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Background: Deep brain stimulation (DBS) has been successfully used for treating certain brain diseases such as movement disorders. High-frequency stimulations (HFS) of charge-balanced biphasic pulses have been used in clinic DBS to minimize the risk of tissue damages caused by the electrical stimulations, while HFS sequences of monophasic pulses have been used in animal experiments to investigate DBS therapy. However, it is not clear whether HFS sequences of monophasic pulses could induce abnormal neuronal responses different from biphasic pulses. Thus, the present study investigates the differences of neuronal responses to HFS of monophasic pulses and biphasic pulses.
Methods: Orthodromic-HFS (O-HFS) and antidromic-HFS (A-HFS) of the two types of pulses (with a 1-min duration) were delivered by bipolar electrodes to the Schaffer collaterals (i.e., afferent fibers) and the alveus fibers (i.e., efferent fibers) of the rat hippocampal CA1 region in-vivo, respectively. Responses of CA1 pyramidal neurons to the stimulations were recorded in the CA1 region. Single pulses of antidromic- and orthodromic-test stimuli were applied before and after HFS to evoke population spikes for evaluating the baseline and the recovery of neuronal activity.
Results: Spreading depression (SD) appeared during sequences of 200 Hz monophasic O-HFS with a high incidence (4/5), but did not appear during corresponding 200 Hz biphasic O-HFS (0/6). The potential waveform of SD was accompanied by a preceding burst of population spikes, propagated slowly, silenced neuronal firing temporarily and resulted in a non-recovery of orthodromically-evoked population spikes (OPS) after the O-HFS. No SD events appeared during the O-HFS with a lower frequency of 100 Hz of monophasic and biphasic pulses (0/5 and 0/6, respectively) nor during the A-HFS of 200 Hz pulses (0/9). However, the antidromically-evoked population spikes (APS) only recovered partially after the 200 Hz A-HFS of monophasic pulses.
Conclusions: The O-HFS with a high enough frequency of monophasic pulses may induce the abnormal neuron activity of SD instantaneously, which may be used as a biomarker to warn the damages caused by improper stimulations in brain tissues.
Keywords
High-frequency stimulation, Monophasic pulse, Biphasic pulse, Spreading depression, Hippocampal CA1 region
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CURRENT STATUS: Published
View the published article at BioMedical Engineering OnLine.
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Editorial decision: Accept
On 24 Feb, 2021
Editor assigned
On 29 Jan, 2021
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On 29 Jan, 2021
Editor invited
On 29 Jan, 2021
Version 1
Posted 08 Jul, 2020
No comments provided
Editorial decision: Major revision
On 10 Jan, 2021
Review #1 received
Received 25 Nov, 2020
Reviewer #1 agreed
On 18 Oct, 2020
Reviewers invited
Invitations sent on 16 Oct, 2020
Editor assigned
On 08 Jul, 2020
Submission checks complete
On 07 Jul, 2020
Editor invited
On 07 Jul, 2020
First submitted
On 04 Jul, 2020
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Biomedical Engineering
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See the published version of this preprint at BioMedical Engineering OnLine.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at BioMedical Engineering OnLine.
No community comments so far
Editorial decision: Accept
On 24 Feb, 2021
Editor assigned
On 29 Jan, 2021
Submission checks complete
On 29 Jan, 2021
Editor invited
On 29 Jan, 2021
Version 1
Posted 08 Jul, 2020
No comments provided
Editorial decision: Major revision
On 10 Jan, 2021
Review #1 received
Received 25 Nov, 2020
Reviewer #1 agreed
On 18 Oct, 2020
Reviewers invited
Invitations sent on 16 Oct, 2020
Editor assigned
On 08 Jul, 2020
Submission checks complete
On 07 Jul, 2020
Editor invited
On 07 Jul, 2020
First submitted
On 04 Jul, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
Subject Areas
Biomedical Engineering
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at BioMedical Engineering OnLine.
Background: Deep brain stimulation (DBS) has been successfully used for treating certain brain diseases such as movement disorders. High-frequency stimulations (HFS) of charge-balanced biphasic pulses have been used in clinic DBS to minimize the risk of tissue damages caused by the electrical stimulations, while HFS sequences of monophasic pulses have been used in animal experiments to investigate DBS therapy. However, it is not clear whether HFS sequences of monophasic pulses could induce abnormal neuronal responses different from biphasic pulses. Thus, the present study investigates the differences of neuronal responses to HFS of monophasic pulses and biphasic pulses.
Methods: Orthodromic-HFS (O-HFS) and antidromic-HFS (A-HFS) of the two types of pulses (with a 1-min duration) were delivered by bipolar electrodes to the Schaffer collaterals (i.e., afferent fibers) and the alveus fibers (i.e., efferent fibers) of the rat hippocampal CA1 region in-vivo, respectively. Responses of CA1 pyramidal neurons to the stimulations were recorded in the CA1 region. Single pulses of antidromic- and orthodromic-test stimuli were applied before and after HFS to evoke population spikes for evaluating the baseline and the recovery of neuronal activity.
Results: Spreading depression (SD) appeared during sequences of 200 Hz monophasic O-HFS with a high incidence (4/5), but did not appear during corresponding 200 Hz biphasic O-HFS (0/6). The potential waveform of SD was accompanied by a preceding burst of population spikes, propagated slowly, silenced neuronal firing temporarily and resulted in a non-recovery of orthodromically-evoked population spikes (OPS) after the O-HFS. No SD events appeared during the O-HFS with a lower frequency of 100 Hz of monophasic and biphasic pulses (0/5 and 0/6, respectively) nor during the A-HFS of 200 Hz pulses (0/9). However, the antidromically-evoked population spikes (APS) only recovered partially after the 200 Hz A-HFS of monophasic pulses.
Conclusions: The O-HFS with a high enough frequency of monophasic pulses may induce the abnormal neuron activity of SD instantaneously, which may be used as a biomarker to warn the damages caused by improper stimulations in brain tissues.
Figure 1
Figure 2
Figure 3
Figure 4
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