Department of Psychology, Florida State University, 1107 W. Call St., Tallahassee, FL 32306, USA.
Department of Psychology, Florida State University, 1107 W. Call St., Tallahassee, FL 32306, USA.
Curr Biol. 2022 May 9;32(9):2067-2075.e4. doi: 10.1016/j.cub.2022.02.076. Epub 2022 Mar 23.
The amygdala-prefrontal-cortex circuit has long occupied the center of the threat system, but new evidence has rapidly amassed to implicate threat processing outside this canonical circuit. Through nonhuman research, the sensory cortex has emerged as a critical substrate for long-term threat memory, underpinned by sensory cortical pattern separation/completion and tuning shift. In humans, research has begun to associate the human sensory cortex with long-term threat memory, but the lack of mechanistic insights obscures a direct linkage. Toward that end, we assessed human olfactory threat conditioning and long-term (9 days) threat memory, combining affective appraisal, olfactory psychophysics, and functional magnetic resonance imaging (fMRI) over a linear odor-morphing continuum (five levels of binary mixtures of the conditioned stimuli/CS+ and CS- odors). Affective ratings and olfactory perceptual discrimination confirmed (explicit) affective and perceptual learning and memory via conditioning. fMRI representational similarity analysis (RSA) and voxel-based tuning analysis further revealed associative plasticity in the human olfactory (piriform) cortex, including immediate and lasting pattern differentiation between CS and neighboring non-CS and a late onset, lasting tuning shift toward the CS. The two plastic processes were especially salient and lasting in anxious individuals, among whom they were further correlated. These findings thus support an evolutionarily conserved sensory cortical system of long-term threat representation, which can underpin threat perception and memory. Importantly, hyperfunctioning of this sensory mnemonic system of threat in anxiety further implicates a hitherto underappreciated sensory mechanism of anxiety.
杏仁核-前额叶皮质回路长期以来一直占据威胁系统的中心地位，但新的证据迅速积累，表明威胁处理不仅仅局限于这个经典回路。通过非人类研究，感觉皮层已成为长期威胁记忆的关键基质，这是由感觉皮层模式分离/完成和调谐转移支撑的。在人类中，研究已经开始将人类感觉皮层与长期威胁记忆联系起来，但由于缺乏机制上的见解，阻碍了直接联系的确立。为此，我们评估了人类嗅觉威胁条件反射和 9 天的长期威胁记忆，结合了情感评估、嗅觉心理物理学和功能磁共振成像 (fMRI)，在一个线性气味变形连续体上（条件刺激/CS+和 CS-气味的五个二元混合物水平）。情感评分和嗅觉感知辨别通过条件作用证实了（显性的）情感和感知学习和记忆。功能磁共振成像代表性相似性分析 (RSA) 和基于体素的调谐分析进一步揭示了人类嗅觉（梨状皮层）的联想可塑性，包括 CS 和相邻非 CS 之间的即时和持续的模式分化，以及晚期出现的、持续的向 CS 的调谐转移。这两个塑性过程在焦虑个体中尤为明显和持久，其中它们进一步相关。这些发现因此支持了长期威胁表示的进化保守的感觉皮层系统，它可以支持威胁感知和记忆。重要的是，焦虑中这种威胁感觉记忆系统的过度功能进一步暗示了焦虑中一个迄今为止被低估的感觉机制。
