What is going on around here? Intolerance of uncertainty predicts threat generalization

Attending to stimuli that share perceptual similarity to learned threats is an adaptive strategy. However, prolonged threat generalization to cues signalling safety is considered a core feature of pathological anxiety. One potential factor that may sustain over-generalization is sensitivity to future threat uncertainty. To assess the extent to which Intolerance of Uncertainty (IU) predicts threat generalization, we recorded skin conductance in 54 healthy participants during an associative learning paradigm, where threat and safety cues varied in perceptual similarity. Lower IU was associated with stronger discrimination between threat and safety cues during acquisition and extinction. Higher IU, however, was associated with generalized responding to threat and safety cues during acquisition, and delayed discrimination between threat and safety cues during extinction. These results were specific to IU, over and above other measures of anxious disposition. These findings highlight: (1) a critical role of uncertainty-based mechanisms in threat generalization, and (2) IU as a potential risk factor for anxiety disorder development

Related to Anxiety: Arbitrarily Applicable Relational Responding and Experimental Psychopathology Research on Fear and Avoidance

Humans have an unparalleled ability to engage in arbitrarily applicable relational responding (AARR). One of the consequences of this ability to spontaneously combine and relate events from the past, present, and future may, in fact, be a propensity to suffer. For instance, maladaptive fear and avoidance of remote or derived threats may actually perpetuate anxiety. In this narrative review, we consider contemporary AARR research on fear and avoidance as it relates to anxiety. We first describe laboratory-based research on the emergent spread of fear- and avoidance-eliciting functions in humans. Next, we consider the validity of AARR research on fear and avoidance and address the therapeutic implications of the work. Finally, we outline challenges and opportunities for a greater synthesis between behavior analysis research on AARR and experimental psychopathology

The impact of intolerance of uncertainty and cognitive behavioural instructions on safety learning

Background Difficulty updating threat associations to safe associations has been observed in individuals who score high in self-reported Intolerance of Uncertainty (IU). Here we sought to determine whether an instruction based on fundamental principles of Cognitive Behavioural Therapy could promote safety learning in individuals with higher levels of IU, whilst controlling for self-reported trait anxiety (STICSA). Methods We measured skin conductance response, pupil dilation and expectancy ratings during an associative threat learning task in which participants either received a cognitive behavioural instruction or no instruction prior to threat extinction (n = 92). Results Analyses revealed that both self-reported IU and STICSA similarly predicted differences in skin conductance response. Only individuals with lower IU/STICSA in the cognitive behavioural instruction condition displayed successful safety learning via skin conductance response. Conclusions These initial results provide some insight into how simple cognitive behavioural instructions combined with exposure are applied differently in individuals with varying levels of self-reported anxiety. The results further our understanding of the role of basic cognitive behavioural principles and self-reported anxiety in safety learning

Neural substrates of individual differences in human fear learning: Evidence from concurrent fMRI, fear-potentiated startle, and US-expectancy data

To provide insight into individual differences in fear learning, we examined the emotional and cognitive expressions of discriminative fear conditioning in direct relation to its neural substrates. Contrary to previous behavioral–neural (fMRI) research on fear learning—in which the emotional expression of fear was generally indexed by skin conductance—we used fear-potentiated startle, a more reliable and specific index of fear. While we obtained concurrent fear-potentiated startle, neuroimaging (fMRI), and US-expectancy data, healthy participants underwent a fear-conditioning paradigm in which one of two conditioned stimuli (CS(+) but not CS(–)) was paired with a shock (unconditioned stimulus [US]). Fear learning was evident from the differential expressions of fear (CS(+) > CS(–)) at both the behavioral level (startle potentiation and US expectancy) and the neural level (in amygdala, anterior cingulate cortex, hippocampus, and insula). We examined individual differences in discriminative fear conditioning by classifying participants (as conditionable vs. unconditionable) according to whether they showed successful differential startle potentiation. This revealed that the individual differences in the emotional expression of discriminative fear learning (startle potentiation) were reflected in differential amygdala activation, regardless of the cognitive expression of fear learning (CS–US contingency or hippocampal activation). Our study provides the first evidence for the potential of examining startle potentiation in concurrent fMRI research on fear learning

Locus coeruleus and dopaminergic consolidation of everyday memory

Item does not contain fulltextThe retention of episodic-like memory is enhanced, in humans and animals, when something novel happens shortly before or after encoding. Using an everyday memory task in mice, we sought the neurons mediating this dopamine-dependent novelty effect, previously thought to originate exclusively from the tyrosine-hydroxylase-expressing (TH+) neurons in the ventral tegmental area. Here we report that neuronal firing in the locus coeruleus is especially sensitive to environmental novelty, locus coeruleus TH+ neurons project more profusely than ventral tegmental area TH+ neurons to the hippocampus, optogenetic activation of locus coeruleus TH+ neurons mimics the novelty effect, and this novelty-associated memory enhancement is unaffected by ventral tegmental area inactivation. Surprisingly, two effects of locus coeruleus TH+ photoactivation are sensitive to hippocampal D1/D5 receptor blockade and resistant to adrenoceptor blockade: memory enhancement and long-lasting potentiation of synaptic transmission in CA1 ex vivo. Thus, locus coeruleus TH+ neurons can mediate post-encoding memory enhancement in a manner consistent with possible co-release of dopamine in the hippocampus

Fear learning circuitry is biased toward generalization of fear associations in posttraumatic stress disorder.

Fear conditioning is an established model for investigating posttraumatic stress disorder (PTSD). However, symptom triggers may vaguely resemble the initial traumatic event, differing on a variety of sensory and affective dimensions. We extended the fear-conditioning model to assess generalization of conditioned fear on fear processing neurocircuitry in PTSD. Military veterans (n=67) consisting of PTSD (n=32) and trauma-exposed comparison (n=35) groups underwent functional magnetic resonance imaging during fear conditioning to a low fear-expressing face while a neutral face was explicitly unreinforced. Stimuli that varied along a neutral-to-fearful continuum were presented before conditioning to assess baseline responses, and after conditioning to assess experience-dependent changes in neural activity. Compared with trauma-exposed controls, PTSD patients exhibited greater post-study memory distortion of the fear-conditioned stimulus toward the stimulus expressing the highest fear intensity. PTSD patients exhibited biased neural activation toward high-intensity stimuli in fusiform gyrus (P<0.02), insula (P<0.001), primary visual cortex (P<0.05), locus coeruleus (P<0.04), thalamus (P<0.01), and at the trend level in inferior frontal gyrus (P=0.07). All regions except fusiform were moderated by childhood trauma. Amygdala-calcarine (P=0.01) and amygdala-thalamus (P=0.06) functional connectivity selectively increased in PTSD patients for high-intensity stimuli after conditioning. In contrast, amygdala-ventromedial prefrontal cortex (P=0.04) connectivity selectively increased in trauma-exposed controls compared with PTSD patients for low-intensity stimuli after conditioning, representing safety learning. In summary, fear generalization in PTSD is biased toward stimuli with higher emotional intensity than the original conditioned-fear stimulus. Functional brain differences provide a putative neurobiological model for fear generalization whereby PTSD symptoms are triggered by threat cues that merely resemble the index trauma