老化於選擇評價歷程的紋狀體去區辨性與額葉過度活化

Abstract

評價決策的歷程包含腹側紋狀體與前額葉，而這區域也呈現老化相關的多巴胺效用下降。在這個研究中，我們假設這樣的效用下降會造成老年人評價歷程的區辨性下降。同時額葉區域也可能有老化相關的過度活化以作為次級歷程來反應受影響價值歷程。我們以功能性磁振造影執行選擇決策的實驗任務，研究老化所造成的評價選擇歷程的神經差異。四十位年輕人以及四十位老年人參與實驗，在功能性磁振造影的過程中，參與者依造螢幕上的輸贏的機率和價值來決定接受或拒絕螢幕上的選擇，並依其選擇給予結果。行為上，老年人在低機率的情況下有較多的接受次數，也同時有相對上更長的反應時間。功能性磁振造影的全腦分析中，老年人相較於年輕人在雙側伏隔核中對於機率的敏感性較低。同時，左側的背外側前額葉在老年人有過度活化的情況，而且在低機率有更高的反應。後續的功能性聯結分析顯示，老年人在左背外側前額葉與右伏隔核有負的功能聯結，而在年輕人上沒有這樣的功能聯結。因此，老年人較無法有效率地處理決策的價值。我們的研究在老化的決策歷程上發現一個嶄新的神經機制，聯結老化在雙側伏隔核的去區辨性與背外側前額葉的過度活化兩者之間於決策歷程上的關係。

The ventral striatum and prefrontal cortex, involved in value prediction during choice processing, show age-related decline in dopamine efficacy. In this study, we postulated that such diminished dopamine efficacy might reduce neural selectivity of value encoding in older adults relative to younger adults. In tandem, there may be age-related overactivation in other frontal areas reflecting secondary processing due to the reduced fidelity of value encoding. We conducted a functional magnetic resonance imaging (fMRI) experiment using a lottery-choice task to investigate age-related neural differences related to choice value processing. 40 younger and 40 older healthy adults saw numbers depicting the probability of winning and losing specified point values in the scanner. For each trial, participants chose to accept or decline the offer and then outcome feedback was provided. Behaviorally, older adults were more likely to accept choices coding low probabilities of winning compared to younger adults, with relatively longer response times in low probability conditions as well. As expected, whole-brain analysis of fMRI data revealed less sensitivity to increasing probability levels in older compared to younger adults in bilateral nucleus accumbens (NAcc). In addition, left dorsal lateral prefrontal cortex (DLPFC) showed overactivation in older relative to younger adults particularly for responses to low probability conditions. Further functional connectivity analysis showed that older adults had negative connectivity between left DLPFC and right NAcc, which was absent in younger adults. Thus, older adults have more difficulty in effectively processing choice values, and specifically overvalue low probability choices. Importantly, our study uncovers a novel mechanistic link between age-related reduction in neural selectivity in the bilateral NAcc and overactivation in the DLPFC during value encoding.