von Schwanenflug Nina, Ramirez-Mahaluf Juan P, Krohn Stephan, Romanello Amy, Heine Josephine, Prüss Harald, Crossley Nicolas A, Finke Carsten
Department of Neurology and Experimental Neurology, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.
Eur J Neurosci. 2023 Feb;57(3):568-579. doi: 10.1111/ejn.15901. Epub 2023 Jan 10.
Patients with anti-N-methyl-aspartate receptor (NMDA) receptor encephalitis suffer from a severe neuropsychiatric syndrome, yet most patients show no abnormalities in routine magnetic resonance imaging. In contrast, advanced neuroimaging studies have consistently identified disrupted functional connectivity in these patients, with recent work suggesting increased volatility of functional state dynamics. Here, we investigate these network dynamics through the spatiotemporal trajectory of meta-state transitions, yielding a time-resolved account of brain state exploration in anti-NMDA receptor encephalitis. To this end, resting-state functional magnetic resonance imaging data were acquired in 73 patients with anti-NMDA receptor encephalitis and 73 age- and sex-matched healthy controls. Time-resolved functional connectivity was clustered into brain meta-states, giving rise to a time-resolved transition network graph with states as nodes and transitions between brain meta-states as weighted, directed edges. Network topology, robustness and transition cost of these transition networks were compared between groups. Transition networks of patients showed significantly lower local efficiency (t = -2.41, p = .029), lower robustness (t = -2.01, p = .048) and higher leap size (t = 2.18, p = .037) compared with controls. Furthermore, the ratio of within-to-between module transitions and state similarity was significantly lower in patients. Importantly, alterations of brain state transitions correlated with disease severity. Together, these findings reveal systematic alterations of transition networks in patients, suggesting that anti-NMDA receptor encephalitis is characterized by reduced stability of brain state transitions and that this reduced resilience of transition networks plays a clinically relevant role in the manifestation of the disease.
抗N-甲基-D-天冬氨酸受体（NMDA）脑炎患者患有严重的神经精神综合征，但大多数患者在常规磁共振成像中未显示异常。相比之下，先进的神经影像学研究一致发现这些患者存在功能连接中断，最近的研究表明功能状态动态的波动性增加。在这里，我们通过元状态转换的时空轨迹来研究这些网络动态，从而对抗NMDA受体脑炎中的脑状态探索进行时间分辨描述。为此，我们采集了73例抗NMDA受体脑炎患者和73例年龄和性别匹配的健康对照的静息态功能磁共振成像数据。时间分辨功能连接被聚类为脑元状态，从而产生一个时间分辨转换网络图，其中状态为节点，脑元状态之间的转换为加权有向边。比较了两组之间这些转换网络的网络拓扑、鲁棒性和转换成本。与对照组相比，患者的转换网络显示出显著更低的局部效率（t = -2.41，p = 0.029）、更低的鲁棒性（t = -2.01，p = 0.048）和更高的跳跃大小（t = 2.18，p = 0.037）。此外，患者模块内与模块间转换的比率和状态相似性显著更低。重要的是，脑状态转换的改变与疾病严重程度相关。总之，这些发现揭示了患者转换网络的系统性改变，表明抗NMDA受体脑炎的特征是脑状态转换稳定性降低，并且这种转换网络弹性的降低在疾病表现中发挥了临床相关作用。
