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精神分裂症患者的执行功能:前额叶-丘脑环路及年龄效应
其他题名Executive functions in patients with schizophrenia: The study of the prefronto-thalamic circuit and the effect of age
耿富磊
学位类型博士
导师陈楚侨
2015-05
学位授予单位中国科学院研究生院
学位授予地点北京
学位专业心理学
摘要精神分裂症患者的执行功能存在缺损,研究证实其前额叶-丘脑环路的异常与执行功能的表现密切相关。然而,目前极少有研究从多模态影像学的角度考查前额叶-丘脑结构环路与执行功能的关系。年龄对精神分裂症患者的脑结构和执行功能有重要的影响,但较少有研究同时考查精神分裂症患者的执行功能、年龄及脑结构三者之间的关系。最近,有研究应用图论研究方法从全脑网络连接的角度解释个体认知功能的差异,目前尚未有研究报道精神分裂症患者的执行功能缺损与全脑白质纤维束网络拓扑属性关系。
本研究拟采用慢性精神分裂症患者作为大样本受测对象,从大脑灰质体积和白质纤维束多模态影像学的角度,探讨精神分裂症患者执行功能缺损及前额叶-丘脑环路在其中的作用,考查年龄对执行功能及前额叶-丘脑环路的影响,最后本研究探索性分析精神分裂症患者全脑白质纤维束网络与其执行功能的关系。
研究一对111 名慢性精神分裂症患者和94 名对照组被试应用言语流畅性、空间工作记忆任务、持续性注意任务、内外维度注意转换和剑桥赌博等任务进行执行功能评估。方差分析表明精神分裂症患者执行功能均存在一定程度的缺损,其中工作记忆和认知灵活性缺损较为严重;精神分裂症患者认知灵活性与阴性症状关系密切;一般线性模型结果表明,随年龄的增大,精神分裂症患者言语流畅性、持续性注意效率和剑桥赌博风险寻求下降趋势显著大于对照组。
研究二考查精神分裂症患者年龄、脑灰质体积和执行功能的关系。对研究一所有的被试进行T1 结构像扫描。基于全脑水平的分析表明精神分裂症患者前额叶各脑区(扣带回除外)、丘脑等皮层下脑结构灰质体积显著下降,证实了慢性精神分裂症患者前额叶-丘脑环路上脑区节点异常。基于感兴趣区的结果表明精神分裂症患者言语流畅性主要与额上回、额中回相关,空间工作记忆与额上回和扣带回相关,持续性注意和额上回、背外侧前额叶和丘脑相关,剑桥赌博风险寻求与丘脑相关。在脑灰质体积年龄效应上,本研究发现随年龄增长精神分裂症患者左侧大脑海马周边脑区、舌回及小脑蚓部灰质体积下降速度大于对照组。本研究还发现精神分裂症患者中年龄到额上回到空间工作记忆、年龄到额中回到言语流畅性、年龄到额中回到风险寻求、年龄到内侧前额叶到风险寻求中介效应显著,即精神分裂症执行功能随年龄的下降,部分由于灰质体积的下降引起。
研究三考查精神分裂症患者年龄、白质纤维束FA 值和执行功能的关系。对研究一的所有被试进行弥散张量磁共振成像扫描。本研究发现精神分裂症患者左侧大脑丘脑前辐射FA 值和胼胝体辐射线额部FA 值下降,证实精神分裂症患者前额叶-丘脑环路白质纤维束连接的异常。相关分析表明精神分裂症患者左侧大脑丘脑前辐射FA 值与剑桥赌博风险寻求正相关、胼胝体辐射线额部FA 值与剑桥赌博风险寻求正相关。本研究还发现在精神分裂症患者中年龄可以通过左侧大脑丘脑前辐射FA 值中介作用影响剑桥赌博风险寻求,年龄还可以通过胼胝体辐射线额部FA 值中介作用影响言语流畅性、持续性注意效率及剑桥赌博风险寻求。
研究四应用图论研究方法探索性分析精神分裂症患者全脑连接与执行功能的关系。对研究一的所有被试进行全脑白质纤维束网络建构,本研究发现精神分裂症患者在度、全局效率、局部效率上显著低于对照组,在最短路径长度上显著高于对照组。偏相关分析表明精神分裂症持续性注意效率与度、全局效率正相关,持续性注意效率与最短路径负相关,剑桥赌博风险寻求与度、全局效率、局部效率、集群系数正相关,剑桥赌博风险寻求与最短路径负相关。
总体看来,精神分裂症患者前额叶-丘脑环路脑灰质体积与脑白质纤维束连接均存在异常,此神经环路的异常与执行功能的缺损密切相关;精神分裂症患者执行功能的老龄化部分是由于其前额叶-丘脑环路老龄化所致;精神分裂症患者执行功能的抑制成分与全脑网络连接相关。
其他摘要Schizophrenia is associated with a wide range of neurocognitive dysfunction, including executive function. Empirical findings have demonstrated that executivefunction deficits are associated with abnormalities of the prefronto-thalamic circuit. However, few studies have examined the relationships between the prefronto-thalamic circuit and executive functions from a multi-modal neuroimaging perspective. Age is also associated with brain structural and functional deficits as well as executive dysfunctions in schizophrenia, but few studies have examined the relationships between executive functions, age and the corresponding changes in brain structure in this clinical group. Recently, some studies had examined individual differences in cognitive functions from the whole brain network perspective using graph theory, but no study has investigated the relationships between executive dysfunction and topological properties of the neuroanatomical network in schizophrenia.
Adopting a multi-modal neuroimaging perspective (mainly grey matter volume and topological properties of brain anatomical network), this examined the role of the prefronto-thalamic circuit in executive dysfunction in schizophrenia. We also examined the age effect on executive dysfunction and the prefronto-thalamic circuit in this clinical group. Finally, we explored the relationship between the topological properties of the neuroanatomical network and executive dysfunction in a large sample of patients with chronic schizophrenia.
In Study One, the verbal fluency test, the spatial working memory task, the sustained attention task, the intra/extra dimension shifting test and the Cambridge Gambling Task were administered to assess executive function in 111 patients with chronic schizophrenia and 94 healthy controls. Results showed that schizophrenia patients exhibited impairment in executive function, with working memory and cognitive shifting components showing the most severe impairment. Cognitive shifting was associated with negative symptoms. Linear regression analysis further demonstrated that the performances in verbal fluency, sustained attention efficacy and risk seeking in the Cambridge Gambling Task reduced inversely with the age of the participants. The effect was particularly large in patients with schizophrenia.
Study Two examined the relationship between age, grey matter volume, and executive function. T1 imaging was obtained for all the participants from Study One. Whole brain analysis revealed that grey matter volume reduction in various areas in the prefrontal cortex (except the cingulate gyrus), the thalamus and other subcortical regions in patients with schizophrenia, suggesting the presence of the abnormal hubs in the prefronto-thalamic circuit in patients with schizophrenia. Region of interest (ROI) analysis showed that verbal fluency was positive associated with grey matter volume of the superior frontal gyrus, and the middle frontal gyrus. Sustained attention was associated with grey matter volume of the superior frontal gyrus, the dorsal lateral prefrontal cortex, and the thalamus. The Cambridge Gambling Task risk seeking item was correlated with grey matter volume of the thalamus. Moreover, we also found reduction in grey matter volume in the left hippocampus, the lingual gyrus, and the vermis with increase in age. This trend was significantly larger in patients with schizophrenia than in healthy controls. We found that the grey matter volume of
the superior frontal gyrus had a mediation effect on the relationship between age and spatial working memory, while the grey matter volume of the middle frontal gyrus and the medial frontal gyrus had a mediation effect on the relationship between age and risk seeking. These results suggest that the effect of age on executive dysfunctions in patients with schizophrenia is partially caused by grey matter volume
reduction in the aforementioned brain regions.
Study Three examined the relationship between age, white matter fiber tracts FA value and executive function. All participants in study One underwent Diffusion Tensor Imaging. We found reduced FA value in the left anterior thalamic radiation and the forceps minor, which suggested abnormal white matter fiber tracts in the prefronto-thalamic circuitry. Positive correlations were found between the left anterior FA value mediated the relationship between age and scores on the risk seeking item of the Cambridge Gambling Task as well as the relationship between age
and verbal fluency, sustained attention, and scores on the risk seeking iem of the Cambridge Gambling Task in patients with schizophrenia compared with healthy controls.
Study Four explored the relationship between whole brain connection and executive functions in patients with schizophrenia using graph theory analysis. Whole brain white matter fiber tracts were constructed in all participants from Study One. We found that patients with schizophrenia showed reduced degrees, global efficiency, local efficiency, and increased shortest path compared with healthy controls. Partial correlation analysis showed positive correlations between sustained attention efficiency and degrees, and global efficiency in patients with schizophrenia. There was a negative correlation between sustained attention efficiency and shortest path. Moreover, positive correlations were found between the risk seeking item of the Cambridge Gambling Task and degrees, global efficiency, local efficiency, and cluster coefficient, whereas a negative correlation was found between the risk seeking item of the Cambridge Gambling Task and the shortest path in patients with schizophrenia compared with healthy controls.
Taken together, patients with schizophrenia exhibit abnormalities in both the prefronto-thalamic circuit grey matter and white matter fiber tracts. This abnormality is closely associated with executive dysfunction. The effect of age on executive function in patients with schizophrenia appears to be partially caused by ageing of the prefronto-thalamic circuit. Inhibition impairments in schizophrenia patients are associated with whole brain connection deficits.
学科领域认知神经科学
语种中文
文献类型学位论文
条目标识符http://ir.psych.ac.cn/handle/311026/19513
专题健康与遗传心理学研究室
作者单位中国科学院心理研究所
推荐引用方式
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耿富磊. 精神分裂症患者的执行功能:前额叶-丘脑环路及年龄效应[D]. 北京. 中国科学院研究生院,2015.
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