Pulse Stimulation Research Articles

Novel Pulsed-Ultrahigh-Frequency Spinal Cord Stimulation Inhibits Mechanical Hypersensitivity and Brain Neuronal Activity in Rats after Nerve Injury.

Spinal cord stimulation (SCS) is an important pain treatment modality. We hypothesized that a novel pulsed-ultrahigh-frequency SCS (pUHF-SCS) could safely and effectively inhibit spared nerve injury-induced neuropathic pain in rats. Epidural pUHF-SCS (± 3V, 2Hz pulses comprising 500 kHz biphasic sinewaves) was implanted at the thoracic vertebrae (T9-T11). Local field brain potentials following hind paw stimulation were recorded. Analgesia was evaluated by von-Frey-evoked allodynia and acetone-induced cold allodynia. The mechanical withdrawal threshold of the injured paw was 0.91 ± 0.28 g lower than that of the sham surgery (24.9 ± 1.2 g). Applying 5-, 10-, or 20-minute pUHF-SCS five times every two days significantly increased the paw withdrawal threshold to 13.3 ± 6.5, 18.5 ± 3.6, and 21.0 ± 2.8 g at 5 hours post-SCS, respectively (p = 0.0002, < 0.0001, and < 0.0001; n = 6/group), and to 6.1 ± 2.5, 8.2 ± 2.7, and 14.3 ± 5.9 g on the second day, respectively (p = 0.123, 0.013, and < 0.0001). Acetone-induced paw response numbers decreased from pre-SCS (41 ± 12) to 24 ± 12 and 28 ± 10 (p = 0.006 and 0.027; n = 9) at 1 and 5 hours post-three rounds of 20-minute pUHF-SCS, respectively. The areas under the curve from the C component of the evoked potentials at the left primary somatosensory and anterior cingulate cortices were significantly decreased from pre-SCS (101.3 ± 58.3 and 86.9 ± 25.5, respectively) to 39.7 ± 40.3 and 36.3 ± 20.7 (p = 0.021, and 0.003; n = 5) at 60 minutes post-SCS, respectively. The intensity thresholds for pUHF-SCS to induce brain and sciatic nerve activations were much higher than the therapeutic intensities and thresholds of conventional low-frequency SCS. pUHF-SCS inhibited neuropathic pain-related behavior and paw stimulation evoked brain activation through mechanisms distinct from low-frequency SCS.

Revolutionizing wound healing: Ultrashort pulse electric fields in seconds for highly aligned extracellular matrix and efficient cell migration

Wound healing is a complicated process for maintaining skin integrity after injury, for which electrical stimulations (ES) have been attributed to promote wound healing by facilitating cell migration. Reducing the duration of the stimulation treatment from hours to minutes to promote efficient wound healing while avoiding cell damage poses a considerable challenge. Here, a promising technology of ultrashort pulse electric field (PEF), microsecond PEF at higher voltage, is proposed and realized to promote wound healing under a much short time (seconds) for the total treatment. We revealed that microsecond PEF regulated actin cytoskeleton reorganization and focal adhesion turnover, promoting fibroblasts migration in 2D cell cultures under the pulse stimulation. This accelerated fibroblast migration was accompanied by the mutual promotion with extracellular matrix (ECM) alignment in 3D microenvironments, which cooperatively benefit the eventual wound healing. These findings were further corroborated by the significant 2.5-fold enhancement observed in the healing of skin wounds in the classical mouse model by day 6 after electrical stimulation. Additionally, we coined an actin- and collagen-dependent mechanism of microsecond PEF-mediated wound healing. The quantitative mechanism proposed here for our novel microsecond pulse electric filed (μsPEF) methodology orients the new practical electric treatment toward a wide range of biomedical applications, such as wound healing, regenerative medicine and tissue engineering.

Muscle Specific Promotors for Gene Therapy - A Comparative Study in Proliferating and Differentiated Cells.

Depending on the therapy approach and disease background, the heterogeneity of muscular tissues complicates the development of targeted gene therapy, where either expression in all muscle types or restriction to only one muscle type is warranted. Muscle specificity can be achieved using promotors mediating tissue specific and sustained physiological expression in the desired muscle types but limited activity in non-targeted tissue. Several muscle specific promotors have been described, but direct comparisons between them are lacking. Here we present a direct comparison of muscle specific Desmin-, MHCK7, microRNA206- and Calpain3 promotor. To directly compare these muscle specific promotors we utilized transfection of reporter plasmids using an in vitro model based on electrical pulse stimulation (EPS) to provoke sarcomere formation in 2D cell culture for quantification of promotor activities in far differentiated mouse and human myotubes. We found that Desmin- and MHCK7 promotors showed stronger reporter gene expression levels in proliferating and differentiated myogenic cell lines than miR206 and CAPN3 promotor. However, Desmin and MHCK7 promotor promoted gene expression also cardiac cells whereas miR206 and CAPN3 promotor expression was restricted to skeletal muscle. Our results provides direct comparison of muscle specific promotors with regard to expression strengths and specificity as this is important feature to avoid undesired transgene expression in non-target muscle cells for a desired therapy approach.

Motor-Evoked Potentials for Early Individual Elements of an Action Sequence During Planning Reflect Parallel Activation Processes.

Several computational models make predictions about the activation states of individual elements of an action sequence during planning and execution; however, the neural mechanisms of action planning are still poorly understood. Simple chaining models predict that only the first response in an action sequence should be active during planning. Conversely, some parallel activation models suggest that during planning, a serial inhibition process places the individual elements of the action into a serial order across a winner-takes-all competitive choice gradient in which earlier responses are more active, and hence likely to be selected for execution compared with later responses. We triggered transcranial magnetic stimulation pulses at 200 or 400ms after the onset of a five-letter word, in which all but one response was planned and typed with the left hand, except for a single letter which required a right index finger response exclusively at one of five serial positions. We measured the resulting motor-evoked potentials at the right index finger as a marker for the activation state of that planned response. We observed no difference in motor-evoked potential amplitude across any serial position when a right index finger response was planned at 200ms after the onset of the word; however, we observed a graded pattern of activation at 400ms, with earlier positions that required a right index finger response showing greater motor-evoked potentials amplitude compared with later positions. These findings provide empirical support for competitive queuing computational models of action planning.

Bidirectional Synaptic Phototransistor Based on Two-Dimensional Ferroelectric Semiconductor for Mixed Color Pattern Recognition.

Optoelectronic synaptic devices capable of processing multiwavelength inputs are critical for neuromorphic vision hardware, which remains an important challenge. Here, we develop a bidirectional synaptic phototransistor based on a two-dimensional ferroelectric semiconductor of α-In2Se3, which exhibits bidirectional potentiated and depressed synaptic weight update under optical pulse stimulation. Importantly, the bidirectional optoelectronic synaptic behavior can be extended to multiwavelengths (blue, green, and red light), which could be used for color recognition. The mechanism underlying the bidirectional synaptic characteristics is attributed to the gate-configurable barrier heights as revealed by the Kelvin probe force microscopy measurement. The α-In2Se3 device exhibits versatile synaptic plasticity such as paired-pulse facilitation, short- and long-term potentiation, and long-term depression. The bidirectional optoelectronic synaptic weight updates under multiwavelength inputs enable a high accuracy of 97% for mixed color pattern recognition.

Stimulated myotube contractions regulate membrane-bound and soluble TLR4 to prevent LPS-induced signaling and myotube atrophy in skeletal muscle cells.

Toll-like receptor 4 (TLR4) activation by lipopolysaccharides (LPS) increases pro-inflammatory cytokine production and upregulation of muscle atrophy signaling pathways. Muscle contractions can suppress LPS/TLR4 axis activation by reducing the protein expression of TLR4 on immune cells. However, the mechanism by which muscle contractions decreases TLR4 remains undefined. Moreover, it is not clear whether muscle contractions affect TLR4 expressed on skeletal muscle cells. The purpose of this study was to uncover the nature and mechanisms by which stimulated myotube contractions using electrical pulse stimulation (EPS) as an in vitro model of skeletal muscle contractions affect TLR4 expression and intracellular signaling to combat LPS-induced muscle atrophy. C2C12 myotubes were stimulated to contract via EPS with and without subsequent LPS exposure. We then examined the isolated effects of conditioned media (CM) collected following EPS and soluble TLR4 (sTLR4) alone on LPS-induced myotube atrophy. Exposure to LPS decreased membrane-bound and sTLR4, increased TLR4 signaling (decreased inhibitor of κBα), and induced myotube atrophy. However, EPS decreased membrane-bound TLR4, increased sTLR4, and prevented LPS-induced signaling and myotube atrophy. CM, that contained elevated levels of sTLR4, prevented LPS-induced upregulation of atrophy-related gene transcripts muscle ring finger 1 (MuRF1) and atrogin-1 and reduced myotube atrophy. Recombinant sTLR4 added to media prevented LPS-induced myotube atrophy. In summary, our study provides the first evidence that sTLR4 has anti-catabolic effects by reducing TLR4-mediated signaling and atrophy. Additionally, the study reveals a novel finding, by demonstrating that stimulated myotube contractions decrease membrane-bound TLR4 and increase the secretion of sTLR4 by myotubes.

Electrical pulse stimulation-induced tetanic exercise simulation increases the secretion of extracellular vesicles from C2C12 myotubes

Extracellular vesicles (EVs) released into the blood during exercise mediate its whole-body health effects. The differentiation of EVs released by skeletal muscle cells in vivo from those released by other cells is challenging, therefore, it is unclear whether exercise increases the number of EVs secreted by skeletal muscle cells. In this study, we investigated whether exercise affects the quantity of EVs released from skeletal muscle cells using in vitro exercise models. C2C12 myotubes were cultured on a gel layer with 1 or 30 Hz electrical pulse stimulation (EPS) to induce contractions as an artificial simulating exercise. We found that tetanic contraction induced by 30 Hz EPS increased the number of secreted EVs. MicroRNA (miRNA)-seq analysis revealed that 30 Hz EPS altered the miRNA in the secreted EVs. Furthermore, expression analysis of genes related to the biogenesis and transport of EVs revealed that the expression of ALG-2 interacting protein X (Alix) was increased in response to 30 Hz EPS, and the peak value of intracellular Ca2+ in myotubes at 30 Hz EPS was higher than that at 1 Hz, indicating that the increase in intracellular Ca2+ concentration may be related to the increased secretion of EVs in response to 30 Hz EPS.

Using a Pulse Protocol to Fix the Individual Dosage of Transcranial and Transspinal Direct Current Electrical Stimulation.

The non-invasive current stimulation protocol differs significantly between the brain and spinal cord, such that when comparing the two, there is a clear predominance of protocols using transcranial direct current stimulation (tDCS) for the brain and of protocols using pulsed stimulation for the spinal cord (psSC). These protocols differ in their effects on the central nervous system and in such important parameters as stimulation intensity. In most cases, tDCS has a fixed amplitude for all subjects/patients, while psSC is usually chosen on a case-by-case basis, according to the thresholds of muscle responses. In our opinion, it is possible to use the experience of identifying thresholds during psSC to adjust the dose of the direct current for transcranial and transspinal electrical stimulation, an approach that may provide more homogeneous tDCS data.

Electrical stimulation in lower motoneuron lesions, from scientific evidence to clinical practice: a successful transition.

Long pulse stimulation in its application in everyday clinical practice still represents a challenge for many therapists and clinicians. It is often unclear how the intervention setup, in particular the parameters pulse width, frequency and amplitude, can influence muscle morphology. In addition, the cause of damage to the lower motoneuron can have multiple reasons and is not anatomically located at the same site. Given the large heterogeneity, it is essential to know the current options and limitations in order to carry out a targeted treatment. A retrospective data analysis of n=128 patients, seen at the Swiss Paraplegic Centre (SPC) in 2022, shows a broad variability in manifestation of lower motoneuron damage. Treatment examples based on different causes of lower motoneuron damage are shown and corresponding stimulation programmes are assigned, as well as the expected results in terms of stimulation duration, volume and configuration.

Impact of female stress urinary incontinence and related treatments on the sexual function of male partners: a systematic review and meta-analysis.

No conclusions have been reached on whether female stress urinary incontinence (SUI) and related treatments affect male partners' sexual function. To assess the effects of female SUI and related treatments on male partners' sexual function. A comprehensive search of the PubMed, Embase, Web of Science, Cochrane, and Scopus databases was performed up to September 6, 2022. Studies were included that investigated the effect of female SUI and related treatments on male partners' sexual function. Male partners' sexual function. Of the 2294 citations identified, 18 studies with 1350 participants were included. Two studies assessed the effect of female SUI without treatment on male partners' sexual function, finding that partners had more erectile dysfunction, more sexual dissatisfaction, and less sexual frequency than partners of women without urinary incontinence. Seven studies directly assessed the effect of female SUI treatments on male partners' sexual function by surveying the male partners. Among these, 4 assessed transobturator suburethral tape (TOT) surgery; 1 assessed TOT and tension-free vaginal tape obturator surgery; and the remaining 2 assessed pulsed magnetic stimulation and laser treatment. Among the 4 TOT studies, 3 used the International Index of Erectile Function (IIEF). TOT surgery significantly improved the total IIEF score (mean difference [MD] = 9.74, P< .00001), along with erectile function (MD = 1.49, P< .00001), orgasmic function (MD = 0.35, P= .001), sexual desire (MD = 2.08, P< .00001), intercourse satisfaction (MD = 2.36, P< .00001), and overall satisfaction (MD = 3.46, P< .00001). However, the improvements in IIEF items may be of unclear clinical significance, as 4 points in the erectile function domain of the IIEF are typically defined as the minimal clinically important difference. In addition, 9 studies indirectly assessed the effect of female SUI surgery on male partners' sexual function by surveying patients with the Pelvic Organ Prolapse/Urinary Incontinence Sexual Questionnaire. The results demonstrated no significant differences in erectile function (MD = 0.08, P= .40) or premature ejaculation (MD = 0.07, P= .54). The effects of female SUI and related treatments on male partners' sexual function were summarized for the first time, providing a reference for future clinical practice and scientific research. A limited number of studies that used various scales met the standardized eligibility criteria. Female SUI may affect male partners' sexual function, and female patients' anti-incontinence surgery does not appear to have a clinically significant improvement on the sexual function of their partners.

Generic dynamic molecular devices by quantitative non-steady-state proton/water-coupled electron transport kinetics

Dynamic molecular devices operating with time- and history-dependent performance raised new challenges for the fundamental study of microscopic non-steady-state charge transport as well as functionalities that are not achievable by steady-state devices. In this study, we reported a generic dynamic mode of molecular devices by addressing the transient redox state of ubiquitous quinone molecules in the junction by proton/water transfer. The diffusion limited slow proton/water transfer-modulated fast electron transport, leading to a non-steady-state transport process, as manifested by the negative differential resistance, dynamic hysteresis, and memory-like behavior. A quantitative paradigm for the study of the non-steady-state charge transport kinetics was further developed by combining the theoretical model and transient state characterization, and the principle of the dynamic device can be revealed by the numerical simulator. On applying pulse stimulation, the dynamic device emulated the neuron synaptic response with frequency-dependent depression and facilitation, implying a great potential for future nonlinear and brain-inspired devices.

Latent toxoplasmosis impairs learning and memory yet strengthens short-term and long-term hippocampal synaptic plasticity at perforant pathway-dentate gyrus, and Schaffer collatterals-CA1 synapses

Investigating long-term potentiation (LTP) in disease models provides essential mechanistic insight into synaptic dysfunction and relevant behavioral changes in many neuropsychiatric and neurological diseases. Toxoplasma (T) gondii is an intracellular parasite causing bizarre changes in host’s mind including losing inherent fear of life-threatening situations. We examined hippocampal-dependent behavior as well as in vivo short- and long-term synaptic plasticity (STP and LTP) in rats with latent toxoplasmosis. Rats were infected by T. gondii cysts. Existence of REP-529 genomic sequence of the parasite in the brain was detected by RT-qPCR. Four and eight weeks after infection, spatial, and inhibitory memories of rats were assessed by Morris water maze and shuttle box tests, respectively. Eight weeks after infection, STP was assessed in dentate gyrus (DG) and CA1 by double pulse stimulation of perforant pathway and Shaffer collaterals, respectively. High frequency stimulation (HFS) was applied to induce LTP in entorhinal cortex-DG (400 Hz), and CA3-CA1 (200 Hz) synapses. T. gondii infection retarded spatial learning and memory performance at eight weeks post-infection period, whereas inhibitory memory was not changed. Unlike uninfected rats that normally showed paired-pulse depression, the infected rats developed paired-pulse facilitation, indicating an inhibitory synaptic network disruption. T. gondii-infected rats displayed strengthened LTP of both CA1-pyramidal and DG-granule cell population spikes. These data indicate that T. gondii disrupts inhibition/excitation balance and causes bizarre changes to the post-synaptic neuronal excitability, which may ultimately contribute to the abnormal behavior of the infected host.

Post-ischemic reorganization of sensory responses in cerebral cortex.

Sensorimotor integration is critical for generating skilled, volitional movements. While stroke tends to impact motor function, there are also often associated sensory deficits that contribute to overall behavioral deficits. Because many of the cortico-cortical projections participating in the generation of volitional movement either target or pass-through primary motor cortex (in rats, caudal forelimb area; CFA), any damage to CFA can lead to a subsequent disruption in information flow. As a result, the loss of sensory feedback is thought to contribute to motor dysfunction even when sensory areas are spared from injury. Previous research has suggested that the restoration of sensorimotor integration through reorganization or de novo neuronal connections is important for restoring function. Our goal was to determine if there was crosstalk between sensorimotor cortical areas with recovery from a primary motor cortex injury. First, we investigated if peripheral sensory stimulation would evoke responses in the rostral forelimb area (RFA), a rodent homologue to premotor cortex. We then sought to identify whether intracortical microstimulation-evoked activity in RFA would reciprocally modify the sensory response. We used seven rats with an ischemic lesion of CFA. Four weeks after injury, the rats' forepaw was mechanically stimulated under anesthesia and neural activity was recorded in the cortex. In a subset of trials, a small intracortical stimulation pulse was delivered in RFA either individually or paired with peripheral sensory stimulation. Our results point to post-ischemic connectivity between premotor and sensory cortex that may be related to functional recovery. Premotor recruitment during the sensory response was seen with a peak in spiking within RFA after the peripheral solenoid stimulation despite the damage to CFA. Furthermore, stimulation in RFA modulated and disrupted the sensory response in sensory cortex. The presence of a sensory response in RFA and the sensitivity of S1 to modulation by intracortical stimulation provides additional evidence for functional connectivity between premotor and somatosensory cortex. The strength of the modulatory effect may be related to the extent of the injury and the subsequent reshaping of cortical connections in response to network disruption.

Semi-Implantable Wireless Power Transfer (WPT) System Integrated With On-Chip Power Management Unit (PMU) for Neuromodulation Application

Miniaturization of the neuromodulation system is important for non-invasive or sub-invasive optogenetic application. This work presents an optimized wireless power transfer (WPT) system integrated with an on-chip rectification circuitry and an off-chip stimulation circuitry for optogenetic stimulation of freely moving rodents. The proposed WPT system is built using parallel transmitter (TX) coils on printed circuit board (PCB) and wire-wound based receiver (RX) coil followed by a seven-stage voltage doubler and a low dropout regulator (LDO) circuit designed in 180 nm standard Complementary Metal Oxide Semiconductor (CMOS) process. A pulse stimulation is used to stimulate the neurons which is generated using a commercially available off-the-shelf (COTS) components based oscillator circuit. The intensity of the stimulation is controlled by using a COTS based LED driver circuit which controls the current through the <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\mu$</tex-math></inline-formula> LED. The total dimension of the RX coil is 8 mm × 3.4 mm. The maximum power transfer efficiency (PTE) of the proposed WPT system is <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"><tex-math notation="LaTeX">$\sim$</tex-math></inline-formula> 35% and the power conversion efficiency (PCE) of the rectifier is 52%. The proposed system with reconfigurable stimulation frequency is suitable for exciting different brain areas for long-term health monitoring.

ID: 202712 Loss of Conduction Fidelity in Dorsal Column Axons During Spinal Cord Stimulation With Conventional Frequencies

Epidural spinal cord stimulation (SCS) is an effective therapy for chronic pain, but there remains an opportunity to increase efficacy and response rates. Conventional paresthesia-producing SCS delivers pulse repetition frequencies < 200 Hz. SCS produces analgesia by activating large dorsal column axons which innervate inhibitory interneurons in the dorsal horn (Gate control theory). This understanding and contemporary research presume that dorsal column (DC) axons propagate faithfully every time a stimulation pulse is delivered. However, recent computational studies suggested that there may be a loss of conduction fidelity, or faithful propagation of an action potential for each stimulation pulse, depending on the stimulation frequency. We measured the response of single dorsal column axons to epidural SCS in healthy urethane-anesthetized Sprague-Dawley rats.

Distinct frequencies balance segregation with interaction between different memory types within a prefrontal circuit

Once formed, the fate of memory is uncertain. Subsequent offline interactions between even different memory types (actions versus words) modify retention.1,2,3,4,5,6 These interactions may occur due to different oscillations functionally linking together different memory types within a circuit.7,8,9,10,11,12,13 With memory processing driving the circuit, it may become less susceptible to external influences.14 We tested this prediction by perturbing the human brain with single pulses of transcranial magnetic stimulation (TMS) and simultaneously measuring the brain activity changes with electroencephalography (EEG15,16,17). Stimulation was applied over brain areas that contribute to memory processing (dorsolateral prefrontal cortex, DLPFC; primary motor cortex, M1) at baseline and offline, after memory formation, when memory interactions are known to occur.1,4,6,10,18 The EEG response decreased offline (compared with baseline) within the alpha/beta frequency bands when stimulation was applied to the DLPFC, but not to M1. This decrease exclusively followed memory tasks that interact, revealing that it was due specifically to the interaction, not task performance. It remained even when the order of the memory tasks was changed and so was present, regardless of how the memory interaction was produced. Finally, the decrease within alpha power (but not beta) was correlated with impairment in motor memory, whereas the decrease in beta power (but not alpha) was correlated with impairment in word-list memory. Thus, different memory types are linked to different frequency bands within a DLPFC circuit, and the power of these bands shapes the balance between interaction and segregation between these memories.

ID: 222988 Treatment of Chronic Pain With a Battery-Free Spinal Cord Stimulation System: US nPower TM

A battery-free, spinal cord stimulation (SCS) system with a micro-implantable pulse generator (mIPG; Nalu Medical Inc., Carlsbad, CA) delivers various therapy options including tonic, novel pulsed stimulation pattern (PSP), current steering, burst waveforms, multi-area programs, layered programs, scheduled therapy and combination and paired therapies.

The properties of long-term potentiation at SC-CA1/ TA-CA1 hippocampal synaptic pathways depends upon their input pathway activation patterns.

Long-term potentiation (LTP) has been considered as a cellular mechanism of memory. Since the Schaffer collateral (SC) and temporoammonic (TA) inputs to CA1 are distinct synaptic pathways that could mediate different cognitive functions, this study was therefore aimed to separately study and compare the properties of LTP of these two synaptic pathways. In the current study we used slice electrophysiological methods to compare various properties of these two synaptic pathways in response to single, paired pulse stimulation, and to three standard protocols for inducing LTP: the high frequency electrical stimulation (HFS), theta-burst (TBS), and primed burst (PBs) stimulation. We found that the SC-CA1 synapses could produce bigger maximum synaptic responses than TA-CA1 synapses. In addition, we showed that paired-pulse ratios of the SC-CA1 synapses were higher than TA-CA1 synapses at certain inter-pulses intervals. Finally, we showed a higher LTP% was induced by PBs or TBS at the SC-CA1 synapse than the TA-CA1 synapse. Briefly, our findings suggest the differential basal synaptic transmission, paired-pulse evoked synaptic responses, and LTP exhibition of the hippocampal SC-CA1/ TA-CA1 synaptic pathways, which may rely on spontaneous and evoked activity pattern at the local circuit level.

ID: 223288 Functional Outcomes From a Prospective Study With a Battery-Free Spinal Cord Stimulation System: US nPower

An ongoing, prospective, multi-center, post-market, open-label clinical study was initiated in the US to evaluate a battery-free SCS system (Nalu Medical Inc., Carlsbad, CA), with a micro implantable pulse generator (mIPG) in the treatment of intractable chronic pain in subjects with leg(s) and/or back pain. The system, with its ultra-long pulse width, delivers various therapy options including tonic, novel pulsed stimulation pattern, current steering, burst waveforms, multi-area programs, layered programs, scheduled therapy and combination and paired therapies.

ID: 216037 Prospective Observational Cohort Study Evaluating the Therapeutic Window Using 10kHzSCS: Must We "Close the Loop?"

In paresthesia-based spinal cord stimulation (SCS), the therapeutic window (TW) is the difference between the lowest stimulation pulse amplitude (mA) which barely generates paresthesia and the upper mA where stimulation intensity is too strong. Technologies that ‘close the loop’ on paresthesia intensity attempt to maintain comfort during activities of daily living (ADL) by keeping the mA within a narrow TW, estimated at 1.8mA. Since 10kHzSCS is inherently paresthesia-free, TW relates directly to pain relief: at the low end of TW, not enough stimulation is delivered to modulate neurons to achieve therapy; at a somewhat-higher ‘optimal’ mA value (mAopt), pain relief is maximized; and the high end of TW drives side-effects or reduces activation of therapeutic neurons. In this study, we explored the TW for 10kHzSCS therapy for the first time.