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Modulating limbic circuits in temporal lobe epilepsy: impacts on seizures, memory, mood and sleep

Abstract:
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.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1093/braincomms/fcaf106

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Role:
Author
ORCID:
0000-0001-9844-7617
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Role:
Author
ORCID:
0000-0002-4712-7039
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Author
ORCID:
0000-0002-0693-9495
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Role:
Author
ORCID:
0000-0002-6151-043X
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Role:
Author
ORCID:
0000-0002-2392-8608


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Funder identifier:
https://ror.org/019w4f821
Grant:
101136607
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Funder identifier:
https://ror.org/02caytj08
Grant:
HR0011-20-2-0028
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Funder identifier:
https://ror.org/01s5ya894
Grant:
UH2&3 NS095495
R01-NS112144
U24-NS113637


Publisher:
Oxford University Press
Journal:
Brain Communications More from this journal
Volume:
7
Issue:
2
Article number:
fcaf106
Place of publication:
England
Publication date:
2025-04-07
Acceptance date:
2025-03-07
DOI:
EISSN:
2632-1297
Pmid:
40196395


Language:
English
Keywords:
Pubs id:
2117203
Local pid:
pubs:2117203
Deposit date:
2025-05-15
ARK identifier:

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