Vagus nerve stimulation (VNS) is a form of neuromodulation that stimulates the vagus nerve. VNS had been suggested as an intervention in the late 1800s and was rediscovered in the late 1980s as a ...promising treatment for refractory epilepsy. Since then, VNS has been approved by the U.S. Food and Drug Administration (FDA) for treatment of epilepsy, morbid obesity, and treatment-resistant depression. Unfortunately, VNS is underutilized, as it is costly to implant and often only suggested when all other treatment options have been exhausted. Discovery of a noninvasive method of VNS known as transcutaneous auricular VNS (taVNS), which activates the vagus through stimulation of the auricular branch of the vagus nerve, has reignited excitement around VNS. taVNS has immense potential as a safe, at-home, wearable treatment for various neuropsychiatric disorders. Major strides are being made in both invasive and noninvasive VNS that aim to make this technology more accessible to patients who would find benefit, including the ongoing RECOVER trial, a randomized controlled trial in up to 1,000 individuals to further evaluate the efficacy of VNS for treatment-resistant depression. In this brief review, we first discuss the early history of VNS; then its clinical utility in FDA-approved indications; and, finally, noninvasive VNS.
Novel coronavirus disease (COVID-19) morbidity is not restricted to the respiratory system, but also affects the nervous system. Non-invasive neuromodulation may be useful in the treatment of the ...disorders associated with COVID-19.
To describe the rationale and empirical basis of the use of non-invasive neuromodulation in the management of patients with COVID-10 and related disorders.
We summarize COVID-19 pathophysiology with emphasis of direct neuroinvasiveness, neuroimmune response and inflammation, autonomic balance and neurological, musculoskeletal and neuropsychiatric sequela. This supports the development of a framework for advancing applications of non-invasive neuromodulation in the management COVID-19 and related disorders.
Non-invasive neuromodulation may manage disorders associated with COVID-19 through four pathways: (1) Direct infection mitigation through the stimulation of regions involved in the regulation of systemic anti-inflammatory responses and/or autonomic responses and prevention of neuroinflammation and recovery of respiration; (2) Amelioration of COVID-19 symptoms of musculoskeletal pain and systemic fatigue; (3) Augmenting cognitive and physical rehabilitation following critical illness; and (4) Treating outbreak-related mental distress including neurological and psychiatric disorders exacerbated by surrounding psychosocial stressors related to COVID-19. The selection of the appropriate techniques will depend on the identified target treatment pathway.
COVID-19 infection results in a myriad of acute and chronic symptoms, both directly associated with respiratory distress (e.g., rehabilitation) or of yet-to-be-determined etiology (e.g., fatigue). Non-invasive neuromodulation is a toolbox of techniques that based on targeted pathways and empirical evidence (largely in non-COVID-19 patients) can be investigated in the management of patients with COVID-19.
We present device standards for low-power non-invasive electrical brain stimulation devices classified as limited output transcranial electrical stimulation (tES). Emerging applications of limited ...output tES to modulate brain function span techniques to stimulate brain or nerve structures, including transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), and transcranial pulsed current stimulation (tPCS), have engendered discussion on how access to technology should be regulated. In regards to legal regulations and manufacturing standards for comparable technologies, a comprehensive framework already exists, including quality systems (QS), risk management, and (inter)national electrotechnical standards (IEC). In Part 1, relevant statutes are described for medical and wellness application. While agencies overseeing medical devices have broad jurisdiction, enforcement typically focuses on those devices with medical claims or posing significant risk. Consumer protections regarding responsible marketing and manufacture apply regardless. In Part 2 of this paper, we classify the electrical output performance of devices cleared by the United States Food and Drug Administration (FDA) including over-the-counter (OTC) and prescription electrostimulation devices, devices available for therapeutic or cosmetic purposes, and devices indicated for stimulation of the body or head. Examples include iontophoresis devices, powered muscle stimulators (PMS), cranial electrotherapy stimulation (CES), and transcutaneous electrical nerve stimulation (TENS) devices. Spanning over 13 FDA product codes, more than 1200 electrical stimulators have been cleared for marketing since 1977. The output characteristics of conventional tDCS, tACS, and tPCS techniques are well below those of most FDA cleared devices, including devices that are available OTC and those intended for stimulation on the head. This engineering analysis demonstrates that with regard to output performance and standing regulation, the availability of tDCS, tACS, or tPCS to the public would not introduce risk, provided such devices are responsibly manufactured and legally marketed. In Part 3, we develop voluntary manufacturer guidance for limited output tES that is aligned with current regulatory standards. Based on established medical engineering and scientific principles, we outline a robust and transparent technical framework for ensuring limited output tES devices are designed to minimize risks, while also supporting access and innovation. Alongside applicable medical and government activities, this voluntary industry standard (LOTES-2017) further serves an important role in supporting informed decisions by the public.
•Illustrated that limited output tES devices have specifications that are below most FDA cleared devices.•Argued that limited output tES devices would not introduce risk if they are responsibly manufactured and legally marketed.•Detailed voluntary manufacturer guidance for limited output tES to minimize risks, while supporting access and innovation.•Outlined industry guidance that are consistent with and expand on the current regulatory standards.•Classified FDA product codes for more than 1200 electrical stimulators that have been FDA cleared for marketing since 1977.
Abstract Background A 2006 trial in healthy medical students found that anodal slow oscillating tDCS delivered bi-frontally during slow wave sleep had an enhancing effect in declarative, but not ...procedural memory. Although there have been supporting animal studies, and similar findings in pathological groups, this study has not been replicated, or refuted, in the intervening years. We therefore tested these earlier results for replication using similar methods with the exception of current waveform (square in our study, nearly sinusoidal in the original). Objective/hypothesis Our objective was to test the findings of a 2006 trial suggesting bi-frontal anodal tDCS during slow wave sleep enhances declarative memory. Methods Twelve students (mean age 25, 9 women) free of medical problems underwent two testing conditions (active, sham) in a randomized counterbalanced fashion. Active stimulation consisted of oscillating square wave tDCS delivered during early Non-Rapid Eye Movement (NREM) sleep. The sham condition consisted of setting-up the tDCS device and electrodes, but not turning it on during sleep. tDCS was delivered bi-frontally with anodes placed at F3/F4, and cathodes placed at mastoids. Current density was 0.517 mA/cm2 , and oscillated between zero and maximal current at a frequency of 0.75 Hz. Stimulation occurred during five–five minute blocks with 1-min inter-block intervals (25 min total stimulation). The primary outcomes were both declarative memory consolidation measured by a paired word association test (PWA), and non-declarative memory, measured by a non-dominant finger-tapping test (FTT). We also recorded and analyzed sleep EEG. Results There was no difference in the number of paired word associations remembered before compared to after sleep (active = 3.1 ± 3.0 SD more associations) (sham = 3.8 ± 3.1 SD more associations). Finger tapping improved, (non-significantly) following active stimulation (3.6 ± 2.7 SD correctly typed sequences) compared to sham stimulation (2.3 ± 2.2 SD correctly typed sequences). Conclusion In this study, we failed to find improvements in declarative or performance memory and could not replicate an earlier study using nearly identical settings. Specifically we failed to find a beneficial effect on either overnight declarative or non-declarative memory consolidation via square-wave oscillating tDCS intervention applied bi-frontally during early NREM sleep. It is unclear if the morphology of the tDCS pulse is critical in any memory related improvements.
Background and Objective
Several studies have shown that repetitive transcranial magnetic stimulation (rTMS), applied to the dorsolateral prefrontal cortex (DLPFC), can reduce cue‐elicited craving in ...smokers. Currently, the mechanism of this effect is unknown. We used functional magnetic resonance imaging (fMRI) to explore the effect of a single treatment of rTMS on cortical and sub‐cortical neural activity in non‐treatment seeking nicotine‐dependent participants.
Methods
We conducted a randomized, counterbalanced, crossover trial in which participants attended two experimental visits separated by at least 1 week. On the first visit, participants received either active, or sham rTMS (10 Hz, 5 s‐on, 10 s‐off, 100% motor threshold, 3,000 pulses) over the left DLPFC, and on the second visit they received the opposite condition (active or sham). Cue craving fMRI scans were completed before and after each rTMS session.
Results
A total of 11 non‐treatment seeking nicotine‐dependent cigarette smokers were enrolled in the study six female, average age 39.7 ± 13.2, average cigarettes per day 17.3 ± 5.9. Active rTMS decreased activity in the contralateral medial orbitofrontal cortex (mOFC) and ipsilateral nucleus accumbens (NAc) compared to sham rTMS.
Conclusions
This preliminary data suggests that one session of rTMS applied to the DLPFC decreases brain activity in the NAc and mOFC in smokers.
Scientific Significance
rTMS may exert its anti‐craving effect by decreasing activity in the NAc and mOFC in smokers. Despite a small sample size, these findings warrant future rTMS/fMRI studies in addictions. (Am J Addict 2017;26:788–794)
Approximately 10–20% of women of reproductive age suffer from endometriosis, with 70–90% of these women reporting chronic pain symptoms that persist during their menstrual cycle. We are presenting a ...case in which a novel form of noninvasive brain stimulation called transcranial direct current stimulation was used as an intervention in a 32‐year‐old woman with persistent, chronic pain symptoms caused by endometriosis for 20 years. Ten daily, 20‐min sessions of 2‐mA anodal transcranial direct current stimulation were applied over the left primary motor cortex. Acutely, visual analog scale pain symptoms were reduced by 60%. There were also significant decreases in modules of the Endometriosis Health Profile. At the 4‐month follow‐up, the patient still expressed an overall decrease in pain symptoms of 30%.
Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that may improve oromotor skills when paired with feeding in at-risk infants, but effects on other ...motor function and how motor function relates to white matter (WM) microstructure are unknown.
In this prospective study, infants failing oral feeds and slated for gastrostomy tube (G-tube) placement received taVNS paired with bottle feeding daily for 2-3 weeks. The effects of taVNS-paired feeding on general and specific head movements were investigated using the Specific Test of Early infant motor Performance (STEP) and diffusion MRI obtained before and after taVNS treatment. Scores between and within groups (taVNS responders, attained full oral feeds; non-responders, received G-tubes) were compared.
Performance on head movement items improved significantly in responders but not in non-responders (p < 0.05). Total STEP scores were significantly higher in responders after taVNS treatment than non-responders (p = 0.04). One STEP item, rolling by arm, was associated with significantly greater change in WM tract microstructure (p < 0.05) in the responders.
These results suggest that pairing feeding with taVNS may affect specific head and neck movements to a greater extent in infants who are able to attain full oral feeds.
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