Impact of Early Life Adversity on Reward Processing in Young Adults: EEG-fMRI Results from a Prospective Study over 25 Years

Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway.

多项证据表明，早期逆境暴露所致脑功能异常与中脑边缘多巴胺奖赏通路 (mesolimbic dopamine reward pathway) 密切相关。本研究探讨了早期生活逆境对成年后神经元奖赏加工不同阶段的影响，及其与相关行为表型——注意缺陷与多动障碍 (attention deficit/hyperactivity disorder, ADHD)——的关联。本研究纳入了一项自出生起即进行随访的流行病学队列中的162名健康青年受试者（平均年龄24.4岁，女性占比58%），所有受试者均完成了采用金钱奖赏延迟任务的同步脑电图-功能磁共振成像 (EEG-fMRI) 扫描。研究分别通过受试者3月龄时及2至15岁时开展的标准化家长访谈，对其早期生活逆境水平（采用早期家庭逆境指数 (early family adversity index, EFA) 进行量化）与终生注意缺陷多动障碍症状进行评估。功能磁共振成像感兴趣区分析显示，在奖赏预期阶段，早期家庭逆境指数对奖赏相关脑区（即腹侧纹状体、壳核、丘脑）的激活存在显著影响：随着EFA得分升高，上述脑区的激活程度显著降低。脑电图分析结果显示，伴随负变化 (contingent negative variation, CNV) 也呈现出类似的变化趋势：其振幅随EFA得分升高而降低。与之相反，在奖赏递送阶段，双侧脑岛、右侧苍白球及双侧壳核的激活程度则随EFA得分升高而增强。终生注意缺陷多动障碍症状与奖赏预期阶段左侧腹侧纹状体的激活降低、以及奖赏递送阶段右侧脑岛的激活升高均存在显著关联。本研究结果表明，早期生活逆境对奖赏加工存在差异化的长期影响：表现为奖赏预期阶段的反应低下，以及奖赏接收阶段的反应亢进。此外，与终生注意缺陷多动障碍症状相关的激活模式提示，早期生活应激对注意缺陷与多动障碍的影响可能通过功能异常的奖赏通路介导。