Neuromodulation

General Neurology

Updated 01.13.2025
Released 02.21.2020
Expires For CME 01.13.2028

Neuromodulation

Authors: Jonathan Tiu MD, Florian P Thomas MD MA PhD MS

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Editor: Matthew Lorincz MD PhD

Neuromodulation

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Introduction

Overview

Advances in technology in the last few decades have empowered clinicians with a variety of tools that can increase or decrease the activity of a specific region of the nervous system to achieve an intended clinical effect. This branch of treatment, neuromodulation, has brought about multiple options for improving neurologic symptoms or restoring sensory or motor impairments after neurologic injury. Neuromodulation may exert its effect through various modalities, including direct electric stimulation, site-directed pharmacology, light, or ultrasound. Several invasive and noninvasive neuromodulation treatments and diagnostic tools have entered routine clinical practice. Deep brain stimulation is used for tremors, and intrathecal baclofen reduces spasticity in cerebral palsy, multiple sclerosis, hereditary spastic paraplegia, or spinal cord injury. Electric stimulation of pharyngeal muscles treats dysphagia, and invasive vagus nerve stimulation can improve upper extremity weakness after chronic stroke. Some techniques initially limited to preclinical use, such as optogenetics, are undergoing translation to clinical application. In this article, we present an introductory, rather than comprehensive, overview for the neurology clinician of this exciting but daunting topic. We review general neuromodulation principles and contrast two illustrative clinical conditions.

Key points

	• Neuromodulation is an application of neural engineering that alters the activity of a specific part of the nervous system to achieve a clinical effect.
	• Neuromodulation applications may utilize invasive or noninvasive direct electric stimulation, light, ultrasound, or site-directed pharmacology.
	• A wide array of neuromodulation devices are approved for treating neurologic symptoms, such as seizures, tremors, pain, or headaches.
	• A small but increasing number of neuromodulation devices can help restore neurologic impairments.
	• Neurology clinicians can include neuromodulation in treatment plans as an alternative or adjunct to medications or surgery

Historical note and terminology

The Bolognese physician Giuseppe Veratti may have provided one of the earliest accounts of clinical neuromodulation with his 1748 treatise, Physical and Medical Observations about Electricity. In one chapter of this treatise, he described a 70-year-old woman with tinnitus that improved with 3 days of 5 to 10 minutes of electricity transmitted electrostatically through glass (35).

Routine applications of neuromodulation, however, began with innovations in the middle of the 20^th century. Inspired by the work of French physicians Charles Eyriès and André Djourno, who restored hearing with an electrode in the internal auditory canal in 1957, the American surgeon William House placed the first cochlear implant in 1961 (38). Functional electrical stimulation was also achieved in 1961 when the team of physiatrist Wladimir Liberson developed the first neuroprosthesis by applying peroneal nerve stimulation paired with the swing phase in hemiplegia (29).

Meanwhile, the roots of deep brain stimulation (as well as stereotactic surgery) began in the 1930s, when neurosurgeon Wilder Penfield used an electric probe to identify and ablate the foci of seizures. In 1967, Neurosurgeon Norman Shealy used modified cardiac pacemakers manufactured by the medical device company Medtronic to stimulate the brains of patients with intractable pain. Medtronic developed the first neurostimulator in 1968 for chronic pain. Deep brain stimulation was approved for Parkinson disease in the United States in 1997, and by 2008, deep brain stimulation was “standard and accepted treatment for Parkinson’s disease” (18).

The past 3 or 4 decades have seen the blossoming of additional neuromodulation techniques. In 1981, Alan B Scott pioneered chemodenervation using botulinum toxin for blepharospasm (24). Noninvasive brain stimulation with transcranial magnetic stimulation and minimally invasive vagal nerve stimulation have undergone clinical translation, offering alternatives to pharmacological treatment of neurologic and psychiatric disorders. Further development of low-intensity focused ultrasound and optogenetics is being propelled by a rapidly improving understanding of the clinical and experimental applications of neuromodulation. In 2023, a Swiss group restored ambulation in a patient with traumatic spinal cord injury using a closed-loop brain-spine interface (32).

It is not possible to cover all clinical neuromodulation techniques here. Various techniques are outlined in Table 1 and described thereafter in detail:

Table 1. Classification of Various Technologies Used for Neuromodulation

Electric stimulation
	• Minimally invasive direct electric stimulation • Noninvasive (transcutaneous) electric stimulation • Electromagnetic noninvasive brain stimulation • Remote electric stimulation
Light-based neuromodulation
	• Phototherapy and photobiomodulation • Optogenetics
Sound-based neuromodulation
Pharmacologic neuromodulation
	• Targeted pharmacology • Designer receptors activated only by designer drugs (DREADDs)
Special neuromodulation concepts
	• Closed versus open-loop stimulation • Sensory prosthetics (including visual prostheses) • Sensory substitution • A note about brain-computer interfaces

Electric stimulation

Minimally invasive electric stimulation. The nervous system is an electrochemical signaling system, and modulation of a nerve or population of neurons can be externally achieved by stimulating it directly with an electrode. This direct stimulation is the most widely used mode of neuromodulation and forms the mechanism for several semi-permanent implantable stimulators in common use. Minimally invasive neuromodulation can target both the central and peripheral nervous systems.

In the central nervous system, deep brain stimulation using stereotactically placed electrodes allows direct electrical stimulation to specific targets. Deep brain stimulation of the globus pallidus pars interna or subthalamic nucleus may reduce symptoms of Parkinson disease (30). Other targets in the basal ganglia, such as the ventral intermediate nucleus of the thalamus, may improve essential tremor. Deep brain stimulation is also used for epilepsy (17). Cortical stimulation mapping uses direct electrical stimulation for intraoperative identification of eloquent cortex as well as seizure foci (22). Epidural stimulation of the spinal cord using spinal cord stimulators can target treatment-resistant pain and is being explored for motor rehabilitation in spinal cord injury (23).

Several peripheral nervous system targets can be electrically stimulated for clinical effect. The cochlear implant is a sensory neural prosthesis that helps provide or restore hearing by stimulating the auditory nerve. A cochlear implant converts sound from a digital signal into a radiofrequency signal. This radiofrequency signal is converted to electric currents that directly stimulate wires threaded through the cochlea and stimulate the auditory nerve (55). Stimulation of the vagus nerve provides a wide array of clinical indications; for example, implantable stimulators are in use for depression, epilepsy, and upper extremity rehabilitation after stroke (19).

Lorach and colleagues implemented a brain-spine interface using epidural lumbosacral electric stimulation to restore ambulation in an individual with cervical spinal cord injury. Lesion bypass was achieved with electrocorticographic sensors above the motor cortices as part of a “digital bridge” between the brain and lumbosacral nerve roots (32). Epidural sacral nerve stimulation can also be used to treat bladder or bowel incontinence, although the mechanisms are incompletely understood (13). Tibial nerve stimulation can treat bladder incontinence via retrograde stimulation of the sacral plexus (05).

Although cardiac myocytes share some similar electrochemical properties with neurons, cardiac pacemakers for rhythm disorders function by directly stimulating cardiac muscle and do not strictly speaking fall under the definition of neuromodulation; however, cardiac neuromodulation therapy is being investigated for hypertension by modulating sympathetic nervous system afferents (27). Other neuromodulation applications are available, and the curious reader is encouraged to explore them on the International Neuromodulation Society web site.

Noninvasive (transcutaneous) electric stimulation. Greater efficacy is generally seen with minimally invasive versus noninvasive stimulation. However, noninvasive stimulation has a high level of convenience and portability. Many noninvasive devices are available via specialty pharmacies by prescription or even at the retail level online or in major department stores. Noninvasive electric stimulation of the trigeminal, occipital, or vagus nerves can alleviate various headache syndromes, eg, migraine. Transcutaneous electrical nerve stimulation is readily accessible at the consumer level and is frequently used for chronic pain. Transcutaneous afferent patterned stimulation of the median nerve may alleviate tremor in essential tremor or Parkinson disease (08; 33).

Electromagnetic noninvasive brain stimulation. Several techniques are available for noninvasive direct electric or magnetic stimulation. Repetitive transcranial magnetic stimulation can deliver a high-precision stimulus by inducing a magnetic field with accuracy on the order of millimeters (39). Repetitive transcranial magnetic stimulation can depolarize neurons, which can create a reversible “virtual lesion”; this property allows repetitive transcranial magnetic stimulation to aid in cortical mapping (04).

In contrast, transcranial electrical stimulation can bring neurons closer to depolarization without triggering an action potential. Transcranial electrical stimulation as a category can be divided into transcranial direct current stimulation, transcranial alternating current stimulation, and transcranial random noise stimulation. Of these techniques, transcranial direct current stimulation is the best studied. In transcranial direct current stimulation, current flows from one electrode to the other, allowing for regional stimulation, although its spatial resolution is low (34).

Repetitive transcranial magnetic stimulation is approved in the United States for depression, obsessive-compulsive disorder, smoking cessation, migraine with aura, and cortical mapping for epilepsy (10). Repetitive transcranial magnetic stimulation and transcranial electrical stimulation are promising but remain experimental for use in several symptoms due to stroke. Outcomes of a large number of stroke trials using NIBS remain mixed. One reason for this heterogeneity, specifically for trials using noninvasive direct electric stimulation for motor stroke rehabilitation, may relate to the complex interaction of the two hemispheres after stroke (07).

Remote electrical neuromodulation. Pain localizing to a certain region of the nervous system can be alleviated by stimulating an essentially unrelated nerve territory. The proposed mechanism for this technique, remote electrical neuromodulation, may involve inhibition of central pain processing primarily at the level of the brainstem (01). Remote electrical neuromodulation is approved in the United States to abort breakthrough migraines or prevent migraine.

Light-based neuromodulation

Phototherapy and photobiomodulation. Light at various wavelengths can be used to modulate nervous system activity. Photobiomodulation is limited to red or near-infrared light and is also referred to as low-level laser therapy. Transcranial photobiomodulation can penetrate the skull. Several mechanisms of action have been proposed. One such mechanism involves the absorption of light by cytochrome c oxidase, resulting in a net increase of ATP (37). Photobiomodulation has had mixed evidence for clinical use, but refined approaches are being investigated for neurorehabilitation, neurodegenerative conditions, and back pain. Green light phototherapy acting on the retina may be a promising treatment for headache (21).

Optogenetics. Optogenetics combines genetic engineering with light-based neuromodulation to selectively activate neurons. Selected neurons are engineered to express opsins, ie, proteins that respond to specific wavelengths. When such neurons are exposed to light, conformational changes to the opsins can alter the neuron’s behavior, such as by opening or closing an ion channel and influencing its membrane potential. Optogenetics can provide a high degree of precision. The application of optogenetics has been largely preclinical, but clinical uses are emerging; one group has utilized optogenetics to partially restore visual impairment in a patient with retinitis pigmentosa (48).

Sound-based neuromodulation. Although acoustic stimulation using high-intensity focused ultrasound can permanently ablate neural structures, low-intensity focused ultrasound can reversibly modulate neuronal activity. Mechanisms of low-intensity focused ultrasound may include modification of structural and thermal properties of membranes (11). MRI-guided focused ultrasound is in use for tremors, and applications of low-intensity focused ultrasound for peripheral stimulation are also in investigation (11).

Auditory or acoustic neuromodulation using auditory pathways has been explored. Auditory neuromodulation may have a role in alleviating tinnitus. Binaural acoustic stimulation, particularly with binaural beat stimulation or entrainment, may have a role in modulating mood and cognition in various psychiatric and neurologic conditions (41; 25). Binaural beat stimulation takes advantage of a phenomenon in which stimulation of each ear using sound of two different frequencies produces the illusion or perception of a third tone, or binaural beat, with a frequency that is the difference between the two inputs. Possible mechanisms may involve cortical entrainment (41; 25).

Pharmacologic neuromodulation

Targeted pharmacology. Pharmacology can be considered a form of chemical neuromodulation when an agent is delivered to a specific component of the nervous system (34). Lower extremity spasticity can be controlled via intrathecal baclofen pumps, which deliver baclofen at a programmed rate while minimizing baclofen’s sedating effects. Intrathecal phenol can also be used for spasticity or pain management. Spasticity can also be treated by injecting botulinum toxin or phenol into affected muscles. Botulinum toxin is also used for treating sialorrhea, migraine, and dystonia. Localized nerve blocks using an anesthetic with or without steroids serve as a cornerstone component of pain management.

Designer receptors activated only by designer drugs (DREADDs). Currently used in the preclinical setting, DREADDs allow the study of highly selective neuromodulation using bespoke pharmacology. With this chemogenetic technique, an animal is designed to selectively express drug receptors in a desired part of the body. These receptors are designed to respond to specific, previously unrecognized small molecules. DREADDs achieve comparable effects versus optogenetics but last longer (46).

Special neuromodulation concepts

Closed- versus open-loop stimulation. In open-loop stimulation, stimulation is delivered at a fixed or scheduled interval, regardless of input from the patient. Implantable open-loop devices may stimulate at predefined intervals; this ratio between its “on” and “off” time is its duty cycle.

With closed-loop stimulation, activation of a neuromodulatory device occurs in response to stimuli sensed from the body of the wearer. For example, hemiplegic patients with walking impairment might improve their ambulation using a closed-loop functional electrical stimulation device that senses the position of the foot to time stimulation of the quadriceps or hamstring muscles. Common functional electrical stimulation devices include Bioness® and WalkAide® models (06). Responsive neurostimulation can treat epilepsy by stimulating the brain on detection of pre-defined electrocorticography patterns that may lead to a seizure (47).

Sensory prosthetics (including visual prostheses). Implantable neuromodulation devices can help restore various sensory impairments. The cochlear implant is one such device. The variety of visual prosthetic approaches illustrates how different neuromodulation modalities at multiple potential targets can attain a similar goal of restoring vision. Visual prosthetics achieve lesion bypass by stimulating at the level of the retina or optic nerve or within the brain (45). In turn, retinal stimulation can utilize electrical, optical, magnetic, chemical, or ultrasonic methods (45). For retinal prostheses, retinitis pigmentosa and age-related macular degeneration serve as common disease models as the inner retinal layers, including bipolar and ganglion cells, have preserved function in these conditions (16). Within the brain, electric stimulation via visual prosthetics targets the lateral geniculate nucleus or occipital cortex (16).

Sensory substitution. Neuromodulation applications have been developed to substitute a lost sensory modality using alternative, unimpaired senses. Tactile sensory substitution devices may allow individuals to “see” by translating visual input through a camera into a two-dimensional spatial representation of the visual input onto the skin or even the tongue (16). Other devices can help convert auditory stimuli to tactile stimuli or visual stimuli into auditory stimuli (42).

A note about brain-computer interfaces. Interest in brain-computer interfaces has increased in recent years. Although both brain-computer interfaces and neuromodulation are neural engineering applications, they represent two distinct but overlapping concepts. Motor brain-computer interfaces “skip” traditional neuromuscular pathways by converting motor intent into a digital output rather than stimulating part of the nervous system (49). A sensory brain-computer interface would qualify as neuromodulation if the input stimulates afferents within the brain. In contrast, cochlear implants do not classify as brain-computer interfaces because the stimulation occurs at the level of the peripheral nerve and not directly onto the brain.

Clinical aspects

Description

A neurologist might consider neuromodulation an option in place of or as an adjunct to medication, focal ablations, or more invasive surgical treatments. Some treatments, such as chemodenervation with botulinum toxin, are readily performed in the outpatient office. Others, such as semi-permanent implantable devices, require referrals to appropriate specialist teams. Several considerations are warranted: Is the treatment intermittent or continuous? Will an implantable device interfere with the delivery of other implantable devices, such as pacemakers, and will it be MRI-compatible? How frequently would the device need maintenance or medication refills? What are the risks of treatment failure, and what action plan should a patient take in this event (eg, baclofen withdrawal in patients with intrathecal baclofen pumps)? Do the patient or their care partners have the competence to operate a smartphone-operated device?

As an introduction, we will contrast epilepsy (a condition with a mature selection of neuromodulation treatments) with stroke (a condition that provides a wide array of established and experimental opportunities for neuromodulation). We will also review possible neuromodulation strategies for Alzheimer disease. Details of neuromodulation are available in other MedLink Neurology articles.

Epilepsy. Minimally invasive neuromodulation is an established option in patients with epilepsy resistant to drug treatment. In contrast to epilepsy surgery, in which the goal is curative, neuromodulation for epilepsy is considered palliative, as few patients will achieve seizure freedom longer than 12 months (47). Stimulation of the left vagus nerve provides a minimally invasive open-loop method using a fixed intermittent stimulation schedule (duty cycle). The mechanisms for vagus nerve stimulation in epilepsy are incompletely understood but thought to include regional modulation of norepinephrine and GABA associated with pattern desynchronization (47). Hoarseness and cough are common adverse events. The 50% responder rate, or percentage of patients reporting a reduction in seizures of at least 50%, is reported as 37% at 1 year (47).

Deep brain stimulation of the anterior nucleus of the thalamus is another open-loop technique for epilepsy. The mechanisms of ANT-DBS are poorly understood but are thought to involve desynchronization. ANT-DBS is associated with a small risk of implantation-related intracranial hemorrhage, as well as long-term depression, suicidality, and memory complaints. The 50% responder rate at 1 year for ANT-DBS is reported as 43%, which is similar to the 50% responder rate at 1 year of 44% for responsive neurostimulation (47). In contrast, responsive neurostimulation presents a closed-loop treatment for epilepsy. With responsive neurostimulation, real-time detection of pre-programmed electrocorticographic signals triggers a train of up to five bursts of electric stimulation.

Schematic of anterior nucleus of the thalamus deep brain stimulator and a responsive neurostimulation device

(Reproduced from NINDS and modified from: Edwards CA, Kouzani A, Lee KH, et al. Neurostimulation devices for the treatment of neurologic disorders. Mayo Clin Proc 2017;92(9):1427-44. Other helpful information for patients and p...

Vagus nerve stimulation, ANT-DBS, and responsive neurostimulation are approved for focal epilepsies. Vagus nerve stimulation can be used in children aged 4 years or older with generalized epilepsy or Lennox-Gastaut syndrome. Vagus nerve stimulation and responsive neurostimulation require resistance to two antiseizure medications, whereas ANT-DBS requires resistance to at least three medications (47).

Migraine. Noninvasive neuromodulation devices for both migraine prevention and acute migraine have expanded considerably in the last several years and are routinely prescribed for patients suffering from migraine (20). With the exception of SAVI Dual™, which uses magnetic stimulation, most migraine neuromodulation devices use electric stimulation. These include:

	• External trigeminal neurostimulation. The external trigeminal neurostimulation device Cefaly™ can be used for preventive and acute migraine treatment. Cefaly is available without a prescription.
	• Transcutaneous electrical nerve stimulation. HeadaTerm 2™ is a transcutaneous electrical nerve stimulation device approved for migraine prevention. It is available without a prescription.
	• Combined supraorbital, supratrochlear, and greater occipital nerve stimulation (COT-NS). Relivion® is available by prescription and uses COT-NS for acute treatment of migraine only.
	• Remote electrical neuromodulation. Nerivio® is a remote electrical neuromodulation device available by prescription for preventive and acute treatment of migraine.
	• Noninvasive vagus nerve stimulation. gammaCore™ uses noninvasive vagus nerve stimulation and is available by prescription for preventive and acute treatment of migraine. It is also approved for use in cluster headache, paroxysmal hemicrania, and hemicrania continua.
	• Single-pulse transcranial magnetic stimulation. SAVI Dual™ is a single-pulse transcranial magnetic stimulation device available for preventive and acute treatment of migraine. It is available by prescription. Unlike the above devices, which are forms of peripheral neuromodulation, SAVI Dual™ is a central neuromodulation device. Its hypothesized mechanism of action is that magnetic pulses disrupt cortical spreading depression in the occipital lobe, where it is believed to predominantly originate (31; 26).

Apart from devices, neuromodulation for migraine is also achieved using chemodenervation. Botulinum toxin injected into standardized sites on the head, occiput, and trapezius, as defined in the PREEMPT protocol, can prevent migraine chronic migraine (14).

Stroke. Stroke provides ample established and experimental opportunities for neuromodulation from the hyperacute to the chronic stage. In the hyperacute phase, auricular vagal nerve stimulation is being investigated for neuroprotection (03). From the subacute to chronic phases, both electromagnetic and chemical neuromodulation can serve several purposes. Repetitive transcranial magnetic stimulation to the motor cortex may be used to prognosticate upper extremity function early after stroke. Specifically, as part of the PREP2 algorithm, the detection of a motor-evoked potential at post-stroke days 3 through 7 using repetitive transcranial magnetic stimulation may help differentiate patients who have a good prognosis of upper limb function from those with a poor to limited prognosis (51).

In stroke rehabilitation, neuromodulation can be used to prime the nervous system to enhance the effect of task-specific training. Neuromodulation in this application can be sequential (directly before therapy) or concurrent (during therapy). Peripheral neuromuscular electrical stimulation combined with task-specific exercise has been identified in a network meta-analysis as the most promising modality for the upper extremity (53). In the chronic phase, minimally invasive vagus nerve stimulation may aid upper extremity impairment when paired with therapy. The VNS-REHAB trial assigned 108 participants at least 9 months after stroke with moderate-to-severe arm weakness to vagus nerve stimulation or sham stimulation. A clinically meaningful response on the Fugl-Myer Motor Assessment, upper extremity subscale, was achieved in 47% of the vagus nerve stimulation group versus 24% among controls (12). Pharyngeal stimulation can alleviate dysphagia. A review concluded that neuromuscular electrical stimulation coupled with swallowing therapy improved swallowing in patients with poststroke aphasia (02). Closed-loop functional electrical stimulation devices can aid with spastic gait after stroke by stimulating the quadriceps or hamstrings after the device detects lifting of the affected foot (06). One approach to motor stroke rehabilitation of the upper extremity combines virtual reality with EMG-triggered neuromuscular electrical stimulation (40). One approach to motor stroke rehabilitation of the upper extremity combines virtual reality with EMG-triggered neuromuscular electrical stimulation (40).

Noninvasive brain stimulation with repetitive transcranial magnetic or cortical electric stimulation has been investigated for stroke rehabilitation, though variable outcomes amidst a dizzying number of stimulation protocols highlight the complexity of this modality (07). A meta-analysis concluded that there is “robust evidence” for the efficacy of repetitive transcranial magnetic stimulation in improving upper extremity function during multiple phases of stroke (09). A network meta-analysis of transcranial direct current stimulation after stroke showed that cathodal transcranial direct current stimulation was promising in improving function with activities of daily living (SMD = 0.42) but did not improve arm function based on Fugl-Myer scores (15).

Neuromodulation may be used to treat many complications of stroke. Chemodenervation using botulinum toxin or phenol can reduce both upper and lower extremity spasticity, and botulinum toxin can help with overactive bladder. Preliminary evidence supports that deep brain stimulation may aid central poststroke pain and that peripheral nerve stimulation may help alleviate hemiplegic shoulder pain (44).

Alzheimer dementia. It is worth including ongoing efforts in using neuromodulation for Alzheimer dementia. Deep brain stimulation of the hippocampal fornix (DBS-f) is being investigated for Alzheimer disease. Following promising improvements in glucose metabolism and slowed rates of hippocampal degeneration in earlier work using DBS-f, phase IIb of the ADvance trial evaluated 12 months of DBS-f in patients with mild probable Alzheimer disease (28). Although the primary outcome of the ADvance trial was negative, a post hoc secondary analysis suggested a better response in participants older than 65 years of age; this benefit was found to persist after 2 years (28). Phase III of the trial (ADvance II) is underway (NCT03622905).

A 2022 meta-analysis concluded that noninvasive brain stimulation is effective for Alzheimer disease, with a medium effect seen with repetitive transcranial magnetic stimulation and a mild effect with transcranial direct current stimulation; the benefits on cognition may last from weeks to months (50). Given its pro-cholinergic effect, vagus nerve stimulation presents another promising treatment for Alzheimer disease (54).

Indications

The indications for neuromodulation continue to expand. Table 2 lists a non-comprehensive list of current options. Additional information can be found at the International Neuromodulation Society website.

Table 2. Neuromodulation Treatments

Chronic pain	Spinal cord stimulation is available for post-laminectomy syndrome with radicular pain, complex regional pain syndrome, and pain associated with coronary artery disease. Morphine and ziconotide can be administered intrathecally. Transcutaneous electrical nerve stimulation units are widely available without a prescription.
Depression	In the United States, repetitive transcranial magnetic stimulation and vagus nerve stimulation are approved for depression. Other modalities include electroconvulsive therapy, magnetic seizure therapy, and direct cortical stimulation.
Epilepsy	Established neuromodulation methods include vagus nerve stimulation, deep brain stimulation, and closed-loop responsive neurostimulation.
Essential tremor	Essential tremor can respond to minimally invasive deep brain stimulation or transcutaneous afferent patterned stimulation.
Irritable bowel syndrome	Percutaneous electrical nerve field stimulation, a form of noninvasive auricular vagus nerve stimulation, is available for functional abdominal pain in irritable bowel syndrome.
Migraine	Trigeminal nerve electrical stimulation is indicated to prevent migraine or treat breakthrough migraine. Remote electrical neuromodulation and noninvasive vagus nerve stimulation can prevent and treat acute migraine. Combined trigeminal and occipital stimulation is available for acute migraine. Chemodenervation with botulinum toxin injected into standardized sites on the head, occiput, and trapezius, as defined in the PREEMPT protocol, can prevent migraine in chronic migraine (14).
Overactive bladder	Minimally invasive neuromodulation for overactive bladder includes sacral nerve stimulation and posterior tibial nerve stimulation. Chemodenervation with botulinum toxin is also used.
Parkinson disease	Neuromodulation for Parkinson disease includes deep brain stimulation, transcutaneous afferent patterned stimulation, and high-intensity focused ultrasound.
Stroke	Minimally invasive vagus nerve stimulation can be combined with rehabilitation for upper extremity weakness. Noninvasive brain stimulation with cortical electrical stimulation and repetitive transcranial magnetic stimulation remain experimental. Complications of stroke treatable with neuromodulation dysphagia, spasticity, and spastic bladder.

Contraindications

Contraindications to neuromodulation are not universal and vary with the specific technique and the stimulation site. When a patient already has an implantable electronic device, such as pacemakers and hearing amplification devices, consideration of a second device for neuromodulation raises concern for electromagnetic interference(52). There can be interactions between neuromodulation treatments and medication. A notable pharmacologic interaction exists between transcranial direct current stimulation for patients on carbamazepine; the sodium channel blockade by carbamazepine can nullify transcranial direct current stimulation (36). Noninvasive electric stimulation is contraindicated over areas of skin breakdown; however, data support that electrical stimulation may enhance wound healing (43).

Adverse effects

Adverse effects are specific to the type of neuromodulation. Noninvasive direct electric stimulation may lead to skin irritation. Vagus nerve stimulation may be associated with hoarseness or cough. Implantable neuromodulation devices have a risk of infection. Deep brain stimulation is infrequently associated with intraoperative intraparenchymal hemorrhage and depression.

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Jonathan Tiu MD

Dr. Tiu of Hackensack University School of Medicine has no relevant financial relationships to disclose.
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Florian P Thomas MD MA PhD MS

Dr. Thomas of Hackensack Meridian School of Medicine has no relevant financial relationships to disclose.
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Matthew Lorincz MD PhD

Dr. Lorincz of the University of Michigan has no relevant financial relationships to disclose.
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K K Jain MD†

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Neuromodulation

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General Neurology

Neuromodulation

Neuromodulation

Introduction

Overview

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Historical note and terminology

Table 1. Classification of Various Technologies Used for Neuromodulation

Electric stimulation

Light-based neuromodulation

Pharmacologic neuromodulation

Special neuromodulation concepts

Clinical aspects

Description

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Table 2. Neuromodulation Treatments

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Neuromodulation

Introduction

Overview

Key points

Historical note and terminology

Table 1. Classification of Various Technologies Used for Neuromodulation

Electric stimulation

Light-based neuromodulation

Pharmacologic neuromodulation

Special neuromodulation concepts

Clinical aspects

Description

Indications

Table 2. Neuromodulation Treatments

Contraindications

Adverse effects

Media

References

Contributors

Authors

Editor

Former Authors

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Renal failure: neurologic complications

Neurologic manifestations of celiac disease and gluten sensitivity

Neurogastroenterology

Use of focused ultrasound in neurologic disorders

Prognosis after cardiac arrest

Diplopia

Isolated sixth nerve palsy

Radial neuropathy

This is an article preview.
Start a Free Account
to access the full version.