RT Journal Article SR Electronic T1 The Basolateral Amygdalae and Frontotemporal Network Functions for Threat Perception JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0314-16.2016 DO 10.1523/ENEURO.0314-16.2016 A1 Ruud Hortensius A1 David Terburg A1 Barak Morgan A1 Dan J. Stein A1 Jack van Honk A1 Beatrice de Gelder YR 2017 UL http://www.eneuro.org/content/early/2017/02/23/ENEURO.0314-16.2016.abstract AB While 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 amygdala damage and 12 matched controls were measured with fMRI while they attended to the facial expression of a threatening face-body compound stimuli. Basolateral amygdala 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, multi-role, 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.Significance Statement Humans are experts in recognizing potential threat signals. While the role of the human amygdalae is widely acknowledged, the contributions of the different amygdalae nuclei and associated neural networks in threat perception remain poorly understood. Here we investigate the importance of the basolateral amygdalae and their connections with temporal and frontal regions during the processing of task-irrelevant threatening bodily signals. We tested five individuals with selective basolateral amygdalae damage. The results show that after basolateral amygdalae damage activity was increased in the frontal network but decreased in the temporal network. Together with anomalous activity in regions important for action, these results point to a disruption along three axes during threat perception, namely ambiguity resolution, safety signaling, and action preparation.