臺灣博碩士論文加值系統

背景：
腦中風是全球都在關注的健康議題，中風所導致的單側上肢損傷會造成病患長期的失能與依賴。動作觀察治療(action observation therapy, AOT)是由鏡像神經元系統為基礎發展而來的一種新興復健療法，中風病患藉由觀察健康成人所執行的動作/任務影片，並試圖去模仿與練習執行該動作，以達到動作功能的改善。鏡像治療(mirror therapy, MT)則是請中風病患觀看鏡子中反射的健側手影像所產生的視幻覺來促進動作功能改善。本研究的目的是比較這兩種基於鏡像神經元系統發展，但透過不同視覺回饋的治療模式對於亞急性中風患者在上肢動作功能的改善，並使用腦磁圖(Magnetoencephalography, MEG)來探討動作觀察任務與鏡像任務在大腦神經機制活動的差異。

方法：
本研究招募了11位受試者並隨機分派至動作觀察治療組或鏡像治療組，受試者接受每天60分鐘、每周5次並持續3周的治療介入。臨床評估依據國際健康功能與身心障礙分類系統來選擇，身體功能層級包含傅格梅爾動作評量之上肢分測驗(Fugl-Meyer Assessment, FMA-UL)、箱子與積木測驗(Box and Block Test, BBT)與修訂版諾丁漢感覺評估量表(revised Nottingham Sensory Assessment, rNSA)，活動與參與層級的評估工具則包含沃夫動作功能量表(Wolf Motor Function Test, WMFT)、功能性獨立量表(Functional Independence Measure, FIM)、動作活動日誌(Motor Activity Log, MAL)與中風影響量表(Stroke Impact Scale, SIS)。使用曼惠特尼U檢定比較兩組組間之療效，並使用符號檢定比較組內之改變量。另外，共4位受試者參加腦磁圖(MEG)實驗，並執行動作觀察相關任務與鏡像相關任務等一共6個不同的實驗情境。使用Kruskal-Wallis差異檢定來分別比較兩個任務中不同情境下beta振幅活動之差異，事後分析則是使用曼惠特尼U檢定。

結果：
有6位受試者被分派至AOT組、5位被分派到MT組。AOT組在FMA-UL的總分(p = .05)與遠端動作次量表(p = .04)、BBT(p = .05)有達到組內的統計顯著差異，此外，AOT組在WMFT的時間次量表(p = .03)、FIM的總分(p = .03)與動作次量表(p = .03)、MAL的使用量(p = .03)與動作品質(p = .03)以及SIS的生理功能領域(p = .05)和手部功能次量表(p = .04)皆有達到組內顯著改善；MT組則是在WMFT的動作品質(p = .04)、FIM的總分(p = .04)與動作次量表(p = .04)、MAL的使用量(p = .04)與動作品質(p = .04)以及SIS的手部功能次量表(p = .04)皆有達到組內顯著改善。此外，MEG實驗結果顯示，動作觀察任務之不同實驗情境有達到統計顯著差異(p = .03)，事後檢定結果呈現”觀察合併執行” (p = .03)與”單純執行” (p = .03)情境的beta振幅活動相較於控制情境(resting condition)有顯著的下降。”觀察合併執行”情境在動作觀察任務中有最低的beta振幅活動，然而”觀察合併執行”之情境的beta振幅活動並沒有顯著低於”單純觀察”情境(p = .11)與”單純執行”情境(p = .89)；在鏡像任務之不同實驗情境也同樣有達到統計顯著差異(p = .04)，事後檢定結果發現”有鏡像”情境相較於”沒有鏡像”情境的beta振幅活動亦未達統計顯著差異(p = .69)；而比較”觀察合併執行”情境與”有鏡像”情境的beta振幅活動仍未達統計顯著差異(p = .49)。

結論：
AOT與MT皆能改善亞急性中風患者的上肢動作功能與日常生活功能，AOT在上肢動作功能恢復相較於MT有改善較多的趨勢。此外，腦磁圖實驗結果發現動作觀察情境與鏡像情境皆能活化亞急性中風病人患側大腦的主要動作皮質區。未來建議使用較大樣本與合併療效追蹤的研究來進一步驗證此研究的發現。

Introduction:
Stroke is an important health issue worldwide. Patients with stroke commonly have unilateral upper-limb (UL) motor impairments which result in long-term dependence of patients. Action observation therapy (AOT) is a new rehabilitation approach based on the mechanism of mirror neuron system (MNS). During AOT, patients were asked to observe the actions performed by another healthy person in the videos and imitate the actions intentionally. Mirror therapy (MT) is another recent prominent rehabilitation intervention. MT required patients to look at the reflection of the unaffected hand in the mirror and imagine it as the affected one, which is known as mirror visual feedback. Both AOT and MT apply different patterns of visual feedback but involve motor observation and imagery and share some similar neural bases of MNS. However, their effectiveness in stroke rehabilitation is equivocal. Therefore, there were two purposes of this study. The first study aim was to investigate and compare treatment effects between AOT and MT on UL motor function measured by clinical scales in patients with subacute stroke. The second aim was to examine neural mechanisms between action observation related task and mirror related task by using the Magnetoencephalography (MEG).

Methods:
Eleven participants were recruited in this study to receive AOT or MT intervention for 60 minutes per day, 5days per week for 3 weeks. The clinical outcomes were selected based on the International Classification of Functioning, Disability and Health (ICF). Body functions level was assessed by the upper-limb subscale of Fugl-Meyer Assessment (FMA-UL), Box and Block Test (BBT) and revised Nottingham Sensory Assessment (rNSA). The Activity and Participation levels were assessed by the Wolf Motor Function Test (WMFT), Functional Independence Measure (FIM), Motor Activity Log (MAL) and physical function domains of Stroke Impact Scale (SIS). Mann-Whitney U test was applied to evaluate the treatment effects between the 2 groups. Wilcoxon Rank Sum Test was applied to examine within-group changes. In the MEG experiment, four participants were recruited to execute 6 conditions in action observation related task and mirror related task. Kruskal-Wallis test was used to examine the differences on the beta oscillation activity with different conditions of the 2 tasks. Mann-Whitney U test was used for the post hoc analysis.

Results:
There were 6 participants randomly assigned to the AOT group and 5 participants assigned to the MT group. The AOT group significant improved on the total score (p = .05) and distal part score (p = .04) of the FMA-UL and BBT (p = .05). Besides, the AOT also improved on the WMFT-Time (p = .03), the total score (p = .03) and motor subscale (p = .03) of FIM, MAL-AOU (p = .03), MAL-QOM (p = .03), and hand function subscale (p = .04) and physical domains (p = .05) of the SIS. MT could significantly enhance on the WMFT-FAS (p = .04), the total score (p = .04) and motor subscale (p = .04) of FIM, MAL-AOU (p = .04), MAL-QOM (p = .04), and hand function subscale (p = .04) of the SIS. In addition, the results of MEG recordings showed significant differences in different conditions of action observation related task (p = .03). The post hoc analysis showed that the beta oscillation activities of “combined video and action” (p = .03) and “action only” (p = .03) conditions had significant decline compared to the “resting” condition. The beta oscillation activity of “combined video and action” condition decreased more compared with the activity of “action only” and “video only” conditions, although no statistically significant differences were found between these conditions. The comparison of beta oscillation activity among in the conditions of mirror related task also showed significant difference (p = .04). In the comparison between “mirror” condition and “no mirror” condition, there was no significant difference (p = .69). Further, no significant difference of beta oscillation activity was found in “combined video and action” condition compared with “mirror” condition (p = .49).

Conclusion:
Both AOT and MT improved UL motor function and daily function in patients with subacute stroke. AOT have more improvement on UL motor function than MT. The findings of MEG suggested that both action observation and mirror conditions can facilitate activation of primary motor cortex in patients with subacute stroke. Further studies to enroll more participants and administer a follow-up assessment are suggested.

Recommendation Letter from the Thesis Advisor
Thesis Oral Defense Committee Certification
Acknowledgements iii
Chinese Abstract v
English Abstract viii
CHAPTER 1. INTRODUCTION 01
1.1 Background 01
1.2 Study Objectives 02
1.3 Significance of the Study 03
CHAPTER 2. LITERATURE REVIEW 04
2.1 Epidemiology and Impacts of Stroke 04
2.2 Mirror Neuron System 05
2.2.1 Introduction of Mirror Neuron System 05
2.2.2 The Role of Mirror Neuron System in Upper-Limb Stroke Rehabilitation 07
2.3 Action Observation Therapy 08
2.3.1 Introduction of Action Observation Therapy 08
2.3.2 Effects of Action Observation Therapy on Upper-Limb Motor Function in Patients with Stroke 09
2.3.3 Possible Mechanisms and Neurophysiological Basis of Action Observation Therapy 10
2.4 Mirror Therapy 12
2.4.1 Introduction of Mirror Therapy 12
2.4.2 Effects of Mirror Therapy on Upper-Limb Motor Function in Patients with Stroke 13
2.4.3 Possible Neural Mechanisms of Mirror Therapy 15
2.5 Summary 16
2.6 Study Purposes and Hypotheses 17
CHAPTER 3. METHODS 19
3.1 Participants 19
3.2 Study Design and Procedure 19
3.3 Sample Size Estimation 20
3.4 Interventions 20
3.4.1 Action Observation Therapy Protocol 21
3.4.2 Mirror Therapy Protocol 23
3.5 Outcome Measures 23
3.5.1 Clinical Outcomes 24
3.5.1.1 Upper-Limb Subscale of Fugl-Meyer Assessment (FMA-UL) 24
3.5.1.2 Box and Block Test (BBT) 24
3.5.1.3 Revised Nottingham Sensory Assessment (rNSA) 25
3.5.1.4 Wolf Motor Function Test (WMFT) 25
3.5.1.5 Functional Independence Measure (FIM) 26
3.5.1.6 Motor Activity Log (MAL) 26
3.5.1.7 Stroke Impact Scale (SIS) 27
3.5.2 Monitoring of Adverse Effects 27
3.5.3 Neuroimaging Technique-Magnetoencephalography (MEG) 28
3.5.3.1 Procedures 28
3.5.3.2 The MEG Recordings 29
3.5.3.3 MEG Data Analysis 30
3.6 Statistical Analysis 31
CHAPTER 4. RESULTS 33
4.1 Baseline Clinical and Demographic Characteristics 33
4.2 Treatment Effects on Clinical Outcomes 33
4.2.1 Treatment Effects on the Body Functions Level of ICF Model 34
4.2.2 Treatment Effects on the Activity and Participation Levels of ICF Model 35
4.2.3 Summary of Treatment Effects 36
4.3 Monitoring of Possible Adverse Effects 37
4.4 The Results of MEG Recordings 37
4.4.1 The Results of Action Observation Related Task 38
4.4.2 The Results of Mirror Related Task 38
4.4.3 The Results of Comparisons in “Combined Video and Action” and “Mirror” Conditions 39
CHAPTER 5. DISCUSSION 40
5.1 Summary of the Study Results 40
5.2 The Findings of Clinical Outcomes 41
5.2.1 Benefits of the AOT Group 41
5.2.2 Benefits of the MT Group 42
5.2.3 Comparison of AOT and MT Effects 43
5.3 The Findings on MEG Recordings 45
5.3.1 The Findings of the Action Observation Related Task 46
5.3.2 The Findings of the Mirror Related Task 47
5.3.3 Comparisons of the Findings in “Combined Video and Action” and “Mirror” Conditions 47
5.4 Study Limitations and Recommendations for Further Studies 48
5.5 Implications of This Study 49
CHAPTER 6. CONCLUSION 50
REFERENCES 51
FIGURES 68
TABLES 82
APPENDICES 89

List of Figures
Figure 1. Flowchart of Participant Enrollment 68
Figure 2. Action Observation Therapy 69
Figure 3. Mirror Therapy 70
Figure 4. Protocol of Action Observation Therapy 71
Figure 5. Protocol of Mirror Therapy 72
Figure 6. The Results of the Clinical Outcomes of Body Functions Level 73
Figure 7. The Results of the Clinical Outcomes of Body Functions Level (Continued) 74
Figure 8. The Results of the Clinical Outcomes of Activity and Participation Levels 75
Figure 9. The Results of the Clinical Outcomes of Activity and Participation Levels (Continued) 76
Figure 10. Whole-Head 306-Channel Magnetoencephalography 77
Figure 11. Four Conditions in the Action Observation Related Task 78
Figure 12. The Time-Frequency Power Analysis in Each Condition 79
Figure 13. The Results of the Beta Oscillation Activity in Action Observation Related Task 80
Figure 14. The Results of the Beta Oscillation Activity in Mirror Related Task 81

List of Tables
Table 1. Baseline Clinical and Demographic Characteristics 82
Table 2. Descriptive and Inferential Statistics for Clinical Outcomes of Body Functions Level 83
Table 3. Descriptive and Inferential Statistics for Revised Nottingham Sensory Assessment (rNSA) 84
Table 4. Descriptive and Inferential Statistics for Clinical Outcomes of Activity and Participation Levels 85
Table 5. Descriptive and Inferential Statistics for Clinical Outcomes of Activity and Participation Levels (Continued) 86
Table 6. Monitoring of Possible Adverse Effect 87
Table 7. The Power of Beta Oscillation Activity in 6 Condition of Individual Subjects 88

List of Appendices
Appendix 1. List of AROM Exercise 89
Appendix 2. List of Reaching Tasks and Object Manipulation Tasks 90
Appendix 3. List of Functional Tasks 91

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