Anterior Cingulate Desynchronization and Functional Connectivity with the Amygdala During a Working Memory Task Predict Rapid Antidepressant Response to Ketamine
Anterior Cingulate Desynchronization and Functional Connectivity with the Amygdala During a Working Memory Task Predict Rapid Antidepressant Response to Ketamine
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DOI：
10.1038/npp.2010.24
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发表时间：
2010-06-01
影响因子：
7.6
通讯作者：
Zarate, Carlos A., Jr.
中科院分区：
文献类型：
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作者：
Salvadore, Giacomo;Cornwell, Brian R.;Zarate, Carlos A., Jr.
膝前扣带皮层（pgACC）活动过度可区分治疗应答者和各种抗抑郁药物干预（包括氯胺酮，一种N-甲基-D-天冬氨酸受体拮抗剂）的非应答者。pgACC过度活跃的证据在非情绪工作记忆任务中的患者与抑郁症（MDD）强调了这一地区的重要性，处理情绪突出和认知刺激。然而，目前还不清楚pgACC活性是否也可以作为工作记忆任务中抗抑郁反应的潜在生物标志物，这与先前对情绪唤起任务的研究一致。本研究验证了以下假设：在N-back任务期间，广泛使用的工作记忆范式、低预处理pgACC活性以及pgACC和杏仁核之间的一致性将与氯胺酮后的临床改善相关。在接受单次氯胺酮输注前1至3天，从15名无药物MDD患者的工作记忆表现中获得脑磁图（MEG）记录。功能激活模式进行了分析，使用先进的MEG源分析。进行源相干性分析以量化pgACC和杏仁核之间的长程功能连接的程度。在氯胺酮给药4小时内，对增加的工作记忆负荷表现出最少pgACC参与的患者表现出最大的症状改善（r = 0.82，p = 0.0002，错误发现率（FDR））
Pregenual anterior cingulate cortex (pgACC) hyperactivity differentiates treatment responders from non-responders to various pharmacological antidepressant interventions, including ketamine, an N-methyl-D-aspartate receptor antagonist. Evidence of pgACC hyperactivition during non-emotional working memory tasks in patients with major depressive disorder (MDD) highlights the importance of this region for processing both emotionally salient and cognitive stimuli. However, it is unclear whether pgACC activity might serve as a potential biomarker of antidepressant response during working memory tasks as well, in line with previous research with emotionally arousing tasks. This study tested the hypothesis that during the N-back task, a widely used working memory paradigm, low pretreatment pgACC activity, as well as coherence between the pgACC and the amygdala, would be correlated with the clinical improvement after ketamine. Magnetoencephalography (MEG) recordings were obtained from 15 drug-free patients with MDD during working memory performance 1 to 3 days before receiving a single ketamine infusion. Functional activation patterns were analyzed using advanced MEG source analysis. Source coherence analyses were conducted to quantify the degree of long-range functional connectivity between the pgACC and the amygdala. Patients who showed the least engagement of the pgACC in response to increased working memory load showed the greatest symptomatic improvement within 4 h of ketamine administration (r = 0.82, p = 0.0002, false discovery rate (FDR)