幻聽對思覺失調症早期情緒處理及靜息態大腦神經振盪之影響：腦磁圖研究

Abstract

本論文旨在研究幻聽對精神分裂症早期情緒處理和靜息狀態神經振蕩的影響。大多數患有精神分裂症的人會經歷具有負面或威脅相關性質的幻聽(auditory hallucinations);然而，幻聽對聽覺皮層情緒的早期感知處理的影響仍然相對未知。在論文的第一部分，我們採用隱含的(implicit)情緒任務來研究幻聽對精神分裂症患者中情緒韻律的早期神經中樞處理(刺激後100毫秒內)的影響。我們假設患者的情緒反應異常可能隨著幻聽的嚴重程度而變化，也可能與社會認知受損有關。我們分別記錄他們的臨床症狀和情緒智力做為評估社會認知的指標。使用腦磁圖記錄聽覺對中性和情緒韻律(快樂，悲傷，憤怒和恐懼)的反應，其中包括M50和M100成分。然後，根據情緒特異性反應指數分數(通過對中性聲音反應的歸一化)進行群組比較，再以此分數和情緒智力表現進行相關性分析。我們的研究結果表明，幻聽在低階的聽覺處理中就會對早期的情緒反應產生影響。在處理情緒較少之刺激(悲傷)的功能障礙可能是精神分裂症的特徵(trait-feature)。然而，持續性幻聽則偏好高覺醒之負面情緒，可視為幻聽狀態的特徵(state-feature)，此偏好進而會導致幻聽患者的社會認知受損。論文的第二部分旨在利用腦磁圖研究幻聽對靜息狀態大腦活動在訊號源空間中不同頻段的影響。我們假設精神分裂症會有的異常功率調節且此異常會與臨床症狀有關。我們的研究結果表明θ和α頻帶的振盪活動能力隨著幻聽的嚴重程度而變化。與正常受試者相比，精神分裂症患者在多感覺皮層區域(multisensory cortical regions，即軀體感覺，聽覺和視覺)中發現異常的靜息活動，暗示感覺整合損傷可能導致低階的神經信號到複雜的大腦皮層整合缺損。而邊緣系統中的β過度活動支持了過度活躍的多巴胺系統會導致精神分裂症的觀點。這些發現提供我們對不同表現型之精神分裂症(有或沒有幻聽)的神經機制有更深入的了解。

This research aims at studying effects of auditory hallucinations on early emotional processing and resting-state brain oscillations in schizophrenia. Most individuals with schizophrenia (SPs) experience auditory hallucinations (AH) of a negative or threat-related nature; however, the impact of AH on the early perceptual processing of emotions at the auditory cortex remains relatively unknown. In the first part of the thesis, we employed an implicit emotional task to investigate the effects of AH on the early central processing of emotional prosody (within 100 milliseconds after stimulus onset) in SPs. We hypothesized that abnormalities in the emotional responses of SPs may vary with the severity of AH and may also be associated with impaired social cognition. We assessed clinical symptoms and emotional intelligence (EI) as an index of social cognition. Auditory responses, including M50 and M100 components, to neutral and emotional prosody (happy, sad, angry, and fearful) were recorded using magnetoencephalography. We then compared the groups in terms of the emotion-specific response index scores (normalized by the response to neutral sound) followed by correlation analysis with EI performance. Our results revealed that AH influence early emotional responses at the low level of auditory processing. Dysfunction in the processing of less emotionally salient stimuli (sadness) may be a trait-feature of schizophrenia. Nevertheless, a predilection toward negative emotions with high arousal in persistent AH may act as a state-feature incurring the impairment of social cognition. The second part of the thesis study aims to investigate the effects of AH on resting-state brain activity based on source space in various frequency bands using magnetoencephalography (MEG). We hypothesized that abnormal power modulations in schizophrenia may be found and correlated with clinical symptoms. Our findings demonstrated that powers of oscillatory activity in theta and alpha bands were varied with the severity of auditory hallucinations in SPs. Aberrant resting activities in SPs were found in multisensory cortical regions (i.e. somatosensory, auditory, and visual) as compared with CP, implicating that sensory processing impairments may result in impairments in the integration of low-level neural signals into complex cortical representations. Beta hyperactivity in limbic system is supported the idea that an overactive dopaminergic system causes schizophrenia. These findings provide insight into the neural mechanisms underlying distinct phenotypes of SPs (with or without AH).