Knight DC, Smith CN, Cheng DT, Stein EA, Helmstetter FJ. Amygdala and hippocampal activity during acquisition and extinction of human fear conditioning. Cogn Affect Behav Neurosci 4: 317-325

University of Wisconsin, Milwaukee, Wisconsin 53201, USA.
Cognitive Affective & Behavioral Neuroscience (Impact Factor: 3.29). 10/2004; 4(3):317-25. DOI: 10.3758/CABN.4.3.317
Source: PubMed


Previous functional magnetic resonance imaging (fMRI) studies have characterized brain systems involved in conditional response acquisition during Pavlovian fear conditioning. However, the functional neuroanatomy underlying the extinction of human conditional fear remains largely undetermined. The present study used fMRI to examine brain activity during acquisition and extinction of fear conditioning. During the acquisition phase, participants were either exposed to light (CS) presentations that signaled a brief electrical stimulation (paired group) or received light presentations that did not serve as a warning signal (control group). During the extinction phase, half of the paired group subjects continued to receive the same treatment, whereas the remainder received light alone. Control subjects also received light alone during the extinction phase. Changes in metabolic activity within the amygdala and hippocampus support the involvement of these regions in each of the procedural phases of fear conditioning. Hippocampal activity developed during acquisition of the fear response. Amygdala activity increased whenever experimental contingencies were altered, suggesting that this region is involved in processing changes in environmental relationships. The present data show learning-related amygdala and hippocampal activity during human Pavlovian fear conditioning and suggest that the amygdala is particularly important for forming new associations as relationships between stimuli change.

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    • "This hypothesis is also supported by findings of rapid amygdala habituation during repeated exposure to generally aversive (Wendt, Weike, Lotze, and Hamm, 2011) or fear-relevant pictures (Wendt, Schmidt, Lotze, and Hamm, 2012). In the current study, however, we could not confirm the hypothesis suggested by Knight et al. (2004) that the amygdala detects changes in CS–UCS associations. Although participants had to learn a new association of the UCS and a novel geometric shape in each run, the initial amygdala differentiation between CS+ and CS− cue onset did not reappear at the first trial block of the second and third run. "
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    ABSTRACT: Studying neural networks and behavioral indices such as potentiated startle responses during fear conditioning has a long tradition in both animal and human research. However, most of the studies in humans do not link startle potentiation and neural activity during fear acquisition and extinction. Therefore, we examined startle blink responses measured with electromyography (EMG) and brain activity measured with functional MRI simultaneously during differential conditioning. Furthermore, we combined these behavioral fear indices with brain network activity by analyzing the brain activity evoked by the startle probe stimulus presented during conditioned visual threat and safety cues as well as in the absence of visual stimulation. In line with previous research, we found a fear-induced potentiation of the startle blink responses when elicited during a conditioned threat stimulus and a rapid decline of amygdala activity after an initial differentiation of threat and safety cues in early acquisition trials. Increased activation during processing of threat cues was also found in the anterior insula, the anterior cingulate cortex (ACC), and the periaqueductal grey (PAG). More importantly, our results depict an increase of brain activity to probes presented during threating in comparison to safety cues indicating an involvement of the anterior insula, the ACC, the thalamus, and the PAG in fear-potentiated startle processing during early extinction trials. Our study underlines that parallel assessment of fear-potentiated startle in fMRI paradigms can provide a helpful method to investigate common and distinct processing pathways in humans and animals and, thus, contribute to translational research. Copyright © 2015. Published by Elsevier B.V.
    Full-text · Article · Feb 2015 · International journal of psychophysiology: official journal of the International Organization of Psychophysiology
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    • "Selective lesions to the amygdala impair both cued and contextual fear conditioning in animals (LeDoux, 2000). Similarly, amygdala activity increases during the acquisition relative to the extinction phase (Phelps et al., 2001; Knight et al., 2004), and there is a strong correlation between amygdala reactivity and conditioned SCRs during fear acquisition (Cheng et al., 2003; Phelps et al., 2004) in humans. The amygdala is also involved in the fast detection of potentially harming stimuli (LeDoux, 2000; Öhman and Mineka, 2001), which might represent a highly adaptive process. "
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    ABSTRACT: Avoidance is considered as a central hallmark of all anxiety disorders. The acquisition and expression of avoidance, which leads to the maintenance and exacerbation of pathological fear is closely linked to Pavlovian and operant conditioning processes. Changes in conditionability might represent a key feature of all anxiety disorders but the exact nature of these alterations might vary across different disorders. To date, no information is available on specific changes in conditionability for disorder-irrelevant stimuli in specific phobia (SP). The first aim of this study was to investigate changes in fear acquisition and extinction in spider-fearful individuals as compared to non-fearful participants by using the de novo fear conditioning paradigm. Secondly, we aimed to determine whether differences in the magnitude of context-dependent fear retrieval exist between spider-fearful and non-fearful individuals. Our findings point to an enhanced fear discrimination in spider-fearful individuals as compared to non-fearful individuals at both the physiological and subjective level. The enhanced fear discrimination in spider-fearful individuals was neither mediated by increased state anxiety, depression, nor stress tension. Spider-fearful individuals displayed no changes in extinction learning and/or fear retrieval. Surprisingly, we found no evidence for context-dependent modulation of fear retrieval in either group. Here, we provide first evidence that spider-fearful individuals show an enhanced discriminative fear learning of phobia-irrelevant (de novo) stimuli. Our findings provide novel insights into the role of fear acquisition and expression for the development and maintenance of maladaptive responses in the course of SP.
    Full-text · Article · Oct 2014 · Frontiers in Behavioral Neuroscience
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    • "The insula has been reported to be involved in conveying a cortical representation of fear to the amygdala (Phelps et al., 2001). Knight et al. (2004) and Milad et al. (2007) proposed that the ACC is involved in the expression of the fear response. It has often been reported that the hippocampus is involved in fear conditioning. "
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    ABSTRACT: Extinction is an important mechanism to inhibit initially acquired fear responses. There is growing evidence that the ventromedial prefrontal cortex (vmPFC) inhibits the amygdala and therefore plays an important role in the extinction of delay fear conditioning. To our knowledge, there is no evidence on the role of the prefrontal cortex in the extinction of trace conditioning up to now. Thus, we compared brain structures involved in the extinction of human delay and trace fear conditioning in a between-subjects-design in an fMRI study. Participants were passively guided through a virtual environment during learning and extinction of conditioned fear. Two different lights served as conditioned stimuli (CS); as unconditioned stimulus (US) a mildly painful electric stimulus was delivered. In the delay conditioning group (DCG) the US was administered with offset of one light (CS+), whereas in the trace conditioning group (TCG) the US was presented 4 s after CS+ offset. Both groups showed insular and striatal activation during early extinction, but differed in their prefrontal activation. The vmPFC was mainly activated in the DCG, whereas the TCG showed activation of the dorsolateral prefrontal cortex (dlPFC) during extinction. These results point to different extinction processes in delay and trace conditioning. VmPFC activation during extinction of delay conditioning might reflect the inhibition of the fear response. In contrast, dlPFC activation during extinction of trace conditioning may reflect modulation of working memory processes which are involved in bridging the trace interval and hold information in short term memory.
    Full-text · Article · May 2014 · Frontiers in Human Neuroscience
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