Overgeneralization Of Conditioned Fear Research Articles

Anhedonia is associated with overgeneralization of conditioned fear during late adolescence and early adulthood

BackgroundPavlovian fear paradigms involve learning to associate cues with threat or safety. Aberrances in Pavlovian fear learning correlate with psychopathology, especially anxiety disorders. This study evaluated symptom dimensions of anxiety and depression in relation to Pavlovian fear acquisition and generalization. Methods256 participants (70.31 % female) completed a Pavlovian fear acquisition and generalization paradigm at ages 18–19 and 21–22 years. Analyses focused on indices of learning (self-reported US expectancy, skin conductance). Multilevel models tested associations with orthogonal symptom dimensions (Anhedonia-Apprehension, Fears, General Distress) at each timepoint. ResultsAll dimensions were associated with weaker acquisition of US expectancies at each timepoint. Fears was associated with overgeneralization only at age 21–22. General Distress was associated with overgeneralization only at age 18–19. Anhedonia-Apprehension was associated with overgeneralization at ages 18–19 and 21–22. ConclusionsAnhedonia-Apprehension disrupts Pavlovian fear acquisition and increases overgeneralization of fear. These effects may emerge during adolescence and remain into young adulthood. General Distress and Fears also contribute to overgeneralization of fear, but these effects may vary as prefrontal mechanisms of fear inhibition continue to develop during late adolescence. Targeting specific symptom dimensions, particularly Anhedonia-Apprehension, may decrease fear generalization and augment interventions built on Pavlovian principles, such as exposure therapy.

Overgeneralization of conditioned fear in patients with social anxiety disorder.

While abnormal responses to threat, including overgeneralization to conditioned fear, have been postulated to play a critical role in pathological anxiety, the relevance of previous findings to social anxiety disorder (SAD) is unclear. We investigated conditioned and generalized fear responses in patients with SAD using socially relevant stimuli. A total of 26 patients with SAD and 25 healthy controls participated in a fear conditioning and generalization paradigm consisting of two neutral faces as conditioned stimuli (CS+ or CS-) and an angry face with contemptuous comments as unconditioned stimuli. Eight morphed faces of two conditioned stimuli in each continuum were given to test generalization. Behavioral data and physiological responses were acquired. Successful conditioning was observed in the risk ratings for both groups, while only a marginal indication of conditioning was noted in physiological measures. During the generalization phase, patients rated the risk higher than CS- when the stimuli close to CS- contained a portion of CS+ features. Larger skin conductance responses to this stimulus were linked to higher fear of negative evaluation. In addition, patients spent a longer time evaluating safe and ambiguous stimuli than healthy controls and exhibited consistently high levels of subjective arousal. Taken together, our findings suggest that SAD patients may exhibit a tendency towards overgeneralization of fear responses and show distinct patterns in processing generalized threat stimuli compared to healthy controls. Even though overgeneralization was not evident in physiological measures, it is necessary to consider this behavioral characteristic in the clinical management of patients with SAD.

Fear conditioning and fear generalization in children and adolescents with anxiety disorders

Overgeneralization of conditioned fear is associated with anxiety disorders (AD). Most results stem from studies done in adult patients, but studies with children are rare, although the median onset of anxiety disorders lies already in childhood. Thus, the goal of the present study was to examine fear learning and generalization in youth participants, aged 10–17 years, with AD (n = 39) compared to healthy controls (HC) (n = 40). A discriminative fear conditioning and generalization paradigm was used. Ratings of arousal, valence, and US expectancy (the probability of an aversive noise following each stimulus) were measured, hypothesizing that children with AD compared to HC would show heightened ratings of arousal and US expectancy, and decreased positive valence ratings, respectively, as well as overgeneralization of fear. The results indicated that children with AD rated all stimuli as more arousing and less pleasant, and demonstrated higher US expectancy ratings to all stimuli when compared to HC. Thus, rather than displaying qualitatively different generalization patterns (e.g., a linear vs. quadratic slope of the gradient), differences between groups were more quantitative (similar, but parallel shifted gradient). Therefore, overgeneralization of conditioned fear does not seem to be a general marker of anxiety disorders in children and adolescents.

Chronic unilateral inhibition of GABA synthesis in the amygdala increases specificity of conditioned fear in a discriminative fear conditioning paradigm in rats

Neural activity in the amygdala is critical for fear learning. In anxiety disorder patients, bilateral hyperactivity of the amygdala can be observed. This hyperactivation is often associated with the facilitation of fear learning and/or over-generalization of conditioned fear. In contrast, hypoactivity of the amygdala, e.g. by pharmacological interventions, attenuates or blocks fear learning. To date, little is known about how neural excitability of the amygdala affects specificity or generalization of fear. Therefore, the present study utilized chronic inhibition of GABA synthesis in the amygdala to increase excitability and investigated the effect on the specificity of fear learning. In rats, unilateral cannulas aiming at the amygdala were implanted. The cannulas were connected to subcutaneously implanted osmotic mini pumps that delivered either the GABA synthesis inhibitor L-allylglycine or its inactive enantiomer D-allylglycine. Following one week of chronic GABA synthesis manipulation, the rats were submitted to a discriminative fear conditioning protocol. In addition, anxiety-like behavior in the light-dark box was measured. Our data show that chronic unilateral L-AG infusions into the amygdala improve the specificity of learned fear, support safety learning, and reduce fear generalization and anxiety. This data demonstrates that moderately increased amygdala excitability can be beneficial for the specificity of fear learning and highlights the potential application for therapeutic interventions.

Over-Generalization of Conditioned Fear in Patients with Social Anxiety Disorder

Over-Generalization of Conditioned Fear in Patients with Social Anxiety Disorder

Noradrenergic stimulation increases fear memory expression

Fear responses are typically not limited to the actual threatening stimulus but generalize to other stimuli resembling the threatening stimulus. Although this fear generalization is generally adaptive, fear overgeneralization is maladaptive and assumed to contribute to anxiety disorders. Despite the clinical relevance of fear (over)generalization, how the extent of fear generalization is modulated remains not well understood. Based on the known effects of stress on learning and memory, we tested here the impact of major stress mediators, glucocorticoids and noradrenergic arousal, on fear generalization. In a laboratory-based, placebo-controlled, double-blind, between-subject design, 125 healthy participants first underwent a fear conditioning procedure. About 24 h later, participants received orally either a placebo, hydrocortisone, the α2-adrenoceptor antagonist yohimbine, leading to increased noradrenergic stimulation, or both drugs before a test of fear generalization. Skin conductance responses as well as explicit rating data revealed that yohimbine intake led to enhanced fear memory expression, i.e. an enhanced responding to the CS+ but not to stimuli resembling the CS+. Moreover, neither enhanced safety learning nor a mere enhancement of perceptual discrimination ability could explain this result. In contrast to yohimbine, hydrocortisone had no significant effect on fear memory. These findings suggest that noradrenergic arousal strengthens fear memory expression and have important implications for mental disorders in which the overgeneralization of conditioned fear is prominent.

Individual differences in human fear generalization\u2014pattern identification and implications for anxiety disorders

Previous research indicates that anxiety disorders are characterized by an overgeneralization of conditioned fear as compared with healthy participants. Therefore, fear generalization is considered a key mechanism for the development of anxiety disorders. However, systematic investigations on the variance in fear generalization are lacking. Therefore, the current study aims at identifying distinctive phenotypes of fear generalization among healthy participants. To this end, 1175 participants completed a differential fear conditioning phase followed by a generalization test. To identify patterns of fear generalization, we used a k-means clustering algorithm based on individual arousal generalization gradients. Subsequently, we examined the reliability and validity of the clusters and phenotypical differences between subgroups on the basis of psychometric data and markers of fear expression. Cluster analysis reliably revealed five clusters that systematically differed in mean responses, differentiation between conditioned threat and safety, and linearity of the generalization gradients, though mean response levels accounted for most variance. Remarkably, the patterns of mean responses were already evident during fear acquisition and corresponded most closely to psychometric measures of anxiety traits. The identified clusters reliably described subgroups of healthy individuals with distinct response characteristics in a fear generalization test. Following a dimensional view of psychopathology, these clusters likely delineate risk factors for anxiety disorders. As crucial group characteristics were already evident during fear acquisition, our results emphasize the importance of average fear responses and differentiation between conditioned threat and safety as risk factors for anxiety disorders.

T18. Trait Anxiety Associated With Differences in BOLD Activation During Fear Generalization Task

Pathological anxiety has been associated with overgeneralization of conditioned fear, wherein safe stimuli are perceived as threatening due to perceptual similarity to a threat. Neuroimaging studies have implicated structures, including the insula, hippocampus, ventromedial prefrontal cortex, and precuneus, to be sensitive to stimulus differentiation.

Neural Substrates of Overgeneralized Conditioned Fear in PTSD.

Heightened generalization of fear from an aversively reinforced conditioned stimulus (CS+, a conditioned danger cue) to resembling stimuli is widely accepted as a pathogenic marker of posttraumatic stress disorder (PTSD). Indeed, a distress response to benign stimuli that "resemble" aspects of the trauma is a central feature of the disorder. To date, the link between overgeneralization of conditioned fear and PTSD derives largely from clinical observations, with limited empirical work on the subject. This represents the first effort to examine behavioral and brain indices of generalized conditioned fear in PTSD using systematic methods developed in animals known as generalization gradients: the gradual decline in conditioned responding as the presented stimulus gradually differentiates from CS+. Gradients of conditioned fear generalization were assessed using functional MRI and behavioral measures in U.S. combat veterans who served in Iraq or Afghanistan and had PTSD (N=26), subthreshold PTSD (N=19), or no PTSD (referred to as trauma control subjects) (N=17). Presented stimuli included rings of graded size, with extreme sizes serving as CS+ (paired with shock) and as a nonreinforced conditioned stimulus (CS-, a conditioned safety cue), and with intermediate sizes forming a continuum of similarity between CS+ and CS-. Generalization gradients were assessed as response slopes from CS+, through intermediate ring sizes, to CS-, with less steep slopes indicative of stronger generalization. Relative to trauma control subjects, PTSD patients showed stronger conditioned generalization, as evidenced by less steep generalization gradients in both behavioral risk ratings and brain responses in the left and right anterior insula, left ventral hippocampus, dorsolateral and dorsomedial prefrontal cortex, and caudate nucleus. Severity of PTSD symptoms across the three study groups was positively correlated with levels of generalization at two such loci: the right anterior insula and left ventral hippocampus. The results point to evidence of brain-based markers of overgeneralized fear conditioning related to PTSD. These findings provide further understanding of a central yet understudied symptom of trauma-related psychopathology.

PS24. Neural Circuitry of Over-Generalization of Conditioned Fear in Generalized Anxiety Disorder

PS24. Neural Circuitry of Over-Generalization of Conditioned Fear in Generalized Anxiety Disorder

Overgeneralization of Conditioned Fear in the Anxiety Disorders

According to many conditioning accounts of clinical anxiety, the central pathogen can be found in aberrant acquisition or extinction of learned fear to neutral stimuli (i.e., conditioned stimuli [CS]) paired with an aversive unconditioned stimulus (US). While overresponding to the CS is an important candidate source of anxiety pathology, both clinical observation and mounting experimental data implicate generalization of fear to stimuli resembling the CS as an equally promising candidate (e.g., Grillon & Morgan, 1999; Lissek et al., 2005; Lissek et al., 2010; Mineka & Zinbarg, 1996). Important to the current issue on ‘‘Trauma and Memory,’’ generalization of fear to stimuli resembling those present during a traumatic event is a core feature of the posttraumatic stress response (American Psychiatric Association, 2000) and is likely influenced by conditioning-dependent modifications to the neural representation of the CS stored in memory. The current paper (1) summarizes the connection between conditioned-fear generalization and pathologic anxiety including a recent empirical example demonstrating the link and (2) explores memorial substrates of conditioned generalization and the ways they are related to overgeneralization of the kind seen in anxiety pathology.

P01-138 - Impaired discriminative fear learning in panic disorder

ObjectivesFear conditioning (FC) has been proposed as crucial factor in the etiology and maintenance of panic disorder (PD). This study compared the acquisition of discriminative fear learning between PD patients and healthy subjects (CTR). The main purpose was to test the hypothesis that abnormalities in this process may exist in this population, particularly referred to conditioned responses (CRs) and discriminative fear learning acquisition.MethodsAversive discriminative conditioning paradigm was administered to 45 patients with a DSM-IV diagnosis of PD with agoraphobia and to 43 healthy subjects. The visual-auditory conditioning paradigm is composed by four visual stimuli as conditioned stimulus (CSs) and a startlingly loud sound as the unconditioned stimulus (US). Only one stimulus (CS+) was followed by the US, instead remainder stimuli were never paired with the US (CS-). The protocol consisted of 3 phases: habituation (HAB), acquisition (ACQ) and extinction (EXT). Skin conductance response (SCR) was used as dependent variable.ResultsDuring HAB phase no differences were found in response to all stimuli. During ACQ phase, the two groups did not differ in response to CS+; instead patients showed significantly greater reactivity to CS- than controls.ConclusionResults suggest equal level of fear acquisition and impaired discriminative fear learning in PD population; moreover discriminative deficit is driven by enhanced safety learning rather than any abnormality in excitatory danger learning. Enhanced responding to CS- among PD may also be interpreted as over-generalization of conditioned fear. Our result have important clinical implication, particularly for behaviour cognitive therapy in Panic Disorder.

Overgeneralization of Conditioned Fear as a Pathogenic Marker of Panic Disorder

Classical conditioning features prominently in many etiological accounts of panic disorder. According to such accounts, neutral conditioned stimuli present during panic attacks acquire panicogenic properties. Conditioned stimuli triggering panic symptoms are not limited to the original conditioned stimuli but are thought to generalize to stimuli resembling those co-occurring with panic, resulting in the proliferation of panic cues. The authors conducted a laboratory-based assessment of this potential correlate of panic disorder by testing the degree to which panic patients and healthy subjects manifest generalization of conditioned fear. Nineteen patients with a DSM-IV-TR diagnosis of panic disorder and 19 healthy comparison subjects were recruited for the study. The fear-generalization paradigm consisted of 10 rings of graded size presented on a computer monitor; one extreme size was a conditioned danger cue, the other extreme a conditioned safety cue, and the eight rings of intermediary size created a continuum of similarity from one extreme to the other. Generalization was assessed by conditioned fear potentiating of the startle blink reflex as measured with electromyography (EMG). Panic patients displayed stronger conditioned generalization than comparison subjects, as reflected by startle EMG. Conditioned fear in panic patients generalized to rings with up to three units of dissimilarity to the conditioned danger cue, whereas generalization in comparison subjects was restricted to rings with only one unit of dissimilarity. The findings demonstrate a marked proclivity toward fear overgeneralization in panic disorder and provide a methodology for laboratory-based investigations of this central, yet understudied, conditioning correlate of panic. Given the putative molecular basis of fear conditioning, these results may have implications for novel treatments and prevention in panic disorder.