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A Study of Dementia by Linear and Nonlinear Analyses of Electroencephalography and Electrocardiography
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失智症已是現今醫療及社會福利機構的ㄧ大負擔，預測到2040年全世界將有八千萬失智人口。因為目前有效的治療都強調早期使用的好處。人們積極的尋找疾病早期或是與預後有關的標記。兩大失智症病因為阿茲海默症以及血管型失智症，再其次則為路易氏體型失智症以及額顳葉型失智症。病理學上的研究仍未能解釋各型的成因，不過兩大病因皆與血管方面的危險因子有關。
阿茲海默症由基底額葉到大腦皮質及海馬迴的乙烯膽鹼系統是受損的。乙烯膽鹼系統被認為在大腦各項功能扮演重要腳色，如清醒及睡眠周期、視覺訊號處理、學習、以及記憶等功能。心與腦之間有密切關係，”neurovisceral integration model” 描述出從大腦前額葉皮質到達心臟的竇房結的整個中樞自主神經網路，並強調中樞自主神經中心以右邊的大腦前額葉皮質為主。
本研究應用各種線性及非線性分析法，來研究非侵犯性檢查-腦波及心電圖之訊號。生理訊號都受制於複雜的調控系統，其特性為既非穩定亦非線性，故分析方法須考慮或克服這些障礙。傳統的線性分析，多根基於傅立葉轉換，無法很細微及即時的提供訊息。目前常用方法中，線性但適合非穩定訊號的方法有小波分析及Wigner分佈等；非線性但穩定的分析法則多基於混沌理論，有如碎形及熵的各種運算；非線性且非穩定訊號的分析法則首推Hilbert-Huang transform (HHT)，其應用已在生物訊號的領域裡有很好的結果。
在心電圖方面，心跳兩兩之間的時間 (RR interval, RRI)，取決於竇房結去極化的速度，此則受制於自主神經系統的調控，於是研究心率變異便能代表心臟的自主神經系統調控。而當副交感神經作用較強時，HF升高、LF/HF ratio降低。LF則可能受交感及副交感神經兩者共同作用，並受壓力感受器系統調控，VLF則代表較慢的調控，可能代表一些血管運動、腎素-血管緊張素-醛固酮系統、以及人體熱調節系統。ULF則代表更長時間的影響。心率變異分析，用於失智症方面的報告結果不一。睡眠中的心律變異比清醒時高已在多個研究中獲得證實，而且不管是在REM sleep或Non-REM sleep皆然。睡眠呼吸中止症對於兩大型失智症皆是危險因子，這睡眠呼吸中止可以新的分析方法，由心電圖分析得知。
腦內的各項功能，皆需要各個不同區域的神經元做功能性聯結。這可以腦波上不同區域間的波在統計學上有互相依賴 (interdependence) 關係的狀況來代表，稱為耦合。腦波依頻段可分為alpha、beta、theta、delta、及gamma波，其來源不明。在失智的情況下，alpha波的強度變小、分佈前移、耦合變小。
Cross correlation and spectral coherence 以及 synchronization likelihood 是兩種近年來最具代表性的方法，前者為線性後者為非線性分析，皆是用以探討腦波各個channels 間關係的數學運算法，可以量化大腦皮質細胞間的同步化以及功能性耦合。如果大腦因為老化、藥物或是病變而使各區域間的聯繫受阻的話，同步化以及功能性耦合應該下降。
動脈硬化與血管型失智症及阿茲海默症皆有密切關係，有許多測量動脈硬化的參數可用來預測中風的危險性。生活型態例如社交參與、運動習慣、菸、酒等都與認知能力的下降有關。喝水量則尚無報告。
研究方法及材料
本研究設定為一個以老人科門診患者為對象來源、觀察性、病例對照、並且前瞻性追蹤的形態進行。通過署立台南醫院的臨床試驗同意 (IRB-2008004)。疾病組為65歲及以上的失智老人，第一次被診斷，其簡易認知功能測試經調整是否識字後分數小於等於26者。總計疾病組60人 (age: 80.52±5.6 , range:67-93, AD/VD: 24 /36 , male/female: 30/30, MMSE=19.8±6.9)，對照組29人(age: 75.28±6.5, range:65-87, male/female: 16/13, MMSE=28.4±0.9, MMSE=28.4±0.9)。檢查項目包括常規性腦波、24小時心電圖數位記錄、腦血管超音波、認知功能測驗 (mini-mental status examination (MMSE), clock-drawing test, clock-completion test, number transcoding task, trail making test, world list from CERAD-Plus, Boston naming test)、行動及活動量表 (Barthel index, timed up-and-go, Tinneti test)、憂鬱指數 (geriatric depressive scale)。疾病組並有腦部影像學檢查。
數據分析以MATLAB進行，運算腦波的spectral coherence、cross correlation coefficient of IMFs、multiscale entropy (MSE)，以及RRI的time domain and frequency domain data、multiscale entropy (MSE)。
結果與討論
比較特別的發現是: 1. 由HHT解構後的訊號所做的功能性耦合分析, 腦部各區的變數廣泛的與臨床心理測驗分數在校正性別年齡後成正比, 這意味大腦智能的運作是以全面的方式（holistic manner）進行。相較於線性方法，則只有在少數以額葉及顳葉為主的 channels看到此現象。 2. 失智患者比起對照組，有較顯著的vagal dominance during sleep 的現象。 3. MSE of EEG在各種尺度、各個channel下，皆與智能測驗分數成正比。 4. MSE of EKG 某些特定尺度的值與sum of MSEs of EEG 在廣泛channels的值，皆有很強的線性負相關。可由與線性參數的值對照(MSE 值與LF/HF ratio成正比)得到失智的腦有較低的副交感神經輸出（parasympathetic output）的結論, 或者可直接懷疑心律與腦的律動存在相同或極相關的成分。此外清醒的心電圖只與eye-closed resting 的腦波相關連 (Fz、T4、F3、Pz、O2、F8、F4、P4、C3、P3、F2)，而睡眠時的心電圖則與photic stimulation的腦波相關連(F2、T5、F4、T3、F1、T4、Cz、C3、O2、Pz、O1、Fz、F3、F7、C4)。清醒心電圖關連右腦的channels比較多，而睡眠心電圖則關連兩腦。 5. 比較三種情況下的腦波 (休息閉眼、閃光刺激、以及快速呼吸) 所得的結果，以閃光刺激所得結果最為顯著。 6. 各種不同的智能測驗，對照腦波的結果看來，word list、clock drawing、trail making、number transcoding鑑別力可說比MMSE還好。 7. 有Glabellar sign 者清醒的 LF/HF 較低。 8. 糖尿病患者睡眠的HF、LF、及清醒的 HF較低。 9. 血管超音波沒有發現顯著參數。
展望
本研究已顯示出腦波及心電圖的確藏有標記智能程度的參數。下一步計畫以社區中的老人為對象，收集腦波心電圖以及智能測驗分數，做長期的追蹤，然後運用所找到的較合適的分析方法，來尋找可以當為早期診斷或危險因子的標記。
另外對藥物治療之監測也很可行，對藥物有反應者如果腦波的參數有其特徵性，那麼也許可以早期投藥以預防疾病，或者用於預告無效而尋求其他的治療。
心與腦的關係，以腦波與心電圖的關係來繼續探討，應是值得投入的領域。
關鍵字: 失智症、心電圖、腦波、線性/非線性分析、耦合、熵、
Hilbert-Huang 轉換Introduction
The load of caring for demented patients is increasing globally very fast as eighty million demented population is expected in 2040. Alzheimer’s disease (AD) and vascular dementia (VD) are the two major causes of dementia. Since all current therapies for dementia depend on early diagnoses, risk and predicative factors for dementia are crucial. AD and VD share common risk factors as aging and vascular risks such as diabetes, hypertension, metabolic syndrome, homocystinemia, atrial fibrillation, and smoking. There are bidirectional connections between the heart and the brain. A neurovisceral integration model with laterality on the right prefrontal cortex was proposed to describe the pathways.
EEG and EKG are nonstationary and nonlinear signals. The traditional Fourier spectrum is too coarse and fails to represent instantaneous changes. Nonstaionary but linear methods such as Wigner-Ville distribution and Wavelet have other drawbacks that hinder its adaptivity to ever-changing signals. Methods based on theories of chaos, fractal and entropy, quantifying either similarity, disorder, or stability, are suitable for nonlinear but stationary data. The Hilbert–Huang transform(HHT) on the other hand, is adaptive to nonlinear and nonstationary signals. The advantages of the HHT over traditional Fourier-based methods have been appreciated in many studies of different physiological systems.
The study of heart rate variability (HRV), namely the variability of RR intervals (RRI), which reflects depolarization of the sinoatrial node, can monitor the autonomic system. The cholinergic deficits in the brain of dementia may affect the central autonomic network. Yet the HRV changes in dementia in previous reports were not congruent. A higher risk of dementia was shown in people with obstructive sleep apnea, which could be indicated by some newly developed methods of HRV analysis.
Understanding how functional interactions among different brain regions are crucial to the study of higher cortical functions. The cross correlation and coherence analysis are two of the classical methodologies of linear approach. While the synchronization likelihood, which calculates the probability of similarity between two signals in phase space is a nonlinear approach. From synchronization to the execution of particular tasks of the brain, there hide still many puzzles such as ‘binding problem’.
Social participation, exercise, smoking, and alcohol drinking may affect cognitive performance, while water intake insufficiency has yet to be proved.
Methods
This is a hospital-based, case control, and observational study with prospective follow-up of two groups (dementia and control). Various neuro-psychological and motility tests were performed in all subjects. As vascular risks are important in both types of dementia, carotid echosonography was also taken for each subject. Life style and eating behaviors were also compared. Both linear and nonlinear methods such as short time Fourier transform, spectral coherence, Hilbert Hung transform (HHT), multiscale entropy (MSE), and synchronization likelihood (SL) were performed for EEG signals. Heart rate variability was calculated individually in both awake and sleep EKG signals with linear analysis and MSE.
Results and Discussions
The demented group consists of 60 subjects (female/male=30/30, age 80.5±5.6, VD/AD=37/23, MMSE=19.8±6.9), while the control group consists of 29 subjects (female/male=13/16. age 75.3±6.4, MMSE=28.4±0.9).
Significant findings are as following: 1. The cross correlation coefficients of data decomposed by HHT suggest that the brain functions in a more holistic manner. 2. The phenomenon of ‘Vagal dominance during sleep’ was only shown in the demented group. 3. The values of all scales of MSE from a wide range of electrodes are positively correlated with scores of mental abilities or mobility. 4. The MSE of RRI showed no correlation to mental capacities, but it had significantly negative correlations to the MSE of EEG in multiple area. Interestingly, the EEGs of closed-eye resting were associated to the RRIs during the awake state, while the EEGs of photic stimulation were mostly associated to the RRIs during sleep. 5. The photic stimulation yielded the most copious results. 6. Word list, clock drawing, trail making, and number transcoding tests had better differentiating power than MMSE. 7. Subjects with positive Glabellar signs had a lower LF/HF during awake state. 8. Diabetic subjects had lower HF and LF during sleep, and HF during awake state. 9. There was no correlation among the severity of carotid atherosclerosis to either mental capacities, parameters of EEG or parameters of EKG. 10. EEG of Dementia showed loss of coupling, complexity and stationarity
Prospect
A community based design with long time following is the next plan. It aims at risk factors and markers for early diagnosis by the analysis of EEG. Therapy monitoring by EEG is an ongoing study with some promising primitive results. The cross-talk between the brain and the heart could be further explored noninvasively by the information hidden in EKG and EEG.
Key words: dementia, EKG, EEG, functional couplings, linear /nonlinear analysis, Multiscale Entropy, Hilbert- Huang Transformatio
Optimization of Image Qualities in Polarized Stereoscopic System
No full text在偏光立體投影系統(Polarized Stereoscopic System)中，是採用兩台投影機分別投射左右眼影像，經過偏振片與延遲片的光學元件，最後在觀察者端觀看到立體的影像。但在偏光式立體投影系統中，因為投影螢幕大小以及投影距離的限制，投影機光源入射螢幕的角度為斜向35度入射，在此光源投射的條件下，當觀察者頭偏角度過大會有交互干擾與色差的問題，造成影像品質變差。 研究上採用偏振片與四分之一波長延遲片的瓊斯矩陣，透過瓊斯矩陣的運算，以模擬的方法計算相對應的交互干擾。並透過色度圖CIE 1976與色差公式對影像的色差進行分析。在不同頭偏角度與光源入射角度下，對於:交互干擾與色差這兩項品質因子，利用延遲片角度的堆疊設計，達到影像品質的優化。 本論文對這兩項品質因子:交互干擾與色差，分別在各頭偏角度與各光源入射角度下，採用窮舉法找出最佳的延遲片角度設計，來達成交互干擾與色差的優化。針對交互干擾部分，欲壓低長波長波段的交互干擾，又不會造成短波長波段交互干擾的劣化，而提出交互干擾容忍量的設計方法，以此方法設計在頭偏角度15度時可以達到16%的改善程度，在頭偏角度45度時採用20%容忍量時可以達到60%的改善程度。針對色差部分可以利用延遲片角度設計，來達到有頭偏情況下色彩的表現與無頭偏時一樣好。當同時對色差與交互干擾作優化時，透過分析色差與交互干擾的重要性，得知交互干擾重要高於色差，以交互干擾影響程度為色差10倍條件去設計，色差變差，但差異值僅0.0001~0.0009的數量級，反觀交互干擾的最大優化量接近1。 在未來的研究中，不只可以改變延遲片的角度設計，也可以透過不同的延遲片材料與厚度設計方式，對交互干擾或是色差得到進一步的優化，來達成偏光立體投影系統中更好的影像品質。We adopt two projectors to project left and right images separately in polarized stereoscopic system. The light passes through the optical components such as polarizers and retarders. Finally, the observers can watch the stereoscopic images. Because of the screen size and projection distance, light is projected from the projector with an oblique angle of 35 degrees in the polarized stereoscopic system. Under this situation, observers will suffer from worse image qualities due to crosstalk or color shift when they are with severe head rotation. We can use the simulation method to calculate crosstalk by using the representative Jones matrix of polarizer and quarter-wave retarder and calculating the product of Jones matrices for the system. We can evaluate the color shift for images by chromatic diagram and color shift formula based on CIE 1976. We can optimize the image qualities by designing the angles of stacked retarder for minimizing crosstalk or color shift under different angles of head rotation and light incidence. We can find the optimized retarder angles by using exhausted method to achieve the optimization of crosstalk and color shift under different angles of head rotation and light incidence. We want to reduce the crosstalk within long wavelength range, but we don''t want the crosstalk to get worse within wavelength range during optimizing crosstalk. Due to the crosstalk problem, we propose a solution with a certain maximum residue levels of crosstalk. We can achieve 16% improvement ratio under head rotation of 15 degrees and 60% improvement ratio in head rotation of 45 degrees with 20% maximum residue levels. We can achieve color shift optimization under head rotation situation just as under no head rotation situation. When we want to optimize crosstalk and color shift simultaneously, we try to analyze the importance of crosstalk and color shift and conclude that crosstalk is more important than color shift in image qualities optimization. If we adopt the criterion of crosstalk being 10 times important than color shift, we can get the maximum optimized value of 1 for crosstalk. Instead of getting better crosstalk, we suffer from worse color shift. But the worse value of color shift is within the range of 0.0001 to 0.0009. The difference is negligible. We will not only tune the retarder angles but also design different materials and thickness to further improve crosstalk and color shift in the future and achieve better image qualities in polarized stereoscopic system
Correlation analysis between ECG and EEG signals based on signal complexity
No full text緒論 生命的祕密至今無解。各種律動組合成人體的運作，是維持生命的要素。這些律動彼此交互影響、形成迴路、並共同與擾動的、多變的環境發生應對。他們提供組成生命所需有序的功能。回顧歷史，心臟在許多不同文化裡被視為是情緒和智慧的本源。大多數的神經科學家認為意識及思考只是大腦及其相關的神經生理功能。然而，心臟在腦形成以前已經開始跳動。傳統說法，心與腦經由神經及荷爾蒙兩種路徑互相溝通，其溝通是否也能經由個別律動內所隱藏的動態變化，則令人好奇。心律變異是心臟自主神經系統的指標，腦波動態變化則被證明與意識活動有關。本論文始於複習非線性訊號分析。生物訊號屬於多尺度、非線性且非穩定性序列，混沌理論是否可行不需執著，非隨機的複雜性的確存在於生物信號中。我選擇以探討規則的統計為中心的複雜性分析來探討心腦連結問題。同步記錄及非同步記錄的腦波及心電圖都將被使用。實驗對象使用一群老人，基本上心臟功能健康、而意識功能則從健全到失智拉開分布。腦的電磁活動運轉非常迅速，類穩定的腦波信號是非常短的，處於幾十秒的尺度。因此我採用符號動力學方法來分析同步信號。腦波的來源至今未有定論，其中新近被討論的皮層慢電位，其頻率範圍接近心臟的。我採用非線性、直覺性的方法來著手探討皮層慢電位。並且對於腦波之電位及即時頻率兩個成分將分開探討。 研究方法及材料 實驗對象包含89個老年門診病患，分為三個族群，38個血管型失智症、22個阿茲海默症、以及29個智能健全的對照組。多尺度熵分析(Multiscale entropy)用以分析非同步的腦波心電圖，符號動力學方法用以分析同步的腦波心電圖。另外分散信號的方法用以將波幅及即時頻率分開。傅立葉頻譜低頻對高頻比(LF/HF)用以代表交感副交感神經平衡指數。 結果與討論 在非同步信號經由多尺度熵分析，我發現心腦信號之複雜動態間，的確存在線性關係。但短暫的同步信號之間並無關聯證據。這可能因為同步於腦波的心律變異太短，無法穩定表現個案特質。不過，符號動力學方法顯示: 每個分散的腦波局部高峰，其電位值的變異與智能相關，但是腦波的及時頻率並不相關。這表是局部同步激發的皮質神經元數量而非其激發的時機與智能相關。熵的值，或說複雜度，亦即規則性的強弱並不代表健康度。不同方法測量的是生物信號的不同尺度。在腦波分析方面，分散信號的方法所得到的資訊，並不亞於全波形的分析。失智的病理表現可能是連續性而非階梯式的。Introduction The secret of life remains extremely concealed. There are all sorts of rhythms in human bodies and they are central to life. The rhythms interact with each other as well as the outside fluctuating, noisy environment under the control of innumerable feedback systems. They provide an orderly function that enables life. The heart has been considered the source of emotional experience and wisdom in many cultures throughout the ages. Most neuroscientists consider consciousness or even thought is merely an epiphenomenon of the human brain function and its associated neurophysiology. However, the heart begins to beat before the brain is formed. Conventionally, both neural and humoral pathways connect the heart with the brain. Whether the interplay between the heart and brain could be explored through their rhythms is the question. Heart rate variability is recognized as the indicator of cardiac autonomic function. The dynamics of human electroencephalography (EEG) dynamics has been proved to be related to cognitive activities. This dissertation starts with reviewing the nonlinear methods in analyzing biological rhythms, which are multiscale, nonlinear and non-stationary. Regardless of whether chaos is present, deterministic complexity exists in biological rhythms. Regularity based complexity was chosen after comparisons. The goal is to find correlations between EEG and electrocardiography (ECG) through regularity based complexity analysis. Both simultaneous and non-simultaneous data would be examined. The experimental subjects are from a geriatric sample with varied cognitive abilities and basically healthy hearts. The electromagnetic activity of the brain works at an extremely fast speed, and the quasi-stationary epochs of EEG are, in general, short lasting, in the order of tens of seconds. Therefore symbolic techniques were introduced when exploring the very short simultaneous EEG and R-R interval (RRI) data. The origin of EEG remains unknown. Slow cortical potential (SCP), one component of EEG, is in the frequency range similar to that of the heart, and would be explored in an intuitive nonlinear way. In addition, the amplitude and instantaneous frequency of EEG would be separately approached. Methods The sample consisted of 89 geriatric outpatients in three patient groups: 38 fresh cases of vascular dementia (VD), 22 fresh cases of Alzheimer’s disease (AD) and 29 controls. Multiscale entropy (MSE) analysis was applied to the non-simultaneous EEG and RRI data. Symbolic analysis was applied to the simultaneous EEG and RRI data. Discrete events (local peaks) of EEG were extracted to separate the amplitude and instantaneous frequency. The low-to-high frequency power (LF/HF) ratio of RRI was calculated to represent sympatho-vagal balance. Results and Discussions MSE revealed correlations between the signal complexity of brain and cardiac activities in non-simultaneous data. Linear correlation between the MSE value and the score of the mini-mental state examination was first found. Symbolic dynamics failed to correlate the heart to the brain. This is due to that the RRI is too short to represent the characteristics of a subject. The symbolic analysis revealed important information that the EEG dynamics which relates to either the cognitive functions or the underlying pathologies of dementia are embedded within the dynamics of the amount of but not the interval between each synchronized firing of adjacent cerebral neurons. Just like RRI of ECG, discrete events of EEG also provided important information. The relative value of complexity does not indicate health condition straightly. It depends on the method and the scale or dimension that particular method measures. Discrete events provide no less information than continuous waveforms of EEG. Pathological condition is continuous rather than stepwise
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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