Lissek Shmuel, Bradford Daniel E, Alvarez Ruben P, Burton Philip, Espensen-Sturges Tori, Reynolds Richard C, Grillon Christian
Mood and Anxiety Disorders Program, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA, Department of Psychology, University of Minnesota-Twin Cities, MN, USA, Department of Psychology, University Wisconsin-Madison, Madison, WI, USA, and Laureate Institute for Brain Research, Tulsa, OK, USAMood and Anxiety Disorders Program, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA, Department of Psychology, University of Minnesota-Twin Cities, MN, USA, Department of Psychology, University Wisconsin-Madison, Madison, WI, USA, and Laureate Institute for Brain Research, Tulsa, OK, USA
Mood and Anxiety Disorders Program, National Institute of Mental Health, Intramural Research Program, NIH, DHHS, Bethesda, MD, USA, Department of Psychology, University of Minnesota-Twin Cities, MN, USA, Department of Psychology, University Wisconsin-Madison, Madison, WI, USA, and Laureate Institute for Brain Research, Tulsa, OK, USA.
Soc Cogn Affect Neurosci. 2014 Aug;9(8):1134-42. doi: 10.1093/scan/nst096. Epub 2013 Jun 6.
Recent research on classical fear-conditioning in the anxiety disorders has identified overgeneralization of conditioned fear as an important conditioning correlate of anxiety pathology. Unfortunately, only one human neuroimaging study of classically conditioned fear generalization has been conducted, and the neural substrates of this clinically germane process remain largely unknown. The current generalization study employs a clinically validated generalization gradient paradigm, modified for the fMRI environment, to identify neural substrates of classically conditioned generalization that may function aberrantly in clinical anxiety. Stimuli include five rings of gradually increasing size with extreme sizes serving as cues of conditioned danger (CS+) and safety (CS-). The three intermediately sized rings serve as generalization stimuli (GSs) and create a continuum-of-size from CS+ to CS-. Results demonstrate 'positive' generalization gradients, reflected by declines in responding as the presented stimulus differentiates from CS+, in bilateral anterior insula, dorsomedial prefrontal cortex, and bilateral inferior parietal lobule. Conversely, 'negative' gradients, reflected by inclines in responding as the presented stimulus differentiates from CS+ were instantiated in bilateral ventral hippocampus, ventromedial prefrontal cortex and precuneus cortex. These results as well as those from connectivity analyses are discussed in relation to a working neurobiology of conditioned generalization centered on the hippocampus.
近期针对焦虑症中经典恐惧条件作用的研究已确定，条件性恐惧的过度泛化是焦虑病理的一个重要条件作用相关因素。不幸的是，仅进行了一项关于经典条件性恐惧泛化的人类神经影像学研究，而这一临床相关过程的神经基质在很大程度上仍不为人知。当前的泛化研究采用了一种经过临床验证的泛化梯度范式，并针对功能磁共振成像环境进行了修改，以确定经典条件性泛化的神经基质，这些基质在临床焦虑中可能存在异常功能。刺激包括五个尺寸逐渐增大的圆环，其中尺寸极大的圆环作为条件性危险线索（CS+），尺寸极小的圆环作为安全线索（CS-）。三个中等尺寸的圆环作为泛化刺激（GSs），并创建了一个从CS+到CS-的尺寸连续体。结果显示，在双侧前脑岛、背内侧前额叶皮层和双侧顶下小叶中，随着呈现的刺激与CS+的差异增大，反应下降，呈现出“正”泛化梯度。相反，在双侧腹侧海马体、腹内侧前额叶皮层和楔前叶皮层中，随着呈现的刺激与CS+的差异增大，反应上升，呈现出“负”梯度。这些结果以及连通性分析的结果将结合以海马体为中心的条件性泛化工作神经生物学进行讨论。
