The relation between cortisol and functional connectivity in people with and without stress-sensitive epilepsy
The relation between cortisol and functional connectivity in people with and without stress-sensitive epilepsy
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DOI：
10.1111/epi.13947
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发表时间：
2018-01-01
期刊：
影响因子：
5.6
通讯作者：
Zijlmans, Maeike
中科院分区：
文献类型：
--
作者：
den Heijer, Jonas M.;Otte, Willem M.;Zijlmans, Maeike
目的：应激是最常见的应激诱发因素。我们最近发现了癫痫发作的应激敏感性的生物学基础：应激敏感性癫痫患者的皮质醇水平与脑电图（EEG）上的局灶性发作间期癫痫样放电（IED）相关。在这里，我们的目标是确定皮质醇对癫痫大脑的影响是全局性的还是局部性的，以及皮质醇是否影响所有的大脑还是只影响那些对压力敏感的人。由于癫痫与功能性脑连接的变化有关，我们研究了皮质醇与压力敏感和非压力敏感癫痫患者的全局和局部（以节点为中心）功能性连接措施变化之间的关系。在清醒后的前5小时内，每15分钟收集一次唾液用于皮质醇测量。每15分钟记录一次，评估θ-波段功能连接。我们计算了所有通道之间的平均相位滞后指数（PLI）作为全局功能连接的度量。我们使用网络强度，即每个通道的平均PLI，作为焦点功能连接性测量。我们使用线性混合模型将皮质醇、全局和局部功能连接（强度）与IED频率相关。结果：皮质醇与应激敏感性癫痫发作患者的整体功能连接呈负相关（估计值-0.0020; P < .01），而与无应激敏感性癫痫发作患者的整体功能连接不相关（估计值-0.0003; P = .46）。这种关系的发生与通道上是否存在IED无关（没有IED的通道和压力敏感性：估计值-0.0019; P <0.01，非压力敏感性-0.0003; P = 0.41）。无论癫痫发作的压力敏感性或通道类型如何，整体和局灶功能连接性与IED频率呈负相关。意义：患有压力敏感性癫痫的人对皮质醇的全脑神经元反应与非压力敏感性癫痫的人不同。这为了解压力敏感性癫痫的癫痫发作起源提供了基础，这可能需要不同的治疗方法。
Objective: The most common reported seizure-precipitant is stress. We recently showed a biologic basis for stress sensitivity of seizures: cortisol levels in people with stress-sensitive epilepsy correlated with focal interictal epileptiform discharges (IEDs) on electroencephalography (EEG). Here we aimed to determine whether the effect of cortisol on the epileptic brain is global or focal, and whether cortisol affects all brains or just those of stress-sensitive people. Because epilepsy is associated with changes in functional brain connectivity, we studied the relationship between cortisol and changes in global and focal (node-centered) functional connectivity measures for individuals with stress-sensitive and non-stress-sensitive epilepsy.Methods: Seventeen people with epilepsy underwent long-term (>24 h) EEG recording. During the first 5h after waking, saliva was collected every 15min for cortisol measurements. Theta-band functional connectivity was assessed for every 15min of the recording. We calculated the average phase-lag index (PLI) between all channels as a measure of global functional connectivity. We used network Strength, the averaged PLI per channel, as focal functional connectivity measure. We correlated cortisol, global, and focal functional connectivity (Strength) with IED frequency using linear mixed models. Analyses were split for people with and without stress-sensitivity of seizures.Results: Cortisol was negatively correlated with global functional connectivity in people with stress-sensitive seizures (estimate -0.0020; P < .01), whereas not in those without stress-sensitivity (estimate -0.0003; P = .46). This relationship occurred irrespective of the presence of IEDs on a channel (channels without IEDs and stress-sensitivity: estimate -0.0019; P < .01, non-stress-sensitive -0.0003; P = .41). Global and focal functional connectivity were negatively correlated with IED frequency, irrespective of stress sensitivity of seizures or channel type.Significance: People with stress-sensitive epilepsy have a whole-brain neuronal response to cortisol that is different from that of people with non-stress-sensitive epilepsy. This offers a basis for understanding seizure genesis in stress-sensitive epilepsy, which might require a different treatment approach.