Cortical Map Plasticity as a Function of Vagus Nerve Stimulation Intensity

Borland, Michael S.; Vrana, William A.; Moreno, Nicole A.; Fogarty, Elizabeth A.; Buell, Elizabeth P.; Sharma, Pryanka; Kilgard, Michael P.

doi:10.1016/j.brs.2015.08.018

Cited by 110 publications

(152 citation statements)

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“…In animal models and humans, moderate intensity stimulation yields significantly greater memory retention compared with lower and higher intensity stimulation [10,38,39]. A recent report demonstrates a similar inverted-U relationship of VNS on map reorganization in auditory cortex [133]. In this study, rats received repeated presentations of a mid-frequency tone paired with different stimulation intensities of VNS over the course of 20 days.…”

Section: Optimizing Vns Parametersmentioning

confidence: 73%

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Hays

2016

Neurotherapeutics

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Pathological neural activity could be treated by directing specific plasticity to renormalize circuits and restore function. Rehabilitative therapies aim to promote adaptive circuit changes after neurological disease or injury, but insufficient or maladaptive plasticity often prevents a full recovery. The development of adjunctive strategies that broadly support plasticity to facilitate the benefits of rehabilitative interventions has the potential to improve treatment of a wide range of neurological disorders. Recently, stimulation of the vagus nerve in conjunction with rehabilitation has emerged as one such potential targeted plasticity therapy. Vagus nerve stimulation (VNS) drives activation of neuromodulatory nuclei that are associated with plasticity, including the cholinergic basal forebrain and the noradrenergic locus coeruleus. Repeatedly pairing brief bursts of VNS sensory or motor events drives robust, event-specific plasticity in neural circuits. Animal models of chronic tinnitus, ischemic stroke, intracerebral hemorrhage, traumatic brain injury, and post-traumatic stress disorder benefit from delivery of VNS paired with successful trials during rehabilitative training. Moreover, mounting evidence from pilot clinical trials provides an initial indication that VNS-based targeted plasticity therapies may be effective in patients with neurological diseases and injuries. Here, I provide a discussion of the current uses and potential future applications of VNS-based targeted plasticity therapies in animal models and patients, and outline challenges for clinical implementation.

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Section: Optimizing Vns Parametersmentioning

confidence: 73%

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Hays

2016

Neurotherapeutics

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“…There is growing evidence that the beneficial effects of VNS are limited to moderate current levels (Clark et al, 1995, Clark et al, 1998, Clark et al, 1999, Zuo, Smith and Jensen., 2007b, Borland et al, 2016). It has been proposed that higher current levels may activate responses in other brain regions that limit the effective range of VNS.…”

Section: Resultsmentioning

confidence: 99%

“…Stimulation intensity influences VNS-dependent norepinephrine release, neural plasticity, memory enhancement, and clinical seizure suppression, suggesting that neural activity in the LC activity is modulated by VNS intensity (Clark et al, 1995, Clark et al, 1999, Roosevelt et al, 2006, Zuo, Smith and Jensen., 2007a, Ghani et al, 2015, Borland et al, 2016). We examined LC firing rate across a range of VNS stimulation intensities from 0.1 to 2.5 mA, while holding other parameters constant (Fig 3A; Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…The vagus nerve was stimulated at standard parameters of sixteen 0.8 mA 100 μs biphasic pulses at 30 Hz (Engineer et al, 2011, Porter et al, 2011, Borland et al, 2016, Hulsey et al, 2016). In addition, a broad stimulus set was delivered with varying pulse number per train (0 – 64 pulses), stimulation current intensity (0 – 2.5 mA), pulse frequency (0 – 120 Hz), and pulse width (0 – 500 μs) totaling 23 distinct stimulation parameters (Tables 1–3).…”

Section: Methodsmentioning

confidence: 99%

“…Studies evaluating the memory- and plasticity-enhancing effects of VNS across a range of stimulation parameters report an inverted-U response, in which moderate intensity stimulation yields a greater effect than lower or higher intensities (Clark et al, 1998, Clark et al, 1999, Borland et al, 2016). One plausible explanation for the inverted-U response is VNS-dependent activation of a low threshold system that promotes plasticity and an overriding high threshold system that occludes plasticity.…”

Section: Introductionmentioning

confidence: 99%

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Parametric characterization of neural activity in the locus coeruleus in response to vagus nerve stimulation

Hulsey

Riley

Loerwald

et al. 2017

Experimental Neurology

234

214

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Vagus nerve stimulation (VNS) has emerged as a therapy to treat a wide range of neurological disorders, including epilepsy, depression, stroke, and tinnitus. Activation of neurons in the locus coeruleus (LC) is believed to mediate many of the effects of VNS in the central nervous system. Despite the importance of the LC, there is a dearth of direct evidence characterizing neural activity in response to VNS. A detailed understanding of the brain activity evoked by VNS across a range of stimulation parameters may guide selection of stimulation regimens for therapeutic use. In this study, we recorded neural activity in the LC and the mesencephalic trigeminal nucleus (Me5) in response to VNS over a broad range of current amplitudes, pulse frequencies, train durations, inter-train intervals, and pulse widths. Brief 0.5 s trains of VNS drive rapid, phasic firing of LC neurons at 0.1 mA. Higher current intensities and longer pulse widths drive greater increases in LC firing rate. Varying the pulse frequency substantially affects the timing, but not the total amount, of phasic LC activity. VNS drives pulse-locked neural activity in the Me5 at current levels above 1.2 mA. These results provide insight into VNS-evoked phasic neural activity in multiple neural structures and may be useful in guiding the selection of VNS parameters to enhance clinical efficacy.

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Transcutaneous Auricular Vagus Nerve Stimulation for Chronic Insomnia Disorder

Zhang,

Zhao,

Qin

et al. 2024

JAMA Netw Open

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IMPORTANCEEvidence from randomized clinical trials of transcutaneous auricular vagus nerve stimulation (taVNS) for chronic insomnia disorder is lacking.OBJECTIVETo evaluate the efficacy and safety of taVNS for chronic insomnia compared with the sham taVNS.DESIGN, SETTING, and PARTICIPANTSThis randomized clinical trial was conducted from October 2021 to December 2022 at a single center in Beijing, China. Patients with chronic insomnia disorder with a Pittsburgh Sleep Quality Index (PSQI) of at least 8 were enrolled. Statistical analysis was performed from June to September 2023.INTERVENTIONSPatients were allocated to the active taVNS group or sham taVNS group with a 1:1 ratio. Both groups received the stimulation for 30 minutes each time, twice a day, 5 consecutive days a week, with an 8-week treatment and a 12-week follow-up.MAIN OUTCOMES AND MEASURESThe primary end point was the mean change from baseline through week 8 in PSQI scores. Minimal clinically important difference was 2.5 points. Secondary outcomes included mental health, sleepiness, and fatigue. Safety was also evaluated.RESULTSA total of 72 participants were randomized to either active taVNS group (36 participants; mean [SD] age, 45.2 [14.5] years; 27 [75.0%] female) or the sham taVNS group (36 participants; mean [SD] age, 44.6 [13.9] years; 31 [86.1%] female); 68 participants completed the 8-week intervention. The least-square mean changes from baseline to week 8 in PSQI were −8.2 (95% CI, −9.3 to −7.0) points in the taVNS group and −3.9 (95% CI, −5.1 to −2.7) points in the sham group. Both groups experienced statistically significant improvements from before to after the intervention. However, active taVNS showed a clinically meaningful 4.2-point greater reduction (95% CI, −5.9 to −2.6 points; P &lt; .001; Cohen d effect size, 1.2) in PSQI compared with the sham group (minimal clinically important difference = 2.5 points). Secondary outcomes, including mental health and fatigue, showed similar favorable results. The efficacy of taVNS was sustained throughout the 20-week study period.CONCLUSIONS AND RELEVANCEIn this randomized clinical trial, taVNS significantly reduced insomnia severity. Clinically meaningful enhancements in PSQI scores were observed compared with sham stimulation, with the benefits of taVNS sustained over a 20-week period. Future multicenter clinical trials with large sample sizes are needed to validate its effectiveness across diverse populations.Trial RegistrationChinese Clinical Trial Registry: ChiCTR2100051319

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Cortical Map Plasticity as a Function of Vagus Nerve Stimulation Intensity

Cited by 110 publications

References 37 publications

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Enhancing Rehabilitative Therapies with Vagus Nerve Stimulation

Parametric characterization of neural activity in the locus coeruleus in response to vagus nerve stimulation

Transcutaneous Auricular Vagus Nerve Stimulation for Chronic Insomnia Disorder

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