Schwaderlapp Niels, Paschen Enya, LeVan Pierre, von Elverfeldt Dominik, Haas Carola A
Division of Medical Physics, Department of Diagnostic and Interventional Radiology, Faculty of Medicine, University Medical Center Freiburg, University of Freiburg, Freiburg im Breisgau, Germany.
BrainLinks-BrainTools Center, University of Freiburg, Freiburg im Breisgau, Germany.
Front Neuroimaging. 2024 Aug 14;3:1423770. doi: 10.3389/fnimg.2024.1423770. eCollection 2024.
Electrical neurostimulation is currently used to manage epilepsy, but the most effective approach for minimizing seizure occurrence is uncertain. While functional MRI (fMRI) can reveal which brain areas are affected by stimulation, simultaneous deep brain stimulation (DBS)-fMRI examinations in patients are rare and the possibility to investigate multiple stimulation protocols is limited. In this study, we utilized the intrahippocampal kainate mouse model of mesial temporal lobe epilepsy (mTLE) to systematically examine the brain-wide responses to electrical stimulation using fMRI. We compared fMRI responses of saline-injected controls and epileptic mice during stimulation in the septal hippocampus (HC) at 10 Hz and demonstrated the effects of different stimulation amplitudes (80-230 μA) and frequencies (1-100 Hz) in epileptic mice. Motivated by recent studies exploring 1 Hz stimulation to prevent epileptic seizures, we furthermore investigated the effect of prolonged 1 Hz stimulation with fMRI. Compared to sham controls, epileptic mice showed less propagation to the contralateral HC, but significantly stronger responses in the ipsilateral HC and a wider spread to the entorhinal cortex and septal region. Varying the stimulation amplitude had little effect on the resulting activation patterns, whereas the stimulation frequency represented the key parameter and determined whether the induced activation remained local or spread from the hippocampal formation into cortical areas. Prolonged stimulation of epileptic mice at 1 Hz caused a slight reduction in local excitability. In this way, our study contributes to a better understanding of these stimulation paradigms.
目前，电神经刺激用于治疗癫痫，但将癫痫发作次数降至最低的最有效方法尚不确定。虽然功能磁共振成像（fMRI）可以揭示哪些脑区受到刺激的影响，但对患者进行同步深部脑刺激（DBS）-fMRI检查的情况很少见，并且研究多种刺激方案的可能性有限。在本研究中，我们利用内侧颞叶癫痫（mTLE）的海马内红藻氨酸小鼠模型，通过fMRI系统地检查全脑对电刺激的反应。我们比较了在10 Hz刺激隔区海马（HC）期间，注射生理盐水的对照小鼠和癫痫小鼠的fMRI反应，并展示了不同刺激幅度（80 - 230 μA）和频率（1 - 100 Hz）对癫痫小鼠的影响。受近期探索1 Hz刺激预防癫痫发作研究的启发，我们还通过fMRI研究了长时间1 Hz刺激的效果。与假手术对照组相比，癫痫小鼠向对侧HC的传播较少，但同侧HC的反应明显更强，并且向内嗅皮质和隔区的扩散更广。改变刺激幅度对所产生的激活模式影响不大，而刺激频率是关键参数，它决定了诱导激活是保持局部性还是从海马结构扩散到皮质区域。对癫痫小鼠进行1 Hz的长时间刺激会导致局部兴奋性略有降低。通过这种方式，我们的研究有助于更好地理解这些刺激模式。
