A systematic review of computational models for the design of spinal cord stimulation therapies: from neural circuits to patient‐specific simulations

Liang, Lucy; Damiani, Arianna; Brocco, Matteo Del; Rogers, Evan; Jantz, Maria; Fisher, Lee E.; Gaunt, Robert A.; Capogrosso, Marco; Lempka, Scott F.; Pirondini, Elvira

doi:10.1113/jp282884

Cited by 10 publications

(9 citation statements)

References 85 publications

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“…placement relative to the spinal cord midline) and utilizing lookup tables of optimized parameters for the situation that best matches the conditions for the individual patient. Furthermore, these sources of intrapatient variability can be accounted for in patient-specific computational models [14,34,67,68] in which we can then apply our optimization framework to determine optimal patient-specific stimulation parameters. It is also important to recognize that the application of our optimization framework is not limited to chronic pain management using SCS.…”

Section: Discussionmentioning

confidence: 99%

An optimization framework for targeted spinal cord stimulation

Mirzakhalili,

Rogers,

Lempka

2023

J. Neural Eng.

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Objective. Spinal cord stimulation (SCS) is a common neurostimulation therapy to manage chronic pain. Technological advances have produced new neurostimulation systems with expanded capabilities in an attempt to improve the clinical outcomes associated with SCS. However, these expanded capabilities have dramatically increased the number of possible stimulation parameters and made it intractable to efficiently explore this large parameter space within the context of standard clinical programming procedures. Therefore, in this study, we developed an optimization approach to define the optimal current amplitudes or fractions across individual contacts in an SCS electrode array(s). Approach. We developed an analytic method using the Lagrange multiplier method along with smoothing approximations. To test our optimization framework, we used a hybrid computational modeling approach that consisted of a finite element method model and multi-compartment models of axons and cells within the spinal cord. Moreover, we extended our approach to multi-objective optimization to explore the trade-off between activating regions of interest (ROIs) and regions of avoidance (ROAs). Main results. For simple ROIs, our framework suggested optimized configurations that resembled simple bipolar configurations. However, when we considered multi-objective optimization, our framework suggested nontrivial stimulation configurations that could be selected from Pareto fronts to target multiple ROIs or avoid ROAs. Significance. We developed an optimization framework for targeted SCS. Our method is analytic, which allows for the fast calculation of optimal solutions. For the first time, we provided a multi-objective approach for selective SCS. Through this approach, we were able to show that novel configurations can provide neural recruitment profiles that are not possible with conventional stimulation configurations (e.g. bipolar stimulation). Most importantly, once integrated with computational models that account for sources of interpatient variability (e.g. anatomy, electrode placement), our optimization framework can be utilized to provide stimulation settings tailored to the needs of individual patients.

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Section: Discussionmentioning

confidence: 99%

An optimization framework for targeted spinal cord stimulation

Mirzakhalili,

Rogers,

Lempka

2023

J. Neural Eng.

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“…1) The conventional quasi-static assumption in neuromodulation regarding the physics of current passage through macroscopic tissue [36]- [38], including SCS [39], leading to the governing Laplace equation. The electric field generated in the spinal cord by SCS is a function of the stimulation dose (electrode position, current) and the anatomy/macroscopic tissue properties [40].…”

Section: General Approach and Quasi-uniform-mirror Rationalementioning

confidence: 99%

Dorsal horn dendrite polarization during Spinal Cord Stimulation (SCS) predicted using the quasi-uniform-mirror assumption

Zannou,

Koochesfahani,

Russo

et al. 2024

Preprint

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While the mechanisms of Spinal Cord Stimulation are traditionally assumed to follow pacing of dorsal columns axons, the development of sub-paresthesia SCS and new waveforms has encouraged consideration of different cellular targets. Given their relative proximity to the stimulation electrodes and role in pain processing (e.g., synaptic processing and gate control theory), spinal cord dorsal horn interneurons may be direct targets of stimulation. We developed a novel computational modeling pipeline termed 'quasi-uniform-mirror assumption' and apply it to predict polarization of dorsal horn inter-neuron cell types (Islet type, Central type, Stellate/Radial, Vertical-like) to SCS. The quasi-uniform-mirror assumption allows prediction, for each cell type and location in the dorsal horn, the peak and axis of dendritic polarization as well as the impact of stimulation pulse width. For long pulse (dc), the peak polarization per mA of SCS with a bipolar montage were: Islet type 3.5 mV, Central type 2 mV, Stellate/Radial 1.4 mV, Vertical-like 2.5 mV. For Stellate/Radial the peak dendritic polarization was dorsal-ventral, and for Islet type Central peak dendrite polarization was in the rostral-caudal axis. For Islet type and Central type cells peak dendrite polarization was between stimulation electrodes, while for Stellate/Radial and Vertical-like peak dendrite polarization was under stimulation electrodes. The impact of pulse width depended on cell membrane time constants, which in the quasi-uniform-mirror assumption are uniform first-order. Assuming 1 ms time constant, for a 1 ms or 100 us pulse width, the peak dendrite polarization decreases (from the dc values) by ~33% and ~88%. These results suggest, for the conditions modeled, maximum polarization is of islet-cells in the superficial dorsal horn at locations between electrodes; applying 2 mA 1 ms pulse SCS, the peak islet-cell dendrite polarization is ~4.7 mV. Polarizations of a few mV have been shown to modulate synaptic processing through sub-threshold mechanisms.

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“…To test this, we have used epidural electrodes to pair motor cortex stimulation with dorsal (sensory) spinal cord stimulation in rats. Epidural spinal cord stimulation recruits a large number of sensory axons as they enter the spinal cord (Capogrosso et al 2013; Liang et al 2023; McIntosh et al 2023). In one preclinical study, our group showed that timing motor cortex and dorsal epidural spinal stimulation to converge in the spinal cord markedly increased the motor evoked potential (MEP) (by 155%), while convergence in motor cortex resulted in a much smaller effect (17%) (Pal et al 2022).…”

Section: Introductionmentioning

confidence: 99%

Timing dependent synergies between motor cortex and posterior spinal stimulation in humans

McIntosh,

Joiner,

Goldberg

et al. 2023

Preprint

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Electrical stimulation of the brain and spinal cord can strengthen sensorimotor circuits and improve movement through associative plasticity. Current paired stimulation paradigms target the motor system alone or sensorimotor connections in cortex. We developed a paired stimulation approach in rats that targets sensory and motor connections in the cervical spinal cord. Since the circuits necessary for paired stimulation are conserved between species, we hypothesized that paired stimulation of motor cortex and posterior cervical spinal cord in humans would produce synergistic muscle responses but only when stimulation is properly timed. In 59 individuals undergoing clinically indicated cervical spine surgery, the motor cortex was stimulated with scalp electrodes and the spinal cord with epidural electrodes while muscle responses were recorded in arm and leg muscles. Spinal electrodes were placed over either the posterior or anterior spinal cord, and the interval between cortex and spinal cord stimulation was varied. Pairing stimulation between the motor cortex and posterior, but not anterior, spinal cord stimulation produced motor evoked potentials that were over five times larger than brain stimulation alone. This strong augmentation occurred when descending motor and spinal afferent stimuli were timed to converge in the cervical spinal cord. Paired stimulation also increased the selectivity of muscle responses relative to unpaired brain or spinal cord stimulation. Finally, paired stimulation effects were present regardless of the severity of myelopathy as measured by clinical signs or spinal cord imaging. The large effect size of this paired stimulation makes it a promising candidate for therapeutic neuromodulation.Significance StatementPairs of stimuli that alter nervous system function typically target the motor system alone or the sensorimotor convergence in cortex. In humans undergoing clinically indicated surgery we tested a paired brain and spinal cord stimulation paradigm that we developed in rats to target sensorimotor convergence in the cervical spinal cord. Arm and hand muscle responses to paired stimulation were six times larger than brain or spinal cord stimulation alone and more selective to the targeted muscles when applied to the posterior but not anterior spinal cord. The paired stimulation effect was independent of the degree of myelopathy, suggesting that it could be applied as therapy in people affected by spinal cord injury.

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A systematic review of computational models for the design of spinal cord stimulation therapies: from neural circuits to patient‐specific simulations

Cited by 10 publications

References 85 publications

An optimization framework for targeted spinal cord stimulation

An optimization framework for targeted spinal cord stimulation

Dorsal horn dendrite polarization during Spinal Cord Stimulation (SCS) predicted using the quasi-uniform-mirror assumption

Timing dependent synergies between motor cortex and posterior spinal stimulation in humans

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