A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulation
Background: Deep brain stimulation is an established therapy for several neurological disorders; however, its effects on neuronal activity vary across brain regions and depend on stimulation settings. Understanding these variable responses can aid in the development of physiologically-informed stimu...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2021-07-01
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| Series: | Brain Stimulation |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1935861X21000929 |
| _version_ | 1830481961673555968 |
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| author | Luka Milosevic Suneil K. Kalia Mojgan Hodaie Andres M. Lozano Milos R. Popovic William D. Hutchison Milad Lankarany |
| author_facet | Luka Milosevic Suneil K. Kalia Mojgan Hodaie Andres M. Lozano Milos R. Popovic William D. Hutchison Milad Lankarany |
| author_sort | Luka Milosevic |
| collection | DOAJ |
| description | Background: Deep brain stimulation is an established therapy for several neurological disorders; however, its effects on neuronal activity vary across brain regions and depend on stimulation settings. Understanding these variable responses can aid in the development of physiologically-informed stimulation paradigms in existing or prospective indications. Objective: Provide experimental and computational insights into the brain-region-specific and frequency-dependent effects of extracellular stimulation on neuronal activity. Methods: In patients with movement disorders, single-neuron recordings were acquired from the subthalamic nucleus, substantia nigra pars reticulata, ventral intermediate nucleus, or reticular thalamus during microstimulation across various frequencies (1–100 Hz) to assess single-pulse and frequency-response functions. Moreover, a biophysically-realistic computational framework was developed which generated postsynaptic responses under the assumption that electrical stimuli simultaneously activated all convergent presynaptic inputs to stimulation target neurons. The framework took into consideration the relative distributions of excitatory/inhibitory afferent inputs to model site-specific responses, which were in turn embedded within a model of short-term synaptic plasticity to account for stimulation frequency-dependence. Results: We demonstrated microstimulation-evoked excitatory neuronal responses in thalamic structures (which have predominantly excitatory inputs) and inhibitory responses in basal ganglia structures (predominantly inhibitory inputs); however, higher stimulation frequencies led to a loss of site-specificity and convergence towards neuronal suppression. The model confirmed that site-specific responses could be simulated by accounting for local neuroanatomical/microcircuit properties, while suppression of neuronal activity during high-frequency stimulation was mediated by short-term synaptic depression. Conclusions: Brain-region-specific and frequency-dependant neuronal responses could be simulated by considering neuroanatomical (local microcircuitry) and neurophysiological (short-term plasticity) properties. |
| first_indexed | 2024-12-21T17:26:36Z |
| format | Article |
| id | doaj.art-0fbdfaa0d22b4f9fae9a01647eca57c0 |
| institution | Directory Open Access Journal |
| issn | 1935-861X |
| language | English |
| last_indexed | 2024-12-21T17:26:36Z |
| publishDate | 2021-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Brain Stimulation |
| spelling | doaj.art-0fbdfaa0d22b4f9fae9a01647eca57c02022-12-21T18:56:02ZengElsevierBrain Stimulation1935-861X2021-07-01144807821A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulationLuka Milosevic0Suneil K. Kalia1Mojgan Hodaie2Andres M. Lozano3Milos R. Popovic4William D. Hutchison5Milad Lankarany6Krembil Brain Institute, University Health Network, Toronto, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Canada; KITE, Toronto Rehabilitation Institute, University Health Network, Toronto, Canada; CRANIA, University Health Network and University of Toronto, Toronto, Canada; Corresponding author. 399 Bathurst St, Room11MP301, Toronto, ON, M5T 2S8, Canada.Krembil Brain Institute, University Health Network, Toronto, Canada; KITE, Toronto Rehabilitation Institute, University Health Network, Toronto, Canada; CRANIA, University Health Network and University of Toronto, Toronto, Canada; Division of Neurosurgery, Toronto Western Hospital, University Health Network, Toronto, Canada; Department of Surgery, University of Toronto, Toronto, CanadaKrembil Brain Institute, University Health Network, Toronto, Canada; CRANIA, University Health Network and University of Toronto, Toronto, Canada; Division of Neurosurgery, Toronto Western Hospital, University Health Network, Toronto, Canada; Department of Surgery, University of Toronto, Toronto, CanadaKrembil Brain Institute, University Health Network, Toronto, Canada; CRANIA, University Health Network and University of Toronto, Toronto, Canada; Division of Neurosurgery, Toronto Western Hospital, University Health Network, Toronto, Canada; Department of Surgery, University of Toronto, Toronto, CanadaInstitute of Biomedical Engineering, University of Toronto, Toronto, Canada; KITE, Toronto Rehabilitation Institute, University Health Network, Toronto, Canada; CRANIA, University Health Network and University of Toronto, Toronto, CanadaCRANIA, University Health Network and University of Toronto, Toronto, Canada; Department of Surgery, University of Toronto, Toronto, Canada; Department of Physiology, University of Toronto, Toronto, CanadaKrembil Brain Institute, University Health Network, Toronto, Canada; Institute of Biomedical Engineering, University of Toronto, Toronto, Canada; KITE, Toronto Rehabilitation Institute, University Health Network, Toronto, CanadaBackground: Deep brain stimulation is an established therapy for several neurological disorders; however, its effects on neuronal activity vary across brain regions and depend on stimulation settings. Understanding these variable responses can aid in the development of physiologically-informed stimulation paradigms in existing or prospective indications. Objective: Provide experimental and computational insights into the brain-region-specific and frequency-dependent effects of extracellular stimulation on neuronal activity. Methods: In patients with movement disorders, single-neuron recordings were acquired from the subthalamic nucleus, substantia nigra pars reticulata, ventral intermediate nucleus, or reticular thalamus during microstimulation across various frequencies (1–100 Hz) to assess single-pulse and frequency-response functions. Moreover, a biophysically-realistic computational framework was developed which generated postsynaptic responses under the assumption that electrical stimuli simultaneously activated all convergent presynaptic inputs to stimulation target neurons. The framework took into consideration the relative distributions of excitatory/inhibitory afferent inputs to model site-specific responses, which were in turn embedded within a model of short-term synaptic plasticity to account for stimulation frequency-dependence. Results: We demonstrated microstimulation-evoked excitatory neuronal responses in thalamic structures (which have predominantly excitatory inputs) and inhibitory responses in basal ganglia structures (predominantly inhibitory inputs); however, higher stimulation frequencies led to a loss of site-specificity and convergence towards neuronal suppression. The model confirmed that site-specific responses could be simulated by accounting for local neuroanatomical/microcircuit properties, while suppression of neuronal activity during high-frequency stimulation was mediated by short-term synaptic depression. Conclusions: Brain-region-specific and frequency-dependant neuronal responses could be simulated by considering neuroanatomical (local microcircuitry) and neurophysiological (short-term plasticity) properties.http://www.sciencedirect.com/science/article/pii/S1935861X21000929Basal gangliaDeep brain stimulationSynapseSynaptic depressionThalamus |
| spellingShingle | Luka Milosevic Suneil K. Kalia Mojgan Hodaie Andres M. Lozano Milos R. Popovic William D. Hutchison Milad Lankarany A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulation Brain Stimulation Basal ganglia Deep brain stimulation Synapse Synaptic depression Thalamus |
| title | A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulation |
| title_full | A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulation |
| title_fullStr | A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulation |
| title_full_unstemmed | A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulation |
| title_short | A theoretical framework for the site-specific and frequency-dependent neuronal effects of deep brain stimulation |
| title_sort | theoretical framework for the site specific and frequency dependent neuronal effects of deep brain stimulation |
| topic | Basal ganglia Deep brain stimulation Synapse Synaptic depression Thalamus |
| url | http://www.sciencedirect.com/science/article/pii/S1935861X21000929 |
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