Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
McLean Hospital, Belmont, MA, USA.
Psychopharmacology (Berl). 2022 Aug;239(8):2573-2584. doi: 10.1007/s00213-022-06149-x. Epub 2022 Apr 26.
Modafinil has been proposed as a potentially effective clinical treatment for neuropsychiatric disorders characterized by cognitive control deficits. However, the precise effects of modafinil, particularly on brain network functions, are not completely understood.
To address this gap, we examined the effects of modafinil on resting-state brain activity in 30 healthy adults using microstate analysis. Electroencephalographic (EEG) microstates are discrete voltage topographies generated from resting-state network activity.
Using a placebo-controlled, within-subjects design, we examined changes to microstate parameters following placebo (0 mg), low (100 mg), and high (200 mg) modafinil doses. We also examined the functional significance of these microstates via associations between microstate parameters and event-related potential indexes of conflict monitoring and automatic error processing (N2 and error-related negativity) and behavioral responses (accuracy and RT) from a subsequent flanker interference task.
Five microstates emerged following each treatment condition, including four canonical microstates (A-D). Modafinil increased microstate C proportion and occurrence regardless of dose, relative to placebo. Modafinil also decreased microstate A proportion and microstate B proportion and occurrence relative to placebo. These modafinil-related changes in microstate parameters were not associated with similar changes in flanker ERPs or behavior. Finally, modafinil made transitions between microstates A and B less likely and transitions from A and B to C more likely.
Previous fMRI work has correlated microstates A and B with auditory and visual networks and microstate C with a salience network. Thus, our results suggest modafinil may deactivate large-scale sensory networks in favor of a higher order functional network during resting-state in healthy adults.
莫达非尼已被提议作为一种潜在有效的临床治疗方法，用于治疗以认知控制缺陷为特征的神经精神疾病。然而，莫达非尼的确切作用，特别是对大脑网络功能的影响，还不完全清楚。
为了解决这一差距，我们使用微状态分析研究了 30 名健康成年人在莫达非尼作用下的静息态大脑活动。脑电图（EEG）微状态是从静息态网络活动中产生的离散电压拓扑。
使用安慰剂对照、个体内设计，我们研究了安慰剂（0mg）、低（100mg）和高（200mg）莫达非尼剂量后微状态参数的变化。我们还通过微状态参数与冲突监测和自动错误处理（N2 和错误相关负波）的事件相关电位指标以及随后的侧抑制干扰任务中的行为反应（准确性和 RT）之间的关联，研究了这些微状态的功能意义。
在每种治疗条件下，都出现了五个微状态，包括四个典型的微状态（A-D）。与安慰剂相比，莫达非尼增加了微状态 C 的比例和出现率，而与剂量无关。莫达非尼还降低了微状态 A 的比例和微状态 B 的比例和出现率，与安慰剂相比。微状态参数的这些莫达非尼相关变化与侧抑制 ERPs 或行为的类似变化无关。最后，莫达非尼使 A 和 B 之间的状态转换的可能性降低，使 A 和 B 到 C 的转换的可能性增加。
以前的 fMRI 工作已经将微状态 A 和 B 与听觉和视觉网络相关联，而微状态 C 与突显网络相关联。因此，我们的结果表明，莫达非尼可能会使大型感觉网络失活，有利于健康成年人在静息状态下的高级功能网络。
