2017-01-012024-05-14https://scholars.lib.ntu.edu.tw/handle/123456789/657606摘要：感覺系統異常在許多神經退化性疾病的早期即會出現, 甚至比運動與認知障礙更早發生。由於感覺和運動系統的整合異常與不正常之運動控制有關, 研究運動障礙疾病中的感覺異常提供我們在疾病惡化前早期診斷的機會。巴金森氏症 (Parkinson’s disease) 是一種具有顯著運動缺失的退化性疾病，起因於大腦基底核中多巴胺神經元的漸進性缺失，然而此病症早期呈現的感覺缺失與執行功能障礙之神經機制目前仍不清楚。初步證據亦顯示在步態訓練中給予節律性聽覺刺激 (rhythmic auditory stimulation) 可改善巴金森氏症患者的感覺與運動功能，但我們對這中間運動網絡與感覺系統的互動機制所知非常有限。為探討此議題，本研究將募集巴金森氏症患者與健康成年人，研究巴金森氏症患者在處理非痛覺與痛覺異常時之腦部神經病理機轉。同時，我們也將探討在進行節律性聽覺刺激之步態訓練前後，運動、感覺與認知功能變化的相互關係。我們將使用功能性磁振造影收集腦部的血氧相依訊號 (blood oxygenation level-dependent signals)，來量測當受試者在接受節律性聽覺刺激之步態訓練前與後處理非痛覺與痛覺刺激之腦部反應。功能性磁振造影的訊號將進一步與感覺行為、電生理檢查、血液中關於巴金森氏症的生物標記以及每個人的基因背景做相關性分析。我們首先假設異常之基底核-丘腦-大腦皮質迴路 (striato-thalamo-cortical circuitry)，特別是基底核 (basal ganglia) 和大腦輔助運動皮質區 (supplementary motor area)，與巴金森氏症患者處理時序性震動刺激之障礙有關。至於痛覺, 我們認為紋狀體 (striatum) 處理痛覺訊號的異常會使得不正確的訊息從視丘傳遞到大腦皮質，導致巴金森氏症患者無法準確的評估痛覺刺激。我們進一步假設節律性聽覺刺激之步態訓練可以藉由增進小腦-丘腦-大腦皮質迴路 (cerebello-thalamo-cortical circuitry) 的功能來改善巴金森氏症患者的運動與感覺功能，尤其是加強小腦與前運動皮質區(premotor area) 的活化與功能性連結，藉以代償巴金森氏症患者功能異常之基底核-丘腦-大腦皮質迴路。此研究之結果將增長我們對於人類如何處理體感覺以及感覺系統與運動系統互動關係之瞭解，同時也提供了一個對於改善巴金森氏症患者感覺運動缺損的非藥物治療策略。<br> Abstract: Involvement of the sensory system develops early and even predates the diagnosis of motor or cognitive symptoms in neurodegenerative disease. Since impaired sensorimotor integration contributes to abnormal motor control, investigating sensory abnormalities in movement disorders thus affords an opportunity to make early diagnosis before the disease deteriorates. Although patients with Parkinson’s disease (PD), a motor-predominant neurodegenerative disorder characterized byrelentlessly progressive loss of dopaminergic neurons in basal ganglia, display aberrant processing of somatosensation and executive functions, the underlying neural mechanisms remain to be elucidated.Preliminary evidence also suggests that rhythmic auditory stimulation (RAS) with gait training can improve sensorimotor symptoms in PD, but how motor networks interact with the sensory system to underpin this phenomenon remains unknown. To address these issues, the current research will recruit patients with PD and healthy adults to investigate the pathogenic mechanisms related to the abnormal processing of painful and nonpainful sensations in PD. Using functional magnetic resonance imaging (fMRI), we will collect blood oxygenation level-dependent signals of the brain to measure brain responses when subjects process painful and nonpainful stimulation before and after RAS procedures. fMRI signals will be correlated with the motor and sensory behaviors, electrophysiological data, serum biomarkers of PD, and individual genetic background. We first hypothesize that alterations in thestriato-thalamo-cortical (STC) circuitry, especially supplementary motor area, underlie derangedtemporal processing of vibrotactile stimulation in PD. With regard to pain, we postulate that aberrant processing of nociceptive information in the striatum produces incorrect signals from the thalamus to sensorimotor-related cortical areas, which renders PD patients incapable of estimating a painful stimulus precisely. We expect that RAS with gait training will improve patients’ sensorimotor functions through enhancing the activity and functional connectivity of the cerebello-thalamo-cortical (CTC) network, particularly the cerebellum and premotor area, to compensate for the dysfunctional STC loop in PD. Results obtained from this research will enhance our knowledge on how humans process somatosensation as well as the interrelationship among motor, sensory and cognitive systems, providing promising nonpharmacological therapeutic strategies to improve sensorimotor deficits in PD in the future.巴金森氏症功能性磁振造影感覺Parkinson''s diseasefMRIsensation