Kilohertz electrical stimulation evokes robust cellular responses like conventional frequencies but distinct population dynamics

Abstract Intracranial electrical kilohertz stimulation has recently been shown to achieve similar therapeutic benefit as conventional frequencies around 140 Hz. However, it is unknown how kilohertz stimulation influences neural activity in the mammalian brain. Using cellular calcium imaging in awake...

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Main Authors: Cara R. Ravasio, Krishnakanth Kondabolu, Samuel Zhou, Eric Lowet, Erynne San Antonio, Rebecca A. Mount, Sukhneet K. Bhogal, Xue Han
Format: Article
Language:English
Published: Nature Portfolio 2025-01-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-024-07447-0
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author Cara R. Ravasio
Krishnakanth Kondabolu
Samuel Zhou
Eric Lowet
Erynne San Antonio
Rebecca A. Mount
Sukhneet K. Bhogal
Xue Han
author_facet Cara R. Ravasio
Krishnakanth Kondabolu
Samuel Zhou
Eric Lowet
Erynne San Antonio
Rebecca A. Mount
Sukhneet K. Bhogal
Xue Han
author_sort Cara R. Ravasio
collection DOAJ
description Abstract Intracranial electrical kilohertz stimulation has recently been shown to achieve similar therapeutic benefit as conventional frequencies around 140 Hz. However, it is unknown how kilohertz stimulation influences neural activity in the mammalian brain. Using cellular calcium imaging in awake mice, we demonstrate that intracranial stimulation at 1 kHz evokes robust responses in many individual neurons, comparable to those induced by conventional 40 and 140 Hz stimulation in both the hippocampus and sensorimotor cortex. The evoked responses at the single-cell level are shaped by prominent network inhibition and critically depend on brain region. At the network level, all frequencies lead to pronounced population suppression except 1 kHz in the cortex, which evokes balanced excitatory and inhibitory population effects. Thus, kilohertz stimulation robustly modulates neural activity at both the single-neuron and population network levels through mechanisms distinct from conventional frequency stimulation, highlighting the clinical potential of intracranial kilohertz neuromodulation.
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spelling doaj-art-43d2b52c30754561ab77f5cde437fb4d2025-01-12T12:35:45ZengNature PortfolioCommunications Biology2399-36422025-01-018111410.1038/s42003-024-07447-0Kilohertz electrical stimulation evokes robust cellular responses like conventional frequencies but distinct population dynamicsCara R. Ravasio0Krishnakanth Kondabolu1Samuel Zhou2Eric Lowet3Erynne San Antonio4Rebecca A. Mount5Sukhneet K. Bhogal6Xue Han7Department of Biomedical Engineering, Boston UniversityDepartment of Biomedical Engineering, Boston UniversityDepartment of Biomedical Engineering, Boston UniversityDepartment of Biomedical Engineering, Boston UniversityDepartment of Biomedical Engineering, Boston UniversityDepartment of Biomedical Engineering, Boston UniversityDepartment of Biomedical Engineering, Boston UniversityDepartment of Biomedical Engineering, Boston UniversityAbstract Intracranial electrical kilohertz stimulation has recently been shown to achieve similar therapeutic benefit as conventional frequencies around 140 Hz. However, it is unknown how kilohertz stimulation influences neural activity in the mammalian brain. Using cellular calcium imaging in awake mice, we demonstrate that intracranial stimulation at 1 kHz evokes robust responses in many individual neurons, comparable to those induced by conventional 40 and 140 Hz stimulation in both the hippocampus and sensorimotor cortex. The evoked responses at the single-cell level are shaped by prominent network inhibition and critically depend on brain region. At the network level, all frequencies lead to pronounced population suppression except 1 kHz in the cortex, which evokes balanced excitatory and inhibitory population effects. Thus, kilohertz stimulation robustly modulates neural activity at both the single-neuron and population network levels through mechanisms distinct from conventional frequency stimulation, highlighting the clinical potential of intracranial kilohertz neuromodulation.https://doi.org/10.1038/s42003-024-07447-0
spellingShingle Cara R. Ravasio
Krishnakanth Kondabolu
Samuel Zhou
Eric Lowet
Erynne San Antonio
Rebecca A. Mount
Sukhneet K. Bhogal
Xue Han
Kilohertz electrical stimulation evokes robust cellular responses like conventional frequencies but distinct population dynamics
Communications Biology
title Kilohertz electrical stimulation evokes robust cellular responses like conventional frequencies but distinct population dynamics
title_full Kilohertz electrical stimulation evokes robust cellular responses like conventional frequencies but distinct population dynamics
title_fullStr Kilohertz electrical stimulation evokes robust cellular responses like conventional frequencies but distinct population dynamics
title_full_unstemmed Kilohertz electrical stimulation evokes robust cellular responses like conventional frequencies but distinct population dynamics
title_short Kilohertz electrical stimulation evokes robust cellular responses like conventional frequencies but distinct population dynamics
title_sort kilohertz electrical stimulation evokes robust cellular responses like conventional frequencies but distinct population dynamics
url https://doi.org/10.1038/s42003-024-07447-0
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