Persistent synaptic inhibition of the subthalamic nucleus by high frequency stimulation
Background: Deep brain stimulation (DBS) provides symptomatic relief in a growing number of neurological indications, but local synaptic dynamics in response to electrical stimulation that may relate to its mechanism of action have not been fully characterized. Objective: The objectives of this stud...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-09-01
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| Series: | Brain Stimulation |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1935861X2200198X |
| _version_ | 1828726292497825792 |
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| author | Leon A. Steiner Andrea A. Kühn Jörg RP. Geiger Henrik Alle Milos R. Popovic Suneil K. Kalia Mojgan Hodaie Andres M. Lozano William D. Hutchison Luka Milosevic |
| author_facet | Leon A. Steiner Andrea A. Kühn Jörg RP. Geiger Henrik Alle Milos R. Popovic Suneil K. Kalia Mojgan Hodaie Andres M. Lozano William D. Hutchison Luka Milosevic |
| author_sort | Leon A. Steiner |
| collection | DOAJ |
| description | Background: Deep brain stimulation (DBS) provides symptomatic relief in a growing number of neurological indications, but local synaptic dynamics in response to electrical stimulation that may relate to its mechanism of action have not been fully characterized. Objective: The objectives of this study were to (1) study local synaptic dynamics during high frequency extracellular stimulation of the subthalamic nucleus (STN), and (2) compare STN synaptic dynamics with those of the neighboring substantia nigra pars reticulata (SNr). Methods: Two microelectrodes were advanced into the STN and SNr of patients undergoing DBS surgery for Parkinson's disease (PD). Neuronal firing and evoked field potentials (fEPs) were recorded with one microelectrode during stimulation from an adjacent microelectrode. Results: Inhibitory fEPs could be discerned within the STN and their amplitudes predicted bidirectional effects on neuronal firing (p = .013). There were no differences between STN and SNr inhibitory fEP dynamics at low stimulation frequencies (p > .999). However, inhibitory neuronal responses were sustained over time in STN during high frequency stimulation but not in SNr (p < .001) where depression of inhibitory input was coupled with a return of neuronal firing (p = .003). Interpretation: Persistent inhibitory input to the STN suggests a local synaptic mechanism for the suppression of subthalamic firing during high frequency stimulation. Moreover, differences in the resiliency versus vulnerability of inhibitory inputs to the STN and SNr suggest a projection source- and frequency-specificity for this mechanism. The feasibility of targeting electrophysiologically-identified neural structures may provide insight into how DBS achieves frequency-specific modulation of neuronal projections. |
| first_indexed | 2024-04-12T13:40:10Z |
| format | Article |
| id | doaj.art-3dc59ec240394bbb90d7cfa425592b1a |
| institution | Directory Open Access Journal |
| issn | 1935-861X |
| language | English |
| last_indexed | 2024-04-12T13:40:10Z |
| publishDate | 2022-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Stimulation |
| spelling | doaj.art-3dc59ec240394bbb90d7cfa425592b1a2022-12-22T03:30:53ZengElsevierBrain Stimulation1935-861X2022-09-0115512231232Persistent synaptic inhibition of the subthalamic nucleus by high frequency stimulationLeon A. Steiner0Andrea A. Kühn1Jörg RP. Geiger2Henrik Alle3Milos R. Popovic4Suneil K. Kalia5Mojgan Hodaie6Andres M. Lozano7William D. Hutchison8Luka Milosevic9Krembil Brain Institute, University Health Network, Canada; Department of Neurology, Charité-Universitätsmedizin Berlin, Germany; Berlin Institute of Health (BIH), Germany; Institute of Neurophysiology, Charité-Universitätsmedizin Berlin, GermanyDepartment of Neurology, Charité-Universitätsmedizin Berlin, GermanyInstitute of Neurophysiology, Charité-Universitätsmedizin Berlin, GermanyInstitute of Neurophysiology, Charité-Universitätsmedizin Berlin, GermanyKITE Research Institute, University Health Network, Canada; Institute of Biomedical Engineering, University of Toronto, CanadaKrembil Brain Institute, University Health Network, Canada; KITE Research Institute, University Health Network, Canada; Department of Surgery, University of Toronto, CanadaKrembil Brain Institute, University Health Network, Canada; Department of Surgery, University of Toronto, CanadaKrembil Brain Institute, University Health Network, Canada; Department of Surgery, University of Toronto, CanadaKrembil Brain Institute, University Health Network, Canada; Department of Surgery, University of Toronto, Canada; Department of Physiology, University of Toronto, CanadaKrembil Brain Institute, University Health Network, Canada; KITE Research Institute, University Health Network, Canada; Institute of Biomedical Engineering, University of Toronto, Canada; Corresponding author. 399 Bathurst St, 11MP301, Toronto, ON, M5T 2S8, Canada.Background: Deep brain stimulation (DBS) provides symptomatic relief in a growing number of neurological indications, but local synaptic dynamics in response to electrical stimulation that may relate to its mechanism of action have not been fully characterized. Objective: The objectives of this study were to (1) study local synaptic dynamics during high frequency extracellular stimulation of the subthalamic nucleus (STN), and (2) compare STN synaptic dynamics with those of the neighboring substantia nigra pars reticulata (SNr). Methods: Two microelectrodes were advanced into the STN and SNr of patients undergoing DBS surgery for Parkinson's disease (PD). Neuronal firing and evoked field potentials (fEPs) were recorded with one microelectrode during stimulation from an adjacent microelectrode. Results: Inhibitory fEPs could be discerned within the STN and their amplitudes predicted bidirectional effects on neuronal firing (p = .013). There were no differences between STN and SNr inhibitory fEP dynamics at low stimulation frequencies (p > .999). However, inhibitory neuronal responses were sustained over time in STN during high frequency stimulation but not in SNr (p < .001) where depression of inhibitory input was coupled with a return of neuronal firing (p = .003). Interpretation: Persistent inhibitory input to the STN suggests a local synaptic mechanism for the suppression of subthalamic firing during high frequency stimulation. Moreover, differences in the resiliency versus vulnerability of inhibitory inputs to the STN and SNr suggest a projection source- and frequency-specificity for this mechanism. The feasibility of targeting electrophysiologically-identified neural structures may provide insight into how DBS achieves frequency-specific modulation of neuronal projections.http://www.sciencedirect.com/science/article/pii/S1935861X2200198XDeep brain stimulationParkinson's diseaseSynaptic dynamicsSynaptic depressionSubthalamic nucleusSubstantia nigra pars reticulata |
| spellingShingle | Leon A. Steiner Andrea A. Kühn Jörg RP. Geiger Henrik Alle Milos R. Popovic Suneil K. Kalia Mojgan Hodaie Andres M. Lozano William D. Hutchison Luka Milosevic Persistent synaptic inhibition of the subthalamic nucleus by high frequency stimulation Brain Stimulation Deep brain stimulation Parkinson's disease Synaptic dynamics Synaptic depression Subthalamic nucleus Substantia nigra pars reticulata |
| title | Persistent synaptic inhibition of the subthalamic nucleus by high frequency stimulation |
| title_full | Persistent synaptic inhibition of the subthalamic nucleus by high frequency stimulation |
| title_fullStr | Persistent synaptic inhibition of the subthalamic nucleus by high frequency stimulation |
| title_full_unstemmed | Persistent synaptic inhibition of the subthalamic nucleus by high frequency stimulation |
| title_short | Persistent synaptic inhibition of the subthalamic nucleus by high frequency stimulation |
| title_sort | persistent synaptic inhibition of the subthalamic nucleus by high frequency stimulation |
| topic | Deep brain stimulation Parkinson's disease Synaptic dynamics Synaptic depression Subthalamic nucleus Substantia nigra pars reticulata |
| url | http://www.sciencedirect.com/science/article/pii/S1935861X2200198X |
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