Vagus Nerve Stimulation (VNS)

Overview

Vagus nerve stimulation is, in many ways, the strangest member of the neuromodulation family. It requires surgery to implant, then works slowly over months, and once it's working, the benefit keeps accruing for a year or two. That profile makes it genuinely useful for a specific population — patients with chronic, markedly treatment-resistant depression who have tried most everything else — and genuinely mismatched for acute presentations where speed matters.

This page is written for both patients considering VNS and clinicians supporting or managing VNS patients. The distinction between those audiences isn't as sharp as it is for TMS or ECT; VNS is enough of a commitment that patients considering it tend to want the same level of detail their clinicians do.

What VNS is

VNS uses a small implanted pulse generator — about the size of a cardiac pacemaker — to deliver regular electrical pulses to the left cervical vagus nerve. The generator sits under the skin below the left collarbone. A thin wire (the "lead") runs from the generator, tunneled beneath the skin of the chest and neck, to the vagus nerve itself where it wraps around the nerve and delivers the stimulation.

Once turned on, the device runs continuously on a preset schedule — for example, stimulating for 30 seconds every 5 minutes, 24 hours a day. Patients don't have to do anything to activate it. The device doesn't need to be charged. The battery lasts approximately 8–10 years before requiring a minor outpatient replacement procedure.

How VNS was discovered for depression

VNS has been used for epilepsy since the early 1990s. The antidepressant effect was discovered incidentally — epilepsy patients treated with VNS reported that their mood improved as a side effect of seizure control. This led to dedicated trials for depression, and eventually to FDA approval for treatment-resistant depression in 2005.

How it works in the brain

The vagus nerve is a bidirectional information highway between the body and the brainstem. When VNS stimulates the vagus nerve, it's primarily activating afferent fibers — those that carry signals up from the body to the brain. These signals first reach the nucleus tractus solitarius in the brainstem, then propagate to the locus coeruleus, raphe nuclei, amygdala, hippocampus, and prefrontal cortex — regions involved in mood, arousal, and reward regulation.

The mechanism is thought to involve gradual changes in noradrenergic and serotonergic signaling, plus inflammation reduction and neuroplasticity effects that accumulate over months. The slow onset almost certainly reflects the fact that these are adaptive changes that take time to develop, rather than acute effects that could be measured immediately.

How VNS is different from other treatments

VNS has an unusual therapeutic profile that sets it apart from TMS, ECT, ketamine, and pharmacotherapy:

• Slow onset. Benefits typically emerge over 3–12 months of continuous stimulation, with full effect often taking 12–24 months. This is dramatically longer than any other antidepressant intervention. Patients considering VNS need to understand they are making a long-horizon decision.
• Durable response. When VNS works, the benefit tends to accumulate rather than wane. The 5-year Aaronson registry data showed that VNS patients pulled away from treatment-as-usual progressively over time — the gap was widest at 5 years, not narrowest.
• Continuous, not episodic. Unlike TMS or ECT treatment courses, VNS is always on. There is no "index course" to complete, no tapering schedule, no maintenance sessions to schedule.
• Complementary. VNS is typically used alongside ongoing pharmacotherapy and sometimes alongside maintenance ECT or TMS, rather than as a replacement. It's additive rather than substitutive.
• One-time procedure. Unlike TMS (requires 30+ daily visits) or ECT (requires acute course + ongoing maintenance), VNS requires one surgical procedure and then background operation. The tradeoff: the procedure is surgical rather than outpatient clinical.

Who VNS is for

VNS is indicated for adults with chronic or recurrent treatment-resistant depression who have not responded to at least four adequate antidepressant trials. In practice, the typical VNS candidate has:

• Long-standing depression (years, often decades)
• Multiple failed medication trials across drug classes
• Often prior experience with ECT, with partial benefit but unable or unwilling to continue maintenance ECT indefinitely
• Capacity to tolerate a slow, uncertain response curve and continue with ongoing support while waiting for benefit

The ECT-dependent patient: a particularly good fit

One specific population stands out as especially well-suited to VNS: patients who have responded well to ECT but are dependent on ongoing maintenance ECT to stay well. Maintenance ECT is effective but logistically heavy — ongoing procedures under general anesthesia, accumulating cognitive effects, time off work, transportation needs, periodic relapses when sessions are missed or spaced too far apart.

The Aaronson 2017 registry data specifically examined this group and found that patients with a history of ECT response had the highest 5-year cumulative VNS response rate of any subgroup studied (71.3% with adjunctive VNS vs. 56.9% with treatment as usual alone). The clinical reasoning is that ECT responsiveness identifies a depression that responds to neuromodulation broadly, not just to the specific mechanism of seizure induction. VNS appears able to step into that role — offering a less disruptive, less cognitively demanding, "always on" approach to keeping these patients well.

A 10-case series of patients receiving both maintenance ECT and VNS (Aaronson 2021) and a French case series (Frontiers in Psychiatry 2023) both showed that patients were able to substantially reduce the frequency of maintenance ECT after VNS implantation, with a meaningful subset able to discontinue ECT entirely. This isn't a randomized comparison and the numbers are small, but the signal is consistent with the larger registry data.

When VNS isn't the right fit

VNS is less appropriate for patients who need rapid response to acute suicidality or crisis — by the time VNS is meaningfully working, months have passed. For those situations, ECT or rapid-acting ketamine are much better fits. VNS is also not usually first-line for moderate treatment-resistant depression where TMS hasn't been tried; the cost, surgical nature, and slow timeline of VNS make it a later-in-the-sequence option rather than an early one.

Patients should also be in a position to commit to long-term follow-up. VNS isn't a procedure you get and then forget about — parameter adjustments and monitoring are part of the treatment, particularly during the first 1–2 years.

The evidence

The VNS evidence base has been complicated and is worth walking through in detail. Both the strengths and the limitations matter for understanding when VNS makes sense.

Early evidence (2000s) and FDA approval

Early open-label trials in the 2000s (Rush 2000; Marangell 2002; Sackeim 2001) showed promising response rates of 30–50% over 12 months in patients with treatment-resistant depression. These trials established the pattern that has been consistently observed since: slow onset, cumulative benefit over months to years, modest response rates within the first 3 months but meaningful gains by 12 months and beyond.

The pivotal sham-controlled RCT that led to FDA approval (Rush 2005a) was a 10-week short-term trial, and it did not separate active VNS from sham at that primary endpoint. A companion naturalistic 12-month follow-up (Rush 2005b) showed substantially better outcomes in the VNS group than in a comparable treatment-as-usual cohort. The FDA approved VNS for treatment-resistant depression in 2005 on the basis of the longer-term data, but the failure of the short-term RCT created a credibility problem that has shaped the field's reception of VNS ever since.

In 2007, CMS (Medicare) issued a non-coverage determination for VNS in treatment-resistant depression, citing the 2005 RCT as insufficient evidence. Many private insurers followed CMS's lead, which is the principal reason VNS has remained substantially underutilized clinically relative to its evidence profile.

Aaronson 2017: the 5-year observational registry

The single most important piece of evidence for VNS's long-term efficacy is the Treatment-Resistant Depression Registry, published by Aaronson and colleagues in the American Journal of Psychiatry in 2017. This was a 5-year, prospective, open-label, nonrandomized observational study conducted at 61 US sites with 795 enrolled patients, comparing adjunctive VNS plus treatment-as-usual against treatment-as-usual alone.

The patient population was severely treatment-resistant: all participants had a current major depressive episode of at least 2 years' duration or three or more lifetime episodes, all had failed at least four prior antidepressant treatments, and many had a history of ECT. Mean baseline MADRS was 33.1 in the VNS arm and 29.3 in the treatment-as-usual arm — both in the moderate-to-severe range. Patients with psychosis or rapid-cycling bipolar disorder were excluded.

Several aspects of the registry results are clinically meaningful:

• The benefit accrued over time. The cumulative response gap between VNS and treatment-as-usual was visible by 12 months and continued to widen through 5 years — the opposite of the pattern most psychiatric treatments show, where response is highest early and tends to attenuate with time.
• Suicidality outcomes favored VNS. Both arms improved on suicidality measures from baseline, but VNS produced significantly greater reductions on two of three measures (QIDS-SR item 12 and the investigator-completed suicidality assessment), with a strong trend on the third (MADRS item 10).
• Bipolar and unipolar patients both benefited. Subanalyses showed similar efficacy across diagnoses, with effects evident by 12 months and continued through 5 years.
• The design has real limitations. This was an open-label, non-randomized observational registry; patients and clinicians were not blinded; treatment-as-usual was less intensive than in a controlled trial. The registry was sponsored by the device manufacturer (Cyberonics, now LivaNova). These limitations are real, and any honest reading of the data has to account for them.

Even acknowledging those limitations, the size, duration, and consistency of the registry findings make Aaronson 2017 the most informative single dataset on VNS for treatment-resistant depression to date. CMS's failure to use this evidence to update its 2007 coverage decision was the central frustration driving the next major trial: RECOVER.

The RECOVER trial (2024–2025)

RECOVER (Conway et al., Brain Stimulation 2025) was designed specifically to answer CMS's evidence requirements with a rigorously controlled trial. It was co-sponsored by LivaNova and CMS, conducted from September 2019 to May 2024 at 84 US sites, and enrolled 493 adults with markedly treatment-resistant depression. All participants had failed at least 4 adequate antidepressant trials in the current episode; the cohort had a mean baseline MADRS of 34.6 and an average duration of major depressive episode of more than 20 years — an extraordinarily ill population (Conway 2024, RECOVER baseline characterization paper).

Trial design specifics:

• All 493 patients received VNS device implantation
• 249 randomized to active stimulation; 244 to sham (no stimulation)
• Active and sham conditions maintained for 12 months
• Primary endpoint: percent time in MADRS response (≥50% reduction from baseline) across months 3–12
• Multiple secondary endpoints, including clinician-rated CGI-I, patient self-report (QIDS-SR), and offsite blinded rater (QIDS-C)
• 88.4% of enrolled patients completed the 12-month trial
• Parameter adjustments were limited during the blinded period to maintain blinding integrity

What RECOVER found

The headline result: the trial missed its primary endpoint. Percent time in MADRS response was not significantly different between active VNS and sham. This was a real disappointment for the field and for advocates expecting RECOVER to produce a clean coverage-justifying result.

However, the secondary endpoints — pre-specified, not post-hoc — told a more complex story. Active VNS produced statistically significant advantages on:

• Clinician-rated improvement (CGI-I) — both percent time in response (p=0.004) and percent time in partial response (p<0.001)
• Patient self-report (QIDS-SR) — percent time in response (p=0.049)
• Offsite blinded clinician ratings (QIDS-C) — percent time in partial response (p=0.006)
• Daily function and quality of life — consistently better in active VNS across multiple validated instruments (Rush et al., RECOVER QoL paper, Brain Stimulation 2025)

The pattern across these results is informative: three independent rater perspectives — the treating clinician, the patient, and an offsite blinded rater — all detected an antidepressant signal favoring active VNS, even when the primary MADRS-based metric did not. Partial response (≥30% improvement) was the most sensitive measure, which makes clinical sense in a population where full 50% response and remission are exceptionally hard endpoints to hit.

Why might the primary endpoint have failed?

Several factors plausibly contributed to the strong sham response and the resulting primary endpoint miss:

• Procedural placebo effect. A 12-month sham implantation is an extraordinary commitment. Patients who volunteer for it are highly invested in their care, receive enhanced clinical attention as part of the trial protocol, and have undergone real surgery — all of which can produce substantial improvement on patient-reported and clinician-rated measures.
• Enhanced treatment as usual. All RECOVER participants received structured ongoing care that was likely more intensive than what most of these patients had received in routine practice.
• The MADRS as a metric. Percent time in MADRS response across a 9-month window may simply be too narrow a metric to capture the kinds of partial, gradually-accumulating improvements that VNS produces in this population — which is exactly what the partial-response secondary endpoints showed.
• Blinding-driven parameter restrictions. Real-world VNS practice involves periodic parameter optimization (current, pulse width, duty cycle) over the first 1–2 years to find the dose that works for an individual. RECOVER constrained these adjustments to maintain blinding, which may have reduced active-arm efficacy.

Where the evidence stands now

In June 2025, LivaNova initiated the formal CMS reconsideration process to seek Medicare coverage for VNS in treatment-resistant depression. The application is built on the RECOVER data, the Aaronson 2017 registry, and several follow-on RECOVER analyses (the Rush quality-of-life paper, the Sackeim symptom characterization paper, and the upcoming 24-month durability data). The reconsideration process typically takes 12–18 months. Whether or not CMS reverses its 2007 decision will substantially affect access to VNS for the patients who would benefit most.

Practical considerations

The implantation procedure

VNS implantation is an outpatient surgical procedure performed by a neurosurgeon. Patients go home the same day. Details:

• Duration: Typically 1–2 hours under general anesthesia
• Incisions: Two small incisions — one below the left collarbone for the pulse generator, one in the left side of the neck for the lead attachment to the vagus nerve
• Recovery: Mild incision pain and restricted activity for 1–2 weeks; most patients return to normal activity quickly
• Surgical complication rate: Low; risks include infection, bleeding, injury to surrounding nerves or vessels. Serious complications are rare.

Activation and titration

The device is typically activated 2–4 weeks post-op to allow incision healing. At the first activation visit, initial parameters are set at a low level and gradually increased over subsequent visits based on tolerability. Most patients notice a mild sensation in the throat during stimulation (throat tightness, slight voice change, coughing). These sensations usually become less noticeable with time as the patient adapts, and parameters can be adjusted if they remain bothersome.

Device management and follow-up

Once activated, the device requires periodic check-ups by the psychiatrist or neurologist managing the patient:

• Every 3–6 months during the first 1–2 years, during which parameters may be adjusted to optimize response
• Less frequent (annually) once stable
• Visits involve interrogation of the device via an external programmer (painless, takes a few minutes), review of response and side effects, and any parameter adjustments

Side effects

The most common VNS side effects occur during stimulation and typically diminish with time or with parameter adjustment:

• Voice changes (most common)
• Cough
• Throat tightness or discomfort
• Shortness of breath with exertion during stimulation (dyspnea was the one safety signal that distinguished active from sham VNS in RECOVER)
• Infection at the implant site (uncommon, mostly early post-op)

Most side effects are mild and don't require discontinuation. Severe or persistent side effects can usually be managed with stimulation parameter adjustment (decreasing current, pulse width, or duty cycle).

Battery and device replacement

The battery lasts approximately 8–10 years depending on stimulation parameters. When the battery depletes, the pulse generator is replaced with an outpatient procedure — a smaller surgery than the original implantation, since the lead remains in place. Some patients may have multiple generator replacements over the course of decades of treatment.

Cost and insurance coverage

Device plus implantation costs approximately $25,000. Insurance coverage for VNS in depression is currently limited:

• Medicare: Limited coverage; CMS reconsideration process is active as of June 2025
• Private insurance: Variable; some insurers cover, most don't; prior authorization is almost always required
• Manufacturer programs: LivaNova has had patient assistance programs; current availability should be verified with the device rep

MRI compatibility

Modern VNS devices are MR-conditional, meaning MRIs can be safely performed with specific scanning protocols (typically head MRI at certain strengths and with certain coil types). Older VNS devices may be MR-unsafe or have more restrictive MR conditions. Always confirm the specific device model and check MR compatibility before imaging.

Where VNS fits in the neuromodulation landscape

For most patients with treatment-resistant depression, the typical sequence is:

1. Antidepressant trials across drug classes with augmentation strategies
2. Psychotherapy (typically CBT or IPT)
3. TMS (noninvasive, FDA-cleared for TRD, reasonable first neuromodulation option)
4. ECT (highest efficacy, best for severe or urgent cases) or ketamine/esketamine (rapid-acting)
5. VNS (for patients with chronic illness who've been through the above with partial or inadequate benefit)

This isn't a rigid sequence — clinical urgency, patient preference, side effect profiles, and practical considerations (insurance, geography, logistics) all shift the ordering. But the general principle holds: VNS tends to earn its place after other options have been tried, not as a first or second-line intervention.

VNS vs. maintenance ECT

A meaningful comparison for some patients is VNS versus indefinite maintenance ECT. Both are appropriate for chronic treatment-resistant depression with demonstrated ECT responsiveness. Tradeoffs:

• Maintenance ECT: Known response, faster time to effect, but requires ongoing procedures under general anesthesia, has cumulative cognitive costs, and is logistically burdensome
• VNS: Single surgical procedure then background operation, no ongoing general anesthesia, minimal cognitive burden — but slow onset and uncertain response

Some patients do well transitioning from maintenance ECT to VNS; others need both strategies concurrently; others do better continuing with maintenance ECT. The right choice depends on the patient's specific history and preferences. As discussed in section 4, the Aaronson 2017 registry showed the highest 5-year cumulative response rate of any subgroup in patients with prior ECT response — this is the patient profile where the case for considering VNS is strongest.

Ongoing management of existing VNS patients

Patients with existing VNS devices are typically managed by their outpatient psychiatrist, with parameter adjustments and troubleshooting provided in collaboration with the VNS device manufacturer's clinical support team (LivaNova field clinical engineers). This is a routine part of the psychiatric care of VNS patients and doesn't typically require specialized neurosurgical follow-up unless there's a device complication.

If you (or your patient) has a VNS device and need ongoing management — including parameter adjustments, response evaluation, side effect management, or coordination of care — our program welcomes these patients. Use the general Prisma Health Neuromodulation Program contact on the home page.

References

Key primary sources for the VNS evidence base. Organized thematically. PMIDs and DOIs included where available.

Original approval era

1. Rush AJ, George MS, Sackeim HA, et al. Vagus nerve stimulation (VNS) for treatment-resistant depressions: a multicenter study. Biol Psychiatry. 2000;47(4):276–286. doi:10.1016/s0006-3223(99)00304-2. PMID: 10686262.
2. Sackeim HA, Rush AJ, George MS, et al. Vagus nerve stimulation (VNS) for treatment-resistant depression: efficacy, side effects, and predictors of outcome. Neuropsychopharmacology. 2001;25(5):713–728. doi:10.1016/S0893-133X(01)00271-8. PMID: 11682255.
3. Marangell LB, Rush AJ, George MS, et al. Vagus nerve stimulation (VNS) for major depressive episodes: one year outcomes. Biol Psychiatry. 2002;51(4):280–287. doi:10.1016/s0006-3223(01)01343-9. PMID: 11958778.
4. Rush AJ, Marangell LB, Sackeim HA, et al. Vagus nerve stimulation for treatment-resistant depression: a randomized, controlled acute phase trial. Biol Psychiatry. 2005;58(5):347–354. doi:10.1016/j.biopsych.2005.05.025. PMID: 16139580. (The 10-week sham-controlled RCT — the trial that did not separate active from sham at the primary endpoint.)
5. Rush AJ, Sackeim HA, Marangell LB, et al. Effects of 12 months of vagus nerve stimulation in treatment-resistant depression: a naturalistic study. Biol Psychiatry. 2005;58(5):355–363. doi:10.1016/j.biopsych.2005.05.024. PMID: 16139581. (The 12-month naturalistic comparator study, published in the same issue, that informed FDA approval.)

Long-term outcomes — the 5-year registry

1. Aaronson ST, Sears P, Ruvuna F, Bunker M, Conway CR, Dougherty DD, Reimherr FW, Schwartz TL, Zajecka JM. A 5-year observational study of patients with treatment-resistant depression treated with vagus nerve stimulation or treatment as usual: comparison of response, remission, and suicidality. Am J Psychiatry. 2017;174(7):640–648. doi:10.1176/appi.ajp.2017.16010034. PMID: 28359201. (The TRD Registry: n=795, 61 sites, prospective open-label observational. Cumulative 5-year response 67.6% VNS+TAU vs. 40.9% TAU; remission 43.3% vs. 25.7%; ECT-responder subgroup 71.3% vs. 56.9%.)
2. Conway CR, Kumar A, Xiong W, Bunker M, Aaronson ST, Rush AJ. Chronic vagus nerve stimulation significantly improves quality of life in treatment-resistant major depression. J Clin Psychiatry. 2018;79(5):18m12178. doi:10.4088/JCP.18m12178. PMID: 30153410. (Quality-of-life analysis of the same registry cohort.)

VNS combined with or replacing maintenance ECT

1. Aaronson ST, Goldwaser EL, Kutzer DJ, McAllister-Williams RH, Sackeim HA. Vagus nerve stimulation in patients receiving maintenance therapy with electroconvulsive therapy: a series of 10 cases. J ECT. 2021;37(2):84–87. doi:10.1097/YCT.0000000000000724. PMID: 33840794. (Case series suggesting VNS may allow reduction or discontinuation of maintenance ECT.)
2. Daniel C, Doudard A, Bartolomei F, et al. Vagus nerve stimulation allows to cease maintenance electroconvulsive therapy in treatment-resistant depression: a retrospective monocentric case series. Front Psychiatry. 2023;14:1305603. doi:10.3389/fpsyt.2023.1305603. (French case series — 7 patients; 4/7 stopped ECT entirely after VNS implantation.)
3. McAllister-Williams RH, Sousa S, Kumar A, Greco T, Bunker MT, Aaronson ST, Conway CR, Rush AJ. The effects of vagus nerve stimulation on the course and outcomes of patients with bipolar disorder in a treatment-resistant depressive episode: a 5-year prospective registry. Int J Bipolar Disord. 2020;8(1):13. doi:10.1186/s40345-020-0178-4. PMID: 32279135. (Bipolar subgroup analysis from the 5-year registry.)

The RECOVER trial and analyses (2024–2025)

1. Conway CR, Aaronson ST, Sackeim HA, Duffy W, Stedman M, Quevedo J, et al. Clinical characteristics and treatment exposure of patients with marked treatment-resistant unipolar major depressive disorder: a RECOVER trial report. Brain Stimul. 2024;17(2):448–459. doi:10.1016/j.brs.2024.03.016. PMID: 38574853. (Baseline characterization paper: documents the extraordinary treatment resistance of the RECOVER cohort — mean MADRS 34.6, mean lifetime MDE duration 20+ years.)
2. Conway CR, Aaronson ST, Sackeim HA, Duffy W, Stedman M, Quevedo J, et al. Vagus nerve stimulation in treatment-resistant depression: a one-year, randomized, sham-controlled trial. Brain Stimul. 2025;18(3):676–689. doi:10.1016/j.brs.2024.12.1191. PMID: 39706521. (The main RECOVER results paper: n=493, 84 sites, 12-month sham-controlled trial. Primary MADRS endpoint not met; significant active-VNS advantages on CGI-I, QIDS-SR, QIDS-C, and partial-response measures.)
3. Rush AJ, Sackeim HA, Conway CR, Bunker MT, Hollon SD, Demyttenaere K, et al. Effects of vagus nerve stimulation on daily function and quality of life in markedly treatment-resistant major depression: findings from a one-year, randomized, sham-controlled trial. Brain Stimul. 2025;18(3):690–699. doi:10.1016/j.brs.2024.12.1190. (Quality-of-life and daily-function paper from RECOVER — consistent active-VNS advantage across multiple validated functional instruments.)
4. Sackeim HA, Aaronson ST, Conway CR, et al. Characterizing the effects of vagus nerve stimulation on symptom improvement in markedly treatment-resistant major depressive disorder: a RECOVER trial report. J Affect Disord. 2025;382:244–256. doi:10.1016/j.jad.2025.04.019. (Detailed symptom-level analysis of RECOVER outcomes.)
5. Best SRD, Allen R, Conway CR. Beyond the primary outcome: why the RECOVER trial for vagus nerve stimulation matters in treatment-resistant depression. Brain Stimul. 2025;18(3):665–666. doi:10.1016/j.brs.2025.02.011. (Editorial commentary contextualizing the RECOVER findings.)

Mechanism and reviews

1. Carreno FR, Frazer A. Vagal nerve stimulation for treatment-resistant depression. Neurotherapeutics. 2017;14(3):716–727. doi:10.1007/s13311-017-0537-8. PMID: 28585220.
2. Müller HHO, Moeller S, Lücke C, Lam AP, Braun N, Philipsen A. Vagus nerve stimulation (VNS) and other augmentation strategies for therapy-resistant depression (TRD): review of the evidence and clinical advice for use. Front Neurosci. 2018;12:239. doi:10.3389/fnins.2018.00239. PMID: 29692707.
3. Austelle CW, O'Leary GH, Thompson S, Gruber E, Kahn A, Manett AJ, Short B, Badran BW. A comprehensive review of vagus nerve stimulation for depression. Neuromodulation. 2022;25(3):309–315. doi:10.1111/ner.13528. PMID: 35211642.

Sources for clinical commentary quoted on this page

1. Sheppard Pratt Health System. New Study Finds Promising Treatment Option for Treatment-Resistant Depression (press release). March 31, 2017. Accessed via sheppardpratt.org. (Source for the Aaronson quote on VNS for ECT-dependent and ECT-failed patients, issued at the time of the AJP 2017 publication.)