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Related Concept Videos

Muscle Stimulation Frequency01:22

Muscle Stimulation Frequency

The contraction strength of muscles is regulated by motor neurons, which modulate the frequency of action potentials dispatched to the motor units based on the body's requirements. This process of varying the muscle stimulation frequency allows muscles to contract with a force that is precisely tailored to the needs of the moment, whether lifting a feather or a heavy box.
Wave summation
At low firing rates, motor neurons induce individual twitch contractions in muscle fibers. These twitches...

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Brain State-dependent Brain Stimulation with Real-time Electroencephalography-Triggered Transcranial Magnetic Stimulation
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Optimizing responsive neurostimulation targeting based on interictal high-frequency oscillations and phase-amplitude

Sotaro Kanai1, Atsuro Daida1, Yipeng Zhang2

  • 1Division of Pediatric Neurology, Department of Pediatrics, UCLA Mattel Children's Hospital, David Geffen School of Medicine, Los Angeles, California, USA.

Epilepsia
|October 17, 2025
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Summary

High-frequency oscillations (HFOs) and phase-amplitude coupling (PAC) on intracranial EEG can guide responsive neurostimulation (RNS) device placement. Shorter distances between RNS electrodes and these biomarkers correlate with better seizure reduction, outperforming traditional seizure onset zone targeting.

Keywords:
drug‐resistant epilepsyintracranial EEGmodulation indexneuromodulation

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Area of Science:

  • Neuroscience
  • Epileptology
  • Biomarker Discovery

Background:

  • Drug-resistant epilepsy (DRE) poses significant challenges for patient management.
  • Responsive neurostimulation (RNS) offers a therapeutic option for DRE.
  • Accurate targeting of RNS electrodes is crucial for optimal clinical outcomes.

Purpose of the Study:

  • To investigate if interictal high-frequency oscillations (HFOs) and phase-amplitude coupling (PAC) can serve as spatial biomarkers for guiding RNS targeting.
  • To compare the efficacy of HFO/PAC-guided targeting with conventional seizure onset zone (SOZ) based targeting.

Main Methods:

  • Retrospective analysis of patients with DRE undergoing iEEG monitoring and RNS implantation.
  • Calculation of interictal HFOs and delta-HFO PAC using open-source tools (PyHFO, PACTv0.31).
  • Computation of weighted median distances from iEEG electrodes to RNS electrodes, adjusted for HFO and PAC.
  • Receiver operating characteristic (ROC) analysis with leave-one-out cross-validation to evaluate predictive performance.

Main Results:

  • Patients with good seizure reduction (≥50% decrease) had significantly shorter distances between RNS electrodes and peak HFO/PAC sites compared to poor outcome patients.
  • Optimal targeting involved distances within 20-30 mm between stimulation sites and peak biomarker locations, achieving an area under the curve (AUC) > 0.70 for both HFOs and PAC.
  • HFO/PAC-guided targeting outperformed SOZ-based targeting in predicting good outcomes.
  • Exploratory analysis suggested favorable outcomes with thalamic electrodes stimulating areas of elevated HFO or PAC.

Conclusions:

  • Interictal HFOs and delta-HFO PAC distribution can serve as effective spatial biomarkers for RNS electrode placement in DRE.
  • This biomarker-guided approach offers a feasible and potentially more effective alternative to conventional SOZ-based targeting.
  • The availability of validated open-source tools facilitates the clinical implementation and prospective validation of this method.