Acute ketamine administration alters the brain responses to executive demands in a verbal working memory task: an FMRI study.
Acute ketamine administration alters the brain responses to executive demands in a verbal working memory task: an FMRI study.
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DOI：
10.1038/sj.npp.1300438
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发表时间：
2004-06
影响因子：
7.6
通讯作者：
Fletcher, PC
中科院分区：
文献类型：
--
作者：
Honey, RAE;Honey, GD;O'Loughlin, C;Sharar, SR;Kumaran, D;Bullmore, ET;Menon, DK;Donovan, T;Lupson, VC;Bisbrown-Chippendale, R;Fletcher, PC
我们使用功能磁共振成像来确定氯胺酮对与工作记忆任务相关的激活的大脑系统的影响。健康志愿者接受安慰剂、氯胺酮50 ng/ml血药浓度和100 ng/ml氯胺酮的静脉输注。他们在执行一项言语工作记忆任务时被扫描，在这项任务中，我们改变了执行要求(操作过程与维持过程)和助记负荷(3个与5个呈现字母)。我们之前已经证明，氯胺酮在操作任务中会产生特定的行为障碍。在目前的研究中，我们修改了任务，以匹配药物和安慰剂条件下的表现，并使用了与事件相关的功能磁共振设计，使我们能够从分析中删除不成功的试验。我们的结果表明，氯胺酮对由额叶皮质、顶叶皮质和壳核组成的大脑系统中的工作记忆具有任务特异性的影响。当受试者被要求将呈现的字母按字母顺序排列，而不是保持呈现的顺序时，氯胺酮在这个系统中与显著更大的活动有关，即使在这些表现匹配的条件下也是如此。氯胺酮的作用不随负荷增加而增加。这表明，我们的发现不能用氯胺酮在任务难度增加时的非特异性影响来解释。相反，我们的发现提供了证据，表明低剂量、亚解离剂量的氯胺酮对操纵任务所涉及的控制过程具有显著影响。此外，我们已经证明，即使公开的行为测量没有显示损害的证据，氯胺酮的影响也可以通过功能磁共振来阐明。
We have used functional MRI to determine the effects of ketamine on brain systems activated in association with a working memory task. Healthy volunteers received intravenous infusions of placebo, ketamine at 50 ng/ml plasma concentration, and ketamine at 100 ng/ml. They were scanned while carrying out a verbal working memory task in which we varied the executive requirements (manipulation vs maintenance processes) and the mnemonic load (three vs five presented letters). We previously showed that ketamine produces a specific behavioral impairment in the manipulation task. In the current study, we modified tasks in order to match performance across drug and placebo conditions, and used an event-related fMRI design, allowing us to remove unsuccessful trials from the analysis. Our results suggest a task-specific effect of ketamine on working memory in a brain system comprising frontal cortex, parietal cortex, and putamen. When subjects are required to manipulate presented letters into alphabetical order, as opposed to maintaining them in the order in which they were presented, ketamine is associated with significantly greater activity in this system, even under these performance-matched conditions. No significant effect of ketamine was seen in association with increasing load. This suggests that our findings are not explicable in terms of a nonspecific effect of ketamine when task difficulty is increased. Rather, our findings provide evidence that the predominant effects of low, subdissociative doses of ketamine are upon the control processes engaged by the manipulation task. Furthermore, we have shown that ketamine’s effects may be elucidated by fMRI even when overt behavioral measures show no evidence of impairment.
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影响因子：
3.6
作者：
Hirsch, SR;Das, I;deBelleroche, J
通讯作者：
deBelleroche, J
影响因子：
17.7
作者：
Conklin, HM;Curtis, CE;Iacono, WG
通讯作者：
Iacono, WG
影响因子：
2.5
作者：
D'Esposito, M;Postle, BR;Lease, J
通讯作者：
Lease, J
影响因子：
17.7
作者：
Curtis, VA;Bullmore, ET;McGuire, PK
通讯作者：
McGuire, PK
影响因子：
5.7
作者：
Genovese, CR;Lazar, NA;Nichols, T
通讯作者：
Nichols, T