Proximal threats promote enhanced acquisition and persistence of reactive fear-learning circuits

被引:31
|
作者
Faul, Leonard [1 ]
Stjepanovic, Daniel [1 ,2 ]
Stivers, Joshua M. [1 ]
Stewart, Gregory W. [1 ]
Graner, John L. [1 ]
Morey, Rajendra A. [3 ]
LaBar, Kevin S. [1 ,3 ]
机构
[1] Duke Univ, Dept Psychol & Neurosci, Durham, NC 27708 USA
[2] Univ Queensland, Ctr Youth Subst Abuse Res, St Lucia, Qld 4072, Australia
[3] Duke Univ, Dept Psychiat & Behav Sci, Med Ctr, Durham, NC 27710 USA
基金
美国国家科学基金会;
关键词
proximity; fear conditioning; virtual reality; representational similarity analysis; cerebellum; POSTTRAUMATIC-STRESS-DISORDER; PERIAQUEDUCTAL GRAY; PREFRONTAL CORTEX; CONDITIONED POTENTIATION; FUNCTIONAL TOPOGRAPHY; HUMAN CEREBELLUM; SYNAPTIC CHANGES; EXTINCTION; BRAIN; AMYGDALA;
D O I
10.1073/pnas.2004258117
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Physical proximity to a traumatic event increases the severity of accompanying stress symptoms, an effect that is reminiscent of evolutionarily configured fear responses based on threat immi-nence. Despite being widely adopted as a model system for stress and anxiety disorders, fear-conditioning research has not yet char-acterized how threat proximity impacts the mechanisms of fear acquisition and extinction in the human brain. We used three-dimensional (3D) virtual reality technology to manipulate the ego-centric distance of conspecific threats while healthy adult partici-pants navigated virtual worlds during functional magnetic resonance imaging (fMRI). Consistent with theoretical predictions, proximal threats enhanced fear acquisition by shifting conditioned learning from cognitive to reactive fear circuits in the brain and reducing amygdala-cortical connectivity during both fear acquisi-tion and extinction. With an analysis of representational pattern similarity between the acquisition and extinction phases, we fur-ther demonstrate that proximal threats impaired extinction effi-cacy via persistent multivariate representations of conditioned learning in the cerebellum, which predicted susceptibility to later fear reinstatement. These results show that conditioned threats encountered in close proximity are more resistant to extinction learning and suggest that the canonical neural circuitry typically associated with fear learning requires additional consideration of a more reactive neural fear system to fully account for this effect.
引用
收藏
页码:16678 / 16689
页数:12
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