臺灣博碩士論文加值系統

背景：疼痛是種令人困擾的臨床症狀。過去文獻指出，疼痛程度會隨著不同情緒狀態而改變。本研究藉由腦磁波圖探討正向情緒的持續效應對於疼痛感知及疼痛相關情緒之調控作用。
資料與方法：二十二位健康受試者於觀賞一分鐘的中性或有趣短片後接受五次雷射疼痛刺激。每接受一次疼痛刺激後，受試者需以口頭報告其感受到的疼痛強度以及不愉悅程度。實驗進行時以全頭式腦磁圖儀量測腦磁波訊號，行為資料以重複測量變異數分析法(Repeated measures analysis of variance)分析。腦部活化影像則是以光束構成法(Beamforming approach)分析腦磁波訊號，推算出全腦皮質活動隨著時間的變化，繼而利用配對樣本檢定法(Paired-t test)估算不同條件間腦神經活化之差異。最後，我們運用無母數相關性分析法(Spearman rank correlation analysis)檢測大腦皮質活化與行為資料的相關性以及大腦皮質活動之間的相關性。
結果：行為資料結果顯示，受試者於觀賞有趣短片後接受疼痛刺激時，當下的不愉悅度較觀賞中性短片低。而受試者不注意比注意疼痛刺激時所感受到的疼痛強度較小。由腦部影像結果得知，正向情緒的持續效應使得腦中疼痛相關區域活化減少，這些區域包括：右側前額葉(ventrolateral prefrontal cortex)、左側腦島(insula)、後扣帶迴(posterior cingulate cortex, PCC)、上顳頂葉交界區(superior temporal gyrus/temporo-parietal junction, STG/TPJ)以及右側尾狀核(caudate)。其中左側STG/TPJ與疼痛強度為正相關，PCC以及右側尾狀核與當下的不愉悅度呈現負相關。
結論：由行為資料與腦部影像結果推測，正向情緒的持續效應的確對於疼痛感知及疼痛相關情緒產生調控作用。

Introduction: Pain is an unpleasant experience and a disturbing problem. Previous studies demonstrated that positive emotional stimuli can decrease pain-related brain activities. In this thesis, we aimed at investigating how prolonged positive emotion modulates pain perception and subjective pleasantness by mapping brain activation using magnetoencephalography (MEG).
Methods: Twenty-two healthy subjects (11 females; years 21 – 42) were recruited. Each subject was asked to watch a one-minute video clip (8 neutral and 8 comic in total) followed by receiving 5 laser stimulation (right hand) and verbally reporting pain intensity and pleasantness. MEG signals were recorded throughout the experiment. Repeated measures analysis of variance with Bonferroni post hoc test was used for the analysis of psychophysical data. A beamforming approach was employed to image the dynamic changes of cortical activity in a whole brain manner. Cortical-behavioral and inter-cortical correlation coefficients were estimated by Spearman rank correlation analysis.
Results: The psychophysical results demonstrated the prolonged effect of the previous aroused positive emotion on subjective pleasantness after painful stimuli (p < 0.001). Pain intensity decreased when the subjects did not attend to painful stimuli (p < 0.01). In neuroimaging results, the prolonged effect of positive emotion was verified through decreased pain-evoked activity at the right ventrolateral prefrontal cortex, left insula, posterior cingulate cortex (PCC), superior temporal gyrus/temporo-parietal junction (STG/TPJ), and right caudate. The correlation results showed the positive correlation between pain intensity and STG/TPJ activity and pleasantness ratings positively correlated to the activity of PCC and caudate.
Conclusions: Our results showed the prolonged effect of positive emotion on pain modulation. This is helpful for clinical patients who need to receive painful treatment/rehabilitation therapy. We can make good use of the waiting time before clinical treatment well by delivering some positive emotional stimuli. By doing so, we could expect that the patients’ pain perception and unpleasantness would decrease during the treatment for better clinical outcome.

Chapter 1 Introduction 1
1.1 Pain perception 2
1.2 Pain modulation 5
1.3 The role of emotion in pain modulation 6
1.4 Magnetoencephalography 10
1.5 Thesis scope 12
Chapter 2 Materials and Methods 13
2.1 Subjects 14
2.2 Experimental design 15
2.3 Laser stimulation 18
2.4 Video stimuli 19
2.5 MEG recording and MRI acquisition 22
2.6 Data analysis 22
2.6.1 Behavior data analysis 22
2.6.2 Signal preprocessing and source imaging 23
2.6.3 Statistical analysis 24
2.6.4 Correlation analysis 26
Chapter 3 Results 27
3.1 Behavioral results 28
3.2 Neuroimaging results 29
3.2.1 Emotional effect on pain modulation 29
3.2.2 Attentional effect on pain modulation 36
3.3 Cortico-behavioral correlation results 43
3.4 Inter-cortical correlation results 46
Chapter 4 Discussion 49
Chapter 5 Conclusions 53
References 56

Bantick S, Wise R, Ploghaus A, Clare S, Smith S, Tracey I. Imaging how attention modulates pain in humans using functional MRI. Brain 2002;125(2):310-319.
Benarroch E. Descending monoaminergic pain modulation: bidirectional control and clinical relevance. Neurology 2008;71(3):217-221.
Bentley D, Derbyshire S, Youell P, Jones A. Caudal cingulate cortex involvement in pain processing: an inter-individual laser evoked potential source localisation study using realistic head models. Pain 2003;102(3):265-271.
Blanke O, Arzy S. The out-of-body experience: disturbed self-processing at the temporo-parietal junction. The Neuroscientist 2005;11(1):16-24.
Burgdorf J, Panksepp J. The neurobiology of positive emotions. Neuroscience & Biobehavioral Reviews 2006;30(2):173-187.
Chen Y, Cheng C, Hsieh J, Chen L. Maximum contrast beamformer for electromagnetic mapping of brain activity. IEEE Transactions on Biomedical Engineering 2006;53(9):1765-1774.
Chudler E, Dong W. The role of the basal ganglia in nociception and pain. Pain 1995;60(1):3-38.
Coen S, Yaguez L, Aziz Q, Mitterschiffthaler M, Brammer M, WILLIAM S, Gregory L. Negative mood affects brain processing of visceral sensation. Gastroenterology 2009;137(1):253-261.
Coghill RC, Talbot JD, Evans AC, Meyer E, Gjedde A, Bushnell MC, Duncan GH. Distributed processing of pain and vibration by the human brain. Journal of Neuroscience 1994;14(7):4095.
Dantsker E, Froehlich O, Tanaka S, Kouznetsov K, Clarke J, Lu Z, Matijasevic V, Char K. High-T superconducting gradiometer with a long baseline asymmetric flux transformer. Applied Physics Letters 1997;71:1712.
de Wied M, Verbaten M. Affective pictures processing, attention, and pain tolerance. Pain 2001;90(1-2):163-172.
Deco G, Rolls E, Horwitz B. What” and Where” in visual working memory: a computational neurodynamical perspective for integrating fMRI and single-neuron data. Journal of Cognitive Neuroscience 2004;16(4):683-701.
Driver J, Noesselt T. Multisensory Interplay Reveals Crossmodal Influences on 'Sensory-Specific' Brain Regions, Neural Responses, and Judgments. Neuron 2008;57(1):11-23.
Fishbain DA, Cole B, Cutler RB, Lewis J, Rosomoff HL, Fosomoff RS. Is pain fatiguing? A structured evidence-based review. Pain Medicine 2003;4(1):51-62.
Fredrickson BL. What good are positive emotions? Review of general psychology 1998;2:300-319.
Gazzaley A, Rissman J, D'ESPOSITO M. Functional connectivity during working memory maintenance. Cognitive, Affective, & Behavioral Neuroscience 2004;4(4):580-599.
Hackett T, De La Mothe L, Ulbert I, Karmos G, Smiley J, Schroeder C. Multisensory convergence in auditory cortex, II. Thalamocortical connections of the caudal superior temporal plane. The Journal of Comparative Neurology 2007;502(6):924-952.
Hamalainen M, Hari R, Ilmoniemi R, Knuutila J, Lounasmaa O. Magnetoencephalography—theory, instrumentation, and applications to noninvasive studies of the working human brain. Reviews of modern Physics 1993;65(2):413-497.
Hari R, Forss N. Magnetoencephalography in the study of human somatosensory cortical processing. Philosophical Transactions of the Royal Society B: Biological Sciences 1999;354(1387):1145.
Iannetti G, Zambreanu L, Cruccu G, Tracey I. Operculoinsular cortex encodes pain intensity at the earliest stages of cortical processing as indicated by amplitude of laser-evoked potentials in humans. Neuroscience 2005;131(1):199-208.
Jaaskelainen S, Rinne J, Forssell H, Tenovuo O, Kaasinen V, Sonninen P, Bergman J. Role of the dopaminergic system in chronic pain–a fluorodopa-PET study. Pain 2001;90(3):257-260.
Kenntner-Mabiala R, Andreatta M, Wieser M, Muhlberger A, Pauli P. Distinct effects of attention and affect on pain perception and somatosensory evoked potentials. Biological psychology 2008;78(1):114-122.
Kenntner-Mabiala R, Pauli P. Affective modulation of brain potentials to painful and nonpainful stimuli. Psychophysiology 2005;42(5):559-567.
Liu J, Chen Y, Chen L. Fast and Accurate Registration Techniques for Affine and Nonrigid Alignment of MR Brain Images. Annals of biomedical engineering;38(1):138-157.
Loeser JD, Treede RD. The Kyoto protocol of IASP basic pain terminology. Pain 2008;137(3):473-477.
Lu HC, Hsieh JC, Lu CL, Niddam DM, Wu YT, Yeh TC, Cheng CM, Chang FY, Lee SD. Neuronal correlates in the modulation of placebo analgesia in experimentally-induced esophageal pain: a 3T-fMRI study. Pain 2010;148(1):75-83.
Margulies D, Kelly A, Uddin L, Biswal B, Castellanos F, Milham M. Mapping the functional connectivity of anterior cingulate cortex. Neuroimage 2007;37(2):579-588.
Nakata H, Tamura Y, Sakamoto K, Akatsuka K, Hirai M, Inui K, Hoshiyama M, Saitoh Y, Yamamoto T, Katayama Y. Evoked magnetic fields following noxious laser stimulation of the thigh in humans. NeuroImage 2008;42(2):858-868.
Niddam D, Chan R, Lee S, Yeh T, Hsieh J. Central representation of hyperalgesia from myofascial trigger point. NeuroImage 2008;39(3):1299-1306.
Ostir GV, Berges IM, Ottenbacher ME, Clow A, Ottenbacher KJ. Associations Between Positive Emotion and Recovery of Functional Status Following Stroke. Psychosomatic Medicine 2008;70(4):404.
Phillips M, Gregory L, Cullen S, Cohen S, Ng V, Andrew C, Giampietro V, Bullmore E, Zelaya F, Amaro E. The effect of negative emotional context on neural and behavioural responses to oesophageal stimulation. Brain 2003;126(3):669.
Plaghki L, Mouraux A. How do we selectively activate skin nociceptors with a high power infrared laser? Physiology and biophysics of laser stimulation. Neurophysiologie Clinique/Clinical Neurophysiology 2003;33(6):269-277.
Ploner M, Platzen J, Pollok B, Gross J, Schnitzler A. Evoked response amplitudes from somatosensory cortices do not determine reaction times to tactile stimuli. European Journal of Neuroscience 2007;25(12):3734-3741.
Ploner M, Schmitz F, Freund HJ, Schnitzler A. Parallel activation of primary and secondary somatosensory cortices in human pain processing. Journal of neurophysiology 1999;81(6):3100.
Rhudy J, Williams A. Gender differences in pain: Do emotions play a role? Gender Medicine 2005;2(4):208-226.
Rhudy JL, Williams AE, McCabe KM, Russell JL, Maynard LJ. Emotional control of nociceptive reactions (ECON): Do affective valence and arousal play a role? Pain 2008;136(3):250-261.
Roy M, Piche M, Chen J, Peretz I, Rainville P. Cerebral and spinal modulation of pain by emotions. Proceedings of the National Academy of Sciences 2009;106(49):20900.
Schlereth T, Baumgartner U, Magerl W, Stoeter P, Treede R. Left-hemisphere dominance in early nociceptive processing in the human parasylvian cortex. NeuroImage 2003;20(1):441-454.
Svensson P, Minoshima S, Beydoun A, Morrow T, Casey K. Cerebral processing of acute skin and muscle pain in humans. Journal of neurophysiology 1997;78(1):450-460.
Tommaso M, Sardaro M, Livrea P. Aesthetic value of paintings affects pain thresholds. Consciousness and Cognition 2008;17(4):1152-1162.
Tracey I, Mantyh P. The cerebral signature for pain perception and its modulation. Neuron 2007;55(3):377-391.
Tracey I, Ploghaus A, Gati J, Clare S, Smith S, Menon R, Matthews P. Imaging attentional modulation of pain in the periaqueductal gray in humans. Journal of Neuroscience 2002;22(7):2748-2752.
Tulving E, Kapur S, Craik FI, Moscovitch M, Houle S. Hemispheric encoding/retrieval asymmetry in episodic memory: Positron emission tomography findings. Proceedings of the National Academy of Sciences of the United States of America 1994;91(6):2016.
Villemure C, Bushnell M. Mood influences supraspinal pain processing separately from attention. Journal of Neuroscience 2009;29(3):705-715.
Villemure C, Bushnell MC. Cognitive modulation of pain: how do attention and emotion influence pain processing. Pain 2002;95(3):195-199.
Vogt B, Vogt L, Laureys S. Cytology and functionally correlated circuits of human posterior cingulate areas. Neuroimage 2006;29(2):452-466.
Vogt BA. Pain and emotion interactions in subregions of the cingulate gyrus. Nature Reviews Neuroscience 2005;6(7):533-544.
Weisenberg M, Raz T, Hener T. The influence of film-induced mood on pain perception. Pain 1998;76(3):365-375.
Wiech K, Farias M, Kahane G, Shackel N, Tiedeb W, Traceya I. An fMRI study measuring analgesia enhanced by religion as a belief system. Pain 2009;139:467-476.
Wiech K, Ploner M, Tracey I. Neurocognitive aspects of pain perception. Trends in cognitive sciences 2008;12(8):306-313.
Wiech K, Tracey I. The influence of negative emotions on pain: behavioral effects and neural mechanisms. Neuroimage 2009;47(3):987-994.
Zhang G, Yang C, Zhang D, Gao H, Zhang Y, Jiao R, Zhang H, Liang Y, Xu M. Noradrenergic mechanism involved in the nociceptive modulation of nociceptive-related neurons in the caudate putamen. Neuroscience letters 2010;480(1):59-63.