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The impact of high frequency stimulation parameters on the pattern of discharge of subthalamic neurons

The impact of high frequency stimulation parameters on the pattern of discharge of subthalamic neurons
The impact of high frequency stimulation parameters on the pattern of discharge of subthalamic neurons
In clinical conditions, high-frequency stimulation (HFS) of subthalamic (STN) neurons in Parkinson's disease is empirically applied at ?100 Hz (130–185 Hz), with pulses of short duration (60–100 µs) and 1- to 3-mA amplitude. Other parameter values produce no effect or aggravate the symptoms. To gain a better understanding of the mechanisms that underlie the therapeutic action of HFS, we have compared the effects of different combinations of parameter values delivered by clinical stimulators on the activity of STN neurons recorded in whole cell patch-clamp configuration in slices. We showed that none of tested combinations of parameters silenced the neurons. Non-therapeutic combinations i.e., low-frequency pulses (10–50 Hz), even at large amplitude or width, further excited the STN neurons with respect to their spontaneous activity. In contrast, combinations in the therapeutic range (80–185 Hz, 90–200 µs, 500–800 µA) replaced the preexisting activity by spikes, time-locked to the stimuli and thus presenting a striking regularity. When increasing pulse width or amplitude in this high-frequency range, the dual effect was still present but the activity generated became more irregular. We propose that during HFS at clinically relevant parameters, STN neurons behave as stable oscillators entirely driven by the stimulation, giving an average stable STN output that overrides spontaneous activity and introduces high-frequency regular spiking in the basal ganglia network.
0022-3077
3662-3669
Garcia, Liliana
c9c42bae-f632-44b5-ba0d-7ddc8399fc54
D'Alessandro, Giampaolo
bad097e1-9506-4b6e-aa56-3e67a526e83b
Fernagut, Pierre-Olivier
36bc768b-536f-445e-a48c-ad19bcec36f1
Bioulac, Bernard
a0fe511b-6de8-4cb6-9395-27bd81f2f904
Hammond, Constance
9e3ccab2-6aab-4200-89b3-77ec86e08c71
Garcia, Liliana
c9c42bae-f632-44b5-ba0d-7ddc8399fc54
D'Alessandro, Giampaolo
bad097e1-9506-4b6e-aa56-3e67a526e83b
Fernagut, Pierre-Olivier
36bc768b-536f-445e-a48c-ad19bcec36f1
Bioulac, Bernard
a0fe511b-6de8-4cb6-9395-27bd81f2f904
Hammond, Constance
9e3ccab2-6aab-4200-89b3-77ec86e08c71

Garcia, Liliana, D'Alessandro, Giampaolo, Fernagut, Pierre-Olivier, Bioulac, Bernard and Hammond, Constance (2005) The impact of high frequency stimulation parameters on the pattern of discharge of subthalamic neurons. Journal of Neurophysiology, 94, 3662-3669. (doi:10.1152/jn.00496.2005).

Record type: Article

Abstract

In clinical conditions, high-frequency stimulation (HFS) of subthalamic (STN) neurons in Parkinson's disease is empirically applied at ?100 Hz (130–185 Hz), with pulses of short duration (60–100 µs) and 1- to 3-mA amplitude. Other parameter values produce no effect or aggravate the symptoms. To gain a better understanding of the mechanisms that underlie the therapeutic action of HFS, we have compared the effects of different combinations of parameter values delivered by clinical stimulators on the activity of STN neurons recorded in whole cell patch-clamp configuration in slices. We showed that none of tested combinations of parameters silenced the neurons. Non-therapeutic combinations i.e., low-frequency pulses (10–50 Hz), even at large amplitude or width, further excited the STN neurons with respect to their spontaneous activity. In contrast, combinations in the therapeutic range (80–185 Hz, 90–200 µs, 500–800 µA) replaced the preexisting activity by spikes, time-locked to the stimuli and thus presenting a striking regularity. When increasing pulse width or amplitude in this high-frequency range, the dual effect was still present but the activity generated became more irregular. We propose that during HFS at clinically relevant parameters, STN neurons behave as stable oscillators entirely driven by the stimulation, giving an average stable STN output that overrides spontaneous activity and introduces high-frequency regular spiking in the basal ganglia network.

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Published date: 2005

Identifiers

Local EPrints ID: 29312
URI: http://eprints.soton.ac.uk/id/eprint/29312
ISSN: 0022-3077
PURE UUID: fed79080-86ec-4e99-b135-1edd2b0aa4a3
ORCID for Giampaolo D'Alessandro: ORCID iD orcid.org/0000-0001-9166-9356

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Date deposited: 11 May 2006
Last modified: 09 Jan 2022 02:47

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Contributors

Author: Liliana Garcia
Author: Pierre-Olivier Fernagut
Author: Bernard Bioulac
Author: Constance Hammond

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