Frontotemporal degeneration (FTD) is characterized by reduced global brain flexibility along with GABAergic/glutamatergic neurotransmitter deficits. We aimed to assess the relationship between dynamical properties of time-varying whole-brain network connectivity as well as static large-scale networks and neurotransmitter imbalance using resting-state functional MRI and transcranial magnetic stimulation (TMS) in sixty-six patients with FTD. We assessed GABAergic and glutamatergic neurotransmission by TMS, considering short- and long-interval intracortical inhibition and intracortical facilitation, and large-scale networks connectivity as well as four indexes of meta-state dynamic fluidity: (1) number of distinct meta-states, (2) number of switches from one meta-state to another, (3) span of the realized meta-states, and (4) total distance traveled in the state space. No significant correlations between TMS parameters and large-scale networks connectivity were observed. However, we observed a significant correlation between short-interval intracortical inhibition-intracortical facilitation and four meta-states (all indexes p < 0.02, false discovery rate-corrected). This study suggests that neurotransmitter imbalance dysregulates brain dynamic fluidity, linking microscopic and macroscopic changes in FTD.

中文翻译：

---

神经递质失衡使额颞叶变性中的大脑动态流动性失调

额颞叶变性 (FTD) 的特征是全球大脑灵活性降低以及 GABA 能/谷氨酸能神经递质缺陷。我们旨在使用静息态功能性 MRI 和经颅磁刺激 (TMS) 在 66 名 FTD 患者中评估时变全脑网络连接的动态特性以及静态大规模网络与神经递质失衡之间的关系。我们通过 TMS 评估 GABA 能和谷氨酸能神经传递，考虑短间隔和长间隔皮质内抑制和皮质内促进、大规模网络连接以及元状态动态流动性的四个指标：（1）不同元状态的数量， (2) 从一种元状态到另一种元状态的切换次数，(3) 实现的元状态的跨度，(4) 在状态空间中行进的总距离。没有观察到 TMS 参数与大规模网络连接之间的显着相关性。然而，我们观察到短间隔皮质内抑制 - 皮质内促进与四种元状态之间存在显着相关性（所有指数 p < 0.02，错误发现率校正）。这项研究表明，神经递质失衡会失调大脑动态流动性，将 FTD 的微观和宏观变化联系起来。