Yam Mor, Glatt Sigal, Nosatzki Shai, Mirelman Anat, Hausdorff Jeffrey M, Goldstein Lilach, Giladi Nir, Fahoum Firas, Maidan Inbal
Laboratory of Early Markers of Neurodegeneration, Centre for the Study of Movement, Cognition, and Mobility, Tel Aviv Sourasky Medical Centre, Neurological Institute, Tel Aviv, Israel.
Sagol School of Neuroscience, Tel Aviv University, Tel Aviv, Israel.
Front Neurol. 2022 Feb 7;13:793212. doi: 10.3389/fneur.2022.793212. eCollection 2022.
Juvenile myoclonic epilepsy (JME) is one of the most common epileptic syndromes; it is estimated to affect 1 in 1,000 people worldwide. Most people with JME respond well to medication, but up to 30% of them are drug-resistant. To date, there are no biomarkers for drug resistance in JME, and the poor response to medications is identified in retrospect. People with JME have frontal dysfunction manifested as impaired attention and difficulties in inhibiting habitual responses and these dysfunctions are more pronounced in drug-resistant individuals. Frontal networks play an important role in walking and therefore, gait can be used to overload the neural system and expose subtle changes between people with drug-responsive and drug-resistant JME. Electroencephalogram (EEG) is a promising tool to explore neural changes during real-time functions that combine a cognitive task while walking (dual tasking, DT). This exploratory study aimed to examine the alteration in electrical brain activity during DT in people with drug-responsive and drug-resistant JME. A total of 32 subjects (14 males and 18 females) participated: 11 drug-responsive (ages: 31.50 ± 1.50) and 8 drug-resistant (27.27 ± 2.30) people with JME, and 13 healthy controls (29.46 ± 0.69). The participants underwent EEG examination during the performance of the visual Go/NoGo (vGNG) task while sitting and while walking on a treadmill. We measured latencies and amplitudes of N2 and P3 event-related potentials, and the cognitive performance was assessed by accuracy rate and response time of Go/NoGo events. The results demonstrated that healthy controls had earlier N2 and P3 latencies than both JME groups (N2: = 0.034 and P3: = 0.011), however, a limited ability to adjust the N2 amplitude during walking was noticeable in the drug-resistant compared to drug-responsive. The two JME groups had lower success rates (drug-responsive < 0.001, drug-resistant = 0.004) than healthy controls, but the drug-resistant showed longer reaction times compared to both healthy controls ( = 0.033) and drug-responsive ( = 0.013). This study provides the first evidence that people with drug-resistant JME have changes in brain activity during highly demanding tasks that combine cognitive and motor functions compared to people with drug-responsive JME. Further research is needed to determine whether these alterations can be used as biomarkers to drug response in JME.
青少年肌阵挛癫痫(JME)是最常见的癫痫综合征之一;据估计,全球每1000人中就有1人受其影响。大多数JME患者对药物反应良好,但其中高达30%的人耐药。迄今为止,JME中尚无耐药性的生物标志物,对药物反应不佳是在事后确定的。JME患者存在额叶功能障碍,表现为注意力受损以及抑制习惯性反应困难,且这些功能障碍在耐药个体中更为明显。额叶网络在行走中起重要作用,因此,步态可用于使神经系统负荷过载,并揭示药物反应性和耐药性JME患者之间的细微变化。脑电图(EEG)是一种很有前景的工具,可用于探索在结合行走时的认知任务(双重任务,DT)的实时功能期间的神经变化。这项探索性研究旨在检查药物反应性和耐药性JME患者在DT期间脑电活动的变化。共有32名受试者(14名男性和18名女性)参与:11名药物反应性JME患者(年龄:31.50±1.50)、8名耐药性JME患者(27.27±2.30)以及13名健康对照者(29.46±0.69)。参与者在坐在椅子上以及在跑步机上行走时执行视觉Go/NoGo(vGNG)任务期间接受EEG检查。我们测量了N2和P3事件相关电位的潜伏期和波幅,并通过Go/NoGo事件的准确率和反应时间评估认知表现。结果表明,健康对照者的N2和P3潜伏期比两个JME组都早(N2: = 0.034,P3: = 0.011),然而,与药物反应性患者相比,耐药性患者在行走期间调节N2波幅的能力有限。两个JME组的成功率均低于健康对照者(药物反应性组 < 0.001,耐药性组 = 0.004),但与健康对照者( = 0.033)和药物反应性患者( = 0.013)相比,耐药性患者的反应时间更长。这项研究提供了首个证据,表明与药物反应性JME患者相比,耐药性JME患者在结合认知和运动功能的高要求任务期间脑活动存在变化。需要进一步研究以确定这些变化是否可作为JME中药物反应的生物标志物。