Yan C-G, Rincón-Cortés M, Raineki C, Sarro E, Colcombe S, Guilfoyle D N, Yang Z, Gerum S, Biswal B B, Milham M P, Sullivan R M, Castellanos F X
CAS Key Laboratory of Behavioral Science, Institute of Psychology, Beijing, China.
Magnetic Resonance Imaging Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.
Transl Psychiatry. 2017 Jan 17;7(1):e1005. doi: 10.1038/tp.2016.276.
Caregiver maltreatment induces vulnerability to later-life psychopathology. Clinical and preclinical evidence suggest changes in prefrontal and limbic circuitry underlie this susceptibility. We examined this question using a rat model of maternal maltreatment and methods translated from humans, resting-state functional magnetic resonance imaging (R-fMRI). Rat pups were reared by mothers provided with insufficient or abundant bedding for nest building from postnatal (PN) days 8 to 12 and underwent behavioral assessments of affect-related behaviors (forced swim, sucrose preference and social interaction) in adolescence (PN45) and early adulthood (PN60). R-fMRI sessions were conducted under light anesthesia at both ages. Offspring reared with insufficient bedding (that is, maltreated) displayed enduring negative affective behaviors. Amygdala-prefrontal cortex (PFC) functional connectivity increased significantly from adolescence to adulthood in controls, but not in maltreated animals. We computed the fractional amplitude of low-frequency fluctuations (fALFF), an index of intrinsic brain activity, and found that fALFF in medial prefrontal cortex and anterior cingulate cortex (MPFC/ACC) increased significantly with age in controls but remained unchanged in maltreated animals during adolescence and adulthood. We used a seed-based analysis to explore changes in functional connectivity between this region and the whole brain. Compared with controls, maltreated animals demonstrated reduced functional connectivity between MPFC/ACC and left caudate/putamen across both ages. Functional connectivity between MPFC/ACC and right caudate/putamen showed a group by age interaction: decreased in controls but increased in maltreated animals. These data suggest that maltreatment induces vulnerability to psychopathology and is associated with differential developmental trajectories of prefrontal and subcortical circuits underlying affect regulation.
照顾者虐待会导致日后出现精神病理学问题的易感性。临床和临床前证据表明，前额叶和边缘系统神经回路的变化是这种易感性的基础。我们使用母体虐待的大鼠模型以及从人类研究中转化而来的方法——静息态功能磁共振成像（R-fMRI）来研究这个问题。从出生后（PN）第8天到第12天，给大鼠幼崽提供不足或充足的筑巢垫料，由母鼠抚养，然后在青春期（PN45）和成年早期（PN60）对其进行与情感相关行为的行为评估（强迫游泳、蔗糖偏好和社交互动）。在这两个年龄段，均在轻度麻醉下进行R-fMRI实验。垫料不足（即受虐待）抚养的后代表现出持久的负面情感行为。在对照组中，杏仁核-前额叶皮质（PFC）功能连接从青春期到成年期显著增加，但在受虐待的动物中则没有。我们计算了低频波动分数（fALFF），这是一种大脑内在活动的指标，发现内侧前额叶皮质和前扣带回皮质（MPFC/ACC）的fALFF在对照组中随年龄显著增加，但在受虐待的动物中，在青春期和成年期保持不变。我们使用基于种子的分析来探索该区域与全脑之间功能连接的变化。与对照组相比，受虐待的动物在两个年龄段中MPFC/ACC与左侧尾状核/壳核之间的功能连接均降低。MPFC/ACC与右侧尾状核/壳核之间的功能连接表现出年龄组间交互作用：在对照组中降低，但在受虐待的动物中增加。这些数据表明，虐待会导致精神病理学问题的易感性，并与情感调节基础的前额叶和皮层下神经回路的不同发育轨迹相关。
