Neuromodulation is "the alteration of nerve activity through targeted delivery of a stimulus, such as electrical stimulation or chemical agents, to specific neurological sites in the body". It is carried out to normalize – or modulate – nervous tissue function. Neuromodulation is an evolving therapy that can involve a range of electromagnetic stimuli, such as a magnetic field (rTMS), an electric current, or a drug delivered directly into the subdural space (intrathecal drug delivery). Emerging applications involve targeted introduction of genes or gene regulators and light (optogenetics), and by 2014, these had been at minimum demonstrated in mammalian models, or first-in-human data had been acquired. The most clinical experience has been with electrical stimulation.
Neurotherapy, in modern use, is a synonym for neuromodulation. While neurotherapy may have a broader meaning, its modern definition focuses exclusively on technological methods that exert an energy-based effect on the development of a balanced nervous system in order to address symptom control and cure several conditions. Neurotherapy is a medical treatment that implements systemic targeted delivery of an energy stimulus or chemical agents to a specific neurological zone in the body to alter neuronal activity and stimulate neuroplasticity in a way that develops (or balances) a nervous system in order to treat different diseases, restore and/or to improve patients' physical strength, cognitive functions, and overall health.International Neuromodulation Society, Retrieved 10 January 2025 from: https://www.neuromodulation.com/
Neuromodulation, whether electrical or magnetic, employs the body's natural biological response by stimulating nerve cell activity that can influence populations of nerves by releasing transmitters, such as dopamine, or other chemical messengers such as the peptide Substance P, that can modulate the excitability and firing patterns of neural circuits. There may also be more direct electrophysiological effects on neural membranes as the mechanism of action of electrical interaction with neural elements. The end effect is a "normalization" of a neural network function from its perturbed state. Presumed mechanisms of action for neurostimulation include depolarizing blockade, stochastic normalization of neural firing, axonal blockade, reduction of neural firing keratosis, and suppression of neural network oscillations. A recent review (2024) has identified relevant etiological hypotheses of non-invasive neuromodulation in different techniques. Data analysis revealed that mitochondrial activity seems to play a central role in different techniques. Analysis of the mother-fetus neurocognitive model Val Danilov I (2024). "Child Cognitive Development with the Maternal Heartbeat: A Mother-Fetus Neurocognitive Model and Architecture for Bioengineering Systems." In International Conference on Digital Age & Technological Advances for Sustainable Development (pp. 216-223). Springer, Cham. http://doi.org/10.1007/978-3-031-75329-9_24 provided insights into the conditions of natural neuromodulation of the fetal nervous system during pregnancy. According to this position, the electromagnetic properties of the mother's heart and its interaction with her own and the fetal nervous system ensure the balanced development of the embryo's nervous system and guarantee the development of the correct architecture of the nervous system with the necessary cognitive functions corresponding to the ecological context and the qualities that make human beings unique. Based on these results, the article suggested the hypothesis of the origin of neurostimulation during gestation. Although the exact mechanisms of neurostimulation remain unknown, the empirical effectiveness has resulted in the surge of its clinical application.
Existing and emerging neuromodulation treatments also include application in medication-resistant epilepsy, chronic head pain conditions, and functional therapy ranging from bladder and bowel or respiratory control to improvement of sensory deficits, such as hearing (cochlear implants and auditory brainstem implants) and vision (retinal implants).Krames, Elliot S, Peckham, P. Hunter, Rezai Ali R, eds. (2009). Neuromodulation, Vol. 1-2. Academic Press. p. 274. . Technical improvements include a trend toward minimally invasive (or noninvasive) systems, as well as smaller, more sophisticated devices that may have automated feedback control, and conditional compatibility with magnetic resonance imaging.
Neuromodulation therapy has been investigated for other chronic conditions, such as Alzheimer's disease, depression, chronic pain, and as an adjunctive treatment in recovery from stroke.
Physiology
Synaptic plasticity
Synaptic plasticity, a particular type of neuroplasticity, is the ability of the nervous system to modify the intensity of interneuronal relationships (synapses), to establish new ones and to eliminate some. This property allows the nervous system to modify its structure and functionality in a more or less lasting way, depending on the events that influence it, such as experience or neuromodulation.
Neuroplasticity Brain plasticity refers to the ability of the brain to modify its structure and functionality depending on the activity of its neurons, related, for example, to stimuli received from the external environment, in reaction to traumatic lesions or pathological changes, and in relation to the development process of the individual or neuromodulation.
A balanced nervous system In the balanced nervous system with required cognitive functions, the sympathetic (SNS) and parasympathetic nervous systems (PNS) operate in synergy while opposing each other. Stimulation of the SNS boosts body activity and attention: it raises heart rate and blood pressure. In contrast, stimulation of the PNS is the rest-and-digest state: it reduces blood pressure and heart rate. The nervous system interplays with the immune system. Through these interactions, the nervous and immune systems ensure the nervous system maintains immune homeostasis.
Medical uses According to the International Neuromodulation Society, neuromodulation-based therapy "addresses symptom control through nerve stimulation" in the following condition categories: Chronic pain Movement disorders Epilepsy Psychiatric disorders Brain injury / Stroke Cardiovascular disorders Gastrointestinal disorders Genitourinary and colorectal disorders Sensory deficits
Types Neurotherapy, like many medical therapies, is based on knowledge from conventional medicine, relying on a scientific approach and evidence-based practice. However, some neuromodulation techniques are still attributed to alternative medicine (healthcare procedures "not readily integrated into the dominant healthcare model") because of their novelty and lack of evidence to support them. The wide range of neurotherapy techniques can be divided into three groups based on the application of energy stimulus:
Electric energy Auditory brainstem implant Cranial electrotherapy stimulation Deep brain stimulation Electrical brain stimulation Electroanalgesia Electroconvulsive therapy (ECT) Functional electrical stimulation (FES) Hypoglossal nerve stimulation"Premarket Approval (PMA) Inspire II Upper Airway Stimulation System". U.S. Food and Drug Administration. April 30, 2014. Retrieved 10.01.2025. from cfPMA/pma.cfm?id=18437 Neurofeedback Microcurrent electrical neuromuscular stimulator Occipital nerve stimulation (ONS) Percutaneous tibial nerve stimulation (PTNS) Peripheral nerve stimulation Sacral nerve stimulation (SNS) / sacral neuromodulation (SNM) Transcranial direct current stimulation (tDCS) Transcranial alternating current stimulation (tACS) Transcranial pulsed current stimulation (tPCS) Transcranial random noise stimulation (tRNS) Transcutaneous electrical nerve stimulation (TENS) Vagus nerve stimulation
Magnetic energy Magnet therapy Magnetic resonance therapy Repetitive transcranial magnetic stimulation (rTMS) Transcranial magnetic stimulation
Electromagnetic radiation Acoustic photonic intellectual neurostimulation (APIN) Light therapy (phototherapy) Ultraviolet light therapy PUVA therapy Photodynamic therapy Photothermal therapy Pulsed electromagnetic field therapy Cytoluminescent therapy Blood irradiation therapy Laser therapy Low-level laser therapy Transcranial pulsed electromagnetic fields (tPEMF)
Invasive electrical neuromodulation methods
Electrical stimulation using implantable devices came into modern usage in the 1980s, and its techniques and applications have continued to develop and expand.Krames, Elliot S.; Peckham, P. Hunter; Rezai, Ali R., eds. (2009). Neuromodulation, Vol. 1-2. Academic Press. pp. 1–1200. . These are methods where an operation is required to position an electrode. The stimulator, with the battery, similar to a pacemaker, may also be implanted, or may remain outside the body.
In general, neuromodulation systems deliver electrical currents and typically consist of the following components: An epidural, subdural, or parenchymal electrode placed via minimally invasive needle techniques (so-called percutaneous leads) or an open surgical exposure to the target (surgical "paddle" or "grid" electrodes), or stereotactic implants for the central nervous system, and an implanted pulse generator (IPG). Depending on the distance from the electrode access point, an extension cable may also be added into the system. The IPG can have either a non-rechargeable battery needing replacement every 2–5 years (depending on stimulation parameters) or a rechargeable battery that is replenished via an external inductive charging system.
Although most systems operate via delivery of a constant train of stimulation, there has recently been an emergence of so-called "feed-forward" stimulation, in which the device's activation is contingent on a physiological event, such as an epileptic seizure. In this circumstance, the device is activated and delivers a desynchronizing pulse to the cortical area that is undergoing an epileptic seizure. This concept of feed-forward stimulation will likely become more prevalent as physiological markers of targeted diseases and neural disorders are discovered and verified. The on-demand stimulation may extend the duration of battery life if sensing and signal-processing demands of the system are sufficiently power-efficient. New electrode designs could yield more efficient and precise stimulation, requiring less current and minimizing unwanted side-stimulation. In addition, to overcome the challenge of preventing lead migration in areas of the body that are subject to motion such as turning and bending, researchers are exploring developing small stimulation systems that are recharged wirelessly rather than through an electrical lead.
Spinal cord stimulation
Spinal cord stimulation is a form of invasive neuromodulation therapy in common use since the 1980s. Its principal use is as a reversible, non-pharmacological therapy for chronic pain management that delivers mild electrical pulses to the spinal cord. In patients who experience pain reduction of 50 percent or more during a temporary trial, a permanent implant may be offered in which, as with a cardiac pacemaker, an implantable pulse generator about the size of a stopwatch is placed under the skin on the trunk. It delivers mild impulses along slender electrical leads leading to small electrical contacts, about the size of a grain of rice, at the area of the spine to be stimulated.