Vagus nerve stimulation (VNS) is well established in the treatment of epilepsy and disorders of depression. The prevalence of depression is high in patients with epilepsy, but still it remains unclear how patients with a comorbidity of epilepsy and symptoms of depression respond to VNS. Methods: We investigated 59 patients with different subtypes of disorders of depression as a comorbidity of epilepsy, who underwent VNS-surgery. Before and one year after VNS surgery, the severity of symptoms of depression was evaluated by a psychiatrist using Montgomery-Åsberg Depression Rating Scale (MADRS) and Beck-Depressions-Inventory (BDI). Response towards epilepsy was measured by a seizure reduction of at least 50%. Results: Symptoms of depression ameliorated in response to VNS in the overall of all patients MADRS 29 to 18 (p < 0,001) and BDI 24 to 14 (p < 0,001) and all subtypes of disorders of depression. Seizure reduction of at least 50% was achieved in two out of three of all patients two years after VNS. Conclusion:We were able to show the beneficial effect of VNS in the treatment of patients with pharmacoresistant epilepsy and a comorbidity of symptoms of depression.

Background: Deep Brain Stimulation (DBS) electrode implant trajectories are stereotactically defined using preoperative neuroimaging. To validate the correct trajectory, microelectrode recordings (MER) or local field potential recordings (LFP) can be used to extend neuroanatomical information (defined by magnetic resonance imaging) with neurophysiological activity patterns recorded from micro- and macroelectrodes probing the surgical target site. Currently, these two sources of information (imaging vs. electrophysiology) are analyzed separately, while means to fuse both data streams have not been introduced.Methods: Here we present a tool that integrates resources from stereotactic planning, neuroimaging, MER and high-resolution atlas data to create a real-time visualization of the implant trajectory. We validate the tool based on a retrospective cohort of DBS patients (𝑁 = 52) offline and present single use cases of the real-time platform. Results: We establish an open-source software tool for multimodal data visualization and analysis during DBS surgery. We show a general correspondence between features derived from neuroimaging and electrophysiological recordings and present examples that demonstrate the functionality of the tool.Conclusions: This novel software platform for multimodal data visualization and analysis bears translational potential to improve accuracy of DBS surgery. The toolbox is made openly available and is extendable to integrate with additional software packages.Funding: Deutsche Forschungsgesellschaft (410169619, 424778381), Deutsches Zentrum für Luftund Raumfahrt (DynaSti), National Institutes of Health (2R01 MH113929), Foundation for OCD Research (FFOR).

Deep Brain Stimulation (DBS) electrode implant trajectories are stereotactically defined using preoperative neuroimaging. To validate the correct trajectory, microelectrode recordings (MER) can be used to match the neuroanatomy with expected neurophysiological activity patterns, commonly using up to five trajectories in parallel. However, understanding their location in relationship to basal ganglia anatomy can be challenging. Here we present a tool that integrates resources from stereotactic planning, neuroimaging, MER and high-resolution atlas data to create a real-time visualization of the implant trajectory. We show a general correspondence between features derived from neuroimaging and electrophysiological recordings and present example use cases that demonstrate the functionality of the tool. The software toolbox is made openly available, extendable and holds translational potential in the field of stereotactic neurosurgery.

Epilepsy affects about 1% of the world population and leads to a severe decrease in quality of life due to ongoing seizures as well as high risk for sudden death. Despite an abundance of available treatment options, about 30% of patients are drug-resistant. Several novel therapeutics have been developed using animal models, though the rate of drug-resistant patients remains unaltered. One of probable reasons is the lack of translation between rodent models and humans, such as a weak representation of human pharmacoresistance in animal models. Resected human brain tissue as a preclinical evaluation tool has the advantage to bridge this translational gap. Described here is a method for high quality preparation of human hippocampal brain slices and subsequent stable induction of epileptiform activity. The protocol describes the induction of burst activity during application of 8 mM KCl and 4-aminopyridin. This activity is sensitive to established AED lacosamide or novel antiepileptic candidates, such as dimethylethanolamine (DMEA). In addition, the method describes induction of seizure-like events in CA1 of human hippocampal brain slices by reduction of extracellular Mg 2+ and application of bicuculline, a GABA A receptor blocker. The experimental set-up can be used to screen potential antiepileptic substances for their effects on epileptiform activity. Furthermore, mechanisms of action postulated for specific compounds can be validated using this approach in human tissue (e.g., using patch-clamp recordings). To conclude, investigation of vital human brain tissue ex vivo (here, resected hippocampus from patients suffering from temporal lobe epilepsy) will improve the current knowledge of physiological and pathological mechanisms in the human brain.