Research reported in this publication was supported by funding from the National Institutes of Health National Center of Neuromodulation for Rehabilitation, NIH/NICHD Grant Number P2CHD086844 which was awarded to the Medical University of South Carolina. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or NICHD.

This experimental protocol illustrates a typical taVNS set-up for use in a laboratory or clinical setting in which we target stimulating the anterior wall of the auditory canal (tragus) in a supine posture with an 8mm diameter round metal electrode. These methods can be mimicked for alternative active treatment sites by simply changing electrode position to the cymba concha. All methods and procedures have been IRB approved by the Human Research Protection Program (HRPP) at City College New York.
1. Materials
<ol>
	<li>Ensure all materials required to administer taVNS are prepared (Figure 3). The taVNS stimulator may be either a battery driven device that meets local safety regulations or powered from a conventional electrical outlet with built-in safety mechanisms that prevent unintended electrical surges. A constant current (current controlled) stimulator with a maximum output of 5 mA is required.</li>
	<li>For taVNS, use stimulation electrodes made of a round conductive metal (tin, Ag/AgCl, gold) combined with a conductive medium such as electrolyte gel or conductive paste (see table of materials). Alternatively, use conductive electrodes made with flexible conductive carbon electrodes and conductive gel that may or may not be adhesive. Never place electrodes directly on the skin without a conductive medium, as this may pose unnecessary risk to the participant and can cause discomfort or pain.</li>
	<li>Use computer running script software (see Table of Materials) that is programmed and used to control the stimulator and initiate stimulation with specific parameters. These parameters include current intensity (mA), pulse width (&#956;s), frequency (Hz), duty cycle (On/Off time, s), session duration (min).</li>
	<li>Use alcohol preparation pads (70% isopropyl alcohol) to prepare the skin surface before attaching electrodes to the ear. This removes surface oils from the skin surface and reduces the resistance of the skin, ensuring stimulation is delivered at safe power levels.</li>
</ol>
2. Ear Targeting and Skin Preparation
<ol>
	<li>Use the following general inclusion criteria for conducting taVNS in the research setting: Age 18&#8211;70, no facial or ear pain, no recent ear trauma, no metal implants including pacemakers, not pregnant.</li>
	<li>In the experiments involving healthy participants in a laboratory setting, use the following exclusion criteria: personal or family history of seizure, mood, or cardiovascular disorders, dependence on alcohol or recent illicit drug use, on any pharmacological agents known to increase seizure risk.</li>
	<li>Seat the participant on a comfortable bed or chair in a supine or other relaxed position with legs elevated and head supported.</li>
	<li>Inspect the left ear of the participant. Ensure no jewelry is attached and all make-up and lotion are removed. Confirm there are no skin-related contraindications at the site of stimulation, including sun burn, cuts, lesions, open sores.</li>
	<li>Find the stimulation target, landmarked by the anterior wall of the outer ear canal externally by finding the tragus. Stimulation will be delivered to the portion of the ear canal directly behind the tragus (Figure 4).</li>
	<li>Use an alcohol prep pad to gently scrub the target site, both internally and externally, to decrease skin resistance and increase conductance.</li>
</ol>
3. Electrode Preparation and Placement
<ol>
	<li>If using non-disposable electrodes, visually inspect electrodes to ensure clean, corrosion-free surface is exposed. Ensure that electrodes are disinfected to prevent spread of bacteria between subjects. This can be done using alcohol or sterilization wipes to scrub the electrodes. If using disposable electrodes, skip to step 3.2.</li>
	<li>Spread a thin layer of conductive paste to the surface of the electrode evenly. This will distribute electricity to the stimulation site. For an 8 mm diameter round electrode, a pea-sized amount of paste is sufficient. Spread the paste using a narrow wooden applicator to form a thin layer &#60;1 mm of paste on both electrodes.</li>
	<li>Connect electrode cables to the stimulation device while the device is turned off and verify the polarity of the electrodes (red/positive electrode: anode, black/negative electrode: cathode). This is an important detail as targeting is polarity specific &#8212; the anode (red/positive terminal) is the electrode placed inside the ear canal and targeting the anterior wall of the outer ear canal. The cathode (black/negative terminal) sits on the outside of the ear attached to the tragus. For sham stimulation, the anode is placed on the anterior side of the ear.</li>
	<li>Clip the spring electrode onto the tragus with the anode making contact with the anterior wall of the outer ear canal and the cathode contacting the anterior part of the tragus. 
	NOTE: If conducting sham stimulation, clip the electrode onto the earlobe (active control). Alternatively, sham stimulation may be delivered by attaching stimulation clips to active site and delivering no electrical current (passive control).</li>
	<li>As subjects will feel the pressure of the electrodes clipped to their ear, ensure this pressure is not uncomfortable or disruptive to regional blood flow as demonstrated by pale white skin at clip site or physical pain sensed by the subject. After this point, determine perceptual threshold (PT) which will be described in the next procedural step.</li>
</ol>
4. Determination of Perceptual Threshold (PT)
NOTE: Perceptual threshold is a critical value used to determine the power of taVNS stimulation. This value is defined as the minimum amount of electricity required to perceive electrical stimulation on the skin described as a pricking or tingling sensation.
<ol>
	<li>Determine the PT using a simple step-up and step-down binary parametric search. First turn on the stimulator and set the output to 3 mA. Deliver a 1 second train of taVNS stimulation at desired pulse width (typically 250&#8211;500 &#956;s) and frequency (25 Hz, can vary based on application).</li>
	<li>Ask the subject whether they felt the stimulation. Sensation is generally reported as a &#34;tickle&#34; or &#34;pricking&#34; sensation.
	<ol>
		<li>If YES, turn down stimulation intensity by 50% and repeat step 4.2. If NO, increase stimulation intensity by 50% and repeat step 4.2.</li>
	</ol>
	</li>
	<li>Repeat the process described in step 4.2 until recording a minimum of 4 &#34;YES&#34; responses in which the 4th YES response must come after a NO. The intensity (in mA) of the PT will the value at which the subject says their fourth YES response to.</li>
	<li>Use the example PT threshold finding is listed in Table 1 to assist in PT determination.</li>
</ol>
5. Delivering Stimulation
<ol>
	<li>Once the subject is comfortable stimulation electrodes with properly attached to the desired target, and the perceptual threshold determined at the desired pulse width and frequency, begin the stimulation.</li>
	<li>Use a computer running a pulse generating GUI (e.g., stimDesigner, freeware included with this manuscript) connected to a data acquisition unit (DAQ) to drive the stimulation system. The software should output TTL pulses as programmable settings (Figure 5). The TTL pulses will be sent via a BNC cable to the stimulator &#34;trigger in&#34; port. This interface software/stimulator interface allows modulation of frequency, duty cycle (on/off time), and session duration (Figure 6). The GUI used is attached as a free, open-source resource with this manuscript.
	<ol>
		<li>Ensure that stimulation is delivered at super-threshold levels, such as 200% of PT8,9. For example, if the PT was determined to be 0.8 mA, stimulation will be delivered at 1.6 mA.</li>
		<li>Ensure that the guidelines for duty cycles are followed when conducting long stimulation sessions. Typical duty cycles have 30&#8211;60 s &#34;on&#34; periods and 60&#8211;120 s &#34;off&#34; periods, or 20&#8211;50% duty cycles.</li>
		<li>Vary the length of stimulation session (total time). Studies suggest that 30-60 min stimulation sessions at a 25% duty cycle is safe and free of any acute side effects or adverse events. These sessions can be repeated with 12&#8211;24 h between sessions safely. 
		NOTE: taVNS safety is unclear for longer periods of stimulation sessions, larger percentage duty cycles (&#62;40%), accelerated paradigms, and higher stimulation current doses.</li>
	</ol>
	</li>
</ol>
6. After taVNS
<ol>
	<li>When stimulation is completed, record objective data regarding the stimulation discomfort and side effects. Although taVNS, like implantable VNS, has limited safety concerns8,28, monitor and record sensation, discomfort, and any adverse events on a rating from 0&#8211;1029.</li>
	<li>Remove the stimulation electrode from the ear and clean residual conductive paste from the subject&#39;s ear using an alcohol prep pad.</li>
	<li>Use alcohol to clean and disinfect the stimulation electrode immediately upon removing from the subject&#39;s ear.</li>
	<li>Inspect the ear for redness or irritation at the stimulation site and record any observations.</li>
</ol>

The authors have nothing to disclose.

As in all novel modalities, all the described steps are critical in the safe administration of taVNS. Of ultimate concern is subject safety, which includes not only mitigating risks before taVNS via proper screening, but also monitoring subjects during stimulation for discomfort, pain, or adverse events. Here are the three most important consideration for administering taVNS. Screening for taVNS contraindications - contraindications are as follows: any current or past history of cardiovascular disorders, facial or ear pain, recent ear trauma, metal implants above the level of the neck. For proper subject skin preparation, removing any surface oils, dirt, or makeup from the surface of the skin with alcohol helps with conductivity of the electrodes, reduces stimulation voltage required to drive the stimulator, and ultimately results in a more tolerable and safe stimulation session. It is encouraged to use a stimulator and electrodes meeting Low Output Transcranial Electrical Stimulation (LOTES) guidelines32. LOTES sets guidelines and industry standards for electrical stimulators that are built for stimulation of the head and neck and it is encouraged for groups to read this document before building their own systems. It is recommended to use either a FDA-cleared plug-in stimulator (see Table of Materials), or a low voltage (&#60;50 V), battery powered, constant current stimulator with appropriate safety measures built-in to avoid unintended over-delivery of current to the stimulation site. Ensure that electrodes are manufactured and assembled for specific use in taVNS. Ensure that the current manufacturing and engineering guidelines are followed as a reference if lab-made customized systems are used.
One consideration for taVNS is to ensure that the voltage output of the constant current stimulator can surmount the resistance of the skin and deliver the current required for stimulation. Ohm&#39;s law (V=IR) demonstrates the relationship between current (I) and skin resistance (R). A minimum of a 20 V tabletop stimulator is recommended to avoid an underpowered system. Heat generated from the scalp or environment may degrade the conductive paste. If this occurs, it is recommended to stop stimulation and re-prep skin and electrodes with new conductive paste.
A limitation of taVNS is the vast parameter space. It is unknown as to which is more important &#8212; pulse width or frequency. There is a lacking data in recent taVNS trials that answer such questions. The various behavioral effects are derived from a variety of pulse widths, frequencies and stimulation currents13,33,34,35,36,37,38,39.
At this time, it is suggested that the 500 &#181;s pulse width to be the most biologically active9. With respect to frequency, it has been demonstrated that 25 Hz is an effective frequency, although current investigations into optimal such as higher frequencies (&#62;25 Hz), bilateral stimulation (left and right ears), and investigational burst paradigms are being conducted. Studies exploring different parameters of stimulation, alternative stimulation sites, and duty cycle optimization are needed to advance and refine the taVNS method.
taVNS is a promising non-invasive alternative to conventional VNS. taVNS provides an inexpensive (&#60;$5,000 in the demonstrated experimental setup, cost heavily dependent on type of stimulator used) and straightforward method that can be used to translate positive findings in animal models exploring the use of VNS on a variety of disorders, noninvasively modulate the autonomic nervous system, and potentially miniaturized and optimized for at-home neuromodulation for the treatment of neuropsychiatric and other disorders.
The future potential and possible applications of taVNS are vast. taVNS can serve as a promising adjunct or standalone treatment for neuropsychiatric disorders such as depression and epilepsy, taVNS-paired rehabilitation training to restore or accelerate learning of a behavior40, decrease inflammatory response41,42, and can potentially be used to enhance performance and autonomic function8,10.

Cranial nerve X, better known as the vagus nerve, is a large nerve tract that originates in the brainstem of the central nervous system and travels throughout the periphery, targeting every major organ in the thorax and abdomen (Figure 1)1. Vagus nerve stimulation (VNS) involves surgical implantation of bipolar electrodes around the left cervical branch of the vagus nerve. Electrical pulses are delivered to the vagus nerve via an implanted pulse generator (IPG) surgically implanted in the chest2. Although VNS is currently FDA-approved for epilepsy, refractory depression, and chronic obesity, it is a costly procedure requiring a hospital visit and surgery. Long-term safety of VNS is well established, and the majority of safety considerations regard current intensity related side effects (hoarse voice, throat pain) without serious stimulation-related adverse effects over the past 25 years of its clinical use3.
Recently, a noninvasive form of VNS known as transcutaneous auricular vagus nerve stimulation (taVNS) has emerged4. taVNS delivers electrical stimulation to the auricular branch of the vagus nerve (ABVN), an easily accessible target that innervates the human ear5. Over the last decade, several groups have demonstrated the safety and tolerability of this method6,7,8, including central and peripheral nervous system effects9,10, and behavioral effects7,11,12,13 in neuropsychiatric populations. taVNS is also being explored in individuals as a promising enhancer of cognitive14,15 and social functioning16,17,18. As taVNS is becoming established, it offers the ability for researchers and clinicians to rapidly translate the promising VNS research that has been described in various disorders ranging from neurological and psychological trauma19,20,21, addiction22, inflammation23, and tinnitus24,25.
In principle, taVNS is methodologically similar to conventionally administered transcutaneous electrical nerve stimulation (TENS) used to treat musculoskeletal pain disorders26. The difference is that taVNS is delivered to specific anatomical ear targets that are believed to be innervated by the ABVN5. The field is still determining optimal stimulation targets27, although the two most common placements are the anterior wall of the outer ear canal (tragus) and the cymba conchae. Sham stimulation may be conducted by stimulating the earlobe of the ear, an area believed to have minimal ABVN innervation (Figure 2). Alternatively, sham may be delivered via a passive control method in which electrodes are attached to active sites, but no stimulation is delivered. Stimulation parameters may vary between groups, however according to the literature, stimulation is delivered in a pulsatile fashion (pulse width: 250&#8211;500 &#956;s, frequency: 10&#8211;25 Hz) and delivered at an individualized constant current (&#60;5 mA). Stimulation current varies by individual and experimental protocol, with many groups exploring various intensities as a function of an individual perceptual threshold (PT). The PT is defined as the minimum amount of current eliciting a perceived sensation at the target site and is usually determined via parametric estimation by customized sequential testing (PEST) software described in this report.
taVNS is a safe technique that may be administered in the laboratory or clinical setting. Side-effects of taVNS are minimal, with skin irritation or redness being the most common side-effect. Most taVNS studies explore stimulation of the left ear, as it is believed to be safer, although data in a large trial (Badran et al. 2018) reveal that right-sided stimulation has no increases in the risk of adverse events. Due to the wealth of literature in unilateral-left side stimulation, we will illustrate the typical taVNS set-up for laboratory studies investigating the use of left-sided taVNS as an intervention.

<table><tbody><tr><td>70% Isopropyl Alcohol Wipes</td><td>Any</td><td>N/A</td><td>Any alcohol preparation pads used for skin in appropriate.</td></tr><tr><td>Constant Current Stimulator (Triggerable)</td><td>Soterix Medical</td><td>N/A</td><td>Stimulator manufactured for custom use by Soterix Medical</td></tr><tr><td>Disposable Conductive Electrodes</td><td>Custom Built</td><td>N/A</td><td>Stimulation electrodes are custom built at the City College Neural Engineering Lab (Badran/Bikson)</td></tr><tr><td>Matlab Software w/ Stimulation GUI</td><td>MathWorks</td><td>N/A</td><td>MATLAB used for programing pulse pattern</td></tr><tr><td>Ten20 Conductive Paste</td><td>Weaver and Company</td><td>N/A</td><td>Conductive paste used for administration of stimulation</td></tr></tbody></table>

laboratory administration of transcutaneous auricular vagus nerve stimulation (tavns): technique, targeting, and considerations

Non-invasive vagus nerve stimulation (VNS) may be administered via a novel, emerging neuromodulatory technique known as transcutaneous auricular vagus nerve stimulation (taVNS). Unlike cervically-implanted VNS, taVNS is an inexpensive and non-surgical method used to modulate the vagus system. taVNS is appealing as it allows for rapid translation of basic VNS research and serves as a safe, inexpensive, and portable neurostimulation system for the future treatment of central and peripheral disease. The background and rationale for taVNS is described, along with electrical and parametric considerations, proper ear targeting and attachment of stimulation electrodes, individual dosing via determination of perception threshold (PT), and safe administration of taVNS.

When proper skin preparation is conducted, perceptual thresholds are inversely correlated with stimulation pulse width. As pulse width increases, the perceptual threshold decreases (Figure 7). Initial studies by this group exploring the effect of pulse width on PT in healthy individuals (meeting inclusion/exclusion criteria listed above), determined that the combined overall (n=15, 7 female, mean age 26.5 ± 4.99) PT at 100 μs = 3.92 ± 1.1 mA; 200 μs = 2.24 ± 0.74 mA; 500 μs = 1.24 ± 0.41 mA. These thresholds suggest that a constant current stimulator with capacity of delivering up to 5 mA of current is required for stimulation of 500 μs pulse width parameters, and a minimum of a 10mA stimulator is required for lower pulse widths (Table 2). Fine tuning of the current is required, with increments of 0.1 mA are necessary for precise stimulation.
Delivering stimulation at 200% PT is tolerable and relatively pain free as demonstrated by pain numerical rating scales (NRS) scales9,30. The NRS scale is a rating system for pain from 0-10 in which individuals report pain or discomfort29. Both Active and Sham stimulation rate similarly low pain levels (NRS &lt;3 for all stimulation pulse widths. More specifically, the biologically-active pulse width of 500 μs delivered at 25 Hz is reported on average to rate as Active = 1.98 ± 0.83, Sham = 2.17 ± 1.27 (n=25, 9 female, mean age 25.16 ± 4.16 years) (Table 3). Pain ratings for other parameters are no more painful than the 25 Hz parameter and the details can be found in the groups' prior work30.
Safety and tolerability of 30 min to 1 hour sessions at a 20–50% duty cycle has been widely reported in the literature with some studies delivering multiple sessions in the same day spread 12–15 h apart12,31. No serious adverse events have been reported from 60 subjects participating in several series of experiments with subjects participating from 1 to 8 repeated visits spread a minimum of 24 hours apart.
taVNS, when administered as reported in this manuscript, has been demonstrated to modulate the autonomic nervous system, induce functional brain activity changes as measured by fMRI BOLD, and piloted to treat neuropsychiatric disorders and aid in rehabilitation.
<img alt="Autonomic nervous system diagram showing brain-body connections; inset with cellular cross-section." class="xfigimg" src="/files/ftp_upload/58984/58984fig1.jpg" data-altupdatedat="1747911167000" data-alt="Figure 1"> 
Figure 1: Vagus Nerve Efferent Projections and Cross-section. (A) Efferent projections of the vagus nerve target every major organ on the body with wide effects on bodily function (B) Cross-section of the vagus nerve, demonstrating the inside anatomy of the nerve as a series of bundles of nerves all contained within one major pathway. <a href="https://www.jove.com/files/ftp_upload/58984/58984fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Ear acupuncture diagram with labeled points A1, A2, S for therapy and treatment reference." class="xfigimg" src="/files/ftp_upload/58984/58984fig2.jpg" data-altupdatedat="1747911167000" data-alt="Figure 2"> 
Figure 2: taVNS Ear Targets. Targeting the ABVN can be accomplished by stimulating the anterior wall of the outer ear canal, landmarked notably by the tragus (A1), or cymba conchae (A2). Sham stimulation is administered to the earlobe (S). <a href="https://www.jove.com/files/ftp_upload/58984/58984fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Electrophysiology setup diagram; includes sensor, conductive paste, Matlab GUI, electronic stimulator." class="xfigimg" src="/files/ftp_upload/58984/58984fig3.jpg" data-altupdatedat="1747911167000" data-alt="Figure 3"> 
Figure 3: Key Components. The minimum required components for proper administration of taVNS are the following (A) ear stimulation electrodes, (B) conductive gel and alcohol prep pads, (C) computer capable of sending and receiving TTL pulses to a (D) constant current stimulator to trigger stimulation. <a href="https://www.jove.com/files/ftp_upload/58984/58984fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Transcutaneous stimulation setup, electrodes on ear, monitors for cardiovascular recording, experiment." class="xfigimg" src="/files/ftp_upload/58984/58984fig4.jpg" data-altupdatedat="1747911167000" data-alt="Figure 4"> 
Figure 4: Example Setup. This photo shows an individual receiving taVNS of the left ear while in position to undergo an experimental paradigm. <a href="https://www.jove.com/files/ftp_upload/58984/58984fig4large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="StimDesign setup for external stimulator triggering; includes pulse parameters and waveform graph." class="xfigimg" src="/files/ftp_upload/58984/58984fig5.jpg" data-altupdatedat="1747911167000" data-alt="Figure 5"> 
Figure 5: Screenshot of the GUI used for stimulation. <a href="https://www.jove.com/files/ftp_upload/58984/58984fig5large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Pulse waveform diagram; illustrates parameters pulse width, frequency, amplitude, duty cycle." class="xfigimg" src="/files/ftp_upload/58984/58984fig6.jpg" data-altupdatedat="1747911167000" data-alt="Figure 6"> 
Figure 6: Electrical Stimulation Waveform Manipulations. Direct square wave electrical current can be delivered at various parameters. This figure demonstrates key properties of the waveform that can be changed in order to achieve desired biologic effects. <a href="https://www.jove.com/files/ftp_upload/58984/58984fig6large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Bar chart comparing current vs. pulse width; active vs. sham conditions; error bars show SD." class="xfigimg" src="/files/ftp_upload/58984/58984fig7.jpg" data-altupdatedat="1747911167000" data-alt="Figure 7"> 
Figure 7: Perceptual Threshold Values at Increasing Pulse Widths. As pulse width increases, perceptual threshold (PT) decreases. Most healthy individuals will have a PT within 2 standard deviations (SD) of these mean values. <a href="https://www.jove.com/files/ftp_upload/58984/58984fig7large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Stimulation current response table; current settings vs. response outcomes (Yes/No), experiment results." src="/files/ftp_upload/58984/58984table1.jpg" data-altupdatedat="1747911167000" data-alt="Table 1"> 
Table 1: Example of How to Determine Perceptual Threshold (PT). This table shows an example sequence of Yes/No responses used to parametrically determine PT.
<img alt="Electrical stimulation table; pulse width vs stimulation current; experimental results analysis." src="/files/ftp_upload/58984/58984table2.jpg" data-altupdatedat="1747911167000" data-alt="Table 2"> 
Table 2: Stimulation Current Levels. Values of stimulation current in mA (200% PT) for each pulse width (n=15).
<img alt="Electrophysiology data table; stimulation vs. control, showing current and pain with significance results." src="/files/ftp_upload/58984/58984table3.jpg" data-altupdatedat="1747911167000" data-alt="Table 3"> 
Table 3: PT, Stimulation Current, and Pain Values for Suggested Stimulation Parameters. Values of stimulation current in mA (200% PT) for each pulse width (n=25).
<img alt="Interface for external stimulator setup; pulse sequence parameters, session graph analysis." src="/files/ftp_upload/58984/58984supfig1.jpg" data-altupdatedat="1747911167000" data-alt="Supplemental File Figure"> 
Supplemental File: Freeware GUI used in this protocol. <a href="https://www.jove.com/files/ftp_upload/58984/stimDesigner.zip" target="_blank">Please click here to download this file.</a>

Watch this Scientific Journal Video about Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation taVNS: Technique, Targeting, and Considerations at JoVE.com

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation taVNS: Technique, Targeting, and Considerations

A methodological description of the technique, potential targets, and proper administration of transcutaneous auricular vagus nerve stimulation (taVNS) on the human ear is described.

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations

Non-invasive vagus nerve stimulation (VNS) may be administered via a novel, emerging neuromodulatory technique known as transcutaneous auricular vagus ...

laboratory-administration-transcutaneous-auricular-vagus-nerve

Research

JoVE Journal

Neuroscience

38.4K Views.  City College of New York. We demonstreren transcutane oriculaire Vegas zenuwstimulatie vandaag. Kortom bekend als TAVNS. TAVNS is een echt veelbelovende vervanging voor cervicale geïmplanteerde conventionele Vegas zenuwstimulatie, het is echt een spannende nieuwe vorm van neuromodulatie.Omdat TAVNS veilig en niet invasief is, kan het zijn bereik uitbreiden naar een breed scala aan neuropsychiatrische en menselijke prestatietoepassingen. De procedure is vrij eenvoudig, maar de software voor het leveren van stim...

Video: Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation taVNS: Technique, Targeting, and Considerations

Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been maintaining the behavior. There is close correspondence between fear and human anxiety, and therefore studies of extinction learning might provide insight into the biological nature of anxiety-related disorders such as post-traumatic stress disorder, and they might help to develop strategies to treat them. Preclinical research aims to aid extinction learning and to induce targeted plasticity in extinction circuits to consolidate the newly formed memory. Vagus nerve stimulation (VNS) is a powerful approach that provides tight temporal and circuit-specific release of neurotransmitters, resulting in modulation of neuronal networks engaged in an ongoing task. VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here, we provide a detailed protocol for the preparation of custom-made parts and the surgical procedures required for VNS in rats. Using this protocol we show how VNS can facilitate the extinction of conditioned fear responses in an auditory fear conditioning task. In addition, we provide evidence that VNS modulates synaptic plasticity in the pathway between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA), which is involved in the expression and modulation of extinction memory.

Vagus nerve stimulation (VNS) has emerged as a tool to induce targeted synaptic plasticity in the forebrain to modify a range of behaviors. This protocol describes how to implement VNS to facilitate the consolidation of fear extinction memory.

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been ...

Behavior

A Tactile Automated Passive-Finger Stimulator (TAPS)

Although tactile spatial acuity tests are used in both neuroscience research and clinical assessment, few automated devices exist for delivering controlled spatially structured stimuli to the skin. Consequently, investigators often apply tactile stimuli manually. Manual stimulus application is time consuming, requires great care and concentration on the part of the investigator, and leaves many stimulus parameters uncontrolled. We describe here a computer-controlled tactile stimulus system, the Tactile Automated Passive-finger Stimulator (TAPS), that applies spatially structured stimuli to the skin, controlling for onset velocity, contact force, and contact duration. TAPS is a versatile, programmable system, capable of efficiently conducting a variety of psychophysical procedures. We describe the components of TAPS, and show how TAPS is used to administer a two-interval forced-choice tactile grating orientation test.
Corresponding Author: Daniel Goldreich

A Tactile Automated Passive-Finger Stimulator TAPS

We describe a computer-controlled device for investigating the sense of touch: the Tactile Automated Passive-finger Stimulator (TAPS). We describe the components of TAPS, and show how TAPS is used to administer a two-interval forced-choice tactile grating orientation test.

Although tactile spatial acuity tests are used in both neuroscience research and clinical assessment, few automated devices exist for delivering ...

Biology

Effects of Transcranial Alternating Current Stimulation on the Primary Motor Cortex by Online Combined Approach with Transcranial Magnetic Stimulation

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific frequency and in turn modulate ongoing cortical oscillatory activity. This neurotool allows the establishment of a causal link between endogenous oscillatory activity and behavior. Most of the tACS studies have shown online effects of tACS. However, little is known about the underlying action mechanisms of this technique because of the AC-induced artifacts on Electroencephalography (EEG) signals. Here we show a unique approach to investigate online physiological frequency-specific effects of tACS of the primary motor cortex (M1) by using single pulse Transcranial Magnetic Stimulation (TMS) to probe cortical excitability changes. In our setup, the TMS coil is placed over the tACS electrode while Motor Evoked Potentials (MEPs) are collected to test the effects of the ongoing M1-tACS. So far, this approach has mainly been used to study the visual and motor systems. However, the current tACS-TMS setup can pave the way for future investigations of cognitive functions. Therefore, we provide a step-by-step manual and video guidelines for the procedure.

Transcranial Alternating Current Stimulation (tACS) allows the modulation of cortical excitability in a frequency-specific fashion. Here we show a unique approach which combines online tACS with single pulse Transcranial Magnetic Stimulation (TMS) in order to "probe" cortical excitability by means of Motor Evoked Potentials.

Transcranial Alternating Current Stimulation (tACS) is a neuromodulatory technique able to act through sinusoidal electrical waveforms in a specific ...

Bilateral Assessment of the Corticospinal Pathways of the Ankle Muscles Using Navigated Transcranial Magnetic Stimulation

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans and can be assessed using transcranial magnetic stimulation (TMS). Given the role of distal leg muscles in upright postural and dynamic tasks, such as walking, a growing research interest in the assessment and modulation of the corticospinal tracts relative to the function of these muscles has emerged in the last decade. However, methodological parameters used in previous work have varied across studies making the interpretation of results from cross-sectional and longitudinal studies less robust. Therefore, use of a standardized TMS protocol specific to the assessment of leg muscles&#39; corticomotor response (CMR) will allow for direct comparison of results across studies and cohorts. The objective of this paper is to present a protocol that provides the flexibility to simultaneously assess the bilateral CMR of two main ankle antagonistic muscles, the tibialis anterior and soleus, using single pulse TMS with a neuronavigation system. The present protocol is applicable while the examined muscle is either fully relaxed or isometrically contracted at a defined percentage of maximum isometric voluntary contraction. Using each subject&#39;s structural MRI with the neuronavigation system ensures accurate and precise positioning of the coil over the leg cortical representations during assessment. Given the inconsistency in CMR derived measures, this protocol also describes a standardized calculation of these measures using automated algorithms. Though this protocol is not conducted during upright postural or dynamic tasks, it&#160;can be used to assess bilaterally any pair of leg muscles, either antagonistic or synergistic, in both neurologically intact and impaired subjects.

The present protocol describes the simultaneous, bilateral assessment of the corticomotor response of the tibialis anterior and soleus during rest and tonic voluntary activation using a single pulse transcranial magnetic stimulation and neuronavigation system.

Distal leg muscles receive neural input from motor cortical areas via the corticospinal tract, which is one of the main motor descending pathway in humans ...

Vagus Nerve Stimulation As an Adjunctive Neurostimulation Tool in Treatment-resistant Depression

Vagus nerve stimulation (VNS) is an approved neurostimulation therapy. The purpose of the method is to treat patients with therapy-resistant depression (TRD). VNS exhibits antidepressive and stabilizing effects. This method is particularly useful as a long-term treatment, in which up to two-thirds of patients respond. The vagus nerve stimulator is positioned on the left vagus nerve during a surgical procedure and is activated telemetrically by a wand connected to a handheld computerized device. The treating physician can perform various adjustments of the vagus nerve stimulator during in-office visits (e.g., by modifying stimulation intensity or stimulation frequency) to achieve maximum therapeutic effects with low side effects. Set-up of the device usually takes several months. Typical side effects include wound infection, temporary salivation, coughing, paralysis of the vocal cords, bradycardia, or even asystole. The patient can stop the VNS by placing a magnet over the generator. The current protocol describes delivery of the specific stimulation tool and methods for adjusting the tuning parameters to achieve the best remission rates in patients with TRD.

Vagus nerve stimulation (VNS) has been shown to be effective as an adjunct treatment for treatment-resistant depression (TRD). VNS leads to antidepressive and antisuicidal effects and quality of life improvements. This protocol offers a step-by-step guide to managing and adjusting a vagus nerve stimulator for efficient treatment of TRD.

Vagus nerve stimulation (VNS) is an approved neurostimulation therapy. The purpose of the method is to treat patients with therapy-resistant depression ...

Medicine

Measurement of Neuromodulation by Transcutaneous Auricular Vagus Nerve  Stimulation

Understanding the Effects of Non&#45;Invasive Transauricular Vagus Nerve Stimulation on EEG and HRV

Several studies have demonstrated promising results of transcutaneous auricular vagus nerve stimulation (taVNS) in treating various disorders; however, no mechanistic studies have investigated this technique's neural network and autonomic nervous system effects. This study aims to describe how taVNS can affect EEG metrics, HRV, and pain levels. Healthy subjects were randomly allocated into two groups: the active taVNS group and the sham taVNS group. Electroencephalography (EEG) and Heart Rate Variability (HRV) were recorded at baseline, 30 min, and after 60 min of 30 Hz, 200-250 &#181;s taVNS, or sham stimulation, and the differences between the metrics were calculated. Regarding vagal projections, some studies have demonstrated the role of the vagus nerve in modulating brain activity, the autonomic system, and pain pathways. However, more data is still needed to understand the mechanisms of taVNS on these systems. In this context, this study presents methods to provide data for a deeper discussion about the physiological impacts of this technique, which can help future therapeutic investigations in various conditions.

Author Spotlight: Exploring the Effects of Transauricular Vagus Nerve Stimulation

This protocol provides information on how to apply transcutaneous auricular vagus nerve stimulation (taVNS) in a clinical trial, including potential biomarkers such as EEG metrics and heart rate variability (HRV) to measure the effect of this treatment on the autonomic nervous system.

Several studies have demonstrated promising results of transcutaneous auricular vagus nerve stimulation (taVNS) in treating various disorders; however, no ...

Abdominal VNS for Treating Inflammatory Conditions in Rat Models

Implantation Surgery for Abdominal Vagus Nerve Stimulation and Recording Studies in Awake Rats

Abdominal vagus nerve stimulation (VNS) can be applied to the subdiaphragmatic branch of the vagus nerve of rats. Due to its anatomical location, it does not have any respiratory and cardiac off-target effects commonly associated with cervical VNS. The lack of respiratory and cardiac off-target effects means that the intensity of stimulation does not need to be lowered to reduce side effects commonly experienced during cervical VNS. Few recent studies demonstrate the anti-inflammatory effects of abdominal VNS in rat models of inflammatory bowel disease, rheumatoid arthritis, and glycemia reduction in a rat model of type 2 diabetes. Rat is a great model to explore the potential of this technology because of the well-established anatomy of the vagus nerve, the large size of the nerve that allows easy handling, and the availability of many disease models. Here, we describe the methods for cleaning and sterilizing the abdominal VNS electrode array and surgical protocol in rats. We also describe the technology required for confirmation of suprathreshold stimulation by recording evoked compound action potentials. Abdominal VNS has the potential to offer selective, effective treatment for a variety of conditions, including inflammatory diseases, and the application is expected to expand similarly to cervical VNS.

Author Spotlight: Exploring Abdominal VNS for Inflammatory Conditions

The present protocol describes the surgical technique for implanting an electrode array onto the abdominal vagus nerve in rats, along with methods for chronic electrophysiology testing and stimulation using the implanted device.

Abdominal vagus nerve stimulation (VNS) can be applied to the subdiaphragmatic branch of the vagus nerve of rats. Due to its anatomical location, it does ...

Treatment of Phantom Limb Pain by Remote Transcranial Direct Current Stimulation

Using Home-based, Remotely Supervised, Transcranial Direct Current Stimulation for Phantom Limb Pain

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low-amplitude direct currents to alter cortical excitability. Previous trials have established the safety and tolerability of tDCS, and its potential to mitigate symptoms. However, the effects are cumulative, making it more difficult to have adherence to the treatment since frequent visits to the clinic or outpatient center are required. Moreover, the time needed for transportation to the center and the related expenses limit the accessibility of the treatment for many participants.
Following guidelines for remotely supervised transcranial direct current stimulation (RS-tDCS) implementation, we propose a protocol designed for remotely supervised and home-based participation that uses specific devices and materials modified for patient use, with real-time monitoring by researchers through an encrypted video conferencing platform. We have developed detailed instructional materials and structured training procedures to allow for self- or proxy-administration while supervised remotely in real time. This protocol has a specific design to have a series of checkpoints during training and execution of the visit. This protocol is currently in use in a large pragmatic study of RS-tDCS for phantom limb pain (PLP). In this article, we will discuss the operational challenges of conducting a home-based RS-tDCS session and show methods to enhance its efficacy with supervised sessions.

Author Spotlight: Insights into Remotely Supervised Neuromodulation Procedure for Phantom Limb Pain

The goal of this study is to describe a protocol for the home-based delivery of remotely supervised transcranial direct current stimulation (RS-tDCS) conserving the standard procedures of in-clinic practice, including safety, reproducibility, and tolerability. The participants included will be patients with phantom limb pain (PLP).

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low-amplitude direct currents to alter cortical ...

Electrical Stimulation Therapy: Non-Surgical Remedy for Varicocele-Induced Pain

Transcutaneous Neuromuscular Electrical Stimulation for Treating Varicocele-Induced Scrotal Pain

Varicocele is a prevalent vascular disorder affecting the male reproductive system, leading to scrotal pain and testicular dysfunction. Epidemiological studies have shown that varicocele occurs in approximately 10% to 15% of adult males, while scrotal pain affects 2% to 10% of the population. Currently, clinical treatment options for varicocele-induced scrotal pain include general therapy, medication, and surgery. Among these, surgical intervention is considered the most effective method, boasting a success rate of 80%. However, it carries risks such as postoperative bleeding, infection, and recurrence, making it less desirable for some patients. In recent years, transcutaneous neuromuscular electrical stimulation has gained wide acceptance for treating various andrological conditions, including erectile dysfunction and premature ejaculation, yielding positive outcomes. This non-invasive technique offers a promising alternative for managing varicocele-induced scrotal pain, potentially reducing the need for surgical intervention and its associated risks. Its growing popularity underscores the need for further research and clinical trials to validate its efficacy and safety in treating this condition.

Author Spotlight: Advancing Varicocele Treatment with Neuromuscular Electrical Stimulation

This protocol outlines the use of transcutaneous neuromuscular electrical stimulation for treating varicocele-induced scrotal pain. It compares visual analog scale (VAS) scores and imaging changes before and after treatment to assess effectiveness. Results indicate that patients experienced improved scrotal pain symptoms following the treatment.

Varicocele is a prevalent vascular disorder affecting the male reproductive system, leading to scrotal pain and testicular dysfunction. Epidemiological ...

Automated Periodic Stimulation Electrode Installation: A Technique to Surgically Implant An Automated Stimulation Device on the Vagus Nerve in a Porcine Model

Source: Wu, C. W., et al. <a href="https://www.jove.com/v/57919">Intra-Operative Neural Monitoring of Thyroid Surgery in a Porcine Model.</a> J. Vis. Exp. (2019).
In this video, we demonstrate the procedure for the installation of an automated periodic stimulation electrode on the vagus nerve for monitoring nerves during thyroid surgeries in a porcine model. This helps in the correct identification of the target nerve during surgical procedures.

Source: Wu, C. W., et al. Intra-Operative Neural Monitoring of Thyroid Surgery in a Porcine Model. J. Vis. Exp. (2019).
In this video, we demonstrate the ...

Laboratory Administration of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS): Technique, Targeting, and Considerations

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