Breathing Inhibited When Seizures Spread to the Amygdala and upon Amygdala Stimulation
Breathing Inhibited When Seizures Spread to the Amygdala and upon Amygdala Stimulation
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DOI：
10.1523/jneurosci.0888-15.2015
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发表时间：
2015-07-15
影响因子：
5.3
通讯作者：
Richerson, George B.
中科院分区：
文献类型：
--
作者：
Dlouhy, Brian J.;Gehlbach, Brian K.;Richerson, George B.
癫痫猝死（SUDEP）越来越被认为是一个常见且具有破坏性的问题。由于呼吸受损被认为在这些死亡中发挥着关键作用，因此我们试图确定人类癫痫发作引起的通气不足的前脑部位。我们利用一次难得的临床机会对一名患有难治性癫痫的研究参与者进行了研究，该参与者的双侧额颞叶电极覆盖范围广泛，同时在癫痫发作期间监测呼吸，并通过颅内电极记录并通过高分辨率脑成像绘制地图。我们发现，当癫痫发作扩散到杏仁核时，会发生中枢性呼吸暂停和 O-2 饱和度降低。在同一患者中，杏仁核的局部电刺激再现了呼吸暂停和 O-2 饱和度降低。在另外两名受试者中观察到杏仁核刺激的类似效果，其中一名没有癫痫症。尽管参与者保持清醒和警惕，但他们完全没有意识到刺激引起的呼吸暂停，也没有表现出呼吸困难。相反，类似持续时间的自愿屏气会导致严重的呼吸困难。这些发现表明人类杏仁核和延髓呼吸网络之间存在功能联系。此外，他们认为癫痫发作扩散到杏仁核可能会导致患者不知道的自主呼吸丧失，因此有可能导致 SUDEP。
Sudden unexpected death in epilepsy (SUDEP) is increasingly recognized as a common and devastating problem. Because impaired breathing is thought to play a critical role in these deaths, we sought to identify forebrain sites underlying seizure-evoked hypoventilation in humans. We took advantage of an extraordinary clinical opportunity to study a research participant with medically intractable epilepsy who had extensive bilateral frontotemporal electrode coverage while breathing was monitored during seizures recorded by intracranial electrodes and mapped by high-resolution brain imaging. We found that central apnea and O-2 desaturation occurred when seizures spread to the amygdala. In the same patient, localized electrical stimulation of the amygdala reproduced the apnea and O-2 desaturation. Similar effects of amygdala stimulation were observed in two additional subjects, including one without a seizure disorder. The participants were completely unaware of the apnea evoked by stimulation and expressed no dyspnea, despite being awake and vigilant. In contrast, voluntary breath holding of similar duration caused severe dyspnea. These findings suggest a functional connection between the amygdala and medullary respiratory network in humans. Moreover, they suggest that seizure spread to the amygdala may cause loss of spontaneous breathing of which patients are unaware, and thus has potential to contribute to SUDEP.