Kilohertz-frequency stimulation of the nervous system: A review of underlying mechanisms
Background: Electrical stimulation in the kilohertz-frequency range has gained interest in the field of neuroscience. The mechanisms underlying stimulation in this frequency range, however, are poorly characterized to date. Objective/hypothesis: To summarize the manifold biological effects elicited...
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doaj-d10cbe54884049a588c863c0d78e90ac2021-05-26T04:25:37ZengElsevierBrain Stimulation1935-861X2021-05-01143513530Kilohertz-frequency stimulation of the nervous system: A review of underlying mechanismsClemens Neudorfer0Clement T. Chow1Alexandre Boutet2Aaron Loh3Jürgen Germann4Gavin JB. Elias5William D. Hutchison6Andres M. Lozano7Division of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, CanadaDivision of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, CanadaDivision of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, CanadaDivision of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, CanadaDivision of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, CanadaDivision of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, CanadaKrembil Research Institute, University of Toronto, Ontario, Canada; Department of Physiology, Toronto Western Hospital and University of Toronto, Ontario, CanadaDivision of Neurosurgery, Department of Surgery, Toronto Western Hospital, University of Toronto, Canada; Krembil Research Institute, University of Toronto, Ontario, Canada; Corresponding author. 399 Bathurst St., WW 4-431, Toronto Western Hospital, Toronto, ON, M5T 2S8, Canada.Background: Electrical stimulation in the kilohertz-frequency range has gained interest in the field of neuroscience. The mechanisms underlying stimulation in this frequency range, however, are poorly characterized to date. Objective/hypothesis: To summarize the manifold biological effects elicited by kilohertz-frequency stimulation in the context of the currently existing literature and provide a mechanistic framework for the neural responses observed in this frequency range. Methods: A comprehensive search of the peer-reviewed literature was conducted across electronic databases. Relevant computational, clinical, and mechanistic studies were selected for review. Results: The effects of kilohertz-frequency stimulation on neural tissue are diverse and yield effects that are distinct from conventional stimulation. Broadly, these can be divided into 1) subthreshold, 2) suprathreshold, 3) synaptic and 4) thermal effects. While facilitation is the dominating mechanism at the subthreshold level, desynchronization, spike-rate adaptation, conduction block, and non-monotonic activation can be observed during suprathreshold kilohertz-frequency stimulation. At the synaptic level, kilohertz-frequency stimulation has been associated with the transient depletion of the available neurotransmitter pool – also known as synaptic fatigue. Finally, thermal effects associated with extrinsic (environmental) and intrinsic (associated with kilohertz-frequency stimulation) temperature changes have been suggested to alter the neural response to stimulation paradigms. Conclusion: The diverse spectrum of neural responses to stimulation in the kilohertz-frequency range is distinct from that associated with conventional stimulation. This offers the potential for new therapeutic avenues across stimulation modalities. However, stimulation in the kilohertz-frequency range is associated with distinct challenges and caveats that need to be considered in experimental paradigms.http://www.sciencedirect.com/science/article/pii/S1935861X21000590Kilohertz-frequencyElectrical stimulationFacilitationDesynchronizationConduction blockStrength-duration response |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Clemens Neudorfer Clement T. Chow Alexandre Boutet Aaron Loh Jürgen Germann Gavin JB. Elias William D. Hutchison Andres M. Lozano |
spellingShingle |
Clemens Neudorfer Clement T. Chow Alexandre Boutet Aaron Loh Jürgen Germann Gavin JB. Elias William D. Hutchison Andres M. Lozano Kilohertz-frequency stimulation of the nervous system: A review of underlying mechanisms Brain Stimulation Kilohertz-frequency Electrical stimulation Facilitation Desynchronization Conduction block Strength-duration response |
author_facet |
Clemens Neudorfer Clement T. Chow Alexandre Boutet Aaron Loh Jürgen Germann Gavin JB. Elias William D. Hutchison Andres M. Lozano |
author_sort |
Clemens Neudorfer |
title |
Kilohertz-frequency stimulation of the nervous system: A review of underlying mechanisms |
title_short |
Kilohertz-frequency stimulation of the nervous system: A review of underlying mechanisms |
title_full |
Kilohertz-frequency stimulation of the nervous system: A review of underlying mechanisms |
title_fullStr |
Kilohertz-frequency stimulation of the nervous system: A review of underlying mechanisms |
title_full_unstemmed |
Kilohertz-frequency stimulation of the nervous system: A review of underlying mechanisms |
title_sort |
kilohertz-frequency stimulation of the nervous system: a review of underlying mechanisms |
publisher |
Elsevier |
series |
Brain Stimulation |
issn |
1935-861X |
publishDate |
2021-05-01 |
description |
Background: Electrical stimulation in the kilohertz-frequency range has gained interest in the field of neuroscience. The mechanisms underlying stimulation in this frequency range, however, are poorly characterized to date. Objective/hypothesis: To summarize the manifold biological effects elicited by kilohertz-frequency stimulation in the context of the currently existing literature and provide a mechanistic framework for the neural responses observed in this frequency range. Methods: A comprehensive search of the peer-reviewed literature was conducted across electronic databases. Relevant computational, clinical, and mechanistic studies were selected for review. Results: The effects of kilohertz-frequency stimulation on neural tissue are diverse and yield effects that are distinct from conventional stimulation. Broadly, these can be divided into 1) subthreshold, 2) suprathreshold, 3) synaptic and 4) thermal effects. While facilitation is the dominating mechanism at the subthreshold level, desynchronization, spike-rate adaptation, conduction block, and non-monotonic activation can be observed during suprathreshold kilohertz-frequency stimulation. At the synaptic level, kilohertz-frequency stimulation has been associated with the transient depletion of the available neurotransmitter pool – also known as synaptic fatigue. Finally, thermal effects associated with extrinsic (environmental) and intrinsic (associated with kilohertz-frequency stimulation) temperature changes have been suggested to alter the neural response to stimulation paradigms. Conclusion: The diverse spectrum of neural responses to stimulation in the kilohertz-frequency range is distinct from that associated with conventional stimulation. This offers the potential for new therapeutic avenues across stimulation modalities. However, stimulation in the kilohertz-frequency range is associated with distinct challenges and caveats that need to be considered in experimental paradigms. |
topic |
Kilohertz-frequency Electrical stimulation Facilitation Desynchronization Conduction block Strength-duration response |
url |
http://www.sciencedirect.com/science/article/pii/S1935861X21000590 |
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