神經調節是近年來在醫學領域中發展的新興技術，其有可能成為治療神經疾病的另類療法。我們的研究採用聚焦超音波，結合其非侵入式，深度穿透和空間聚焦的特性進行神經調節，並通過靜息態功能性磁振造影縱向觀測連通性的變化。依據聚焦超音波在大鼠的刺激位置，我們將實驗組分為兩組。一組是刺激在左半腦腹膜後內側和腹側後外側丘腦核（VPM / VPL），而另一組則是刺激在左半腦的次要視覺皮層外側區域（V2L）。結果表明，兩組在聚焦超音波刺激後，刺激點和各個大腦區域之間均產生較高的連通性，接著在大約3天後連通性會降至起始線。除了刺激點外，其他大腦區域之間也表現出相同的現象，這可能表明聚焦超音波誘導的神經調節可以通過神經系統傳遞進而影響周遭腦區。此外，在刺激後的每個時間點(35分鐘、3小時和3天)，對V2L組別進行刺激後的連通性強度都比VPM / VPL組來的高，這表明對不同目標區域進行刺激可以產生不同程度的神經調節影響。

Neuromodulation is an emerging technique in the medical field recently, which has a potential to be an alternative therapy to cure neural disorders. Our study takes focused ultrasound that combining noninvasiveness, depth penetration, and spatial focus to proceed neuromodualtion and monitors the hyper-connectivity longitudinally through rs-fMRI. We divide our experiment groups into two groups according to the location focused ultrasound stimulated on the rats. One group is targeted unilaterally to the ventral posteromedial and ventral posterolateral thalamic nuclei (VPM/VPL) while another group is targeted unilaterally to the secondary visual cortex lateral area (V2L) in the left hemisphere. The results demonstrate that both groups have the hyper-connectivity among brain regions after focused ultrasound stimulation and decline to baseline about 3 days later. Aside from the target region, other brain regions also exhibit same phenomenon, which may suggest the impact of neuromodulation induced by focused ultrasound can transfer via neural system. Also, the group that stimulates on V2L has higher connectivity strength than the group that stimulates on VPM/VPL group at each time point, which may suggest that stimulating to different target region can carry out different extent impact.

摘要 i
Abstract ii
Chapter 1 INTRODUCTION 1
1.1. Focused ultrasound 1
1.2 Neuromodulation 3
1.2.1 Definition and application of neuromodulation 3
1.2.2 Mechanism of FUS induced neuromodulation 6
1.3 Functional MRI 9
1.3.1. Blood-oxygen-level dependent (BOLD) 9
1.3.2. Resting-state fMRI 10
1.5 Motivation 12
Chapter 2 MATERIALS AND METHODS 13
2.1 Animal preparation 13
2.2. FUS Protocol 18
2.3. MRI Protocol 19
2.4. Data Analysis 20
2.4.1. Preprocessing 20
2.4.2. Magnitude and phase 23
2.4.3. Connectivity map 25
2.4.4. Intragroup comparison 27
2.4.5. U-test map 30
2.4.6. Auditory system effect 31
2.4.7. Topology 32
2.4.8. Statistical analysis 33
Chapter 3 RESULTS 34
3.1. Magnitude versus phase 34
3.2. Connectivity map 35
3.3. Intragroup variation 40
3.4. U-test map 51
3.5. Auditory system effect 59
3.6. Topology 63
Chapter 4 DISCUSSION 72
4.1 Magnitude versus phase 72
4.2 Connectivity map/ U-test map 73
4.3 Intragroup comparison 75
4.4 Auditory effect 76
4.5 Topology 78
4.6 Limitation 79
Chapter 5 CONCLUSION 80
Future work 81
REFERENCES 82
Appendix 88
Turnitin 88
Response of oral defense 89

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