Neural Substrates Underlying Learning-Related Changes of the Unconditioned Fear Response

Kimberly H. Wood1, Dystany Kuykendall1, Lawrence W. Ver Hoef2, David C. Knight1, *
1 Department of Psychology, University of Alabama at Birmingham, Birmingham, AL 35294, UK
2 University of Alabama at Birmingham, School of Medicine; Birmingham VA Medical Center, UK

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© Wood et al.; Licensee Bentham Open.

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the CIRC 235H, 1530 3RD AVE S, Birmingham, AL 35294-0021, Tel: (205) 996-6344; Fax: (205) 975-6320; E-mail:


The ability to predict an impending threat during Pavlovian conditioning diminishes the emotional response that is produced once the threat is encountered. Diminution of the threat response appears to be mediated by somewhat independent associative learning and expectancy-related processes. Therefore, the present study was designed to better understand the neural mechanisms that support associative learning processes, independent of expectancy, that influence the emotional response to a threat. Healthy volunteers took part in a Pavlovian conditioning procedure during which trait anxiety, expectation of the unconditioned stimulus (UCS), skin conductance response (SCR), and functional magnetic resonance imaging (fMRI) signal were assessed. The results showed no evidence for associative learning that was independent of expectation. Threat-related SCR expression was diminished on predictable trials vs. unpredictable trials of the UCS (i.e. conditioned UCR diminution). Similar to SCR, conditioned UCR diminution was observed within the left dorsolateral PFC, dorsomedial PFC, ventromedial PFC, and left anterior insula. In contrast, potentiation of the threat-related fMRI signal response was observed within left dorsolateral PFC, inferior parietal lobule (IPL), and posterior insula. A negative relationship was observed between UCS expectancy and UCR expression within the dorsomedial PFC, ventromedial PFC, and anterior insula. Finally, the anticipatory fMRI signal responses within the PFC, posterior cingulate, and amygdala showed an inverse relationship with threat-related activation within the brain regions that showed UCR diminution. The current findings suggest that the PFC and amygdala support learning-related processes that impact the magnitude of the emotional response to a threat.

Keywords: fMRI, conditioning, unconditioned response, prefrontal cortex, emotion, fear, anxiety, skin conductance.