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研究生: 李盛凱
Lee, Sheng-Kai
論文名稱: 自我呼吸控制對唾液催產素、迷走神經張力和腦功能連結度的影響探討
Changes in Salivary Oxytocin Levels, Cardiac Vagal Tone, and Brain Functional Connectivity: Voluntary Breathing Regulation Effects
指導教授: 蔡坤哲
Tsai, Kuen-Jer.
共同指導教授: 劉長萱
Liou, Michelle
學位類別: 博士
Doctor
系所名稱: 醫學院 - 跨領域神經科學國際博士學位學程
TIGP on The Interdisciplinary Neuroscience
論文出版年: 2024
畢業學年度: 112
語文別: 英文
論文頁數: 120
中文關鍵詞: 自我呼吸調控心率變異分析功能性磁振造影功能性連結度催產素
外文關鍵詞: Voluntary breathing regulation , Heart rate variability, fMRI, Functional connectivity, Oxytocin
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  • 呼吸是日常生活中最基本、同時可以自我調控的生理功能之一,呼吸調控是已知可以暫緩焦慮與憂鬱情緒的臨床介入方法。過去的研究著重在呼吸行為與自律神經系統的交互作用,至於大腦內的功能性迴路,目前文獻中尚無明確的定論。既有的研究主要探討呼吸調節誘發迷走神經活性的路徑;例如在調節呼吸快、慢的研究中發現,不同速率的呼吸過程可透過頸動脈中的壓感接受器(baroreceptor)產生壓感反射(baroreflex),並且促進腦幹中的孤束核(nucleus of the solitary tract)控制下游的前腹外側延腦(rostral ventrolateral medulla)和後腹外側延腦(caudal ventrolateral medulla),調節輸出端的迷走神經活性,進而達到降緩心跳、穩定情緒的功能。然而,在大腦的迴路中,調節呼吸如何影響到掌管情緒調節的前額葉腦區,目前尚停留在討論階段。近年來相關研究也指出,提升迷走神經活性可同時釋放重要的社會荷爾蒙--催產素。基於該荷爾蒙在情緒調控的重要性,本論文主要探討呼吸調控情緒表現的生理過程是否也同時釋放催產素,並藉功能性磁振造影 (fMRI;functional magnetic resonance imaging)技術,釐清呼吸調控和自律神經系統如何作用在腦內的功能性迴路。
    本論文同時使用心率變異指標(Heart rate variability indices)、靜息狀態功能性磁振造影 (resting-state fMRI),唾液荷爾蒙分析,以及心理量表分數等,探討呼吸介入下受試者腦功能性連結迴路的差異,及呼吸行為可能影響的腦區。論文研究核心分成兩部分,第一部分探討快速呼吸與閉氣兩者交替過程中,不同腦區 fMRI訊號的變化,以及呼吸相關的功能性連結迴路。第二部分招募兩組受試者,一組進行呼吸訓練介入,另一組進行鋼琴鍵盤遊戲介入,並探討兩組受試者在實驗介入後腦內靜息狀態功能性連結與催產素濃度差異。第一部分的研究發現,在快速呼吸與閉氣兩者交替的過程中,出現兩個和自律神經系統相關的迴路,且實驗重複看到腹内侧前额葉(ventral medial prefrontal cortex)和其他腦區出現相反的 fMRI訊號變化;第二部分的研究發現,相較於遊戲組,呼吸組在呼吸介入前後,唾液中催產素的濃度明顯上升,且在靜息狀態下海馬迴(hippocampus)相關的連結較弱。
    本論文發現呼吸調控與唾液中催產素濃度的上升有顯著相關,且腦內至少有兩個大型迴路和自律神經系統有關。本論文研究的結果可以協助學者建立呼吸調控和情緒緩和之間神經生理的模型與證據,近一步增進臨床精神醫學的實證基礎。

    Breathing is one of the most fundamental and controllable physiological behaviors in daily life. Breathing regulation has been identified as a clinical method that can temporarily relieve anxiety and depressive symptoms. Previous research has primarily focused on the interaction between respiratory behaviors and the autonomic nervous system (ANS). Thus, there is still an ongoing debate in the scientific community regarding the functional circuits within the brain. Although the pathways inducing vagal nerve activity through respiratory modulation remain under investigation, research into breathing regulation has revealed that a variation in breathing rates may trigger baroreflex responses mediated by baroreceptors in the carotid arteries. This reflex, in turn, stimulates vagal nerve activity by regulating outputs from the rostral ventrolateral medulla and caudal ventrolateral medulla under the control of the nucleus of the solitary tract in the brainstem, resulting in numerous functions, such as reduced heart rate (HR) and stabilized emotions. However, the current scientific consensus on how respiratory regulation in the brain affects the prefrontal cortex for emotion regulation needs to be further clarified. Moreover, recent research has indicated that enhancing vagal activity can promote oxytocin release. Given the growing interest in the role of oxytocin in regulating emotions, this thesis explored whether the physiological process of respiratory regulation was involved in oxytocin release.
    This thesis study applied HR variability indices, resting-state functional magnetic resonance imaging (rs-fMRI), salivary hormone analysis, and psychological scaling scores to investigate the differences in brain functional connectivity of participants after a training exercise in breathing. The study was divided into two core sections. The first section explored changes in fMRI time courses during rapid breathing and breath-holding cycles alongside potential respiratory-related connectivity networks in the brain. These experiments found at least two connectivity networks highly associated with interactions between breathing regulation and the ANS. Notably, the ventral medial prefrontal cortex exhibited fMRI time courses that showed an inverse pattern to those observed in the dysgranular insula cortex, amygdala, and premotor cortex. The second section examined differences between two groups of participants, recruited either for a respiratory training intervention or a piano keyboard game intervention, on the strengths within different rsfMRI connectivity networks and in salivary hormone concentrations. The second section revealed significant increases in salivary oxytocin levels in the experimental group after the breathing training exercise. Additionally, interhemispheric connectivity in the hippocampus and its associated motor areas showed significantly weaker connectivity in the breathing exercise group compared with the group playing piano games. The breathing exercise group also exhibited weaker connectivity between the hippocampus and the salience network.
    This thesis study identified brain connectivity networks associated with breathing regulation and their associations with salivary oxytocin levels. These results are expected to provide a neurophysiological basis and connectivity evidence for the clinical application of respiratory practices in emotion relief and enrich the scientific foundation of psychiatric therapy.

    中文摘要 3 Abstract 5 Acknowledgments 7 Contents 9 Table Contents 12 Figure Contents 13 Appendix 15 Chapter 1 Background 16 1.1 Voluntary breathing regulation 16 1.1.1 Neurophysiological models 16 1.1.2 Brain areas associated with breathing regulation 19 1.2 Salivary hormones 20 1.2.1 Oxytocin and the ANS 20 1.2.2 Distributed oxytocin receptors 21 1.2.3 Changes in oxytocin receptor expression 21 1.2.4 The brain functional networks related to oxytocin 22 1.2.5 Endogenous oxytocin levels 23 1.2.6 Breathing intervention 24 1.3 Experimental hypotheses 25 Chapter 2 Brain Functional Connectivity During Voluntary Breathing Regulation 26 2.1 Methods 26 2.1.1 Participants 26 2.1.2 Breathing control tasks 26 2.1.3 FMRI data acquisition and preprocessing 27 2.1.4 The standardized intraclass correlation index 28 2.1.5 ICC maps 29 2.1.6 Cytoarchitectonic maps of the Julich-Brain atlas 29 2.1.7 Functional connectivity 30 2.2 Results 36 2.2.1 Vagal control network 39 2.2.2 Orbitofrontal network 41 2.2.3 Thalamus network 44 2.2.4 Emotion network 46 2.2.5 Memory network 48 2.2.6 Sensorimotor network 49 2.2.7 Comparison between time courses 51 2.3 Discussion 54 2.3.1 Vagal withdrawal 54 2.3.2 Valsalva maneuver effects 56 2.3.3 Functional organization of brain areas 58 2.3.4 Limitations 60 Chapter 3 Oxytocin-Boosting Benefits of Breathing Regulation: A Resting-State fMRI Experiment 62 3.1 Methods 62 3.1.1 Participants 62 3.1.2 Experimental procedure 62 3.1.3 Experimental tasks 63 3.1.4 ECG recording 65 3.1.5 Psychological scales 65 3.1.6 Salivary hormone assays 66 3.1.7 Resting-state fMRI scan 69 3.1.8 fMRI data acquisition 70 3.1.9 Data analysis 71 3.2 Results 73 3.2.1 Behavioral data 73 3.2.2 Saliva hormone levels 75 3.2.3 Resting-state functional connectivity 76 3.2.4 Connectivity networks 79 3.2.5 Hormones and connectivity 84 3.3 Discussion 86 3.3.1 Oxytocin boosting effects 87 3.3.2 Autonomic responses under voluntary breathing regulation 88 3.3.3 Functional connectivity and voluntary breathing regulation 90 Chapter 4 Conclusion 94 Appendix 97 References 107

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