Karlsgodt Katherine H, Sanz Jacqueline, van Erp Theo G M, Bearden Carrie E, Nuechterlein Keith H, Cannon Tyrone D
Department of Psychology, UCLA, 1285 Franz Hall, Box 951563, Los Angeles, CA 90095-1563, USA.
Schizophr Res. 2009 Mar;108(1-3):143-50. doi: 10.1016/j.schres.2008.12.025. Epub 2009 Feb 3.
Previous neuroimaging studies of working memory (WM) in schizophrenia have generated conflicting findings of hypo- and hyper-frontality, discrepancies potentially driven by differences in task difficulty and/or performance. This study proposes and tests a new model of the performance-activation relationship in schizophrenia by combining changes by load with overall individual differences in performance. Fourteen patients with recent-onset schizophrenia and eighteen controls underwent functional magnetic resonance imaging while performing a parametric verbal WM task. Group level differences followed a linear "cross-over" pattern, such that in controls, activation in the dorsolateral prefrontal cortex (DLPFC) increased as performance decreased, while patients showed the opposite. Overall, low performing patients were hypoactive and high performing patients hyperactive relative to controls. However, patients and controls showed similar functions of activation by load in which activation rises with task difficulty but levels off or slightly decreases at higher loads. Moreover, across all loads and at their own WM capacity, higher performing patients showed greater DLPFC activation than controls, while lower performing patients activated least. This study establishes a novel framework for predicting the relationship between functional activation and WM performance by combining changes of activation by WM load occurring within each subject with the overall differences in activation associated with general WM performance. Essentially, increasing task difficulty correlates asymptotically with increasing activation in all subjects, but depending on their behavioral performance, patients show overall hyper- versus hypofrontality, a pattern potentially derived from individual differences in underlying cellular changes that may relate to levels of functional disability.
先前针对精神分裂症工作记忆（WM）的神经影像学研究得出了额叶功能减退和亢进的相互矛盾的结果，这些差异可能是由任务难度和/或表现的不同所驱动的。本研究通过结合负荷变化与整体表现的个体差异，提出并测试了一种精神分裂症表现-激活关系的新模型。14名近期发病的精神分裂症患者和18名对照在执行参数化言语工作记忆任务时接受了功能磁共振成像检查。组间水平差异呈现线性“交叉”模式，即在对照组中，背外侧前额叶皮质（DLPFC）的激活随着表现下降而增加，而患者则呈现相反情况。总体而言，相对于对照组，表现差的患者激活不足，表现好的患者激活过度。然而，患者和对照组在负荷激活功能方面表现相似，即激活随任务难度增加而上升，但在较高负荷时趋于平稳或略有下降。此外，在所有负荷水平及自身工作记忆能力范围内，表现较好的患者比对照组在DLPFC区域表现出更强的激活，而表现较差的患者激活最少。本研究通过将每个受试者内工作记忆负荷引起的激活变化与一般工作记忆表现相关的激活总体差异相结合，建立了一个预测功能激活与工作记忆表现之间关系的新框架。从本质上讲，任务难度增加与所有受试者激活增加呈渐近相关，但根据其行为表现，患者总体上表现为额叶功能亢进与减退，这种模式可能源于潜在细胞变化的个体差异，而这可能与功能残疾水平有关。
