Henseler I, Falkai P, Gruber O
Department of Psychiatry and Psychotherapy, Georg August University, Göttingen, Germany.
Eur J Neurosci. 2009 Aug;30(4):693-702. doi: 10.1111/j.1460-9568.2009.06850.x. Epub 2009 Aug 3.
Working memory impairment is one of the cardinal cognitive disturbances in schizophrenia and considerable evidence suggests that it can be traced to functional alterations in the brain. The exact allocation of specific deficits to regional specific dysfunctions, however, remains elusive. The aim of this study was to examine the functional integrity of three distinguishable brain systems underlying maintenance-related subprocesses of working memory (articulatory rehearsal, non-articulatory maintenance of phonological information, maintenance of visuospatial information) in patients with schizophrenia. Using an experimental paradigm, which had been designed to selectively activate these different brain systems, we assessed the brain activation of patients and controls with functional magnetic resonance imaging. Compared with controls, patients showed reduced activation of the fronto-opercular, intraparietal and anterior cingulate cortex during the non-articulatory maintenance of phonological information, as well as attenuated deactivation of the hippocampus. Additionally, we found prefrontal activation to depend critically on the patients' current symptom status. During visuospatial maintenance, patients showed impaired activation of the superior parietal, temporal and occipital cortex, combined with enhanced activation of the frontal eye field and the inferior parietal cortex. No abnormal activations were observed during the articulatory rehearsal task. All activation differences were independent of group differences in task performance. Our fine-grained analysis of dysfunctions in particular aspects of working memory circuitry provides evidence for a differential impairment of the brain systems supporting working memory subcomponents in schizophrenia and extends knowledge of the relationship between cognitive deficits, brain activation abnormalities and symptoms in schizophrenia.
工作记忆损害是精神分裂症主要的认知障碍之一，大量证据表明其可追溯至大脑的功能改变。然而，特定缺陷与区域特定功能障碍的确切对应关系仍不明确。本研究旨在检查精神分裂症患者工作记忆维持相关子过程（言语复述、语音信息的非言语维持、视觉空间信息的维持）所涉及的三个可区分脑系统的功能完整性。我们使用一种专门设计用于选择性激活这些不同脑系统的实验范式，通过功能磁共振成像评估患者和对照组的脑激活情况。与对照组相比，患者在语音信息的非言语维持过程中，额眶部、顶内沟和前扣带回皮质的激活减少，海马的失活减弱。此外，我们发现前额叶激活严重依赖于患者当前的症状状态。在视觉空间维持过程中，患者顶叶上部、颞叶和枕叶皮质的激活受损，同时额叶眼区和顶叶下部皮质的激活增强。在言语复述任务中未观察到异常激活。所有激活差异均独立于任务表现的组间差异。我们对工作记忆回路特定方面功能障碍的精细分析为精神分裂症中支持工作记忆子成分的脑系统存在差异损害提供了证据，并扩展了对精神分裂症认知缺陷、脑激活异常和症状之间关系的认识。
