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姓名 楊士賢(Shih-Hsien Yang)  查詢紙本館藏   畢業系所 生物醫學工程研究所
論文名稱 瀕死狀態下大腦功能性聯結之動態變化:觀察氯化鉀注射後大鼠之生理反應
(Brain Shutdown: Dynamic Process of Functional Connectivity Following KCl Injection)
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摘要(中) 意識一直以來都是腦科學甚至是哲學家所感興趣的高階認知功能,但截至目前的研究皆尚未成功解析大腦與意識之間的關聯性。先前研究發現瀕死狀態下血液中含有較高的二氧化碳濃度,還有研究指出瀕死狀態下大腦在頻率上會有強烈的變化。這些研究意謂著大腦在接近死亡時仍有一定程度的活動,並有區域網路間的差異性。為驗證這套理論的真實性,我們建立一套以功能性磁振造影(fMRI)為基準的標準動物實驗流程,藉由觀察大腦在瀕死狀態下,血氧濃度以及功能性聯結的變化。
從技術層面而言,fMRI近年來已成為探討大腦神經影像的主要工具,主要收取大腦血氧濃度對比(BOLD)訊號,可以知道相對應的神經活化程度,並具有非侵入性及高空間解析度的優點,將可用於觀察大腦在不同意識狀態時,大腦網路之間的功能性聯結。因此本實驗使用11隻正常SD大鼠,利用fMRI連續收取15分鐘的訊號,並以注射氯化鉀( KCl )做為標準犧牲流程。我們觀察下列時間序列的大腦功能性聯結:(1)注射KCl前的頭5分鐘(麻醉狀態)、(2)注射KCl後的第5~10分鐘(瀕死狀態)、以及(3)沒有vital sign的最後5分鐘(死亡狀態)。動態指標包含注射KCl後訊號到達最大值之時間,注射後訊號到達最小值之時間,以及訊號下降斜率,分別選取不同腦區:運動皮質區(motor cortex)、感覺皮質區(somatosensory cortex)、預設模式網絡(default mode network, DMN)、尾殼核 (caudate putamen, CPu)、丘腦(thalamus)做為主要觀察的腦區。
結果顯示在不同時間點,老鼠大腦功能性聯結產生了巨大的變化。在麻醉狀態底下,可明顯觀察到大腦有功能性聯結的存在,當注射KCl後,大腦功能性聯結完全消失。而動態指標的結果顯示,如感覺皮質區和DMN等區域需花費更多的時間到達信號的最大值,而下皮層則花費較少的時間。訊號到達最小值所需要較多時間的區域是丘腦,所需要較少時間的是尾殼核,證實了意識消逝的動態過程具有區域的特異性。
摘要(英) Consciousness is always the high-level cognitive function that attracts the neuroscientists or even philosophers. However, the current research has not successfully disclosed the linkage between the brain functions and consciousness. Previous studies have found that under the near-death experience, the blood contains a higher concentration of carbon dioxide and the brain research indicates a strong change across multiple frequency ranges. These studies imply that during near-death state, when the brain undergoes the dying process, the speeds of perishing vary across multiple brain networks, resulting in the swift memory flashes before dying. To verify the speculation, we established a standard processes for animal sacrifice procedure and observe the brain dynamics of sacrificing procedure by functional magnetic resonance imaging (fMRI), which allows us to understand the dynamic loss of consciousness in death.
We used 11 normal SD rats in our experiment. The total acquisition time was 15 minutes and the injection of potassium chloride ( KCl ) was at the 5th minute. Functional connectivity was observed under 3 conditions: (1) the first 300 seconds before KCl injection (anesthesia), (2) the dynamic perish process between the 300~600 seconds (near-death), and (3) the last 300 seconds without vital signs (sacrifice). We first compared the functional connectivity patterns across (1) and (3), and then analyzed the dynamic indices to realize the regional difference in the (2) condition. The dynamic indices included the time to reach the maximum after KCl injection, the time to reach minimum after KCl injection, and slope of the signal drop. Seed were selected on multiple brain regions: motor cortex, somatosensory cortex, the default mode network (DMN), caudate putamen (CPu), thalamus. The results showed the huge change of functional connectivity on rat brain. The dynamic indicators showed that the cortical area, such as somatosensory cortex and DMN regions , required longer time to reach the maximum, and the subcortex spent less time to reach the maximum intensity. In time to minimum, we could see that thalamus had longer time to reach the valley and the caudate putamen (CPu) had shortest time to minimum. Our findings unveiled not only the regional specificity along the near-death process, but also built up an animal fMRI experimental environment for further consciousness investigations.
關鍵字(中) ★ 功能性磁振造影(fMRI)
★ 意識
★ 功能性聯結
★ 氯化鉀(KCl)
關鍵字(英) ★ Functional magnetic resonance imaging (fMRI)
★ consciousness
★ functional connectivity
★ potassium chloride (KCl)
論文目次 中文摘要 i
Abstract ii
致謝 iv
Contents v
List of Figures vii
List of Table ix
Chapter 1 Introduction 1
1.1 Motivation 1
1.2 Hypothesis 1
Chapter 2 Research Background 2
2.1 Physiologies of animal experiments 2
2.1.1 Anesthesia 2
2.1.2 Respiration 4
2.1.3 Other impact 4
2.1.4 Transform from live to death 5
2.2 KCl injection 6
2.2.1 KCl causes immediate death 6
2.2.2 Physiological changes following KCl 7
2.2.3 Brain signal measurement using electrophysiology 8
2.3 Functional MRI 9
2.3.1 BOLD-fMRI 9
2.3.2 Resting state fMRI and functional connectivity 9
2.3.3 Dynamic functional connectivity analysis 10
Chapter 3 Material and Methods 11
3.1 Animal Subjects 11
3.2 Anesthesia 11
3.3 Animal Surgery 12
3.4 Experimental designs and functional imaging acquisition 16
3.5 Preprocessing 19
3.6 Evoked activity and resting-state connectivity 19
3.7 Index for Dynamic Process 20
3.8 Sliding-window analysis 21
3.8.1 EEMD to remove high-frequency noise and low-frequency trend 21
3.8.2 Connectivity dynamics in the sacrifice process 22
Chapter 4 Results 23
4.1 Evoked responses of fMRI 23
4.1.1 Electrical stimulation 23
4.1.2 Cessation of vital signs 24
4.2 Spectral power of resting-state fMRI fluctuations 25
4.2.1 Alive and sacrificed of time domain and frequency domain 25
4.2.2 Dynamic indices 31
4.3 Functional connectivity along dying process 35
4.3.1 Functional connectivity before and after KCl injection 35
4.3.2 Dynamic changes of connectivity in sacrifice 39
Chapter 5 Discussions 43
5.1 Electrical stimulation 43
5.2 Physiological signals 44
5.3 Signal of fitting 45
5.4 Functional connectivity 46
5.5 Alive and sacrificed of frequency domain 47
5.6 Wave of death 48
Chapter 6 Conclusions and Future Works 49
References 50
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指導教授 吳昌衛(Chang-wei Wu) 審核日期 2014-8-29
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