Combining closed-loop transcutaneous auricular vagus nerve stimulation and focal transcranial direct current stimulation as an adjuvant treatment for subacute stroke rehabilitation

Abstract:

Ischemic stroke is the most common neurological disease. The main treatment options include medication, intravenous thrombolysis and endovascular thrombectomy. The benefits of treatments at an acute stage are significant but far from satisfactory. There is no effective treatment for improvement at subacute stage, except rehabilitation. The main goal of this project is to develop an adjuvant treatment for additional improvement under current treatments for both acute and subacute stages. In addition, stroke may induce post-stroke autonomic imbalance, further leading to worse post-stroke functional outcomes and the risk of recurrent stroke.  A combination of closed-loop transcutaneous auricular vagus nerve stimulation (ctaVNS) and focal transcranial direct current stimulation (ftDCS) is proposed.

The function of ctaVNS is to increase the parasympathetic activity for balancing the hyper-sympathetic state in the acute stage and enhancing neural plasticity in the subacute stage. Feedback signals from photoplethysmogram (PPG) and electrodermal activity (EDA) will be used to determine an adequate level of ctaVNS. Variability of PPG signals, inferring heart rate variability, is calculated and its high frequency part, representing the strength of parasympathetic activity, is estimated. At the same time, EDA, representing the sympathetic activity, is also calculated. On the other hand, the purpose of ftDCS is to reduce the cerebral damage in the acute stage and also to enhance the focal neural plasticity in the subacute stage. Spatial filtering based on Laplacian filtering or temporal interference will be used to restrict the size of the stimulated area.

Device development will be divided into three generations. In the first generation, the device consists only of ctaVNS, double stimulation will be implemented in the second generation and sensors and feedback loop are added in the third generation. By the end of this 3-year project, prototype of the first generation device is produced and verified by clinical data, preparing for marketing authorization; the regulation pathway is confirmed and main therapeutic benefits are verified for the second generation device; and integration of device components and design of feedback controller are completed, and a corresponding animal study is scheduled for the third generation device.

跨領域合作計畫：結合回饋式耳迷走神經電刺激術和局部經顱直流電刺激術作為亞急性中風復健之輔助性治療

摘要：

缺血性腦中風是常見的神經科疾病。目前在急性期的治療包含藥物、靜脈溶栓及顱內動脈取栓術。急性期治療成效雖有明顯進步，但仍無法達到讓人完全滿意的程度。中風亞急性期除了復健治療外，目前也欠缺其他有效治療以改善病人運動障礙以及後遺症。此外，中風可能導致自主神經失調，進而增加中風後不好的功能性預後及再發中風的風險。因此，本計畫之主要目標為開發一整合兩種電刺激技術，即回饋式耳迷走神經電刺激(ctaVNS)與局部性經顱直流電刺激(ftDCS)之穿戴式非侵入性自主神經調節裝置，輔助傳統復健治療來改善亞急性期的中風病症。

ctaVNS的作用為活化副交感神經，以平衡急性期過高的交感神經狀態，並增強亞急性期中的神經可塑性。由光體積變化描記圖法(PPG)與皮膚電活動(EDA)訊號估測自主神經的活化程度，並作為ctaVN回授訊號。ftDCS利用空間濾波限制電刺激區域，以降低急性期之腦損傷，並同時強化亞急性之局部神經可塑性。

本計畫將循序漸進，將產品開發分為三代，第一代產品為單純ctaVNS，第二代為ctaVNS+ftDCS雙刺激，而第三代產品為具有回饋之雙刺激裝置。在計畫執行三年後，將完成第一代產品的量產原型機開發和臨床佐證資料收集，為上市許可做準備。第二代產品將完成法規路徑確認和主要功效驗證，同時準備學術型臨床試驗。第三代產品則將完成穿戴式模組的整合與控制器設計驗證，以及動物實驗。

團隊成員：

林宙晴 教授                  國立成功大學神經學科

李順裕 教授                  國立成功大學電機系

張雅雯 教授                  國立成功大學生理所

陳芃婷 教授                  國立成功大學醫工系

宋碧姍 臨床副教授      國立成功大學電機系

謝嘉興 臨床副教授      衛福部台南醫院泌尿科

陳景欣 研究員              國家衛生研究院醫工所