ArticleBrain stimulation
Action potential initiation, propagation, and cortical invasion in the hyperdirect pathway during subthalamic deep brain stimulation.
Article in Brain stimulation. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed.
- Signaling Connectomics: A Brain-wide Framework for Intercellular Communication.Experimental neurobiology · 2026Article
- Clinical utility of evoked potentials for programming subthalamic deep brain stimulation in Parkinsons disease.NPJ Parkinson's disease · 2026Review
- Change in brain molecular landscapes following electrical stimulation of the nucleus accumbens.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Nonlinear dynamics and multiscale mechanisms of deep brain stimulation.Frontiers in neuroscience · 2026Review
- Hyperdirect projections from the supplementary motor area mediate subthalamic stimulation effects on movement initiation and inhibition in Parkinson's disease.Brain communications · 2026Article
- Deep Brain Stimulation: Mechanisms, Cost-Effectiveness, and Precision Applications Across Neurology and Psychiatry.Biomedicines · 2025Review
- Pallidal Deep Brain Stimulation Enhances Habitual Behavior in a Neuro-Computational Basal Ganglia Model During a Reward Reversal Learning Task.The European journal of neuroscience · 2025Article
- Deep brain stimulation alleviates Parkinsonian motor deficits through desynchronizing GABA release in mice.Nature communications · 2025Article
- Computational analysis of two novel deep brain stimulation pulsing patterns on a thalamocortical network model of Parkinson's disease.Frontiers in network physiology · 2025Article
- The improved thalamo-cortical spiking network model of deep brain stimulation.Frontiers in computational neuroscience · 2025Article
- Neuroplasticity in Parkinson's disease.Journal of neural transmission (Vienna, Austria : 1996) · 2024Review
- Quantitative analysis of noninvasive deep temporal interference stimulation: A simulation and experimental study.Heliyon · 2024Article
- Neural signatures of indirect pathway activity during subthalamic stimulation in Parkinson's disease.Nature communications · 2024Article
- Role of HCN channels in the functions of basal ganglia and Parkinson's disease.Cellular and molecular life sciences : CMLS · 2024Review
- Modulation of DBS-induced cortical responses and movement by the directionality and magnitude of current administered.NPJ Parkinson's disease · 2024Article
- Neuronal and synaptic adaptations underlying the benefits of deep brain stimulation for Parkinson's disease.Translational neurodegeneration · 2023Review
- Neurophysiological mechanisms of deep brain stimulation across spatiotemporal resolutions.Brain : a journal of neurology · 2023Review
- The Therapeutic Frequency Profile of Subthalamic Nucleus Deep Brain Stimulation in Rats Is Shaped by Antidromic Spike Failure.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Evolving characterization of the human hyperdirect pathway.Brain structure & function · 2023Review
- Myogenic and cortical evoked potentials vary as a function of stimulus pulse geometry delivered in the subthalamic nucleus of Parkinson's disease patients.Frontiers in neurology · 2023Article
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5 authors.
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Abstract
backgroundHigh frequency (∼130 Hz) deep brain stimulation (DBS) of the subthalamic region is an established clinical therapy for the treatment of late stage Parkinson's disease (PD). Direct modulation of the hyperdirect pathway, defined as cortical layer V pyramidal neurons that send an axon collateral to the subthalamic nucleus (STN), has emerged as a possible component of the therapeutic mechanisms. However, numerous questions remain to be addressed on the basic biophysics of hyperdirect pathway stimulation.
objectiveQuantify action potential (AP) initiation, propagation, and cortical invasion in hyperdirect neurons during subthalamic stimulation.
methodsWe developed an anatomically and electrically detailed computational model of hyperdirect neuron stimulation with explicit representation of the stimulating electric field, axonal response, AP propagation, and synaptic transmission.
resultsWe found robust AP propagation throughout the complex axonal arbor of the hyperdirect neuron. Even at therapeutic DBS frequencies, stimulation induced APs could reach all of the intracortical axon terminals with ∼100% fidelity. The functional result of this high frequency axonal driving of the thousands of synaptic connections made by each directly stimulated hyperdirect neuron is a profound synaptic suppression that would effectively disconnect the neuron from the cortical circuitry.
conclusionsThe synaptic suppression hypothesis integrates the fundamental biophysics of electrical stimulation, axonal transmission, and synaptic physiology to explain a generic mechanism of DBS.
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