臺灣博碩士論文加值系統

偏頭痛是一種常見的神經系統疾病，約有10%左右的人口盛行率，最典型的表現症狀是持續性的搏動疼痛，症狀可持續數個小時，發作期間容易引發噁心、暈眩、對光及聲音高度敏感等症狀，常使得患者的行為受到限制，造成失能。偏頭痛病患多半會服用止痛藥物減緩症狀，然而止痛藥物過度的濫用卻會造成偏頭痛惡化或慢性病化，此種類性的頭痛也被稱為藥物過度使用頭痛。
在過去的研究中發現慢性偏頭痛與藥物過度使用頭痛的患者具有異常的前額活化現象，為了更進一步了解藥物過度使用對前額葉的影響，我們使用近紅外光光譜術系統監測前額葉在面對不同測驗時，正常人與偏頭痛病患在前額葉活化的差異所進行的相關研究。
本研究共招收了16位伴有藥物過度使用頭痛的偏頭痛患者，以及16位健康民眾作為控制組，本研究設計了兩項能夠刺激受測者前額活化的測驗，分別為算術測驗以及小腿束縛測驗，搭配上自製的近紅外光光譜術量測系統進行即時血氧訊號的量測。在結果的呈現包含了受測者因測驗激發前額血氧變化的情形，以及利用血氧訊號中的心跳訊號進行心律變異率的計算。
在算術測驗的結果中顯示偏頭痛患者較正常人有較高的前額血氧活化反應，可能是與病患組擁有較高的壓力感知(Stress perception)有關，而在小腿束縛測驗的結果中，兩組群並未具有統計上的差異。

Migraine is a common nervous system disease and have about 10% prevalence amount the population. The typical symptoms such as recurrent pulsating headaches, nausea, dizziness, and high sensitivity to light and sound is usually induced and the symptom may last for hours. When headaches attack, it often causes the patient's behavior to be limited, resulting in disability. Most migraine patients take painkillers to relieve symptoms. However, excessive abuse of painkillers can cause migraine to worsen into chronic migraine. This type of chronic migraine is also called medication-overuse headache.
In past studies, abnormal frontal lobe activation was found in chronic migraine and medication-overuse headache patients. To further understand the effects of excessive drug use on the prefrontal cortex, we utilized near-infrared spectroscopy (NIRS), mental arithmetic and calf restraint task to evaluate the frontal lobe activation between 16 migraine patients and 16 health controls.
In the result of mental arithmetic task, it is shown that the migraine patient has a higher prefrontal cortex activation than that in the health controls. The higher activation in prefrontal cortex may be related to the patient's higher stress perception. In the result of the calf restraint task, there is no statistical differences between the two groups.

目錄
中文摘要 i
Abstract ii
誌謝 iii
目錄 iv
圖目錄 vi
表目錄 viii
第一章 緒論 1
1-1研究背景 1
1-1-1慢性偏頭痛與藥物過度使用頭痛之定義 2
1-1-2偏頭痛成因 3
1-1-3近紅外光光譜技術 4
1-2文獻回顧 5
1-3研究動機及目的 6
第二章 實驗方法及儀器原理 8
2-1近紅外光光譜術 (Near-infrared spectroscopy, NIRS) 8
2-1-1擴散光學 8
2-1-2組織內物質吸收光譜 9
2-1-3比爾-朗伯定律 (Beer-Lambert law) 11
2-2血氧干預法及實驗流程設計 12
2-2-1算術測驗 (Mental stress task) 14
2-2-2 小腿束縛測驗 (Cuff pain) 15
2-3受測者條件及篩選 17
2-4量測訊號分析及統計方法 18
第三章 實驗量測系統 24
3-1近紅外光光譜術頭架系統 (NIRS-headgear system) 24
3-2系統硬體元件 25
3-3系統韌體及軟體 28
3-3-1系統韌體端 28
3-3-2分時多工存取技術(Time-Division Multiplexing，TDM) 28
3-3-3系統軟體端 29
3-4系統驗證 30
第四章 實驗結果 32
4-1受測者基本資料 32
4-2算術測驗實驗結果 33
4-3小腿束縛測驗實驗結果 39
第五章 研究結果討論 44
5-1算數測驗結果討論 44
5-2小腿束縛測驗結果討論 46
第五章 未來展望 47
參考文獻 49

參考文獻
[1] Lipton, Richard B., et al. "Migraine prevalence, disease burden, and the need for preventive therapy." Neurology 68.5 (2007): 343-349.
[2] Wang, S‐J., et al. "Prevalence of migraine in Taipei, Taiwan: a population‐based survey." Cephalalgia 20.6 (2000): 566-572.
[3] Shevel, Elliot. "The extracranial vascular theory of migraine—a great story confirmed by the facts." Headache: The Journal of Head and Face Pain 51.3 (2011): 409-417.
[4] Waeber, Christian, and Michael A. Moskowitz. "Migraine as an inflammatory disorder." Neurology 64.10 suppl 2 (2005): S9-S15.
[5] Pourshoghi, Ahmadreza, et al. "Cerebral reactivity in migraine patients measured with functional near-infrared spectroscopy." European journal of medical research 20.1 (2015): 96.
[6] Headache Classification Committee of the International Headache Society (IHS). "The international classification of headache disorders, 3rd edition." Cephalalgia 38 (2018): 1-211.
[7] Colas, R., et al. "Chronic daily headache with analgesic overuse Epidemiology and impact on quality of life." Neurology 62.8 (2004): 1338-1342.
[8] Bigal, M. E., et al. "Transformed migraine and medication overuse in a tertiary headache centre—clinical characteristics and treatment outcomes." Cephalalgia 24.6 (2004): 483-490.
[9] Kitaj, Madeleine B., and Michelle Klink. "Pain thresholds in daily transformed migraine versus episodic migraine headache patients." Headache: The Journal of Head and Face Pain 45.8 (2005): 992-998.
[10] Fumal, Arnaud, et al. "Orbitofrontal cortex involvement in chronic analgesic-overuse headache evolving from episodic migraine." Brain 129.2 (2005): 543-550.
[11] Rocca, Maria A., et al. "Brain gray matter changes in migraine patients with T2-visible lesions: a 3-T MRI study." Stroke 37.7 (2006): 1765-1770.
[12] Schoenen, Jean, P. Lenarduzzi, and J. Sianard-Gainko. "Chronic headaches associated with analgesics and/or ergotamine abuse: a clinical survey of 434 consecutive out-patients." New Advances in Headache Research (1989): 255-259.
[13] Bahra, Anish, et al. "Does chronic daily headache arise de novo in association with regular use of analgesics?." Headache: The Journal of Head and Face Pain 43.3 (2003): 179-190.
[14] Wolff, H. G. "The nasal, paranasal and aural structures as sources of headache and other pain." Headache and Other Head Pain (1948): 532-560.
[15] Geppetti, Pierangelo, et al. "Antidromic vasodilatation and the migraine mechanism." The Journal of Headache and Pain 13.2 (2012): 103-111.
[16] Leo, Aristides AP. "Spreading depression of activity in the cerebral cortex." Journal of Neurophysiology 7.6 (1944): 359-390.
[17] Moskowitz, Michael A. "The neurobiology of vascular head pain." Annals of Neurology 16.2 (1984): 157-168.
[18] Dalkara, Turgay, Ala Nozari, and Michael A. Moskowitz. "Migraine aura pathophysiology: the role of blood vessels and microembolisation." The Lancet Neurology 9.3 (2010): 309-317.
[19] Vecchia, Dania, and Daniela Pietrobon. "Migraine: a disorder of brain excitatory–inhibitory balance?." Trends in Neurosciences 35.8 (2012): 507-520.
[20] de Tommaso, Marina, and Vittorio Sciruicchio. "Migraine and central sensitization: clinical features, main comorbidities and therapeutic perspectives." Current Rheumatology Reviews 12.2 (2016): 113-126.
[21] Jobsis, Frans F. "Noninvasive, infrared monitoring of cerebral and myocardial oxygen sufficiency and circulatory parameters." Science 198.4323 (1977): 1264-1267.
[22] Valfrè, Walter, et al. "Voxel‐based morphometry reveals gray matter abnormalities in migraine." Headache: The Journal of Head and Face Pain 48.1 (2008): 109-117.
[23] Olesen, Jes, Bo Larsen, and Martin Lauritzen. "Focal hyperemia followed by spreading oligemia and impaired activation of rCBF in classic migraine." Annals of Neurology 9.4 (1981): 344-352.
[24] Andersson, J. L. R., et al. "Regional cerebral blood flow and oxygen metabolism during migraine with and without aura." Cephalalgia 17.5 (1997): 570-579.
[25] Hadjikhani, Nouchine, et al. "Mechanisms of migraine aura revealed by functional MRI in human visual cortex." Proceedings of the National Academy of Sciences 98.8 (2001): 4687-4692.
[26] Friberg, L., et al. "Migraine pain associated with middle cerebral artery dilatation: reversal by sumatriptan." The Lancet 338.8758 (1991): 13-17.
[27] Thie, A., et al. "Multimodal tests of cerebrovascular reactivity in migraine: a transcranial Doppler study." Journal of Neurology 239.6 (1992): 338-342.
[28] Chen, W‐T., et al. "Peri‐ictal normalization of visual cortex excitability in migraine: an MEG study." Cephalalgia 29.11 (2009): 1202-1211.
[29] Volkow, Nora D., Joanna S. Fowler, and Gene-Jack Wang. "The addicted human brain viewed in the light of imaging studies: brain circuits and treatment strategies." Neuropharmacology 47 (2004): 3-13.
[30] London, Edythe D., et al. "Orbitofrontal cortex and human drug abuse: functional imaging." Cerebral Cortex 10.3 (2000): 334-342.
[31] Gómez-Beldarrain, Marian, et al. "Orbitofrontal dysfunction predicts poor prognosis in chronic migraine with medication overuse." The Journal of Headache and Pain 12.4 (2011): 459-466.
[32] Rocca, Maria A., et al. "Brain gray matter changes in migraine patients with T2-visible lesions: a 3-T MRI study." Stroke 37.7 (2006): 1765-1770.
[33] Liboni, W., et al. "Why do we need NIRS in migraine?." Neurological Sciences 28.2 (2007): S222-S224.
[34] Schillaci, G., et al. "Aortic stiffness and pulse wave reflection in young subjects with migraine A case-control study." Neurology 75.11 (2010): 960-966.
[35] Akın, Ata, and Didem Bilensoy. "Cerebrovascular reactivity to hypercapnia in migraine patients measured with near-infrared spectroscopy." Brain Research 1107.1 (2006): 206-214.
[36] Vernieri, F., et al. "Increased cerebral vasomotor reactivity in migraine with aura: an autoregulation disorder? A transcranial Doppler and near‐infrared spectroscopy study." Cephalalgia 28.7 (2008): 689-695.
[37] Schytz, Henrik Winther, et al. "Intact neurovascular coupling during executive function in migraine without aura: interictal near‐infrared spectroscopy study." Cephalalgia (2009).
[38] Coutts, Louise V., et al. "Time course of the haemodynamic response to visual stimulation in migraine, measured using near-infrared spectroscopy." Cephalalgia 32.8 (2012): 621-629.
[39] Jin, Chenwang, et al. "Structural and functional abnormalities in migraine patients without aura." NMR in Biomedicine 26.1 (2013): 58-64.
[40] Yu, Dahua, et al. "Regional homogeneity abnormalities in patients with interictal migraine without aura: a resting‐state study." NMR in Biomedicine 25.5 (2012): 806-812.
[41] Siesler, Heinz W., et al., eds. Near-infrared spectroscopy: principles, instruments, applications. John Wiley & Sons, (2008).
[42] Dutta, Anirban, et al. "EEG-NIRS based assessment of neurovascular coupling during anodal transcranial direct current stimulation-a stroke case series." Journal of Medical Systems 39.4 (2015): 36.
[43] Tanida, Masahiro, Masako Katsuyama, and Kaoru Sakatani. "Relation between mental stress-induced prefrontal cortex activity and skin conditions: a near-infrared spectroscopy study." Brain Research 1184 (2007): 210-216.
[44] Bär, Karl-Jürgen, et al. "Increased prefrontal activation during pain perception in major depression." Biological Psychiatry 62.11 (2007): 1281-1287.
[45] Tuchin, Valeriĭ Viktorovich, and V. Tuchin. "Tissue optics: light scattering methods and instruments for medical diagnosis." (2007).
[46] A. Bakker, B. Smith, P. Ainslie, and K. Smith, "Near-Infrared Spectroscopy," (2012).
[47] Boas, David A., et al. "The accuracy of near infrared spectroscopy and imaging during focal changes in cerebral hemodynamics." Neuroimage 13.1 (2001): 76-90.
[48] Delpy, David T., et al. "Estimation of optical pathlength through tissue from direct time of flight measurement." Physics in Medicine & Biology 33.12 (1988): 1433.
[49] Duncan, Arlene, et al. "Measurement of cranial optical path length as a function of age using phase resolved near infrared spectroscopy." Pediatric Research 39.5 (1996): 889.
[50] Murayama, Yuta, Lizhen Hu, and Kaoru Sakatani. "Relation Between Prefrontal Cortex Activity and Respiratory Rate During Mental Stress Tasks: A Near-Infrared Spectroscopic Study." Oxygen Transport to Tissue XXXVIII. Springer, Cham, (2016). 209-214.
[51] Betz, Linda T., et al. "Stress reactivity in chronic tinnitus." Scientific Reports 7 (2017): 41521.
[52] Graven-Nielsen, Thomas, and Lars Arendt-Nielsen. "Assessment of mechanisms in localized and widespread musculoskeletal pain." Nature Reviews Rheumatology 6.10 (2010): 599.
[53] Loggia, Marco L., et al. "Disrupted brain circuitry for pain‐related reward/punishment in fibromyalgia." Arthritis & Rheumatology 66.1 (2014): 203-212.
[54] Polianskis, Romanas, Thomas Graven-Nielsen, and Lars Arendt-Nielsen. "Pressure-pain function in desensitized and hypersensitized muscle and skin assessed by cuff algometry." The Journal of Pain 3.1 (2002): 28-37.
[55] Greffrath, Wolfgang, Ulf Baumgärtner, and Rolf-Detlef Treede. "Peripheral and central components of habituation of heat pain perception and evoked potentials in humans." Pain 132.3 (2007): 301-311.
[56] Thayer, Julian F., et al. "A meta-analysis of heart rate variability and neuroimaging studies: implications for heart rate variability as a marker of stress and health." Neuroscience & Biobehavioral Reviews 36.2 (2012): 747-756.
[57] Umetani, Ken, et al. "Twenty-four hour time domain heart rate variability and heart rate: relations to age and gender over nine decades." Journal of the American College of Cardiology 31.3 (1998): 593-601.
[58] Lu, Sheng, et al. "Can photoplethysmography variability serve as an alternative approach to obtain heart rate variability information?." Journal of Clinical Monitoring and Computing 22.1 (2008): 23-29.
[59] Parak, Jakub, et al. "Evaluation of the beat-to-beat detection accuracy of PulseOn wearable optical heart rate monitor." Engineering in Medicine and Biology Society (EMBC), 2015 37th Annual International Conference of the IEEE. IEEE, (2015).
[60] Selvaraj, Nandakumar, et al. "Assessment of heart rate variability derived from finger-tip photoplethysmography as compared to electrocardiography." Journal of Medical Engineering & Technology 32.6 (2008): 479-484.
[61] Tarvainen, Mika P., et al. "Kubios HRV–heart rate variability analysis software." Computer Methods and Programs in Biomedicine 113.1 (2014): 210-220.
[62] Ernst, Gernot. Heart rate variability. Springer, (2016).
[63] Kawashima, Ryuta, et al. "A functional MRI study of simple arithmetic—a comparison between children and adults." Cognitive Brain Research 18.3 (2004): 227-233.
[64] Çiftçi, Koray, et al. "Functional clusters in the prefrontal cortex during mental arithmetic." Signal Processing Conference, 2008 16th European. IEEE, (2008).
[65] Villringer, Arno, et al. "Near infrared spectroscopy (NIRS): a new tool to study hemodynamic changes during activation of brain function in human adults." Neuroscience Letters 154.1-2 (1993): 101-104.
[66] Villringer, Arno, and Britton Chance. "Non-invasive optical spectroscopy and imaging of human brain function." Trends in Neurosciences 20.10 (1997): 435-442.
[67] Ramsey, Nick F., et al. "Towards human BCI applications based on cognitive brain systems: an investigation of neural signals recorded from the dorsolateral prefrontal cortex." IEEE Transactions on Neural Systems and Rehabilitation Engineering 14.2 (2006): 214-217.
[68] Schoofs, Daniela, Diana Preuß, and Oliver T. Wolf. "Psychosocial stress induces working memory impairments in an n-back paradigm." Psychoneuroendocrinology 33.5 (2008): 643-653.
[69] Baek, Hyun Jae, et al. "Reliability of ultra-short-term analysis as a surrogate of standard 5-min analysis of heart rate variability." Telemedicine and e-Health 21.5 (2015): 404-414.
[70] Tromberg, Bruce J., et al. "Non-invasive in vivo characterization of breast tumors using photon migration spectroscopy." Neoplasia 2.1-2 (2000): 26-40.