the same two treatments in the reverse order. The combined effects of both treatments after 16 sessions resulted in significant improvement on clinical, attitudinal, and heart-rate measures. Improvement was maintained at six months follow-up. Eight sessions by each treatment alone also produced significant improvement on clinical and attitudinal measures. Irrelevant fear also produced significant improvement in heart-rate and skin-conductance measures. The two treatments did not differ significantly from each other in their effects, except that irrelevant fear produced significantly more improvement than did relevant flooding in subjective anxiety during phobic imagery. The two treatments had significantly different prognostic correlates. Heightened physiological activity at the start of treatment predicted a good outcome to relevant flooding but not to irrelevant fear. High subjective anxiety during imagery before treatment predicted poor outcome to irrelevant fear. High anxiety during treatment sessions predicted good outcome to irrelevant fear, but did not correlate with outcome to relevant flooding. The experience of relevant and irrelevant fear in fantasy reduced phobic anxiety and avoidance to a similar extent, but appeared to do so through different mechanisms. These mechanisms need not be mutually exclusive and might be additive.

Chronic Cognitive Dysfunction after Traumatic Brain Injury Is Improved with a Phosphodiesterase 4B Inhibitor.

Learning and memory impairments are common in traumatic brain injury (TBI) survivors. However, there are no effective treatments to improve TBI-induced learning and memory impairments. TBI results in decreased cAMP signaling and reduced cAMP-response-element binding protein (CREB) activation, a critical pathway involved in learning and memory. TBI also acutely upregulates phosphodiesterase 4B2 (PDE4B2), which terminates cAMP signaling by hydrolyzing cAMP. We hypothesized that a subtype-selective PDE4B inhibitor could reverse the learning deficits induced by TBI. To test this hypothesis, adult male Sprague-Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. At 3 months postsurgery, animals were administered a selective PDE4B inhibitor or vehicle before cue and contextual fear conditioning, water maze training and a spatial working memory task. Treatment with the PDE4B inhibitor significantly reversed the TBI-induced deficits in cue and contextual fear conditioning and water maze retention. To further understand the underlying mechanisms of these memory impairments, we examined hippocampal long-term potentiation (LTP). TBI resulted in a significant reduction in basal synaptic transmission and impaired expression of LTP. Treatment with the PDE4B inhibitor significantly reduced the deficits in basal synaptic transmission and rescued LTP expression. The PDE4B inhibitor reduced tumor necrosis factor-α levels and increased phosphorylated CREB levels after TBI, suggesting that this drug inhibited molecular pathways in the brain known to be regulated by PDE4B. These results suggest that a subtype-selective PDE4B inhibitor is a potential therapeutic to reverse chronic learning and memory dysfunction and deficits in hippocampal synaptic plasticity following TBI. Currently, there are an estimated 3.2-5.3 million individuals living with disabilities from traumatic brain injury (TBI) in the United States, and 8 of 10 of these individuals report cognitive disabilities (Thurman et al., 1999; Lew et al., 2006; Zaloshnja et al., 2008). One of the molecular mechanisms associated with chronic cognitive disabilities is impaired cAMP signaling in the hippocampus. In this study, we report that a selective phosphodiesterase 4B (PDE4B) inhibitor reduces chronic cognitive deficits after TBI and rescues deficits in hippocampal long-term potentiation. These results suggest that PDE4B inhibition has the potential to improve learning and memory ability and overall functioning for people living with TBI.

Improvement in γ-hydroxybutyrate-induced contextual fear memory deficit by systemic administration of NCS-382.

Low, nonsedative doses of γ-hydroxybutyric acid (GHB) produce short-term anterograde amnesia in humans and memory impairments in experimental animals. We have previously shown that acute systemic treatment of GHB in adolescent female rats impairs the acquisition, but not the expression, of contextual fear memory while sparing both the acquisition and the expression of auditory cued fear memory. In the brain, GHB binds to specific GHB-binding sites as well as to γ-aminobutyric acid type B (GABAB) receptors. Although many of the behavioral effects of GHB at high doses have been attributed to its effects on the GABAB receptor, it is unclear which receptor mediates its relatively low-dose memory-impairing effects. The present study examined the ability of the putative GHB receptor antagonist NCS-382 to block the disrupting effects of GHB on fear memory in adolescent rat. Groups of rats received either a single dose of NCS-382 (3–10 mg/kg, intraperitoneally) or vehicle, followed by an injection of either GHB (100 mg/kg, intraperitoneally) or saline. All rats were trained in the fear paradigm, and tested for contextual fear memory and auditory cued fear memory. NCS-382 dose-dependently reversed deficits in the acquisition of contextual fear memory induced by GHB in adolescent rats, with 5 mg/kg of NCS-382 maximally increasing freezing to the context compared with the group administered GHB alone. When animals were tested for cued fear memory, treatment groups did not differ in freezing responses to the tone. These results suggest that low-dose amnesic effects of GHB are mediated by GHB receptors.

Myocardial infarction sensitizes medial prefrontal cortex to inhibitory effect of locus coeruleus stimulation in rats.

Anxiety is a common comorbidity that develops after myocardial infarction and is now an established independent risk factor for cardiovascular mortality. Here, we assessed anxiety and mapped neural activity of forebrain regions that regulate anxiety in a rat model of myocardial infarction in order to identify sites of dysregulation. Anxiety responses to novel (open field) or aversive stimuli (discriminative auditory fear conditioning) were assessed in rats subjected to coronary artery ligation (CAL) or sham ligation. Forebrain metabolic activity was measured by cytochrome oxidase (CO) histochemistry. Changes in CO activity and the incidence of ventricular arrhythmias were also assessed during modulation of fear circuitry induced by electrical stimulation of the locus coeruleus. Coronary artery ligation had negligible effects on open-field behavior, but increased expression of learned fear and impaired fear cue discrimination. Cytochrome oxidase activity was increased in the medial prefrontal cortex and in the lateral amygdala after CAL. Locus coeruleus stimulation reduced CO activity in the infralimbic medial prefrontal cortex only in rats subjected to CAL. Stimulation of the LC also elicited new ventricular arrhythmias in rats subjected to CAL. Coronary artery ligation sensitizes the infralimbic medial prefrontal cortex to the inhibitory effects of locus coeruleus stimulation. Suppression of infralimbic medial prefrontal cortical activity may impair the ability of rats subjected to CAL to discriminate between cues that signal aversive and neutral events which, in turn, may promote excessive sympathetic activation of the cardiovascular system in response to innocuous stimuli.

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

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.

Neuronal interactions in areas of spatial attention reflect avoidance of disgust, but orienting to danger

For survival, it is necessary to attend quickly towards dangerous objects, but to turn away from something that is disgusting. We tested whether fear and disgust sounds direct spatial attention differently. Using fMRI, a sound cue (disgust, fear or neutral) was presented to the left or right ear. The cue was followed by a visual target (a small arrow) which was located on the same (valid) or opposite (invalid) side as the cue. Participants were required to decide whether the arrow pointed up- or downwards while ignoring the sound cue. Behaviorally, responses were faster for invalid compared to valid targets when cued by disgust, whereas the opposite pattern was observed for targets after fearful and neutral sound cues. During target presentation, activity in the visual cortex and IPL increased for targets invalidly cued with disgust, but for targets validly cued with fear which indicated a general modulation of activation due to attention. For the TPJ, an interaction in the opposite direction was observed, consistent with its role in detecting targets at unattended positions and in relocating attention. As a whole our results indicate that a disgusting sound directs spatial attention away from its location, in contrast to fearful and neutral sounds.

High Current Anxiety Symptoms, But Not a Past Anxiety Disorder Diagnosis, are Associated with Impaired Fear Extinction.

Although impaired fear extinction has repeatedly been demonstrated in patients with anxiety disorders, little is known about whether these impairments persist after treatment. The current comparative exploratory study investigated fear extinction in 26 patients treated for their anxiety disorder in the years preceding the study as compared to 17 healthy control subjects. Fear-potentiated startle and subjective fear were measured in a cue and context fear conditioning paradigm within a virtual reality environment. Results indicated no differences in fear extinction between treated anxiety patients and control subjects. However, scores on the Beck Anxiety Inventory across all participants revealed impaired extinction of fear potentiated startle in subjects with high compared to low anxiety symptoms over the past week. Taken together, this exploratory study found no support for impaired fear extinction in treated anxiety patients, and implies that current anxiety symptoms rather than previous patient status determine the success of extinction.

Identification of Parvalbumin Interneurons as Cellular Substrate of Fear Memory Persistence.

Parvalbumin-positive (PV) basket cells provide perisomatic inhibition in the cortex and hippocampus and control generation of memory-related network activity patterns, such as sharp wave ripples (SPW-R). Deterioration of this class of fast-spiking interneurons has been observed in neuropsychiatric disorders and evidence from animal models suggests their involvement in the acquisition and extinction of fear memories. Here, we used mice with neuron type-targeted expression of the presynaptic gain-of-function glycine receptor RNA variant GlyR α3L185L to genetically enhance the network activity of PV interneurons. These mice showed reduced extinction of contextual fear memory but normal auditory cued fear memory. They furthermore displayed increase of SPW-R activity in area CA3 and CA1 and facilitated propagation of this particular network activity pattern, as determined in ventral hippocampal slice preparations. Individual freezing levels during extinction and SPW-R propagation were correlated across genotypes. The same was true for parvalbumin immunoreactivity in the ventral hippocampus, which was generally augmented in the GlyR mutant mice and correlated with individual freezing levels. Together, these results identify PV interneurons as critical cellular substrate of fear memory persistence and associated SPW-R activity in the hippocampus. Our findings may be relevant for the identification and characterization of physiological correlates for posttraumatic stress and anxiety disorders.

It's all in the anticipation: How perception of threat is enhanced in anxiety.

The importance of top-down factors such as goals and expectations is well-established in both visual perception and anxiety. However, researchers have attributed the perceptual prioritization of threatening stimuli in anxiety to bottom-up, automatic processing of these stimuli while neglecting the role of prestimulus, top-down factors. Furthermore, different kinds of anxiety (dispositional versus induced) impact cognitive functions differently, suggesting that top-down factors may have distinct effects on threat perception. In the present study, we examined whether prestimulus representations of threatening stimuli facilitate perception differently, depending on induced and trait anxiety. Two groups of participants completed a cued discrimination task using threatening or neutral cues to identify subsequently presented fearful and neutral faces, degraded to each participant's perceptual threshold. In Group 1, threat of shock induced anxiety (n = 22; 12 men), whereas in Group 2, no anxiety was induced (n = 29; 7 men). The impact of induced anxiety on perception interacted with trait anxiety. Following fear cues, higher trait anxiety was associated with improved perceptual sensitivity and faster reaction time under threat of shock, and worse perceptual sensitivity and slower reaction time in absence of shock. The present findings represent an important advance in the literature because they elucidate the role of previously ignored top-down factors in threat perception for individuals with varying levels of anxiety and highlight the distinct impact that different types of anxiety have on the perception of threatening stimuli. Furthermore, these findings underline the importance of including top-down factors in future conceptualizations of perceptual bias toward threat in anxiety.

Incidental fear cues increase monetary loss aversion.

In many everyday decisions, people exhibit loss aversion-a greater sensitivity to losses relative to gains of equal size. Loss aversion is thought to be (at least partly) mediated by emotional--in particular, fear-related--processes. Decision research has shown that even incidental emotions, which are unrelated to the decision at hand, can influence decision making. The effect of incidental fear on loss aversion, however, is thus far unclear. In two studies, we experimentally investigated how incidental fear cues, presented during (Study 1) or before (Study 2) choices to accept or reject mixed gambles over real monetary stakes, influence monetary loss aversion. We find that the presentation of fearful faces, relative to the presentation of neutral faces, increased risk aversion-an effect that could be attributed to increased loss aversion. The size of this effect was moderated by psychopathic personality: Fearless dominance, in particular its interpersonal facet, but not self-centered impulsivity, attenuated the effect of incidental fear cues on loss aversion, consistent with reduced fear reactivity. Together, these results highlight the sensitivity of loss aversion to the affective context.

Plasticity of Fear and Safety Neurons of the Amygdala in Response to Fear Extinction.

Fear inhibition learning induces plasticity and remodeling of circuits within the amygdala. Most studies examine these changes in nondiscriminative fear conditioning paradigms. Using a discriminative fear, safety, and reward conditioning task, Sangha et al. (2013) have previously reported several neural microcircuits within the basal amygdala (BA) which discriminate among these cues, including a subpopulation of neurons responding selectively to a safety cue and not a fear cue. Here, the hypothesis that these “safety” neurons isolated during discriminative conditioning are biased to become fear cue responsive as a result of extinction, when fear behavior diminishes, was tested. Although 41% of “safety” neurons became fear cue responsive as a result of extinction, the data revealed that there was no bias for these neurons to become preferentially responsive during fear extinction compared to the other identified subgroups. In addition to the plasticity seen in the “safety” neurons, 44% of neurons unresponsive to either the fear cue or safety cue during discriminative conditioning became fear cue responsive during extinction. Together these emergent responses to the fear cue as a result of extinction support the hypothesis that new learning underlies extinction. In contrast, 47% of neurons responsive to the fear cue during discriminative conditioning became unresponsive to the fear cue during extinction. These findings are consistent with a suppression of neural responding mediated by inhibitory learning, or, potentially, by direct unlearning. Together, the data support extinction as an active process involving both gains and losses of responses to the fear cue and suggests the final output of the integrated BA circuit in influencing fear behavior is a balance of excitation and inhibition, and perhaps reversal of learning-induced changes.