What is "neuromodulation"

n. 1 (context biology English) The regulation of neurons by neurotransmitters 2 (context medicine English) The relief of pain by stimulation of a nerve

Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. This is in contrast to classical synaptic transmission, in which one presynaptic neuron directly influences a single postsynaptic partner. Neuromodulators secreted by a small group of neurons diffuse through large areas of the nervous system, affecting multiple neurons. Major neuromodulators in the central nervous system include dopamine, serotonin, acetylcholine, histamine, and norepinephrine.

Neuromodulation can be conceptualized as a neurotransmitter that is not reabsorbed by the pre-synaptic neuron or broken down into a metabolite. Such neuromodulators end up spending a significant amount of time in the cerebrospinal fluid (CSF), influencing (or "modulating") the activity of several other neurons in the brain. For this reason, some neurotransmitters are also considered to be neuromodulators, such as serotonin and acetylcholine.

Neuromodulation is often contrasted with classical fast synaptic transmission. In both cases the transmitter acts on local postsynaptic receptors, but in neuromodulation, the receptors are typically G-protein coupled receptors while in classical chemical neurotransmission, they are ligand-gated ion channels. Neurotransmission that involves metabotropic receptors (like G-protein linked receptors) often also involves voltage-gated ion channels, and is relatively slow. Conversely, neurotransmission that involves exclusively ligand-gated ion channels is much faster. A related distinction is also sometimes drawn between modulator and driver synaptic inputs to a neuron, but here the emphasis is on modulating ongoing neuronal spiking versus causing that spiking.

Neuromodulation, defined by the International Neuromodulation Society as "the alteration of nerve activity through the delivery of electrical stimulation or chemical agents to targeted sites of the body," is carried out to normalize – or modulate – nerve function. Neuromodulation is an evolving therapy that can involve a range of electromagnetic stimuli such as a strong magnetic field ( repetitive transcranial magnetic stimulation), a very small electric current, or a drug instilled directly in 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.

Electrical stimulation using implantable devices came into modern usage in the 1980s and its techniques and applications have continued to develop and expand. The therapy 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. Although the exact mechanisms of neurostimulation are not known, the empirical effectiveness has led to considerable application clinically.

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 an 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 is now the advent of so-called "feed-forward" stimulation where 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 contribute to longer 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.

Neuromodulation: Technology at the Neural Interface is a peer-reviewed medical journal covering clinical, translational, and basic science research in the field of neuromodulation. It was established in 1998 by founding editor Elliot S. Krames and is published by Wiley on behalf of the International Neuromodulation Society. The editor-in-chief is Robert M. Levy (Marcus Neuroscience Institute).