The Basolateral Amygdalae and Frontotemporal Network Functions for Threat Perception

Abstract

Although the amygdalae play a central role in threat perception and reactions, the direct contributions of the amygdalae to specific aspects of threat perception, from ambiguity resolution to reflexive or deliberate action, remain ill understood in humans. Animal studies show that a detailed understanding requires a focus on the different subnuclei, which is not yet achieved in human research. Given the limits of human imaging methods, the crucial contribution needs to come from individuals with exclusive and selective amygdalae lesions. The current study investigated the role of the basolateral amygdalae and their connection with associated frontal and temporal networks in the automatic perception of threat. Functional activation and connectivity of five individuals with Urbach-Wiethe disease with focal basolateral amygdalae damage and 12 matched controls were measured with functional MRI while they attended to the facial expression of a threatening face-body compound stimuli. Basolateral amygdalae damage was associated with decreased activation in the temporal pole but increased activity in the ventral and dorsal medial prefrontal and medial orbitofrontal cortex. This dissociation between the prefrontal and temporal networks was also present in the connectivity maps. Our results contribute to a dynamic, multirole, subnuclei-based perspective on the involvement of the amygdalae in fear perception. Damage to the basolateral amygdalae decreases activity in the temporal network while increasing activity in the frontal network, thereby potentially triggering a switch from resolving ambiguity to dysfunctional threat signaling and regulation, resulting in hypersensitivity to threat.

Keywords: Urbach–Wiethe disease; amygdalae; basolateral amygdalae; emotion; threat.

Figure 1.

Location and size of the BLA damage. Coronal view of T2-weighted MRIs (left) and a 3D reconstruction (middle) of the lesion for the five individuals with UWD with birth year indicated. Reconstruction of the AMG subnuclei was based on the cytoarchitectonic probability maps from Amunts et al., (2005) in Eickhoff et al., (2005). Black rectangle indicates viewpoint for the 3D reconstruction (right).

Figure 2.

The importance of the IPL in the processing of fearful body expressions. The UWD group showed more activation for fearful versus happy bodies in the right anterior IPL, but less activation in the left fusiform gyrus (top). Increased functional connectivity between the IPL and the subgenual ACC, and the fusiform gyrus and the anterior IPL, was observed in individuals with UWD compared with controls (bottom). Purple outline indicates that the cluster survived whole-brain cluster-size correction with an initial single voxel threshold of p < 0.005.

Figure 3.

Enhancement of prefrontal midline activation during the perception of incongruent threatening face–body compounds after BLA damage. The mOFC, vMPFC, and dMPFC showed increased activity in the UWD group (top left) during incongruent threatening face–body compound perception. Inset shows increased dMPFC activation for incongruent versus congruent face–body compounds in individuals with UWD and decreased vMPFC activation for the same contrast in controls. Individuals with UWD showed decreased functional connectivity between the mOFC and the posterior IPL. The dMPFC showed increased coupling with the VMPFC, but decreased coupling with the superior temporal gyrus and TP in individuals with UWD (right and bottom). Maps are cluster-size corrected except for the within-group maps that are shown with a threshold of p < 0.05 uncorrected for illustration purposes. Purple outline indicates that the cluster survived whole-brain cluster-size correction with an initial single voxel threshold of p < 0.005.

Figure 4.

Disruption of the TP in the processing of incongruent threatening face–body compounds after BLA damage. Activity in the TP was reduced for the UWD group during perception of incongruent threatening face-body compounds (top left). Inset shows decreased bilateral TP activation for incongruent versus congruent face-body compounds in individuals with UWD, and increased bilateral TP activation for the same contrast in controls. Consistent with the dissociation between the frontal and temporal network, decreased functional connectivity was observed in individuals with UWD between the left TP and mOFC and superior frontal gyrus. The right TP showed increased coupling with the inferior temporal gyrus and bilateral middle temporal gyrus (right and bottom). Maps are cluster-size corrected except for the within-group maps that are shown with a threshold of p < 0.05 uncorrected for illustration purposes. Purple outline indicates that the cluster survived whole-brain cluster-size correction with an initial single voxel threshold of p < 0.005.