大腦如何調節自發性節律-平靜狀態下腦部功能性連結之探討與應用

2009-08-012024-05-17https://scholars.lib.ntu.edu.tw/handle/123456789/682930摘要：在常態的自發性活動下，大腦各神經區域之間的關聯性，是一個非常基礎且重要的議題。傳統進行神經認知功能影像的研究大部份著重於給予感官上刺激或是進行高等認知的實驗設計；相對地忽略了這些自發性神經活動所造成的結果而視之為雜訊，這與一般大腦常態之情況大相逕庭。然而，近年來諸多研究藉著以內因性訊號來進行功能關聯性之分析，發現此自發性的活化訊號可能扮演一個重要的角色，這將會是未來一個重要的大腦神經與認知探索之研究方法。近年來，功能性磁振造影研究指出腦部之自發性活化反應，在彼此有同步連結之腦區間有高度的一致性與關聯性。藉由這個特性，在不進行任何外在的刺激給予或是實驗行為之下，我們依然能夠對大腦功能區域加以研究與探索 。這也就是所謂的平靜態大腦功能性磁振造影技術 (Resting-state fMRI)。藉由這項技術，在不施加任何外在刺激的情況下，我們可以獲得大腦功能區域之間互相連結之資訊。此外，平靜態大腦功能性磁振造影技術提供了長期追蹤實驗的可能性，在藥理與身心發展之研究上，這項技術將有著重要助益。由於上述這些重要優勢，在神經科學上使用靜止態大腦功能性磁振造影技術的應用研究與日增進，特別是在神經病理學上，如阿茲海默症(Alzheimer＇s disease) 、精神分裂症(Schizophrenia)、與憂鬱症之研究。但是大多數之病理研究僅著墨於疾病造成之分析上的變化，對其功能性連結之成因置若罔聞，而其基本之生理意義探索之研究，可說是寥寥無幾。有鑑於此，這個研究計畫的第一目標，便是藉由功能性磁振造影(fMRI)與腦電圖(EEG)這兩種大腦研究工具，發展與研究隱藏在這個技術背後的真正生理因素。藉由同步量測功能性磁振造影與腦電圖之訊號，整合功能性磁振造影之高空間解析度與腦電圖之高時間解析能力，功能性連結背後所隱含之生理機制將不再漫無邊際。技術層面上，研究大腦功能區域聯結，最廣為接受的成像方式，仍舊是配合起始區域(Seed)之選擇之傳統大腦血氧依賴成像技術(BOLD, Blood Oxygenation Level Dependence)。但在此種情況下。由於傳統大腦血氧依賴成像技術並不能提供可定量化的實驗結果，且由於其過於簡化的假設，將成為大腦功能區域聯結研究的一項致命傷。也由於這項限制，我們這個計劃的第二個目標，便是結合敝實驗室已發展之定量化功能性造影技術，發展建構更完整與可靠之研究技術，提供更趨於神經來源層級之生理參數，擴展大腦結構與生理研究上的視野，並強化大腦功能區域連結同步分析技術。藉著這些技術上的結合與發展，本項計畫的第一目標亦可得到更進一步的技術支援，且這項技術結合將可以提供在大腦平靜態下不同的生理參數變化，進一步對其大腦功能連結之追溯，或是揭露大腦功能連結之標準模板與模式，有所助益。本計畫的最後一個目標是建構一個屬於台灣華人之大腦功能連結資料庫系統，這個資料庫包含一般無心理疾病病史之普通人與精神分裂症患者。藉由先前所指出之欲發展架構之技術與敝實驗室早先開發之台灣華人大腦結構影像圖譜，我們將可以針對更細微的功能與結構變化相比對，以其在大腦功能連結上得到更具意義之發現。同時，在不同階段的發展情況下之大腦功能連結資訊，將對於人類大腦功能發展是如何由混沌到井然有序的過程，將會有莫大之助益。因此，對於發展一個可用於臨床診斷上的標準模板，發展與建構第一個台灣華人之資料庫將扮演一個關鍵之角色。總括來說，發展與建構上述所言之技術，將對大腦科學研究有莫大助益。第一，對於平靜態大腦功能性連結將有更進一步的生理意義之探討。第二，發展與建構大腦功能連結之取像與分析技術。第三，建構台灣華人之資料庫系統中心，提供臨床診斷與大腦科學研究之標準與參考依歸。這份研究將會把平靜態大腦功能連結技術發展為新世代的診斷工具，並且擴展其應用層面，增進我國大腦科學研究於國際上之競爭力。 <br> Abstract: Multiple spontaneous rhythms are present in our brain even when we are doing nothing, or at a resting state, such as rhythms of emotion, perception, memory…etc. However, how they functionally connect with each other and synthesize the conscious/unconscious symphonies remains as an unsolved question to the modern neuroscientists. Traditional methodologies in exploring the functional connectivity emphasize on the task manipulations and take the spontaneous activity as internal noise. Nevertheless, several studies implied that the spontaneous activity might have an important role by providing the endogenous constraints in neural assemblies. Recently, the functional connectivity between multiple symmetric brain regions were consistently reported using the typical functional magnetic resonance imaging (fMRI) technique at the resting state, with which the interactions between brain regions can be observed without engaging task-performance of a subject. Not only does it contain the advantage of brain connectivity information under a “task-free” procedure, especially for patients who are almost incapable of so-doing, the resting-state fMRI technique also allows the capability of longitudinal observation, which is essential to resolve some critical pathological and/or cognitive issue. Since the unique importance of the resting-state fMRI was addressed explicitly, studies have disclosed its proliferating application to the field of neuroscience. However, most application studies only provided the observations of chronic variations along with diseases without understanding the underlying physiological mechanisms. Therefore, the first aim of the current project is to study the underlying neuron-vasculature mechanism of functional connectivity from both electrophysiological and hemodynamic perspectives during a resting state. With the simultaneous recording of EEG/fMRI signal, the sources of the functional connectivity shall be clarified sophisticatedly with extraordinary fine spatial and temporal resolutions. Besides, to overcome the non-quantifiable and over-simplified features of current functional connectivity analysis, the second aim of the proposal is to develop advanced technologies in expanding the physiological scope and refining the analyses process. With these improvements, the first goal of this proposal would be further supported, and the functional connectivity in the brain will be unveiled with more dynamic and physiological information. The last aim of this project is to construct a Chinese database of functional connectivity and apply it on cognition and psychiatry studies. Discrepancies of the functional connectivity under distinct cognitive or psychiatric status will be compared with normal controls in both spatial and temporal characteristics. Applying the developed technologies and the Chinese brain template, we are subject to construct a Chinese database on functional connectivity, providing a clinical diagnostic standard. In summary, fulfilling this project would shed a light on the brain connectivity in neuroscience, presenting following advantageous features: 1) better understanding the neuro-vascular interaction of functional connectivity, 2) developing advanced techniques for functional connectivity, and 3) constructing the Chinese functional connectivity database and its application on both cognition and psychiatry. These profound profits would greatly promote the functional connectivity to a next-generation diagnostic tool, extensively improve its applicability on pathology and thus, considerably enhance our national competitive ability in neuroscience.大腦如何調節自發性節律-平靜狀態下腦部功能性連結之探討與應用