探討焦慮與迷走神經刺激對巴金森患者於空間限制下重心轉移控制之影響

Abstract

焦慮是巴金森患者常見的非動作表徵，且會加重患者動作障礙與影響動作學習的成效。當巴金森患者處於空間受限的狀態時，可能因焦慮程度增加使平衡步態異常更嚴重。關於巴金森患者之焦慮症狀，無論是藥物或非藥物介入，目前皆尚未有最佳的治療方式。迷走神經刺激為一種降低焦慮程度的神經刺激介入方式，但尚無研究探討經皮迷走神經刺激於空間限制情境下，降低巴金森患者焦慮與提升平衡或行走表現之效果。 實驗一的目的是探討焦慮對巴金森患者重心轉移學習的影響。受試者分為焦慮組與非焦慮組。受試者以控制重心轉移之方式追蹤目標正弦波(速度：0.25赫茲、振幅：10%-90%體重)。實驗流程為前測、訓練(1天)、訓練後當天後測與2天後追蹤測試。主要評估參數有：重心轉移軌跡誤差、重心轉移軌跡平滑度(反映追蹤軌跡校正量)、腦電圖theta與gamma頻帶的相對功率強度。焦慮組於前測時表現出較大的重心轉移誤差和較小的重心轉移追蹤速動方均根，並具有比非焦慮組更大的前額葉theta頻帶、額葉與感覺運動區gamma頻帶相對功率強度。經學習後，非焦慮組降低重心轉移誤差量並增加theta頻帶相對功率強度，焦慮組則僅呈現降低gamma頻帶相對功率強度，但無動作表現進步。 實驗二為交叉設計研究，目的是探討迷走神經刺激對有、無焦慮症狀巴金森患者於空間限制下重心轉移控制的影響。每位受試者均須於重心轉移測試時接受經皮迷走神經刺激或假性經皮迷走神經刺激，受試者分別於接受迷走神經刺激、假性迷走神經刺激下，在三種空間情境進行重心轉移測試，分別為：無空間限制、低空間限制(長90公分、寬90公分)和高空間限制(長70公分、寬70公分)。主要評估參數有：重心轉移軌跡誤差、腦電圖各頻帶之相對功率、主觀焦慮和生理焦慮(皮膚電導反應)。實驗結果顯示具焦慮症狀的巴金森患者於空間限制的情境下，接受迷走神經刺激比起假性迷走神經刺激，有較小的重心轉移軌跡誤差與較低的gamma頻帶相對功率強度。此外，接受假性迷走神經刺激時，於空間限制情境下會有較高的焦慮程度。但迷走神經刺激不會影響無焦慮症狀巴金森患者的重心轉移表現與大腦活動。 實驗三為長期訓練研究，目的是探討結合迷走神經與平衡步態訓練，對具焦慮症狀巴金森患者於空間限制下重心轉移與行走表現的影響。受試者皆為具焦慮症狀巴金森患者，隨機分配迷走神經刺激組與假性迷走神經刺激組。實驗流程為前測、6週平衡訓練(配合迷走神經刺激或假性迷走神經刺激)、後測與8週後追蹤測試。於前測、後測和追蹤測試時，每位受試者在三種不同的情境下進行重心轉移任務：無空間限制、高空間限制、複雜高空間限制(複合波形追蹤)；另在三種情境下進行行走測試：空間限制下的單一作業行走與空間限制下的雙重作業行走(端水杯及算術)。主要評估參數有：重心轉移軌跡誤差、腦電圖在各頻帶的相對功率、步態參數、主觀焦慮和生理焦慮(皮膚電導反應)。實驗結果顯示，迷走神經組在後測和追蹤測試中，於各種空間情境下均可降低種心轉移軌跡誤差、增加gamma頻帶相對功率強度，且焦慮程度也有下降的趨勢。訓練後單一任務和雙重任務步長皆顯著改善，兩組效果能夠持續至追蹤測試。於行走表現上，經訓練後，兩組於單一行走端水行走下均可增加步長，於算術行走下，僅迷走神經刺激組可增加步長。 總結以上研究發現，具焦慮症狀巴金森患者重心轉移控制較差，且訓練效果不顯著。於進行重心轉移動作時給予迷走神經刺激，可有效改善具焦慮症狀巴金森患者，於空間限制情境下之重心轉移表現，並抑制患者因空間限制而提高的焦慮程度。若將迷走神經刺激結合平衡與行走訓練，具焦慮症狀巴金森患者可改善重心轉移與行走表現，且此成效可延續至訓練後二個月。建議臨床可將經皮迷走神經刺激做為具焦慮症狀巴金森患者平衡與步態訓練之輔助工具，以增進其動作學習表現、大腦可塑性與情緒調節。

Anxiety is a common non-motor symptom in people with Parkinson disease (PD), and it can exacerbate motor dysfunction and affect motor learning effectiveness. When PD individuals are in a confined space, increased levels of anxiety may make balance and gait abnormalities severer. While vagus nerve stimulation reduces anxiety, the effects of transcutaneous vagus nerve stimulation (tVNS) on anxiety and balance or gait in PD under space constraints are unexplored. Experiment 1 investigated the impact of anxiety on weight-shifting learning in PD. Subjects were divided into anxiety group and nonanxiety group and tasked with tracking a target sine wave (speed: 0.25 Hz, amplitude: 10%-90% of body weight) by shifting their weight. The experiment included a pretest, training (1 day), a posttest on the same day, and a follow-up test 2 days later. Key measures were: weight-shifting trajectory error, weight-shifting trajectory smoothness (reflecting the amount of correction in the tracking trajectory), and relative power of the theta and gamma bands in EEG. At pretest, the anxiety group demonstrated greater weight-shifting errors and smaller trajectory smoothness, and had greater prefrontal theta band and frontal and sensorimotor gamma band relative power compared to the nonanxiety group. After learning, the nonanxiety group reduced weight-shifting errors and increased theta band relative power, while the anxiety group only showed a reduction in gamma band relative power without any improvement in motor performance. Experiment 2 used a cross-over design to examine tVNS effects on weight-shifting control in PD with and without anxiety in space-constraint. Participants performed weight-shifting task with active or sham tVNS under three spatial conditions: none-constraint, low-constraint (length: 90 cm; width: 90 cm), and high-constraint (length: 70 cm; width: 70 cm). Key measures were weight-shifting error, relative power of different EEG bands, subjective anxiety, and physiological anxiety (skin conductance response). Results showed that PD with anxiety exhibited smaller weight-shifting errors and lower gamma relative power with active tVNS compared to sham tVNS in space-constraint condition. Additionally, sham tVNS led to increased anxiety levels under spatial restrictions. However, tVNS did not affect the weight-shifting performance and brain activity of PD without anxiety. Experiment 3 was a longitudinal study that aimed to investigate the effects of combining tVNS and balance and gait training on weight-shifting and walking performance for PD with anxiety in space-constraint condition. Participants were randomly assigned to the active tVNS or sham tVNS group and underwent a pretest, 6-week training (with active tVNS or sham tVNS), a posttest, and a follow-up test 8 weeks later. They performed weight-shifting tasks under none-constraint, high-constraint, and complicated high-constraint (composite waveform tracking). Subjects also did walk tasks under spatial restrictions: single-task walking and dual-task walking (walking with a cup of water and arithmetic). Key measures included weight-shifting error, EEG relative power in different bands, gait parameters, subjective anxiety, and physiological anxiety. In the active tVNS group, posttest and follow-up results showed reduced weight-shifting errors, increased gamma band relative power, and a trend of decreased anxiety. Training improved step length in single-task and dual-task walking, with effects lasting until the follow-up. Both groups had increased step length in single-task and dual-task walking with a cup, but only the active tVNS group improved during arithmetic walking. PD with anxiety had poorer weight-shifting control and limited training effects. Applying tVNS during weight-shifting could improve weight-shifting control and reduce anxiety under space-constraint conditions. Combining tVNS with balance and gait training could further enhance walking performance in PD with anxiety. Clinically, tVNS could be recommended as an adjunctive tool for balance and gait training in PD with anxiety to enhance motor learning, brain plasticity, and emotional regulation.