The role of mesocorticolimbic networks for emotional adaptation and well-being in the second half of life

抑郁症在晚年生活中很常见，可能会产生毁灭性的后果。另一方面，在大型数据集上的发现表明，从中年开始，人们的情绪幸福感有所增加。复原力研究现在已经开始确定中老年情绪障碍的保护因素。在这里，中皮质边缘网络似乎是至关重要的，因为它们不仅与老年抑郁症有关，而且还与健康的情绪老化有关。例如，大脑中皮质边缘环路调节了对错失机会等遗憾经历的处理。后悔敏感和沉思是抑郁的风险因素，特别是在晚年，而后悔反应的降低与成功衰老有关。到目前为止，尚不清楚应对悔恨的“健康”方式是否真的在一生中逐渐发生变化，这种变化是否存在关键的时间窗口，以及这与大脑中皮质边缘神经回路的功能和结构完整性有何关系。在我们的项目中，我们可以通过利用这个独特的机会研究1000名年龄在45岁到74岁之间的参与者的大规模流行病学数据集来解决这些问题，这些参与者接受了多模式成像评估，并执行了关于错失机会和后悔处理的既定范式。在三个工作包中，我们调查了幸福感、后悔反应和中皮质边缘功能/结构的年龄特征及其相互作用。研究结果将被纳入，以开发一种个人幸福感随年龄增长的预测模型。该模型的预测值可以在独立的数据集上直接进行检验。我们的项目可以为后半生情绪健康的行为和神经调节因素提供全新的见解。强调关键的时间窗口和风险概况可能会为个性化的认知行为预防计划铺平道路，以调节情绪的调节。

Depression in later life is common and can have devastating consequences. On the other hand, findings on large data sets report an increase of emotional well-being from middle age onwards. Resilience research has now started to identify protective factors against mood disorders in middle and late life. Mesocorticolimbic networks seem to be crucial here given their involvement not only in late-life depression but also healthy emotional aging. For instance, mesocorticolimbic circuits modulate the processing of regretful experiences such as missed opportunities. Regret sensitivity and brooding are risk factors for depression, particularly in later life, while a reduced regret responsiveness has been related to successful aging. So far, it is unclear whether the “healthy” way to deal with regret indeed gradually changes across the lifespan, whether there are critical time-windows for such changes and how this is related to the functional and structural integrity of mesocorticolimbic neurocircuits. In our project, we can address these questions by making use of the unique opportunity to study a large-scale epidemiological dataset of 1000 participants between the age of 45 and 74 who undergo a multimodal imaging assessment and perform an established paradigm on missed opportunities and regret processing. In three work packages we investigate age-profiles in well-being, regret-responsiveness and mesocorticolimbic function/structure and their interactions. Findings will be incorporated to develop a prediction model of individual well-being across aging. The predictive value of this model can be directly tested in an independent data set. Our project can provide fundamentally new insights into behavioral and neural modulators of emotional health in the second half of life. Highlighting critical time-windows and risk-profiles may pave the way for individually tailored cognitive-behavioral prevention programs to modulate regulation of emotions.