Silvers Jennifer A, Lumian Daniel S, Gabard-Durnam Laurel, Gee Dylan G, Goff Bonnie, Fareri Dominic S, Caldera Christina, Flannery Jessica, Telzer Eva H, Humphreys Kathryn L, Tottenham Nim
Department of Psychology, University of California, Los Angeles, Los Angeles, California 90095,
Department of Psychology, University of Denver, Denver, Colorado 80208.
J Neurosci. 2016 Jun 15;36(24):6420-30. doi: 10.1523/JNEUROSCI.0038-16.2016.
Early institutional care can be profoundly stressful for the human infant, and, as such, can lead to significant alterations in brain development. In animal models, similar variants of early adversity have been shown to modify amygdala-hippocampal-prefrontal cortex development and associated aversive learning. The current study examined this rearing aberration in human development. Eighty-nine children and adolescents who were either previously institutionalized (PI youth; N = 46; 33 females and 13 males; age range, 7-16 years) or were raised by their biological parents from birth (N = 43; 22 females and 21 males; age range, 7-16 years) completed an aversive-learning paradigm while undergoing functional neuroimaging, wherein visual cues were paired with either an aversive sound (CS+) or no sound (CS-). For the PI youth, better aversive learning was associated with higher concurrent trait anxiety. Both groups showed robust learning and amygdala activation for CS+ versus CS- trials. However, PI youth also exhibited broader recruitment of several regions and increased hippocampal connectivity with prefrontal cortex. Stronger connectivity between the hippocampus and ventromedial PFC predicted significant improvements in future anxiety (measured 2 years later), and this was particularly true within the PI group. These results suggest that for humans as well as for other species, early adversity alters the neurobiology of aversive learning by engaging a broader prefrontal-subcortical circuit than same-aged peers. These differences are interpreted as ontogenetic adaptations and potential sources of resilience.
Prior institutionalization is a significant form of early adversity. While nonhuman animal research suggests that early adversity alters aversive learning and associated neurocircuitry, no prior work has examined this in humans. Here, we show that youth who experienced prior institutionalization, but not comparison youth, recruit the hippocampus during aversive learning. Among youth who experienced prior institutionalization, individual differences in aversive learning were associated with worse current anxiety. However, connectivity between the hippocampus and prefrontal cortex prospectively predicted significant improvements in anxiety 2 years following scanning for previously institutionalized youth. Among youth who experienced prior institutionalization, age-atypical engagement of a distributed set of brain regions during aversive learning may serve a protective function.
早期机构照料对人类婴儿来说可能极具压力，因此可能导致大脑发育的显著改变。在动物模型中，类似的早期逆境已被证明会改变杏仁核 - 海马体 - 前额叶皮质的发育以及相关的厌恶学习。本研究调查了人类发育中的这种养育异常情况。89名儿童和青少年完成了一项厌恶学习范式，同时接受功能神经成像，其中视觉线索与厌恶声音（条件刺激+，CS+）或无声音（条件刺激 -，CS -）配对。这些儿童和青少年中，一部分是曾在机构中生活过的（曾机构照料青少年，PI青年；N = 46；33名女性和13名男性；年龄范围7 - 16岁），另一部分是由亲生父母从出生就抚养长大的（N = 43；22名女性和21名男性；年龄范围7 - 16岁）。对于PI青年，更好的厌恶学习与更高的同时期特质焦虑有关。两组在CS+与CS -试验中均表现出强大的学习能力和杏仁核激活。然而，PI青年还表现出多个区域更广泛的激活以及海马体与前额叶皮质之间连接性增加。海马体与腹内侧前额叶皮质之间更强的连接性预示着未来焦虑（2年后测量）会有显著改善，在PI组中尤其如此。这些结果表明，对于人类以及其他物种而言，早期逆境通过激活比同龄人更广泛的前额叶 - 皮质下回路来改变厌恶学习的神经生物学。这些差异被解释为个体发育适应和潜在的恢复力来源。
先前的机构照料是早期逆境的一种重要形式。虽然非人类动物研究表明早期逆境会改变厌恶学习及相关神经回路，但此前尚无研究在人类中对此进行调查。在此，我们表明，经历过先前机构照料的青年在厌恶学习过程中会激活海马体，而对照组青年则不会。在经历过先前机构照料的青年中，厌恶学习的个体差异与当前更严重的焦虑有关。然而，海马体与前额叶皮质之间的连接性前瞻性地预测了在扫描后2年曾机构照料青年的焦虑会有显著改善。在经历过先前机构照料的青年中，厌恶学习期间一组分布式脑区的年龄非典型激活可能起到保护作用。
