Eich Teal S, Nee Derek Evan, Insel Catherine, Malapani Chara, Smith Edward E
Department of Psychology (TSE, CI, EES), Columbia University, New York, New York.
Helen Wills Neuroscience Institute (DEN), University of California, Berkeley, California.
Biol Psychiatry. 2014 Jul 15;76(2):146-53. doi: 10.1016/j.biopsych.2013.09.032. Epub 2013 Oct 10.
One of the most common deficits in patients with schizophrenia (SZ) is in working memory (WM), which has wide-reaching impacts across cognition. However, previous approaches to studying WM in SZ have used tasks that require multiple cognitive-control processes, making it difficult to determine which specific cognitive and neural processes underlie the WM impairment.
We used functional magnetic resonance imaging to investigate component processes of WM in SZ. Eighteen healthy controls (HCs) and 18 patients with SZ performed an item-recognition task that permitted separate neural assessments of 1) WM maintenance, 2) inhibition, and 3) interference control in response to recognition probes.
Before inhibitory demands, posterior ventrolateral prefrontal cortex (VLPFC), an area involved in WM maintenance, was activated to a similar degree in both HCs and patients, indicating preserved maintenance operations in SZ. When cued to inhibit items from WM, HCs showed reduced activation in posterior VLPFC, commensurate with appropriately inhibiting items from WM. However, these inhibition-related reductions were absent in patients. When later probed with items that should have been inhibited, patients showed reduced behavioral performance and increased activation in mid-VLPFC, an area implicated in interference control. A mediation analysis indicated that impaired inhibition led to increased reliance on interference control and reduced behavioral performance.
In SZ, impaired control over memory, manifested through proactive inhibitory deficits, leads to increased reliance on reactive interference-control processes. The strain on interference-control processes results in reduced behavioral performance. Thus, inhibitory deficits in SZ may underlie widespread impairments in WM and cognition.
精神分裂症（SZ）患者最常见的缺陷之一是工作记忆（WM），它对认知有着广泛的影响。然而，以往研究SZ患者WM的方法使用的任务需要多种认知控制过程，这使得难以确定WM损害背后的具体认知和神经过程。
我们使用功能磁共振成像来研究SZ患者WM的组成过程。18名健康对照者（HCs）和18名SZ患者进行了一项项目识别任务，该任务允许对以下三个方面进行单独的神经评估：1）WM维持，2）抑制，以及3）对识别探针的干扰控制。
在有抑制需求之前，参与WM维持的后侧腹外侧前额叶皮层（VLPFC）在HCs和患者中的激活程度相似，表明SZ患者的维持操作保留。当被提示抑制WM中的项目时，HCs后侧VLPFC的激活减少，这与从WM中适当抑制项目相一致。然而，患者中不存在这些与抑制相关的激活减少。当后来用本应被抑制的项目进行探测时，患者的行为表现下降，且中VLPFC（一个与干扰控制有关的区域）的激活增加。中介分析表明，抑制受损导致对干扰控制的依赖增加和行为表现下降。
在SZ患者中，通过主动抑制缺陷表现出的对记忆的控制受损，导致对反应性干扰控制过程的依赖增加。干扰控制过程的压力导致行为表现下降。因此，SZ患者的抑制缺陷可能是WM和认知广泛受损的基础。
