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.
Footnotes
Authors report no conflict of interest.
Development of the MacBrain Face Stimulus Set was overseen by Nim Tottenham and supported by the John D. and Catherine T. MacArthur Foundation Research Network on Early Experience and Brain Development. B.d.G. and R.H. were partly funded by the project TANGO. The project TANGO acknowledges the financial support of the Future and Emerging Technologies (FET) program within the Seventh Framework Program for Research of the European Commission, under FET-Open grant number: 249858. B.d.G. has also received funding from the European Research Council under the European Union’s Seventh Framework Program (FP7/2007-2013)/ERC grant agreement number 295673. D.T. was supported by grants from the Netherlands Organization for Scientific Research (NWO): VENI 451-13-004. D.J.S. was supported by the Medical Research Council of South Africa. J.v.H. was supported by grants from Utrecht University, the Netherlands Organization of Scientific Research (Brain and Cognition: 056-24-010), the South African MRC/DST Professional Development Program and the University of Cape Town (Brain Behavior Initiative).
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