Hippocampal but not amygdalar volume affects contextual fear conditioning in humans

Abstract

Both animal and human studies have identified a critical role of the hippocampus in contextual fear conditioning. In humans mainly functional magnetic resonance imaging has been used. To extend these findings to volumetric properties, 58 healthy participants underwent structural magnetic resonance imaging and participated in a differential fear conditioning paradigm with contextual stimuli. Ratings of emotional valence, arousal, and contingency as well as skin conductance responses (SCRs) were used as indicators of conditioning. Twenty-nine participants with the smallest hippocampal volumes were compared with 29 persons with the largest hippocampal volumes. Persons with larger hippocampal volume (especially on the right side) learned to discriminate between two conditioned contexts, whereas those with small hippocampal volumes did not, as indicated by SCRs. Further analyses showed that these results could not be explained by amygdalar volumes. In contrast, the participant answers on the self-report measures were not significantly influenced by hippocampal or amygdalar, but by total brain volume, suggesting a role of cortical structures in these more cognitive evaluation processes. Reanalysis of the self-report data using partial hippocampal volumes revealed a significant influence of the posterior but not anterior subvolumes, which is in accordance with theories and empirical findings on hippocampal functioning. This study shows the relevance of hippocampal volume for contextual fear conditioning in healthy volunteers and may have important implications for anxiety disorders.

Neural Correlates of Procedural Variants in Cognitive-Behavioral Therapy: A Randomized, Controlled Multicenter fMRI Study

“…In line with our findings, the hippocampus has been found to be relevant also for other anxiety disorders [62,63], conditioning paradigms [35,49,64,65,66,67,68,69] and seems to be sensitive to exposure [70], CBT treatment [30,71,72], therapy response [30] or recovery in general [73]. Furthermore, the hippocampus has been discussed with regard to the potential contribution to acquisition of irregularities in PD [15] and the optimization of exposure therapy and related learning processes [26].…”

The Carioca High and Low Conditioned Freezing Lines: A New Animal Model of Generalized Anxiety Disorder

“…When returned to the same chamber in the absence of the aversive stimulus, the animal presents a permanent fear reaction to contextual cues previously associated with the footshock. Considerable evidence from animal and human experiments indicate that fear conditioning in response to a discrete CS and contextual cues is mediated by different neural circuitries (Indovina et al, 2011;Ferreira et al, 2003;Kim & Fanselow, 1992;LeDoux, 2000;Pohlack et al, 2011). These results support the hypothesis of at least two dimensions of fear conditioning, and each dimension might be related to clinically distinct anxiety disorders.…”

The hippocampi of children with chromosome 22q11.2 deletion syndrome have localized anterior alterations that predict severity of anxiety

“…54 This is in contrast to the posterior hippocampus, which plays a role in fear memory 55,56 and possibly trait anxiety. 57 The proposed function of the anterior hippocampus in anxiety-like behaviours is to modulate input to the amygdala, which is a central component of emotionally coded memory.…”