Tsikonofilos Konstantinos, Bruyns-Haylett Michael, May Hazel G, Donat Cornelius K, Kozlov Andriy S
Department of Bioengineering, Imperial College London, London, United Kingdom.
Departments of Neuroscience and Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Netw Neurosci. 2025 Jul 29;9(3):1013-1038. doi: 10.1162/netn.a.21. eCollection 2025.
Traumatic brain injury (TBI) is a major cause of disability leading to multiple sequelae in cognitive, sensory, and physical domains, including posttraumatic epilepsy. Despite extensive research, our understanding of its impact on macroscopic brain circuitry remains incomplete. We analyzed electrophysiological functional connectomes in the gamma band from an animal model of blast-induced TBI over multiple time points after injury. We revealed differences in small-world propensity and rich-club structure compared with age-matched controls, indicating functional reorganization following injury. We further investigated cost-efficiency trade-offs, propose a computationally efficient normalization procedure for quantifying the cost of spatially embedded networks that controls for connectivity strength differences, and observed dynamic changes across the injury timeline. To explore potential links between altered network topology and epileptic activity, we employed a brain-wide computational model of seizure dynamics and attribute brain reorganization to a homeostatic mechanism of activity regulation with the potential unintended consequence of driving generalized seizures. Finally, we demonstrated post-injury hyperexcitability that manifests as an increase in sound-evoked response amplitudes at the cortical level. Our work characterizes, for the first time, gamma-band functional network reorganization in a model of brain injury and proposes potential causes of these changes, thus identifying targets for future therapeutic interventions.
创伤性脑损伤（TBI）是导致认知、感觉和身体领域多种后遗症（包括创伤后癫痫）的主要致残原因。尽管进行了广泛研究，但我们对其对宏观脑回路的影响仍不完全了解。我们分析了爆炸诱导的TBI动物模型在损伤后多个时间点的γ波段电生理功能连接组。与年龄匹配的对照组相比，我们发现了小世界倾向和富俱乐部结构的差异，表明损伤后功能重组。我们进一步研究了成本效率权衡，提出了一种计算效率高的归一化程序，用于量化控制连接强度差异的空间嵌入网络的成本，并观察了损伤时间线中的动态变化。为了探索改变的网络拓扑结构与癫痫活动之间的潜在联系，我们采用了全脑癫痫发作动力学计算模型，并将脑重组归因于活动调节的稳态机制，这可能会意外导致全身性癫痫发作。最后，我们证明了损伤后皮质兴奋性增高，表现为皮质水平声音诱发反应幅度增加。我们的工作首次描述了脑损伤模型中γ波段功能网络重组的特征，并提出了这些变化的潜在原因，从而确定了未来治疗干预的靶点。
