Human Fear Conditioning and Extinction in Neuroimaging: A Systematic Review

Department of Psychiatry, University of Muenster, Muenster, Germany.
PLoS ONE (Impact Factor: 3.23). 02/2009; 4(6):e5865. DOI: 10.1371/journal.pone.0005865
Source: PubMed


Fear conditioning and extinction are basic forms of associative learning that have gained considerable clinical relevance in enhancing our understanding of anxiety disorders and facilitating their treatment. Modern neuroimaging techniques have significantly aided the identification of anatomical structures and networks involved in fear conditioning. On closer inspection, there is considerable variation in methodology and results between studies. This systematic review provides an overview of the current neuroimaging literature on fear conditioning and extinction on healthy subjects, taking into account methodological issues such as the conditioning paradigm.

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    • "Furthermore, we used a differential fear-conditioning procedure (Mackintosh, 1983) to present a threatening (CS+) and nonthreatening (CS-) distractor stimulus. Fear-conditioning has proven to be an extremely robust and precise experimental approach for studying fear in animals as well as in humans (e.g., Brown, Kalish, & Farber, 1951; Delgado, Olsson, & Phelps, 2006; LeDoux, 2003; Maren, 2001; Pineles, Orr, & Orr, 2009; Sehlmeyer et al., 2009). In differential fear-conditioning, one biologically neutral stimulus (CS) is associated with a noxious or aversive unconditioned stimulus (US) by presenting it in close temporal proximity (LeDoux, 2014). "
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    ABSTRACT: Threatening stimuli are known to influence atten-tional and visual processes in order to prioritize selection. For example, previous research showed faster detection of threatening relative to nonthreatening stimuli. This has led to the proposal that threatening stimuli are prioritized automatically via a rapid subcortical route. However, in most studies, the threatening stimulus is always to some extent task relevant. Therefore, it is still unclear if threatening stimuli are automatically prioritized by the visual system. We used the additional singleton paradigm with task-irrelevant fear-conditioned distractors (CS+ and CS-) and indexed the time course of eye movement behavior. The results demonstrate automatic prioritization of threat. First, mean latency of saccades directed to the neutral target was increased in the presence of a threatening (CS+) relative to a nonthreatening distractor (CS-), indicating exogenous attentional capture and delayed disengagement of covert attention. Second, more error sac-cades were directed to the threatening than to the nonthreat-ening distractor, indicating a modulation of automatically driven saccades. Nevertheless, cumulative distributions of the saccade latencies showed no modulation of threat for the fastest goal-driven saccades, and threat did not affect the la-tency of the error saccades to the distractors. Together these results suggest that threatening stimuli are automatically prioritized in attentional and visual selection but not via faster processing. Rather, we suggest that prioritization results from an enhanced representation of the threatening stimulus in the oculomotor system, which drives attentional and visual selection. The current findings are interpreted in terms of a neuro-biological model of saccade programming.
    Full-text · Article · Nov 2015 · Cognitive Affective & Behavioral Neuroscience
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    • "Second, only about half of the studies that fulfilled the criteria reported cerebellar activation during fear learning, which emphasizes the considerable variability in the neuroimaging findings. This could be due to the methodological heterogeneity of the individual studies (Sehlmeyer et al., 2009). Third, the meta-analytic approach of the current study provides a quantitative overview of positive results only, and thus should be interpreted with the caveat that it did not take negative findings into account. "
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    ABSTRACT: I.M.J. LANGE, Z. KASANOVA, L. Goossens, N. Leibold, Chris I. De Zeeuw, T. van Amelsvoort, K. Schruers. The Anatomy of Fear Learning in the Cerebellum: A Systematic Meta-analysis. NEUBIOREV-D-14-00305. Recent neuro-imaging studies have implicated the cerebellum in several higher-order functions. Its role in human fear conditioning has, however, received limited attention. The current meta-analysis examines the loci of cerebellar contributions to fear conditioning in healthy subjects, thus mapping, for the first time, the neural response to conditioned aversive stimuli onto the cerebellum. By using the activation likelihood estimation (ALE) technique for analyses, we identified several distinct regions in the cerebellum that activate in response to the presentation of the conditioned stimulus: the cerebellar tonsils, lobules IV-VI, and the culmen. These regions have separately been implicated in fear acquisition, consolidation of fear memories and expression of conditioned fear responses. Their specific role in these processes may be attributed to the general contribution of cerebellar cortical networks to timing and prediction. Our meta-analysis highlights the potential role of the cerebellum in human cognition and emotion in general, and addresses the possibility how deficits in associative cerebellar learning may play a role in the pathogenesis of anxiety disorders. Future studies are needed to further clarify the mechanistic role of the cerebellum in higher order functions and neuropsychiatric disorders.
    Full-text · Article · Oct 2015 · Neuroscience & Biobehavioral Reviews
    • "The amygdala is commonly considered to be the region most implicated in fear conditioning. However, BOLD modulations have also been observed in a wider set of subcortical structures such as thalamus, hippocampus and anterior cingulate cortex [B€ uchel and Dolan, 2000; Knight et al., 2004; Sehlmeyer et al., 2009]. Crucially, the thalamic nuclei play a major role in mediating auditory fear conditioning in rats [Apergis- Schoute et al., 2005; Quirk et al., 1997]. "
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    ABSTRACT: Despite a strong focus on the role of the amygdala in fear conditioning, recent works point to a more distributed network supporting fear conditioning. We aimed to elucidate interactions between subcortical and cortical regions in fear conditioning in humans. To do this, we used two fearful faces as conditioned stimuli (CS) and an electrical stimulation at the left hand, paired with one of the CS, as unconditioned stimulus (US). The luminance of the CS was rhythmically modulated leading to "entrainment" of brain oscillations at a predefined modulation frequency. Steady-state responses (SSR) were recorded by MEG. In addition to occipital regions, spectral analysis of SSR revealed increased power during fear conditioning particularly for thalamus and cerebellum contralateral to the upcoming US. Using thalamus and amygdala as seed-regions, directed functional connectivity was calculated to capture the modulation of interactions that underlie fear conditioning. Importantly, this analysis showed that the thalamus drives the fusiform area during fear conditioning, while amygdala captures the more general effect of fearful faces perception. This study confirms ideas from the animal literature, and demonstrates for the first time the central role of the thalamus in fear conditioning in humans. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    No preview · Article · Aug 2015 · Human Brain Mapping
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