Brown Gregory G, Thompson Wesley K
Psychology Service, VA San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
Curr Top Behav Neurosci. 2010;4:181-214. doi: 10.1007/7854_2010_54.
Functional brain imaging studies of patients with schizophrenia may be grouped into those that assume that the signs and symptoms of schizophrenia are due to disordered circuitry within a critical brain region and studies that assume that the signs and symptoms are due to disordered connections among brain regions. Studies have investigated the disordered functional brain anatomy of both the positive and negative symptoms of schizophrenia. Studies of spontaneous hallucinations find that although hallucinations are associated with abnormal brain activity in primary and secondary sensory areas, disordered brain activation associated with hallucinations is not limited to sensory systems. Disordered activation in non-sensory regions appear to contribute to the emotional strength and valence of hallucinations, to be a factor underlying an inability to distinguish ongoing mental processing from memories, and to reflect the brain's attempt to modulate the intensity of hallucinations and resolve conflicts with other processing demands. Brain activation studies support the view that auditory/verbal hallucinations are associated with an impaired ability of internal speech plans to modulate neural activation in sensory language areas. In early studies, negative symptoms of schizophrenia were hypothesized to be associated with impaired function in frontal brain areas. In support of this hypothesis meta-analytical studies have found that resting blood flow or metabolism in frontal cortex is reduced in schizophrenia, though the magnitude of the effect is only small to moderate. Brain activation studies of working memory (WM) functioning are typically associated with large effect sizes in the frontal cortex, whereas studies of functions other than WM generally reveal smaller effects. Findings from some functional connectivity studies have supported the hypothesis that schizophrenia patients experience impaired functional connections between frontal and temporal cortex, although the nature of the disordered connectivity is complex. More recent studies have used functional brain imaging to study neural compensation in schizophrenia, to serve as endophenotypes in genetic studies and to provide biomarkers in drug development studies. These emerging trends in functional brain imaging research are likely to help stimulate the development of a general neurobiological theory of the complex symptoms of schizophrenia.
对精神分裂症患者的功能性脑成像研究可分为两类，一类假设精神分裂症的体征和症状是由于关键脑区的神经回路紊乱所致，另一类研究则假设这些体征和症状是由于脑区之间的连接紊乱所致。研究已经调查了精神分裂症阳性和阴性症状的功能性脑解剖结构紊乱情况。对自发性幻觉的研究发现，尽管幻觉与初级和次级感觉区域的异常脑活动有关，但与幻觉相关的脑激活紊乱并不局限于感觉系统。非感觉区域的激活紊乱似乎有助于幻觉的情感强度和效价，是无法区分正在进行的心理加工和记忆的一个潜在因素，并反映了大脑调节幻觉强度以及解决与其他加工需求冲突的尝试。脑激活研究支持这样一种观点，即听觉/言语幻觉与内部言语计划调节感觉语言区域神经激活的能力受损有关。在早期研究中，精神分裂症的阴性症状被假设与额叶脑区功能受损有关。为支持这一假设，荟萃分析研究发现，精神分裂症患者额叶皮质的静息血流或代谢减少，尽管这种影响的程度仅为小到中度。对工作记忆（WM）功能的脑激活研究通常在额叶皮质中显示出较大的效应量，而对WM以外功能的研究一般显示出较小的效应。一些功能连接性研究的结果支持了这样的假设，即精神分裂症患者额叶和颞叶皮质之间的功能连接受损，尽管紊乱连接的性质很复杂。最近的研究利用功能性脑成像来研究精神分裂症中的神经代偿，作为基因研究中的内表型，并在药物开发研究中提供生物标志物。功能性脑成像研究中的这些新趋势可能有助于推动精神分裂症复杂症状的一般神经生物学理论的发展。
