靜息態功能性磁振影像(rs-fMRI)可以用來觀察大腦處於靜息狀態時不同區域間的功能性連結，其中預設模式網絡(DMN)是最穩定也最常被探討的一種休息狀態網路(RSN)。目前已有非常多的研究探討DMN的生理機制，而對於DMN生化機制的調變是一個非常值得研究的議題。本論文目的為探討大腦於靜息狀態時的基礎代謝情形跟大腦DMN強度的關係，探討的代謝物包含大腦神經密度的指標(NAA)，腦內主要的神經傳導物質(Glutamate及Glutamine，合稱Glx)以及其他兩種代謝物Cr和Cho。研究先使用REST軟體算功能性連結，得到預設模式網絡並計算對應的強度值FC，之後再藉由兩種方法: AAL分區以及體像素分析法，探討FC跟代謝物濃度之間的相關性。實驗收集30位受試者的rs-fMRI和平面回波頻譜影像(EPSI)資料，研究的結果發現體像素分析法較AAL分區法，可以找出更多在靜息狀態下FC與代謝物具有相關性的位置。從體像素分析法的結果得知NAA、Cho、Glx三種代謝物在內側前額葉(Frontal_Sup_Medial)區域中均出現像素點與FC有正相關性。此外也得知左腦的前扣帶迴(Anterior Cingulate cortex, ACC)的Glx濃度與DMN強度具有正相關性。AAL分區法則只找到代謝物NAA在右腦的楔前葉(precuneus)和運動輔助區(sup_motor_R)與FC有正相關。因此，體像素分析法更有助於了解大腦在靜息狀態下DMN生化機制的調變。

Resting state functional magnetic resonance imaging (rs-fMRI) can be used to observe the functional connections between different regions of brain during resting. Among them, the default mode network (DMN) is one of the most stable and most frequently discussed resting state networks (RSNs). There are many researches focus on physiological mechanism of DMN. Among them, the modulation of DMN biochemical mechanism draws many interests. The purpose of this study is to explore the relationship between the brain's basic metabolic status and the DMN connectivity during rest. The metabolites that we explored include the brain nerve density index (NAA), the main nerve conduction substances in the brain (Glutamate and Glutamine, named Glx), and two other metabolites such as Cr and Cho. The study initially used REST software to analyze functional connectivity, and calculate the corresponding intensity of DMN (named FC in the study). Then AAL partition and voxel based methods are proposed to analyze the correlation between FC and metabolite concentration. rs-fMRI and echo planar spectroscopic imaging (EPSI) data of 30 subjects were collected in this study. Experiment results show that the voxel based analysis method can find more brain regions with correlation between FC and metabolites than the AAL partition method. From the results of the voxel based analysis method, it reveals that three metabolites (NAA, Cho and Glx) have a positive correlation with FC the pixels in the medial prefrontal cortex. In addition, it is also known that Glx concentration is positively correlated with DMN intensity in the left anterior cingulate cortex (ACC). However, the AAL partition method only finds that the metabolite NAA is positively correlated with FC in the right precuneus and right Supplementary Motor Cortex (SMC) areas. Consequently, the voxel analysis method is more efficiently to understand the modulation between metabolite concentrations and FC in DMN.

1.Biswal, B., et al. "Functional connectivity in the motor cortex of resting human brain using echo‐planar MRI." Magnetic resonance in medicine 34(4): 537-541, 1995.

2.Buckner, R. L., et al. "The brain's default network: anatomy, function, and relevance to disease." Ann. NY Acad. Sci. 1124:1-38, 2008.

3.Di Martino, A., et al. "Functional connectivity of human striatum: a resting state FMRI study." Cerebral cortex 18(12): 2735-2747, 2008.

4.Enzi, B., et al. "Glutamate modulates resting state activity in the perigenual anterior cingulate cortex–a combined fMRI–MRS study." Neuroscience 227: 102-109, 2012.

5.Fox, M. D., et al. "The human brain is intrinsically organized into dynamic, anticorrelated functional networks." Proceedings of the National Academy of Sciences 102(27): 9673-9678, 2005.

6.Greicius, M. D., et al. "Functional connectivity in the resting brain: a network analysis of the default mode hypothesis." Proceedings of the National Academy of Sciences 100(1): 253-258, 2003.

7.Greicius, M. D., et al. "Default-mode network activity distinguishes Alzheimer's disease from healthy aging: evidence from functional MRI." Proceedings of the National Academy of Sciences 101(13): 4637-4642, 2004.

8.Harris, R. E., et al. "Elevated insular glutamate in fibromyalgia is associated with experimental pain." Arthritis & Rheumatism: Official Journal of the American College of Rheumatology 60(10): 3146-3152, 2009.

9.He, B. J. and M. E. Raichle, "The fMRI signal, slow cortical potential and consciousness." Trends in cognitive sciences 13(7): 302-309, 2009.

10.Kapogiannis, D., et al. "Posteromedial cortex glutamate and GABA predict intrinsic functional connectivity of the default mode network." Neuroimage 64: 112-119, 2013.

11.Liao, W., et al. "Selective aberrant functional connectivity of resting state networks in social anxiety disorder." Neuroimage 52(4): 1549-1558, 2010.

12.Liu, Y., et al. "Disrupted small-world networks in schizophrenia." Brain 131(4): 945-961, 2008.

13.Northoff, G., et al. "GABA concentrations in the human anterior cingulate cortex predict negative BOLD responses in fMRI." Nature neuroscience 10(12): 1515-1517, 2007.

14.Qi, R., et al. "Abnormal functional connectivity within the default mode network in patients with HBV-related cirrhosis without hepatic encephalopathy revealed by resting-state functional MRI." Brain research 1576: 73-80, 2014.

15.Raichle, M. E., et al. "A default mode of brain function." Proceedings of the National Academy of Sciences 98(2): 676-682, 2001.

16.Stagg, C. J., et al. "Local GABA concentration is related to network-level resting functional connectivity." Elife 3: e01465, 2014.

17.Tsai, S. Y., et al. "Comparison of sagittal and transverse echo planar spectroscopic imaging on the quantification of brain metabolites." Journal of neuroimaging 25(2): 167-174, 2015.

18.黃俊皓, 大腦功能性連結:預設網路強度與代謝物濃度之關聯性. 台北市:國立台灣科技大學， 2014

19.Brown, C. A., et al. "Distinct patterns of default mode and executive control network circuitry contribute to present and future executive function in older adults." Neuroimage 195: 320-332, 2019.

20.Brown, C.A., et al., Age and Alzheimer's pathology disrupt default mode network functioning via alterations in white matter microstructure but not hyperintensities. Cortex, 104: p. 58-74, 2018.