精神分裂症思考失序歷程之神經機制

Abstract

目的：思考失序為精神分裂症的主要病徵之一，與語意認知功能的缺損有關，然而目前對於此病徵以及相關認知功能的神經機制尚未有明確的了解。本研究欲藉由造影技術觀察語意處理缺損的歷程，探討精神分裂症患者思考失序病症之神經機制及相關的語言認知功能缺損。方法：本研究以功能性磁振造影(Functional magnetic resonance imaging, fMRI)檢驗精神分裂症患者思考失序病症的神經機制。實驗一探討二十五位精神分裂症患者之神經活動與病症的關係。實驗二進一步比較二十二位精神分裂症患者與二十二位健康對照組參與者的神經活動差異，並探究思考失序病症之嚴重程度、語言認知功能缺損與腦部神經活動的關係。結果：實驗一發現，精神分裂症患者在處理語意相關的字對時，左腦半球額下迴(left inferior frontal gyrus, LIFG, BA 45)與顳下迴(left inferior temporal gyrus, LITG, BA 20)的腦區活化較多，且思考思緒症狀嚴重程度與此二區與的神經活化強度成正相關。實驗二發現，相較於健康對照組，精神分裂症患者在處理語意相關的字對時，左腦半球額下迴與顳下迴的腦區活化較多，但是在皮質下的尾核(left caudate nucleus, LCN)活化較少。更重要的是，精神分裂症患者由左腦額下迴至顳下迴，及由尾核至額下迴的有效性聯結，相較於健康對照組都來得弱。但是由左腦梭狀迴(left fusiform gyrus, LFG, BA 37)至顳下迴的有效性聯結，卻較健康對照組來得強。此外，由尾核至額下迴的有效性聯結與思考失序症狀嚴重程度有接近顯著負相關的趨勢。最後，精神分裂症患者在左腦額下迴與顳下迴的神經活化強度，與思考失序症狀嚴重程度成正相關。在語言認知功能方面，左腦顳下迴的神經活化強度，與成人魏氏智力測驗語文量表(WAIS verbal scale) 中語文智商(VIQ)、類同(similarities)、算數(arithmetic)、記憶廣度(digit span)分數成負相關。結論：由本研究結果推論精神分裂症患者的語意處理歷程，與健康對照組參與者不同。精神分裂症患者左腦額下迴、顳下迴的神經活動較多，且皆與思考失序症狀的嚴重程度以及語言認知功能的缺損程度成正向關，顯示症狀越嚴重，或是語言認知功能越差的患者進行語意相關作業時，無法有效率地從排列紛亂的語意表徵網絡中提取、選擇正確的語意訊息，以致需要以更多的神經活動資源協助其完成語意處理。此外，本研究提供證據顯示，精神分裂症患者語意處理的神經迴路可能有所缺損。其左額下迴至顳下迴的有效性聯結強度較低，表示其由上而下(top-down)的語意表徵提取、選擇的效率不佳。而左側尾核至左額下迴的有效性聯結強度較低，表示其尾核對額下迴的監控、抑制作用效果不彰，因而可能產生思考失序的症狀。最後，左腦梭狀迴至顳下迴的有效性聯結較強，則表示由於上述兩條較高階的連結缺損，精神分裂症患者必須倚賴較初階的字形視覺訊息做為補償機制，得以完成語意作業的要求。

Purpose: Thought disorder is one of the core symptoms of schizophrenia that relates to cognitive deficits. However, the underlying neural mechanism is not well understood. The present study aimed at exploring the symptom dimension of disorganized thought in schizophrenia by investigating the spatial properties of neural correlates of thought disorder and related cognitive dysfunctions underlying semantic processing. Methods: Functional magnetic resonance imaging (fMRI) was used to investigate the underlying mechanism of disorganized thought for 25 patients with schizophrenia in Experiment 1, and for 22 patients with schizophrenia and 22 healthy controls in Experiment 2. The correlation between the symptom severity of disorganized thought and the neural activity in related brain regions was examined. Verbal measures were used to evaluate individual difference on neural correlates of thought disturbance in the patients. Results: In Experiment 1, greater activation was found in the left inferior frontal gyrus (LIFG, BA 45) and the left inferior temporal gyrus (LITG, BA 20) for the semantically related condition. Moreover, increasing disorganization scores were correlated with greater activation in these two regions for the semantically related condition. In Experiment 2, for the semantically related condition, as compared with the controls, the patients showed significant activation in LIFG and LITG, as well as reduced activation in left caudate nucleus (LCN). In addition, effective connectivity from Dynamic Causal Modeling (DCM) showed that the top-down modulatory effect from LIFG to LITG was stronger in controls while the bottom-up modulatory effect from left fusiform gyrus (LFG, BA37) to LITG was stronger in patients. Also, the modulatory effect from LCN to LIFG was weaker in patients than in controls. Furthermore, there was a trend of negative correlation between disorganized thought and connectivity strength from LCN to LIFG. Finally, there was a positive correlation between disorganized thought and significant activation in LIFG/LITG. There was a negative correlation between verbal sub-items in the WAIS verbal scale and significant activation in LITG in patients. Conclusion: In patients with schizophrenia, the severity of disorganized thought and the verbal-related cognitive deficits may be related to greater activation in the left frontal and temporal region, implying the increased demands on retrieval or selection through aberrant semantic networks. In addition, the weaker top-down modulatory effect from LIFG to LITG, the weaker inhibitory effect from LCN to LIFG, and a trend of negative correlation between disorganized thought and connectivity strength from LCN to LIFG imply a disrupted cortical-subcortical language loop for semantic processing in patients. In contrast, the stronger bottom-up modulatory effect from LFG to LITG in patients implies that they have to rely more on the direct mapping from orthography to semantics in order to counteract the deficits on the top-down connection.