Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong SAR, China.
PLoS One. 2013;8(1):e51704. doi: 10.1371/journal.pone.0051704. Epub 2013 Jan 30.
Following fear conditioning (FC), ex vivo evidence suggests that early dynamics of cellular and molecular plasticity in amygdala and hippocampal circuits mediate responses to fear. Such altered dynamics in fear circuits are thought to be etiologically related to anxiety disorders including posttraumatic stress disorder (PTSD). Consistent with this, neuroimaging studies of individuals with established PTSD in the months after trauma have revealed changes in brain regions responsible for processing fear. However, whether early changes in fear circuits can be captured in vivo is not known.
We hypothesized that in vivo magnetic resonance diffusion tensor imaging (DTI) would be sensitive to rapid microstructural changes elicited by FC in an experimental mouse PTSD model. We employed a repeated measures paired design to compare in vivo DTI measurements before, one hour after, and one day after FC-exposed mice (n=18).
Using voxel-wise repeated measures analysis, fractional anisotropy (FA) significantly increased then decreased in amygdala, decreased then increased in hippocampus, and was increasing in cingulum and adjacent gray matter one hour and one day post-FC respectively. These findings demonstrate that DTI is sensitive to early changes in brain microstructure following FC, and that FC elicits distinct, rapid in vivo responses in amygdala and hippocampus.
Our results indicate that DTI can detect rapid microstructural changes in brain regions known to mediate fear conditioning in vivo. DTI indices could be explored as a translational tool to capture potential early biological changes in individuals at risk for developing PTSD.
在恐惧条件反射（FC）之后，体外证据表明，杏仁核和海马回路中细胞和分子可塑性的早期动力学调节了对恐惧的反应。人们认为，恐惧回路中这种改变的动力学与包括创伤后应激障碍（PTSD）在内的焦虑障碍有病因学上的关系。与此一致的是，对创伤后几个月内患有既定 PTSD 的个体的神经影像学研究揭示了负责处理恐惧的大脑区域的变化。然而，尚不清楚是否可以在体内捕获恐惧回路的早期变化。
我们假设，在实验性 PTSD 小鼠模型中，活体磁共振扩散张量成像（DTI）将对 FC 引起的快速微观结构变化敏感。我们采用重复测量配对设计，比较了 FC 暴露后的小鼠（n=18）在暴露前、暴露后 1 小时和 1 天后的活体 DTI 测量值。
使用体素重复测量分析，FA 在杏仁核中显著增加，然后减少，在海马中减少，然后增加，在扣带回和相邻灰质中分别在 FC 后 1 小时和 1 天增加。这些发现表明，DTI 对 FC 后大脑微观结构的早期变化敏感，并且 FC 在杏仁核和海马中引发了不同的、快速的体内反应。
我们的结果表明，DTI 可以检测到体内介导恐惧条件反射的大脑区域的快速微观结构变化。DTI 指数可以作为一种转化工具，以捕获 PTSD 高危人群中潜在的早期生物学变化。
