Elsevier

NeuroImage

Volume 26, Issue 4, 15 July 2005, Pages 1193-1200
NeuroImage

The role of the human amygdala in the production of conditioned fear responses

https://doi.org/10.1016/j.neuroimage.2005.03.020Get rights and content

Abstract

The amygdala plays a central role in the acquisition and expression of fear memories. Laboratory animal studies indicate that the amygdala both receives sensory information and produces learned behavioral and autonomic fear responses. However, prior functional imaging research in humans has largely focused on amygdala activity elicited by fearful stimuli, giving less attention to this region's role in the production of fear responses. In contrast, the present study used functional magnetic resonance imaging to investigate the amygdala's influence on the generation of conditional fear responses. Significant increases in amygdala activity were observed during the production of conditioned (learning-related), but not orienting, nonspecific, and unconditioned (nonlearning-related) skin conductance responses. Further, greater amygdala activity was demonstrated during conditioned response production than during conditioned stimulus presentation. These results suggest the amygdala not only responds to fearful stimuli, but also generates learning-related changes in human autonomic fear expression.

Section snippets

Participants

Nine healthy right-handed volunteers [5 female and 4 male; age (mean ± SEM): 28.33 ± 1.65 years; age range: 23 to 39 years] participated in this study. All subjects provided written informed consent in compliance with the National Institute of Mental Health Institutional Review Board.

Conditioning procedure

Two pure tones (700 and 1300 Hz) were presented as CSs (10 s duration) during the training session. The CS+ (30 trials) co-terminated with a 500-ms loud (100 dB) white-noise (UCS) on 80% of the trials and 20% of

SCR

Comparison of SCRs elicited by CS+ and CS− presentations indicates that the procedure used in this study supports excitatory conditioning. SCRs were separated into first interval response (FIR: SCRs that occur within the first 5 s following CS onset) and second interval response (SIR: SCRs that occur within seconds 6–10 following CS onset) SCRs. The FIRs and SIRs produced during CS+ (mean ± SEM: FIR = 0.14 ± 0.05, SIR = 0.14 ± 0.06) presentations were larger than those elicited by CS− (mean ±

Discussion

Large fMRI signal changes were observed within a number of brain areas during the production of conditioned, orienting, nonspecific, and unconditioned skin conductance responses. These regions included the anterior cingulate, insula, basal ganglia, cerebellum, thalamus, and areas of the prefrontal, temporal, and parietal cortices (see Fig. 4 and Table 1a). Previous studies exploring the neural mechanisms of SCR production have observed activations within many of these areas (Critchley et al.,

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      Here, paralleling our review of animal studies, we provide a summary of the human brain correlates of delay, trace, and contextual fear conditioning in healthy individuals, respectively, as well as those of fear extinction. According to a substantial number of fMRI studies (Andreatta et al., 2012; Armony and Dolan, 2002; Bach et al., 2011; Buchel et al., 1998; Critchley et al., 2002; Dunsmoor et al., 2008; Eippert et al., 2012; Etkin and Wager, 2007; Fullana et al., 2016; Knight et al., 2004a, 2005; Knight et al., 2009; LaBar et al., 1998; Maier et al., 2012; Marschner et al., 2008; Marstaller et al., 2016; Mechias et al., 2010; Milad et al., 2007a; Savage et al., 2020; Sehlmeyer et al., 2009; Tabbert et al., 2011; Wood et al., 2013, 2012), the most commonly-activated brain regions during delay fear conditioning include the amygdala, anterior cingulate cortex (ACC), and insula. Interestingly, multiple studies show that amygdala responses to the CS+ become diminished over the course of conditioning, possibly indicating a new formation of the CS-US association in the early acquisition of fear memory (Buchel et al., 1998; LaBar et al., 1998; Marschner et al., 2008).

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