Working Memory Encoding and Maintenance Deficits in Schizophrenia: Neural Evidence for Activation and Deactivation Abnormalities
Working Memory Encoding and Maintenance Deficits in Schizophrenia: Neural Evidence for Activation and Deactivation Abnormalities
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DOI：
10.1093/schbul/sbr107
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发表时间：
2013-01-01
影响因子：
6.6
通讯作者：
Barch, Deanna M.
中科院分区：
文献类型：
--
作者：
Anticevic, Alan;Repovs, Grega;Barch, Deanna M.
大量证据表明工作记忆（WM）是精神分裂症（SCZ）的核心缺陷，据称是由于背外侧前额叶皮层功能的主要缺陷所致。最近的研究结果表明，SCZ 还与认知参与过程中某些区域（即默认模式系统）的抑制异常有关，这可能进一步导致 WM 病理学。然而，还没有研究系统地检查 SCZ 中 WM 编码和维持阶段的激活和抑制异常。 28 名患者和 24 名人口统计匹配的健康受试者在 3T 下接受功能性磁共振成像，同时执行延迟样本匹配 WM 任务。各组进行精确匹配，以排除性能影响。各个受试者的编码负载是相同的，以便于跨 WM 阶段进行比较。我们使用假设的模型方法在全脑水平和荟萃分析定义的 WM 区域内检查了激活差异。尽管表现相匹配，但我们发现 SCZ 受试者在编码和维护期间招募较少的区域。此外，我们确定了 2 个与默认系统密切匹配的区域，SCZ 受试者未能在 WM 阶段停用这些区域。最后，前额叶区域的激活可以预测健康受试者的失活程度，但不能预测 SCZ 受试者的失活程度。目前的结果在 SCZ 的 WM 阶段复制并扩展了前额叶募集异常。结果还表明，整个 WM 阶段的失活异常可能是由于前额叶募集效率低下所致。这种区域去激活对于抑制 WM 迹线形成期间的干扰源可能至关重要。因此，失活缺陷可能构成损伤的另一个来源，需要进一步表征以全面了解 SCZ 的 WM 病理学。
Substantial evidence implicates working memory (WM) as a core deficit in schizophrenia (SCZ), purportedly due to primary deficits in dorsolateral prefrontal cortex functioning. Recent findings suggest that SCZ is also associated with abnormalities in suppression of certain regions during cognitive engagement-namely the default mode system-that may further contribute to WM pathology. However, no study has systematically examined activation and suppression abnormalities across both encoding and maintenance phases of WM in SCZ. Twenty-eight patients and 24 demographically matched healthy subjects underwent functional magnetic resonance imaging at 3T while performing a delayed match-to-sample WM task. Groups were accuracy matched to rule out performance effects. Encoding load was identical across subjects to facilitate comparisons across WM phases. We examined activation differences using an assumed model approach at the whole-brain level and within meta-analytically defined WM areas. Despite matched performance, we found regions showing less recruitment during encoding and maintenance for SCZ subjects. Furthermore, we identified 2 areas closely matching the default system, which SCZ subjects failed to deactivate across WM phases. Lastly, activation in prefrontal regions predicted the degree of deactivation for healthy but not SCZ subjects. Current results replicate and extend prefrontal recruitment abnormalities across WM phases in SCZ. Results also indicate deactivation abnormalities across WM phases, possibly due to inefficient prefrontal recruitment. Such regional deactivation may be critical for suppressing sources of interference during WM trace formation. Thus, deactivation deficits may constitute an additional source of impairments, which needs to be further characterized for a complete understanding of WM pathology in SCZ.