Probing hippocampal stimulation in experimental temporal lobe epilepsy with functional MRI

Background Electrical neurostimulation is a potentially effective therapy in epilepsy but the optimal approach is not yet clear. The parameter space is wide and the effects of different stimulations are not immediately obvious. Functional MRI (fMRI) can reveal which brain areas are affected by stimulation and help understand the induced effects. However, simultaneous deep brain stimulation (DBS)-fMRI examinations in patients are rare and the possibility to investigate multiple stimulation protocols is limited. Preclinical stimulation-fMRI studies can provide predictive value and help identify optimal neurostimulation parameters. Objective To systematically investigate the brain-wide responses to hippocampal electrical stimulations in a mouse model of mesial temporal lobe epilepsy (mTLE) using fMRI. Methods We applied electrical stimulation in the intrahippocampal kainate mouse model of mTLE and assessed the effect of different stimulation amplitudes (80-230 µA) and frequencies (1-100 Hz). In addition, the effect of prolonged 1 Hz stimulation was explored. Saline-injected mice served as controls. Results Varying the stimulation amplitudes had little effect on the resulting activation patterns. Low frequency stimulation led to a local response at the stimulation site only, whereas high frequency resulted in a spread of activation from the hippocampal formation into cortical and frontal areas. Prolonged low frequency stimulation reduced excitability. Conclusions While the amplitude parameter offers little opportunity to vary the outcome, the frequency represented the key parameter and determined whether the induced activation remained local or spread across the brain. This is in line with the few DBS-fMRI results obtained in epilepsy patients demonstrating the translational value of fMRI. ### Competing Interest Statement The authors have declared no competing interest. * Ads : afterdischarges DBS : deep brain stimulation HC : hippocampus ihKA : intrahippocampal kainate LFP : local field potential mTLE : mesial temporal lobe epilepsy