Evidence map›Paper›PMID 41386553›Full record

ArticleBrain stimulation

Mechanisms mediating dynamic changes in neural responses during deep brain stimulation.

Jahrane A Dale, Stephen L Schmidt, Kyle T Mitchell, Jennifer J Peters, Dennis A Turner, Warren M Grill

Abstract read
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Article in Brain stimulation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Jahrane A DaleDepartment of Biomedical Engineering, Duke University, Durham, NC, 27708, USA.
Stephen L SchmidtDepartment of Biomedical Engineering, Duke University, Durham, NC, 27708, USA.
Kyle T MitchellDepartment of Neurology, Duke University, Durham, NC, 27705, USA.
Jennifer J PetersDepartment of Biomedical Engineering, Duke University, Durham, NC, 27708, USA.
Dennis A TurnerDepartment of Biomedical Engineering, Duke University, Durham, NC, 27708, USA; Department of Neurosurgery, Duke University, Durham, NC, 27710, USA; Department of Neurobiology, Duke University, Durham, NC, 27710, USA.
Warren M GrillDepartment of Biomedical Engineering, Duke University, Durham, NC, 27708, USA; Department of Neurosurgery, Duke University, Durham, NC, 27710, USA; Department of Neurobiology, Duke University, Durham, NC, 27710, USA; Department of Electrical and Computer Engineering, Duke University, Durham, NC, 27708, USA. Electronic address: warren.grill@duke.edu.

Funding

Medical Scientist Training Program Training GrantT32GM145449 · NIGMS · DUKE UNIVERSITY · PI Christopher D Kontos · 2022 to 2026
$6.6M
Characterizing Evoked Potentials of Deep Brain Stimulation for Parkinson's DiseaseF31NS130997 · NINDS · DUKE UNIVERSITY · PI DALE, JAHRANE ANTONIO · 2023 to 2025
$137k
NIGMS NIH HHS T32 GM145449NINDS NIH HHS F31 NS130997
6 · The paper itself

Abstract

backgroundDeep brain stimulation (DBS) of the subthalamic nucleus (STN) to treat Parkinson's disease (PD) generates local evoked potentials (DLEPs). DLEPs reflect neural activation by DBS, but the mechanisms underlying the dynamic changes in DLEPs during continuous DBS are not understood, and such knowledge is critical to using these signals for DBS programming and closed-loop control.

methodsWe first systematically incorporated short-term synaptic depletion into 4 different synapse types in a biophysically realistic computational model of DLEPs. We then recorded DLEPs in naïve and a virally transfected rat model. Lastly, we conducted a retrospective analysis correlating DLEP dynamics to motor symptom severity in 13 patients with PD.

resultsA bespoke biophysical model suggests that synaptic depression, through synaptic vesicle depletion of activated motor cortical synapses onto STN neurons, causes the dynamic changes in DLEP amplitude and latency during continuous DBS. Virally-driven overexpression of endophilin A1 or alpha-synuclein in rat motor cortex reduces the time constant of DLEP amplitude and latency, supporting a critical role of these synapses in mediating DLEP dynamics. Further, a correlation between the change in UPDRS-III scores with antiparkinsonian medications and the time constant of DLEP amplitude is observed in persons with PD, suggesting DLEP dynamics as a biomarker of PD progression.

conclusionsCollectively, these results suggest short-term synaptic depression of cortical synapses onto STN neurons mediate DLEP dynamics in STN DBS.

Indexed as

Deep Brain StimulationEvoked PotentialsNeuronsParkinson DiseaseSubthalamic NucleusAgedAnimalsFemaleHumansMaleMiddle AgedModels, NeurologicalMotor CortexRatsRetrospective StudiesSynapsesDeep brain stimulationEvoked potentialsParkinson's diseaseSynaptic plasticity

Identifiers

PMID41386553
PMCPMC12965335

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.