TY - JOUR
T1 - Modulating limbic circuits in temporal lobe epilepsy
T2 - impacts on seizures, memory, mood and sleep
AU - Kremen, Vaclav
AU - Sladky, Vladimir
AU - Mivalt, Filip
AU - Gregg, Nicholas M.
AU - Brinkmann, Benjamin H.
AU - Balzekas, Irena
AU - Marks, Victoria
AU - Kucewicz, Michal
AU - Lundstrom, Brian Nils
AU - Cui, Jie
AU - St Louis, Erik K.
AU - Croarkin, Paul
AU - Alden, Eva C.
AU - Joseph, Boney
AU - Fields, Julie
AU - Crockett, Karla
AU - Adolf, Jindrich
AU - Bilderbeek, Jordan
AU - Hermes, Dora
AU - Messina, Steven
AU - Miller, Kai Joshua
AU - Van Gompel, Jamie
AU - Denison, Timothy
AU - Worrell, Gregory A.
N1 - Publisher Copyright:
© The Author(s) 2025. Published by Oxford University Press on behalf of the Guarantors of Brain.
PY - 2025
Y1 - 2025
N2 - 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.
AB - 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.
KW - artificial intelligence and machine learning
KW - electrical brain stimulation
KW - epilepsy comorbidities
KW - intracranial EEG
UR - http://www.scopus.com/inward/record.url?scp=105002123281&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=105002123281&partnerID=8YFLogxK
U2 - 10.1093/braincomms/fcaf106
DO - 10.1093/braincomms/fcaf106
M3 - Article
AN - SCOPUS:105002123281
SN - 2632-1297
VL - 7
JO - Brain Communications
JF - Brain Communications
IS - 2
M1 - fcaf106
ER -