- 學位論文
經顱直流電刺激 (tDCS) 在失眠治療中的神經機轉
The neural mechanisms of transcranial direct current stimulation (tDCS) on insomnia treatment
摘要
經顱直流電刺激（tDCS）已成為調節精神疾病中神經元活動的非侵入性方法之一，但其在治療失眠方面的效果仍然不穩定，這取決於tDCS的參數設置和患者的症狀。我們的研究旨在明確其在失眠治療中的效果及其背後的機制。我們假設，對前額葉皮層進行正極刺激會觸發來自下邊緣皮層（IL）到腹外側視前區（VLPO）的谷氨酸能投射，從而促進睡眠。 我們發現，在施加0.06毫安的電流8分鐘後，一般小鼠(C57BL/6)的非快速眼動（NREM）睡眠顯著增加，效果持續時間可達16至24小時。同樣的，在壓力誘導失眠(stress-induced insomnia)的小鼠中，這種電流不僅減輕了急性應激反應期的影響，還改善了隨後的急性失眠階段。 在研究IL到VLPO的神經通路時，我們使用了僅由設計藥物激活的設計受體（DREADDs）和ibotenic acid進行調節。通過注射clozapine，前者阻斷了這條神經通路，而後者則對IL造成了永久性損傷。這兩種方法的結果均表明，IL-VLPO通路在tDCS誘導的睡眠促進中起著關鍵作用。 這項研究增強了我們對tDCS如何影響睡眠障礙的理解，並為未來的研究和臨床應用提供了寶貴的見解。我們的發現表明，tDCS通過特定的神經通路促進睡眠，這對開發更有效的失眠治療方法具有重要意義。
並列摘要
Transcranial direct current stimulation (tDCS) has emerged as a non-invasive method for modulating neuronal activity in psychiatric disorders, yet its efficacy in treating insomnia remains variable, contingent upon tDCS parameters and patient characteristics. Our study aimed to delineate its effectiveness and underlying mechanisms in insomnia therapy. We postulated that anodal stimulation of the prefrontal cortex triggers glutaminergic projections from the infralimbic cortex (IL) to the ventrolateral preoptic area (VLPO), thereby facilitating sleep. We found that after administering 0.06 mA of electrical currents for 8 minutes, significant promotion of non-rapid eye movement (NREM) sleep was observed in naïve mice, with effects persisting for up to 16-24 hours. Similarly, in mice with stress-induced insomnia, the same current not only ameliorated the acute stress response period but also improved subsequent acute insomnia phases. In experiments investigating the IL-to-VLPO neural pathway, we utilized designer receptors exclusively activated by designer drugs (DREADDs) and ibotenic acid for modulation. The former, achieved through clozapine injection, blocked the neural pathway, while the latter caused permanent damage to the IL. Both methods indicated the pivotal role of the IL-VLPO pathway in tDCS-induced sleep promotion. This research enhances our understanding of how tDCS affects sleep disturbances and offers valuable insights for future studies and the clinical use of sleep therapy.