通过功能连接映射和操作表征癫痫网络。

IF 4.8 2区 医学 Q1 NEUROSCIENCES Neurophotonics Pub Date : 2025-01-01 Epub Date: 2025-01-16 DOI:10.1117/1.NPh.12.S1.S14605
James E Niemeyer, Peijuan Luo, Carmen Pons, Shiqiang Wu, Hongtao Ma, Jyun-You Liou, Daniel Surinach, Suhasa B Kodandaramaiah, Theodore H Schwartz
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引用次数: 0

摘要

意义:尽管有多种抗癫痫药物,但仍有近1/3的癫痫患者出现耐药性癫痫发作。这些患者只能选择侵入性手术,但不能保证癫痫发作的缓解。新的治疗方案的发展取决于阐明癫痫发作和大脑网络的复杂生物学。目的:我们的目的是建立一个实验范式,利用解剖网络信息、功能连接和体内癫痫模型来确定大脑网络及其操作如何影响癫痫发作的传播。方法:在已知解剖网络的指导下,我们应用宽视场钙成像来确定神经活动和癫痫是如何通过网络区域传播的,重点关注初级体感皮层和次级运动皮层。我们使用体内微刺激诱导阈上兴奋性激活,并将这种可重复性刺激与急性药物诱导的自发发作传播进行比较。在一个概念验证实验中,我们在这个双边网络中消融了一个节点,并测量了对传播和招募的影响。在慢性癫痫模型中重复类似的初步实验。结果:体感觉皮层的微刺激以一种独特的模式在整个双侧网络中传播,并伴有顺序可重复的节点募集。癫痫重现了同样的模式,表明对现有通路的劫持。次级运动皮质网络中一个关键节点的消融改变了对侧扩散。提出了早期慢性钴发作的资料。结论:在这里,我们展示了将宽视场钙成像与微刺激、皮质消融和癫痫发作作图相结合的范例,以确定解剖网络如何告知皮质癫痫发作的传播模式。这些实验可以扩展到癫痫的长期跟踪,以研究其他皮层网络的癫痫发生。我们的概念验证研究结果表明,这种模式可能有助于开发针对耐药癫痫患者的新疗法,并可扩展到涉及大脑网络的其他疾病的研究。
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Seizure network characterization by functional connectivity mapping and manipulation.

Significance: Despite the availability of various anti-seizure medications, nearly 1/3 of epilepsy patients experience drug-resistant seizures. These patients are left with invasive surgical options that do not guarantee seizure remission. The development of novel treatment options depends on elucidating the complex biology of seizures and brain networks.

Aim: We aimed to develop an experimental paradigm that uses anatomical network information, functional connectivity, and in vivo seizure models to determine how brain networks, and their manipulation, affect seizure propagation.

Approach: Guided by a known anatomical network, we applied widefield calcium imaging to determine how neural activity and seizures spread through the network regions, focusing on the primary somatosensory cortex and secondary motor cortex. We used in vivo microstimulation to induce suprathreshold excitatory activation and compared this reproducible stimulus with acute pharmacologically induced spontaneous seizure propagation. In a proof-of-concept experiment, we ablated a single node within this bilateral network and measured the effect on propagation and recruitment. Similar preliminary experiments were repeated in a chronic seizure model.

Results: The microstimulation of the somatosensory cortex propagated in a distinct pattern throughout the bilateral network with sequential reproducible node recruitment. Seizures recapitulated this same pattern, indicating a hijacking of existing pathways. Ablation of a key node in the network in the secondary motor cortex changed contralateral spread. Early chronic cobalt seizure data are presented.

Conclusion: Here, we demonstrate a paradigm for combining widefield calcium imaging with microstimulation, cortical ablation, and seizure mapping to determine how anatomical networks inform the propagation patterns of cortical seizures. These experiments can be extended to long-term tracking of epilepsy to study epileptogenesis in other cortical networks. Our proof-of-concept findings suggest that this paradigm may be useful in the development of novel therapies for drug-resistant epilepsy patients and can be extended to the study of other disorders involving brain networks.

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来源期刊
Neurophotonics
Neurophotonics Neuroscience-Neuroscience (miscellaneous)
CiteScore
7.20
自引率
11.30%
发文量
114
审稿时长
21 weeks
期刊介绍: At the interface of optics and neuroscience, Neurophotonics is a peer-reviewed journal that covers advances in optical technology applicable to study of the brain and their impact on the basic and clinical neuroscience applications.
期刊最新文献
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