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Targeting thalamocortical circuits for closed-loop stimulation in Lennox-Gastaut syndrome
Aaron E L Warren1, Christopher R Butson2, Matthew P Hook2
1Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Brain Communications
|May 20, 2024
Summary
This study identifies a new frontal cortex target for treating Lennox-Gastaut syndrome (LGS) epilepsy. Combining thalamic and cortical stimulation may improve seizure control in this severe childhood epilepsy.
Area of Science:
- Neuroscience
- Epileptology
- Neurosurgery
Background:
- Lennox-Gastaut syndrome (LGS) is a severe childhood epilepsy.
- Thalamic stimulation offers some seizure control but rarely achieves complete remission.
- Optimal cortical targets for enhanced stimulation remain unknown.
Purpose of the Study:
- To identify an optimal cortical target for bilateral, closed-loop, thalamocortical stimulation in LGS.
- To advance a dual thalamic and cortical stimulation approach for LGS.
- To investigate the role of premotor frontal cortex in LGS network.
Main Methods:
- Synthesized multi-modal neuroimaging data (EEG-fMRI, PET, dMRI) from LGS patients.
- Averaged imaging maps to identify peak overlap in cortical targets.
- Used functional MRI connectivity to analyze the identified cortical 'hotspot' network.
- Reviewed intracranial electrophysiology in LGS patients with bilateral implants.
Main Results:
- Peak overlap identified in bilateral premotor cortex/caudal middle frontal gyrus.
- Functional connectivity analysis revealed a frontoparietal network associated with LGS.
- Intracranial electrophysiology confirmed epileptiform activity in both cortical and thalamic targets.
- Cortical epileptiform activity often preceded thalamic involvement.
Conclusions:
- The premotor frontal cortex is a key area in LGS and a potential optimal target for neuromodulation.
- Dual thalamocortical stimulation may offer improved seizure detection and broader network modulation compared to thalamus-only approaches.
- A prospective trial of closed-loop thalamocortical stimulation for LGS is ongoing.
