多巴胺與血清素系統對老化關聯風險決策之影響： 功能性與結構性腦造影研究

Abstract

老化被證實與非最佳的價值相關的風險決策相關，此一現象與大腦在生理學上多巴胺與血清素等兩種影響回饋系統的神經傳導物質的系統性老化可能有關，而從中腦/腦幹所發出到新皮質的神經連結更是其中的關鍵。但因為技術與實驗設計的限制，極少研究專注在此，本研究致力於探討年輕人與老年人的中腦到新皮質之間的功能性與白質結構性腦部連結狀態和其在價值關聯性決策中的行為參數之間的關係性，共招募年輕受試者六十五人與年長受試者五十六人。在結構性研究的部分，我們發現在中腦到額葉的白質結構完整性指標在年長組裡相較與年輕組較低，但在中腦到顳葉的連結則呈現相反的結果。另外在複回歸的分析中發現單一連結的結構完整性與行為參數呈現正相關，但到同一腦區的連結之間的交互作用則與行為參數呈現負相關。在功能性研究的部分，我們發現在老年人與年輕人之間額葉與皮質下區域與中腦的功能性連結有所不同，另外在複回歸的分析中發現單一連結的功能性連結與行為參數呈現正相關，但到同一腦區的連結之間的交互作用則與行為參數呈現負相關。從以上結果可以看出多巴胺與血清素系統至單一腦區的功能性與結構性連結之間有著平衡與相互競爭的交互作用，此一結果為未來更多關於此兩神經傳導系統與價值決策研究提供參考。

Aging is associated with suboptimal value-based decisions that affect personal wealth and health prospects in older adults. Such age-related decline in decision-making may stem from biological decline in the dopaminergic and serotonergic systems that are central to reward-learning processes. However, studies examining age-effects on midbrain-to-neocortical associations are scarce. Here, we aim to assess young and older adult differences in midbrain dopamine (ventral tegmental area, VTA) and serotonin (dorsal raphe nuclei, DRN; medial raphe nuclei, MRN) projections to neocortical targets (striatum, prefrontal cortex, medial temporal lobe) associated with decision-making performance in structural and functional prospect using diffusion tensor imaging and resting-state functional imaging. Total 65 younger subjects along with 56 older subjects were recruited to obtain their structural and functional information. We found declined FA value in older adults in the midbrain-frontal connections between compared to younger adults and surprisingly reversed results in some midbrain-subcortical connections. By performing multiple regression analysis, positive main effects were found between FA value of midbrain connections and decision making behavioral index DMT while the interaction between structural connections were found negatively correlated. In functional part, we found midbrain functional connectivity differences in frontal, subcortical and other parts of the brain between older and younger adults. Moreover, positive main effects were found between midbrain-cerebral correlations and DMT while the interaction between functional connections were found negatively correlated. These results indicated that the interaction between midbrain structural and functional connections to same target region may attenuate the main effect of the single connection to DMT, showing a balancing/competing relationship between these connections.