Temporal lobe epilepsy is a common neurological disease characterized by recurrent seizures that often originate within limbic networks involving amygdala and hippocampus. The limbic network is involved in crucial physiologic functions involving memory, emotion and sleep. Temporal lobe epilepsy is frequently drug-resistant, and people often experience comorbidities related to memory, mood and sleep. Deep brain stimulation targeting the anterior nucleus of the thalamus (ANT-DBS) is an established therapy for temporal lobe epilepsy. However, the optimal stimulation parameters and their impact on memory, mood and sleep comorbidities remain unclear. We used an investigational brain sensing-stimulation implanted device to accurately track seizures, interictal epileptiform spikes (IES), and memory, mood and sleep comorbidities in five ambulatory subjects. Wireless streaming of limbic network local field potentials (LFPs) and subject behaviour were captured on a mobile device integrated with a cloud environment. Automated algorithms applied to the continuous LFPs were used to accurately cataloged seizures, IES and sleep-wake brain state. Memory and mood assessments were remotely administered to densely sample cognitive and behavioural response during ANT-DBS in ambulatory subjects living in their natural home environment. We evaluated the effect of continuous low-frequency and duty cycle high-frequency ANT-DBS on epileptiform activity and memory, mood and sleep comorbidities. Both low-frequency and high-frequency ANT-DBS paradigms reduced seizures. However, continuous low-frequency ANT-DBS showed greater reductions in IES, electrographic seizures and better sleep and memory outcomes. These results highlight the potential of synchronized brain sensing and dense behavioural tracking during ANT-DBS for optimizing neuromodulation therapy. While studies with larger patient numbers are needed to validate the benefits of low-frequency ANT-DBS, these findings are potentially translatable to individuals currently implanted with ANT-DBS systems.

BioTechMed Center Brain and Mind Electrophysiology Lab Multimedia Systems Department Faculty of Electronics Telecommunication and Informatics Gdansk University of Technology Gdansk 80 233 Poland

Czech Institute of Informatics Robotics and Cybernetics Czech Technical University Prague Prague 16000 Czech Republic

Department of Biomedical Engineering Faculty of Electrical Engineering and Communication Brno University of Technology Brno 61600 Czech Republic

Department of Engineering Science Medical Research Council Brain Network Dynamics Unit University of Oxford Oxford OX3 7DQ UK

Department of Neurologic Surgery Mayo Clinic Rochester MN 55905 USA

Department of Neurology Bioelectronics Neurophysiology and Engineering Laboratory Mayo Clinic Rochester MN 55905 USA

Department of Physiology and Biomedical Engineering Mayo Clinic Rochester MN 55905 USA

Department of Radiology Mayo Clinic Rochester MN 55905 USA

Departments of Psychiatry and Psychology Mayo Clinic Rochester MN 55905 USA

Divisions of Sleep Neurology and Pulmonary and Critical Care Medicine Departments of Neurology and Medicine Center for Sleep Medicine Mayo Clinic Rochester MN 55905 USA

Faculty of Biomedical Engineering Czech Technical University Prague Kladno 27201 Czech Republic

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medRxiv. 2024 Apr 03:2024.02.09.24302358. doi: 10.1101/2024.02.09.24302358. PubMed

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