結合經皮迷走神經刺激與強化速度之平衡訓練對重心轉移控制之訓練成效：於具焦慮症狀巴金森患者探討

Abstract

研究背景與目的：平衡與焦慮問題為巴金森患者常見症狀，並會顯著影響患者日常生活功能與增加跌倒風險，尤其處於時間壓力(或高動作速度需求)下，此兩項症狀可能會更加嚴重。經皮迷走神經刺激是一種非侵入性的神經調節介入方式，可能有助於改善焦慮和平衡症狀。然而，目前尚未有研究探討經皮迷走神經刺激結合平衡訓練對巴金森患者於高動作速度需求下，對減輕焦慮和改善平衡的影響。因此，本研究的目的為探討結合經皮迷走神經電刺激與平衡訓練對有焦慮症狀的巴金森患者在不同速度需求下的重心轉移動作、行走能力與焦慮程度的影響。 研究方法：本研究共招募30名有焦慮症狀的巴金森患者，主動迷走神經電刺激組16位和假性迷走神經電刺激組14位。每位受試者接受為期6週的平衡訓練(每週2次、每次60分鐘)，隨訓練週數增加動作速度要求。於訓練時分別給予主動迷走神經電刺激或假性迷走神經電刺激。受試者將在訓練前(前測)、訓練後(後測)與後測8週後(追蹤測試)進行重心轉移與行走評估。重心轉移評估分別於三種速度下進行：0.5 Hz、0.1 Hz、複合速度(結合0.6 Hz與0.9 Hz)。於在重心轉移時，同時記錄皮膚電阻訊號(生理焦慮程度)和腦電圖訊號。重心轉移行為參數為：軌跡誤差、轉移幅度、軌跡急動值；腦波參數為：delta (1-4 Hz)、theta (4-8 Hz)、 alpha (8-12 Hz)、beta (12-30 Hz)、low-gamma (30-50 Hz)以及high gamma (50-80 Hz)頻帶的相對頻率強度。行走任務包含單一與雙重作業行走，受試者須分別以自然速度與最快速度行走。行走表現參數為：行走速度、跨步長度、步頻、跨步長度變異性。另以新版世界運動障礙學會巴金森病綜合評量表與巴金森焦慮量表評估受試者的巴金森症狀嚴重度與日常的焦慮程度。 結果：經6週平衡訓練後，僅有主動迷走神經電刺激組在1.0 Hz重心轉移情境下可降低軌跡誤差。而在三種重心轉移情境，兩組皆在後測時呈現較低的重心轉移軌跡急動值，與在追蹤測試時呈現較低的皮膚阻抗數值。腦波結果顯示於後測時，在1.0 Hz情境下，主動迷走神經電刺激組在左側顳葉的delta頻帶強度顯著下降，但假性迷走神經電刺激組則顯著上升。此外，在0.5 Hz與1.0 Hz重心轉移情境，於後測時，主動迷走神經電刺激組的gamma頻帶強度降低、但假性迷走神經電刺激組則上升。於行走表現方面，在自然速度情境，兩組於單一與雙重作業行走的後測時皆增加走路速度；於快速行走情境，相較於假性迷走神經電刺激組，主動迷走神經電刺激組於後測時有較低的步頻。而於臨床量表方面，經過6週的平衡訓練，兩組皆可下降新版世界運動障礙學會巴金森病綜合評量表與巴金森焦慮量表分數，且此進步程度可延續至追蹤測試。 結論與臨床應用：經6週速度強化平衡訓練，具焦慮症狀的巴金森患者無論是接受主動迷走神經電刺激或假性迷走神經電刺激皆可改善重心轉移與行走表現。但主動迷走神經電刺激對快速重心轉移下的精細重心轉移控制提升有更佳的表現，且可避免患者於快速行走時出現小碎步的狀況。本研究結果顯示結合平衡訓練與迷走神經刺激，對具焦慮症狀的巴金森患者是一個安全且有效的訓練模式，然進步成效不一定皆可持續至追蹤測試，建議於具焦慮症狀巴金森患者的訓練需延長訓練間或加強訓練頻率。

Background and Purpose: Balance impairments and anxiety are common symptoms in people with Parkinson’s disease (PD), significantly affecting their daily functioning and increasing the risk of falls. The two symptoms may become even more pronounced under time pressure (or high-speed demand) situations. Transcutaneous vagus nerve stimulation (tVNS), a non-invasive neuromodulation technique, has shown potential in alleviating anxiety and improving balance. However, to date, no studies have investigated the combined effects of tVNS and balance training on reducing anxiety and enhancing balance in people with PD under conditions requiring high movement speed. Therefore, the aim of this study is to examine the effects of combining tVNS with balance training on postural weight-shifting, gait performance, and anxiety levels in people with PD presenting with anxiety symptoms, across speed demands. Methods: This study recruited 30 PD patients with anxiety. There were 16 participants in the active tVNS group and 14 participants in the sham tVNS group. Each participant underwent a 6-week balance training program (twice a week, 60 minutes per session), with active or sham tVNS applied during the training. The training program emphasized speed-demand for movement. Weight-shifting and walking abilities were assessed before training (pre-test), after training (post-test), and 8 weeks after post-test (follow-up test). The weight-shifting task included three speed conditions: 0.5 Hz, 0.1 Hz, and complex (combined 0.6 Hz with 0.9 Hz). During weight-shifting tasks, skin conductance, and electroencephalography (EEG) signals were recorded. The parameters of weight-shifting task included tracking errors, movement amplitude, tracking jerk. Skin conductance level (SCL) was calculated to represent physiological anxiety. EEG was analyzed for relative power in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low-gamma (30-50 Hz), and high-gamma (50-80 Hz) bands at prefrontal, frontal, sensorimotor, parietal-occipital, left temporal, and right temporal area. The walking task included single-task walking and dual-task walking, with natural pace and walking as fast as possible. The walking parameters included walking speed, step length, cadence, and step length variability. In addition, the MDS-sponsored Revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) and Parkinson Anxiety Scale (PAS) were assessed to represent Parkinson severity and daily life anxiety intensity. Results: After 6-week balance training, only the active tVNS group demonstrated a reduction in tracking error in the 1.0 Hz weight-shift condition. Both groups exhibited lower jerk square mean (JSM) values at post-test, and lower SCL at follow-up test in each weight-shifting condition. EEG results revealed that at post-test of the 1.0 Hz condition, the active tVNS group showed a decreased delta power at left temporal area, whereas the sham group showed an significant increased delta power. Moreover, in the 0.5 Hz and 1.0 Hz conditions, the active tVNS group exhibited decreased gamma power at post-test, while the sham group showed an increased gamma power. In the aspect of walking behavior, both groups increased walking speed at post-test during both single-task and dual-task walking with natural speed. While walking as fast as possible, the active tVNS group showed a lower cadence than the sham group at post-test. Regarding clinical scales, after six weeks of balance training, the scores of the MDS-UPDRS and PAS decreased in both groups, and the improvements were maintained to the follow-up test. Conclusion and Clinical Application: After 6-week of speed-emphasis balance training, PD with anxiety showed improvements in weight-shifting control and gait performance, regardless receiving active or sham tVNS. However, the active tVNS group demonstrated better fine-tune control for rapid weight-shifting and safe gait pattern for fast walking. These findings suggest that combining balance training with vagus nerve stimulation is a safe and effective intervention for anxious PD patients. However, not all behavior improvements maintained to follow-up test, indicating that longer training durations or higher training frequency might be necessary for the population of PD with anxiety.