Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia
Relation of prefrontal cortex dysfunction to working memory and symptoms in schizophrenia
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DOI：
10.1176/appi.ajp.158.7.1105
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发表时间：
2001-07-01
影响因子：
17.7
通讯作者：
Cohen, JD
中科院分区：
文献类型：
--
作者：
Perlstein, WM;Carter, CS;Cohen, JD
目的：背外侧前额叶皮层与工作记忆和精神分裂症的病理生理学有关。背外侧前额叶皮层活动，工作记忆功能障碍，精神分裂症的症状之间的关系尚未确定，部分原因是由于患者和任务的复杂性普遍认知障碍。使用参数化操纵工作记忆负荷的任务，作者测试了三个假设：1）精神分裂症患者只有在行为表现将他们与健康对照受试者区分开时，其前额活动才不同，2）背外侧前额皮质功能障碍与较差的任务表现相关，（3）背外侧前额叶皮质功能障碍与认知紊乱有关，而与阴性或阳性症状无关。17名常规药物治疗的精神分裂症患者和16名健康对照受试者进行功能磁共振成像，同时进行多水平的“n-back”顺序字母工作记忆任务。精神分裂症患者右背外侧前额叶皮层的生理激活功能存在缺陷（布罗德曼区46/9）在正常的任务依赖性活动的背景下，在其他地区，但只有在条件下，区分他们从比较科目的任务性能。背外侧前额叶皮质功能障碍越严重的患者表现越差。背外侧前额叶皮层功能障碍选择性与disorganization symptoms.Conclusions：这些结果是一致的假设，即精神分裂症患者的工作记忆功能障碍是由背外侧前额叶皮层的干扰，这种干扰是选择性与认知紊乱。此外，行为表现的模式表明，背外侧前额叶皮层功能障碍并不反映在维持刺激表征本身的赤字，但指出赤字的工作记忆中的更多的联想组件。
Objective: The dorsolateral prefrontal cortex has been implicated in both working memory and the pathophysiology of schizophrenia. A relationship among dorsolateral prefrontal cortex activity, working memory dysfunction, and symptoms in schizophrenia has not been firmly established, partly because of generalized cognitive impairments in patients and task complexity. Using tasks that parametrically manipulated working memory load, the authors tested three hypotheses: 1) patients with schizophrenia differ in prefrontal activity only when behavioral performance differentiates them from healthy comparison subjects, 2) dorsolateral prefrontal cortex dysfunction is associated with poorer task performance, and 3) dorsolateral prefrontal cortex dysfunction is associated with cognitive disorganization but not negative or positive symptoms.Method: Seventeen conventionally medicated patients with schizophrenia and 16 healthy comparison subjects underwent functional magnetic resonance imaging while performing multiple levels of the "n-back" sequential-letter working memory task.Results: Patients with schizophrenia showed a deficit in physiological activation of the right dorsolateral prefrontal cortex (Brodmann's area 46/9) in the context of normal task-dependent activity in other regions, but only under the condition that distinguished them from comparison subjects on task performance. Patients with greater dorsolateral prefrontal cortex dysfunction performed more poorly. Dorsolateral prefrontal cortex dysfunction was selectively associated with disorganization symptoms.Conclusions: These results are consistent with the hypotheses that working memory dysfunction in patients with schizophrenia is caused by a disturbance of the dorsolateral prefrontal cortex and that this disturbance is selectively associated with cognitive disorganization. Further, the pattern of behavioral performance suggests that dorsolateral prefrontal cortex dysfunction does not reflect a deficit in the maintenance of stimulus representations per se but points to deficits in more associative components of working memory.