Bio-Heat Model of Kilohertz-Frequency Deep Brain Stimulation Increases Brain Tissue Temperature

Khadka, Niranjan; Harmsen, Irene E.; Lozano, Andrés M.; Bikson, Marom

doi:10.1111/ner.13120

Cited by 21 publications

(19 citation statements)

References 67 publications

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“…Emerging neuromodulation techniques specifically using kHz frequency stimulation have been developed, in some cases with marked clinical efficacy. This includes transcranial Alternating Current Stimulation (tACS) with sinusoidal kHz waveforms (Chaieb et al, 2011), transcranial Random Noise Stimulation (tRNS) (Antal and Paulus, 2013;Laczo et al, 2014;Terney et al, 2008), kHz Spinal Cord Stimulation (SCS) (Bradley and Redwood City, 2017;Kapural et al, 2015), and recently, kHz Deep Brain Stimulation (DBS) (Harmsen et al, 2019;Khadka et al, 2020). Approaches using interferential or intersectional short pulse stimulation (Esmaeilpour et al, 2020;Grossman et al, 2017;Voroslakos and Takeuchi, 2018) are a special case underpinned by an assumption of sensitivity to amplitude modulated kHz field, but no responses to unmodulated kHz stimulation.…”

Section: Introductionmentioning

confidence: 99%

Limited Sensitivity of Hippocampal Synaptic Function or Network Oscillations to Unmodulated Kilohertz Electric Fields

Esmaeilpour

Jackson

Kronberg

et al. 2020

eNeuro

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Understanding the cellular mechanisms of kilohertz (kHz) electrical stimulation is of broad interest in neuromodulation including forms of transcranial electrical stimulation, interferential stimulation, and high-rate spinal cord stimulation (SCS). Yet, the well-established low-pass filtering by neuronal membranes suggests minimal neuronal polarization in respond to charge-balanced kHz stimulation. The hippocampal brain slice model is among the most studied systems in neuroscience and exhaustively characterized in screening the effects of electrical stimulation. High-frequency electric fields of varied amplitudes (1–150 V/m), waveforms (sinusoidal, symmetrical pule, asymmetrical pulse) and frequencies (1 and10 kHz) were tested. Changes in single or paired-pulse field EPSPs (fEPSP) in CA1 were measured in response to radial-directed and tangential-directed electric fields, with brief (30 s) or long (30 min) application times. The effects of kHz stimulation on ongoing endogenous network activity were tested in carbachol-induced γ oscillation of CA3a and CA3c. Across 23 conditions evaluated, no significant changes in fEPSP were resolved, while responses were detected for within-slice control direct current (DC) fields; 1-kHz sinusoidal and pulse stimulation (≥60 V/m), but not 10 kHz, induced changes in oscillating neuronal network. We thus report no responses to low-amplitude 1-kHz or any 10-kHz fields, suggesting that any brain sensitivity to these fields is via yet to be-determined mechanism(s) of action which were not identified in our experimental preparation.

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Section: Introductionmentioning

confidence: 99%

Limited Sensitivity of Hippocampal Synaptic Function or Network Oscillations to Unmodulated Kilohertz Electric Fields

Esmaeilpour

Jackson

Kronberg

et al. 2020

eNeuro

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“…High-frequency 10 kHz SCS involves a paresthesia-free paradigm as stimulation occurs below the sensory threshold, in contrast to LF-SCS, which relies on paresthesia production and pain overlap. Several working hypotheses for the mechanisms of pain relief with 10 kHz SCS have been proposed [103][104][105][106][107][108], including a reversible depolarization blockade (limiting the propagation of nociceptive signals), desynchronization of neural signals (resulting in pseudo-spontaneous or stochastic neuronal activity in the spinal gate), membrane integration, glial-neuronal interaction, and induced temporal summation, which attenuates the WDR wind-up phenomenon, representing suppression of hyperexcitability in spinal cord neurons. We believe the mechanism of action based on theoretical hypotheses and computational modeling need to be supported by findings from in vitro/in vivo/ex vivo studies.…”

Section: Discussionmentioning

confidence: 99%

Management of Chronic and Neuropathic Pain with 10 kHz Spinal Cord Stimulation Technology: Summary of Findings from Preclinical and Clinical Studies

et al. 2021

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Since the inception of spinal cord stimulation (SCS) in 1967, the technology has evolved dramatically with important advancements in waveforms and frequencies. One such advancement is Nevro’s Senza® SCS System for HF10, which received Food and Drug and Administration (FDA) approval in 2015. Low-frequency SCS works by activating large-diameter Aβ fibers in the lateral discriminatory pathway (pain location, intensity, quality) at the dorsal column (DC), creating paresthesia-based stimulation at lower-frequencies (30–120 Hz), high-amplitude (3.5–8.5 mA), and longer-duration/pulse-width (100–500 μs). In contrast, high-frequency 10 kHz SCS works with a proposed different mechanism of action that is paresthesia-free with programming at a frequency of 10,000 Hz, low amplitude (1–5 mA), and short-duration/pulse-width (30 μS). This stimulation pattern selectively activates inhibitory interneurons in the dorsal horn (DH) at low stimulation intensities, which do not activate the dorsal column fibers. This ostensibly leads to suppression of hyperexcitable wide dynamic range neurons (WDR), which are sensitized and hyperactive in chronic pain states. It has also been reported to act on the medial pathway (drives attention and pain perception), in addition to the lateral pathways. Other theories include a reversible depolarization blockade, desynchronization of neural signals, membrane integration, glial–neuronal interaction, and induced temporal summation. The body of clinical evidence regarding 10 kHz SCS treatment for chronic back pain and neuropathic pain continues to grow. There is high-quality evidence supporting its use in patients with persistent back and radicular pain, particularly after spinal surgery. High-frequency 10 kHz SCS studies have demonstrated robust statistically and clinically significant superiority in pain control, compared to paresthesia-based SCS, supported by level I clinical evidence. Yet, as the field continues to grow with the technological advancements of multiple waveforms and programming stimulation algorithms, we encourage further research to focus on the ability to modulate pain with precision and efficacy, as the field of neuromodulation continues to adapt to the modern healthcare era.

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“…However, more recently this theory has been challenged to suggest there is an inverse relationship between impedance and the energy: E = (V2 9 pulse width 9 f)/R [9]. SCS systems are unable to transition to MRI-conditional modes in states of high impedance, as interactions generated by the MRI machine can [10]. Incidence of thermal heating of tissue already occurs with the use of SCS.…”

Section: Discussionmentioning

confidence: 99%

Failure of SCS MR-Conditional Modes Due to High Impedance: A Review of Literature and Case Series

et al. 2020

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Introduction: Magnetic resonance imaging (MRI) conditional modes are a novel feature for certain Food and Drug Administration (FDA)approved spinal cord stimulation (SCS) devices. However, there is a paucity of literature around the limitation of MRI-conditional modes (''MRI safe''), specifically in clinical scenarios where urgent MRIs may be needed. One such limitation is load impedance, referring to the circuit's resistance to the current being generated by the system. High impedance can limit the MRIconditional mode capability, presenting potential harm to a patient undergoing an MRI or make an MRI unable to be completed. Methods: Three cases were identified, and informed consent was obtained. All information was obtained via retrospective chart review. Results: In this case series of three patients where MRI-conditional SCS systems were unable to be placed in ''MRI safe'' settings, preventing timely MRI study completion in the setting of high impedance, all three were required to undergo alternative imaging including CT scans, and two patients ultimately had the system explanted and one chose to be re-implanted after completion of scans. Conclusion: This case series highlights the need for further investigation of impedance in SCS systems and potential limitations for future MRI usage. The review of literature of impedance in SCS shows both device-and physiologic-related etiologies for changes in impedance that warrant consideration by the implanting physician.

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Bio-Heat Model of Kilohertz-Frequency Deep Brain Stimulation Increases Brain Tissue Temperature

Cited by 21 publications

References 67 publications

Limited Sensitivity of Hippocampal Synaptic Function or Network Oscillations to Unmodulated Kilohertz Electric Fields

Limited Sensitivity of Hippocampal Synaptic Function or Network Oscillations to Unmodulated Kilohertz Electric Fields

Management of Chronic and Neuropathic Pain with 10 kHz Spinal Cord Stimulation Technology: Summary of Findings from Preclinical and Clinical Studies

Failure of SCS MR-Conditional Modes Due to High Impedance: A Review of Literature and Case Series

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