Neurostimulation is the purposeful modulation of the
nervous system
In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes th ...
's activity using invasive (e.g.
microelectrodes
A microelectrode is an electrode used in electrophysiology either for recording neural signals or for the electrical stimulation of nervous tissue (they were first developed by Ida Hyde in 1921). Pulled glass pipettes with tip diameters of ...
) or non-invasive means (e.g.
transcranial magnetic stimulation
Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to induce an electric current at a specific area of the brain through electromagnetic induction. An electric pulse gener ...
or
transcranial electric stimulation
Transcranial direct current stimulation (tDCS) is a form of neuromodulation that uses constant, low direct current delivered via electrodes on the head. It was originally developed to help patients with brain injuries or neuropsychiatric conditio ...
, tES, such as
tDCS or
transcranial alternating current stimulation
Cranial electrotherapy stimulation (CES) is a form of neurostimulation that delivers a small, pulsed, alternating current via electrodes on the head. CES is used with the intention of treating a variety of conditions such as anxiety, depression a ...
, tACS). Neurostimulation usually refers to the electromagnetic approaches to
neuromodulation
Neuromodulation is the physiological process by which a given neuron uses one or more chemicals to regulate diverse populations of neurons. Neuromodulators typically bind to metabotropic, G-protein coupled receptors (GPCRs) to initiate a second ...
.
Neurostimulation technology can improve the life quality of those who are severely paralyzed or have profound losses to various sense organs, as well as for permanent reduction of severe, chronic pain which would otherwise require constant (around-the-clock), high-dose opioid therapy (such as neuropathic pain and spinal-cord injury). It serves as the key part of
neural prosthetics for
hearing aids
A hearing aid is a device designed to improve hearing by making sound audible to a person with hearing loss. Hearing aids are classified as medical devices in most countries, and regulated by the respective regulations. Small audio amplifiers su ...
, artificial vision,
artificial limb
In medicine, a prosthesis (plural: prostheses; from grc, πρόσθεσις, prósthesis, addition, application, attachment), or a prosthetic implant, is an artificial device that replaces a missing body part, which may be lost through trau ...
s, and
brain-machine interfaces. In the case of neural
stimulation
Stimulation is the encouragement of development or the cause of activity generally. For example, "The press provides stimulation of political discourse." An interesting or fun activity can be described as "stimulating", regardless of its physica ...
, mostly an electrical stimulation is utilized and charge-balanced biphasic constant current waveforms or capacitively coupled charge injection approaches are adopted. Alternatively,
transcranial magnetic stimulation
Transcranial magnetic stimulation (TMS) is a noninvasive form of brain stimulation in which a changing magnetic field is used to induce an electric current at a specific area of the brain through electromagnetic induction. An electric pulse gener ...
and
transcranial electric stimulation
Transcranial direct current stimulation (tDCS) is a form of neuromodulation that uses constant, low direct current delivered via electrodes on the head. It was originally developed to help patients with brain injuries or neuropsychiatric conditio ...
have been proposed as non-invasive methods in which either a
magnetic field
A magnetic field is a vector field that describes the magnetic influence on moving electric charges, electric currents, and magnetic materials. A moving charge in a magnetic field experiences a force perpendicular to its own velocity and to ...
or transcranially applied electric currents cause neurostimulation.
Brain stimulation
Brain stimulation has potentials to treat some disorders such as
epilepsy
Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...
. In this method, scheduled stimulation is applied to specific cortical or subcortical targets. There are available commercial devices that can deliver an electrical pulse at scheduled time intervals. Scheduled stimulation is hypothesized to alter the intrinsic neurophysiologic properties of epileptic networks. The most explored targets for scheduled stimulation are the anterior nucleus of the
thalamus
The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...
and the
hippocampus
The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, a ...
. The anterior nucleus of the thalamus has been studied, which has shown a significant seizure reduction with the stimulator ''on'' versus ''off'' during several months after stimulator implantation. Moreover, the
cluster headache
Cluster headache (CH) is a neurological disorder characterized by recurrent severe headaches on one side of the head, typically around the eye(s). There is often accompanying eye watering, nasal congestion, or swelling around the eye on the a ...
(CH) can be treated by using a temporary stimulating electrode at
sphenopalatine ganglion
The pterygopalatine ganglion (aka Meckel's ganglion, nasal ganglion, or sphenopalatine ganglion) is a parasympathetic ganglion found in the pterygopalatine fossa. It is largely innervated by the greater petrosal nerve (a branch of the facial ne ...
(SPG). Pain relief is reported within several minutes of stimulation in this method. To avoid use of implanted electrodes, researchers have engineered ways to inscribe a "window" made of zirconia that has been modified to be transparent and implanted in mice skulls, to allow optical waves to penetrate more deeply, as in
optogenetics
Optogenetics is a biological technique to control the activity of neurons or other cell types with light. This is achieved by expression of light-sensitive ion channels, pumps or enzymes specifically in the target cells. On the level of individ ...
, to stimulate or inhibit individual neurons.
[ Explained by ]
Deep brain stimulation
Deep brain stimulation (DBS) has shown benefits for movement disorders such as
Parkinson's disease
Parkinson's disease (PD), or simply Parkinson's, is a long-term degenerative disorder of the central nervous system that mainly affects the motor system. The symptoms usually emerge slowly, and as the disease worsens, non-motor symptoms becom ...
,
tremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving oscillations or twitching movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, fa ...
and
dystonia
Dystonia is a neurological hyperkinetic movement disorder in which sustained or repetitive muscle contractions result in twisting and repetitive movements or abnormal fixed postures. The movements may resemble a tremor. Dystonia is often inten ...
and affective disorders such as
depression,
obsessive-compulsive disorder,
Tourette syndrome
Tourette syndrome or Tourette's syndrome (abbreviated as TS or Tourette's) is a common neurodevelopmental disorder that begins in childhood or adolescence. It is characterized by multiple movement (motor) tics and at least one vocal (phonic) ...
,
chronic pain
Chronic pain is classified as pain that lasts longer than three to six months. In medicine, the distinction between Acute (medicine), acute and Chronic condition, chronic pain is sometimes determined by the amount of time since onset. Two commonly ...
and cluster headache. DBS can directly change the brain activity in a controlled manner and is hence used to map fundamental mechanisms of brain functions along with neuroimaging methods.
A DBS system consists of three components: the implanted pulse generator (IPG), the lead, and an extension. The implantable
pulse generator
A pulse generator is either an electronic circuit ''or'' a piece of electronic test equipment used to generate rectangular pulses. Pulse generators are used primarily for working with digital circuits; related function generators are used primar ...
(PG) generates stimulation pulses, which are sent to intracranial leads at the target via an extension. The simulation pulses interfere with
neural
In Biology, biology, the nervous system is the Complex system, highly complex part of an animal that coordinates its Behavior, actions and Sense, sensory information by transmitting action potential, signals to and from different parts of its ...
activity at the target site.
The application and effects of DBS, on both normal and diseased brains, involves many parameters. These include the physiological properties of the brain tissue, which may change with disease state. Also important are the stimulation parameters, such as amplitude and temporal characteristics, and the geometric configuration of the electrode and the tissue that surrounds it.
In spite of a huge number of studies on DBS, its mechanism of action is still not well understood. Developing DBS microelectrodes is still challenging.
Non-invasive of brain stimulation
Transcranial magnetic stimulation
Compared to electrical stimulation that utilizes brief, high-voltage electric shock to activate neurons, which can potentially activate pain fibers,
transcranial magnetic stimulation (TMS) was developed by Baker in 1985. TMS uses a magnetic wire above the
scalp
The scalp is the anatomical area bordered by the human face at the front, and by the neck at the sides and back.
Structure
The scalp is usually described as having five layers, which can conveniently be remembered as a mnemonic:
* S: The ski ...
, which carries a sharp and high current pulse. A time variant magnetic field is induced perpendicular to the coil due to the applied pulse which consequently generates an electric field based on
Maxwell's law. The electric field provides the necessary current for a non-invasive and much less painful stimulation. There are two TMS devices called single pulse TMS and repetitive pulse TMS (rTMS) while the latter has greater effect but potential to cause seizure. TMS can be used for therapy particularly in
psychiatry
Psychiatry is the medical specialty devoted to the diagnosis, prevention, and treatment of mental disorders. These include various maladaptations related to mood, behaviour, cognition, and perceptions. See glossary of psychiatry.
Initial psych ...
, as a tool to measure central motor conduction and a research tool to study different aspects of human brain physiology such as motor function, vision, and language. The rTMS method has been used to treat epilepsy with rates of 8–25 Hz for 10 seconds. The other therapeutic uses of rTMS include parkinson diseases, dystonia and mood diseases. Also, TMS can be used to determine the contribution of cortical networks to specific cognitive functions by disrupting activity in the focal brain region.
[ Early, inconclusive, results have been obtained in recovery from coma (]persistent vegetative state
A persistent vegetative state (PVS) or post-coma unresponsiveness (PCU) is a disorder of consciousness in which patients with severe brain damage are in a state of partial arousal rather than true awareness. After four weeks in a vegetative stat ...
) by Pape et al. (2009).
Transcranial electrical stimulation
* Transcranial direct current stimulation
Transcranial direct current stimulation (tDCS) is a form of neuromodulation that uses constant, low direct current delivered via electrodes on the head. It was originally developed to help patients with brain injuries or neuropsychiatric conditio ...
(tDCS)
* Transcranial alternating current stimulation
Cranial electrotherapy stimulation (CES) is a form of neurostimulation that delivers a small, pulsed, alternating current via electrodes on the head. CES is used with the intention of treating a variety of conditions such as anxiety, depression a ...
(tACS)
* Transcranial pulsed current stimulation (tPCS)
* Transcranial random noise stimulation
Transcranial random noise stimulation (tRNS) is a non-invasive brain stimulation technique and a form of transcranial electrical stimulation (tES). Terney et al from Göttingen University was the first group to apply tRNS in humans in 2008. They ...
(tRNS)
Spinal cord stimulation
Spinal cord stimulation
A spinal cord stimulator (SCS) or dorsal column stimulator (DCS) is a type of implantable neuromodulation device (sometimes called a "pain pacemaker") that is used to send electrical signals to select areas of the spinal cord (dorsal columns) for ...
(SCS) is an effective therapy for the treatment of chronic and intractable pain including diabetic neuropathy
Diabetic neuropathy is various types of nerve damage associated with diabetes mellitus. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic c ...
, failed back surgery syndrome, complex regional pain syndrome, phantom limb
A phantom limb is the sensation that an amputated or missing limb is still attached. Approximately 80 to 100% of individuals with an amputation experience sensations in their amputated limb. However, only a small percentage will experience painf ...
pain, ischemic limb pain, refractory unilateral limb pain syndrome, postherpetic neuralgia
Postherpetic neuralgia (PHN) is neuropathic pain that occurs due to damage to a peripheral nerve caused by the reactivation of the varicella zoster virus (herpes zoster, also known as shingles). Typically, the nerve pain (neuralgia) is confined ...
and acute herpes zoster
Shingles, also known as zoster or herpes zoster, is a viral disease characterized by a painful skin rash with blisters in a localized area. Typically the rash occurs in a single, wide mark either on the left or right side of the body or face. ...
pain. Another pain condition that is a potential candidate for SCS treatment is Charcot-Marie-Tooth (CMT) disease, which is associated with moderate to severe chronic extremity pain. SCS therapy consists of the electrical stimulation of the spinal cord to 'mask' pain. The gate theory proposed in 1965 by Melzack and Wall
A wall is a structure and a surface that defines an area; carries a load; provides security, shelter, or soundproofing; or, is decorative. There are many kinds of walls, including:
* Walls in buildings that form a fundamental part of the supe ...
provided a theoretical construct to attempt SCS as a clinical treatment for chronic pain. This theory postulates that activation of large diameter, myelinated primary afferent fibers
Afferent nerve fibers are the axons (nerve fibers) carried by a sensory nerve that relay sensory information from sensory receptors to regions of the brain. Afferent projections ''arrive'' at a particular brain region. Efferent nerve fibers ...
suppresses the response of dorsal horn neurons to input from small, unmyelinated primary afferents.
A simple SCS system consists of three different parts. First, microelectrodes are implanted in the epidural space to deliver stimulation pulses to the tissue. Second, an electrical pulse generator implanted in the lower abdominal area or gluteal region
The gluteal muscles, often called glutes are a group of three muscles which make up the gluteal region commonly known as the buttocks: the gluteus maximus, gluteus medius and gluteus minimus. The three muscles originate from the ilium and s ...
while is connected to the electrodes via wires, and third a remote control to adjust the stimulus parameters such as pulse width and pulse rate in the PG. Improvements have been made in both the clinical aspects of SCS such as transition from subdural placement of contacts to epidural placement, which reduces the risk and morbidity of SCS implantation, and also technical aspects of SCS such as improving percutaneous leads, and fully implantable multi-channel stimulators. However, there are many parameters that need to be optimized including number of implanted contacts, contact size and spacing, and electrical sources for stimulation. The stimulus pulse width and pulse rate are important parameters that need to be adjusted in SCS, which are typically 400 us and 8–200 Hz respectively.[
]
Spinal cord stimulation for movement disorders
Spinal cord stimulation has shown promising results in spinal cord injury and other movement disorders, such as multiple sclerosis. The stimulation, applied over the lumbar spinal cord, works by activating large diameter afferent fibers entering the spinal cord, which then transsynaptically activate and engage spinal neuronal networks. The same target structures can also be activated by transcutaneous electrodes placed over the lower thoracic spine and abdomen. Transcutaneous spinal cord stimulation is completely non-invasive and, as it uses TENS electrodes and stimulators, can be applied at low cost. Yet, in comparison to the implanted epidural variant, the efficacy of transcutaneous spinal cord stimulation depends on the body position and spinal alignment, which could lead to inconsistent result if the body position and posture isn't controlled during the application.
Transcutaneous supraorbital nerve stimulation
Tentative evidence supports transcutaneous supraorbital nerve stimulation. Side effects are few.
Cochlear implants
Cochlear implants
A cochlear implant (CI) is a surgically implanted neuroprosthesis that provides a person who has moderate-to-profound sensorineural hearing loss with sound perception. With the help of therapy, cochlear implants may allow for improved speech unde ...
have provided partial hearing to more than 120,000 persons worldwide as of 2008. The electrical stimulation is used in a cochlear implant to provide functional hearing in totally deafened persons. Cochlear implants include several subsystem components from the external speech processor and radio frequency
Radio frequency (RF) is the oscillation rate of an alternating electric current or voltage or of a magnetic, electric or electromagnetic field or mechanical system in the frequency range from around to around . This is roughly between the upp ...
(RF) transmission link to the internal receiver, stimulator, and electrode arrays. Modern cochlear implant research started in the 1960s and 1970s. In 1961, a crude single electrode device was implanted in two deaf patients and useful hearing with electric stimulation was reported. The first FDA approved complete single channel device was released in 1984.
In cochlear implants, the sound is picked up by a microphone and transmitted to the behind-the-ear external processor to be converted to the digital data. The digitized data is then modulated on a radio frequency signal and transmitted to an antenna
Antenna ( antennas or antennae) may refer to:
Science and engineering
* Antenna (radio), also known as an aerial, a transducer designed to transmit or receive electromagnetic (e.g., TV or radio) waves
* Antennae Galaxies, the name of two collid ...
inside a headpiece. The data and power carrier are transmitted through a pair of coupled coils to the hermetically sealed internal unit. By extracting the power and demodulating the data, electric current commands are sent to the cochlea
The cochlea is the part of the inner ear involved in hearing. It is a spiral-shaped cavity in the bony labyrinth, in humans making 2.75 turns around its axis, the modiolus. A core component of the cochlea is the Organ of Corti, the sensory org ...
to stimulate the auditory nerve through microelectrodes. The key point is that the internal unit does not have a battery and it should be able to extract the required energy. Also to reduce the infection, data is transmitted wirelessly along with power. Inductively coupled coils are good candidates for power and data telemetry, although radio-frequency transmission could provide better efficiency and data rates. Parameters needed by the internal unit include the pulse amplitude, pulse duration, pulse gap, active electrode, and return electrode that are used to define a biphasic pulse and the stimulation mode. An example of the commercial devices include Nucleus 22 device that utilized a carrier frequency of 2.5 MHz and later in the newer revision called Nucleus 24 device, the carrier frequency was increased to 5 MHz. The internal unit in the cochlear implants is an ASIC (application-specific integrated circuit
An application-specific integrated circuit (ASIC ) is an integrated circuit (IC) chip customized for a particular use, rather than intended for general-purpose use, such as a chip designed to run in a digital voice recorder or a high-efficie ...
) chip that is responsible to ensure safe and reliable electric stimulation. Inside the ASIC chip, there is a forward pathway, a backward pathway, and control units. The forward pathway recovers digital information from the RF signal which includes stimulation parameters and some handshaking bits to reduce the communication error. The backward pathway usually includes a back telemetry voltage
sampler that reads the voltage over a period of time on the recording electrode. The stimulator block is responsible to deliver predetermined current by external unit to the microelectrodes. This block includes a reference current and a digital to analog converter
In electronics, a digital-to-analog converter (DAC, D/A, D2A, or D-to-A) is a system that converts a digital signal into an analog signal. An analog-to-digital converter (ADC) performs the reverse function.
There are several DAC architec ...
to transform digital commands to an analog current.
Visual prosthesis
Theoretical and experimental clinical evidences suggest that direct electrical stimulation of the retina might be able to provide some vision to subjects who have lost the photoreceptive elements of their retina
The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which then ...
. Therefore, visual prostheses are developed to restore vision for the blind by using the stimulation. Depending upon which visual pathway location is targeted for neural stimulation, different approaches have been considered. Visual pathway consists mainly of the eye, optic nerve
In neuroanatomy, the optic nerve, also known as the second cranial nerve, cranial nerve II, or simply CN II, is a paired cranial nerve that transmits visual system, visual information from the retina to the brain. In humans, the optic nerve i ...
, lateral geniculate nucleus
In neuroanatomy, the lateral geniculate nucleus (LGN; also called the lateral geniculate body or lateral geniculate complex) is a structure in the thalamus and a key component of the mammalian visual pathway. It is a small, ovoid, ventral projec ...
(LGN), and visual cortex
The visual cortex of the brain is the area of the cerebral cortex that processes visual information. It is located in the occipital lobe. Sensory input originating from the eyes travels through the lateral geniculate nucleus in the thalamus and ...
. Therefore, retinal, optic nerve and visual cortex stimulation are the three different methods used in visual prostheses.
Retinal degenerative diseases, such as retinitis pigmentosa
Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visual field). As peripheral vision worsens, people may ...
(RP) and age-related macular degeneration
Macular degeneration, also known as age-related macular degeneration (AMD or ARMD), is a medical condition which may result in blurred or no vision in the center of the visual field. Early on there are often no symptoms. Over time, however, som ...
(AMD), are two likely candidate diseases in which retinal stimulation may be helpful. Three approaches called intraocular epiretinal, subretinal and extraocular transretinal stimulation are pursued in retinal devices that stimulate remaining retinal neural cells to bypass lost photoreceptors and allow the visual signal to reach the brain via the normal visual pathway. In epiretinal approach, electrodes are placed on the top side of the retina near ganglion cells
{{stack,
A ganglion cell is a cell found in a ganglion. Examples of ganglion cells include:
* Retinal ganglion cell (RGC) found in the ganglion cell layer of the retina
* Cells that reside in the adrenal medulla, where they are involved in th ...
, whereas the electrodes are placed under the retina in subretinal approaches. Finally, the posterior scleral surface of the eye is the place in which extraocular approach electrodes are positioned. Second Sight and the Humayun group at USC are the most active groups in the design of intraocular retinal prostheses. The ArgusTM 16 retinal implant is an intraocular retinal prosthesis utilizing video processing technologies.
Regarding to the visual cortex stimulation, Brindley, and Dobelle were the first ones who did the experiments and demonstrated that by stimulating the top side of the visual cortex most of the electrodes can produce visual percept.[ More recently Sawan built a complete implant for intracortical stimulation and validated the operation in rats.
]
LGN, which is located in the midbrain to relay signals from the retina to the visual cortex, is another potential area that can be used for stimulation. But this area has limited access due to surgical difficulty. The recent success of deep brain stimulation techniques targeting the midbrain
The midbrain or mesencephalon is the forward-most portion of the brainstem and is associated with vision, hearing, motor control, sleep and wakefulness, arousal (alertness), and temperature regulation. The name comes from the Greek ''mesos'', " ...
has encouraged research to pursue the approach of LGN stimulation for a visual prosthesis.
Cardiac electrostimulation devices
Implantable pacemakers were proposed for the first time in 1959 and became more sophisticated since then. The therapeutic application of pacemakers consists of numerous rhythm disturbances including some forms of tachycardia
Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal (su ...
(too fast a heart beat), heart failure
Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...
, and even stroke
A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...
. Early implantable pacemakers worked only a short time and needed periodic recharging by an inductive link. These implantable pacemakers needed a pulse generator to stimulate heart muscles
Skeletal muscles (commonly referred to as muscles) are organs of the vertebrate muscular system and typically are attached by tendons to bones of a skeleton. The muscle cells of skeletal muscles are much longer than in the other types of muscle ...
with a certain rate in addition to electrodes. Today, modern pulse generators are programmed non-invasively by sophisticated computerized machines using RF, obtaining information about the patient's and device's status by telemetry. Also they use a single hermetically sealed lithium iodide
Lithium iodide, or LiI, is a compound of lithium and iodine. When exposed to air, it becomes yellow in color, due to the oxidation of iodide to iodine. It crystallizes in the NaCl motif. It can participate in various hydrates.Wietelmann, Ulrich ...
(LiI) cell as the battery. The pacemaker circuitry includes sense amplifiers to detect the heart's intrinsic electrical signals, which are used to track heart activity, rate adaptive circuitry, which determine the need for increased or reduced pacing rate, a microprocessor, memory to store the parameters, telemetry control for communication protocol and power supplies to provide regulated voltage.
Stimulation microelectrode technologies
Microelectrodes are one of the key components of the neurostimulation, which deliver the current to neurons. Typical microelectrodes have three main components: a substrate (the ''carrier''), a conductive metal layer, and an insulation material. In cochlear implants, microelectrodes are formed from platinum-iridium alloy. State-of-the-art electrodes include deeper insertion to better match the tonotopic
In physiology, tonotopy (from Greek tono = frequency and topos = place) is the spatial arrangement of where sounds of different frequency are processed in the brain. Tones close to each other in terms of frequency are represented in topologically ...
place of stimulation to the frequency band assigned to each electrode channel, improving efficiency of stimulation, and reducing insertion related trauma. These cochlear implant electrodes are either straight or spiral such as Med-El
MED-EL is a global medical technology company specializing in hearing implants and devices. They develop and manufacture products including cochlear implants, middle ear implants and bone conduction systems.
MED-EL is a privately owned compa ...
Combi 40+ and Advanced Bionics Helix microelectrodes respectively. In visual implants, there are two types of electrode arrays called planar type or three dimensional needle or pillar type, where needle type array such as Utah array is mostly used for cortical and optic nerve stimulations and rarely used in retinal implants due to the possible damage of retina. However, a pillar-shaped gold electrode array on thin-film polyimide
Polyimide (sometimes abbreviated PI) is a polymer containing imide groups belonging to the class of high-performance plastics. With their high heat-resistance, polyimides enjoy diverse applications in roles demanding rugged organic materials, e.g ...
has been used in an extraocular implant. On the other hand, planar electrode arrays are formed from flexible polymers, such as silicone
A silicone or polysiloxane is a polymer made up of siloxane (−R2Si−O−SiR2−, where R = organic group). They are typically colorless oils or rubber-like substances. Silicones are used in sealants, adhesives, lubricants, medicine, cooking ...
, polyimide, and Parylene
Parylene is the common name of a polymer whose backbone consists of ''para''- benzenediyl rings –– connected by 1,2-ethanediyl bridges –––. It can be obtained by polymerization of ''para''-xylylene .
The name is also used for se ...
as candidates for retinal implants.
Regarding to DBS microelectrodes an array, which can be controlled independently, distributed throughout the target nucleus would permit precise control of the spatial distribution of the stimulation, and thus, allow better personalized DBS. There are several requirements for DBS microelectrodes that include long lifetime without injury to the tissue or degradation of the electrodes, customized for different brain sites, long-term biocompatibility
Biocompatibility is related to the behavior of biomaterials in various contexts. The term refers to the ability of a material to perform with an appropriate host response in a specific situation. The ambiguity of the term reflects the ongoing de ...
of the material, mechanically durable in order to reach the target without being damaged during handling by the implant surgeon, and finally uniformity of performance across the microelectrodes in a particular array. Tungsten
Tungsten, or wolfram, is a chemical element with the symbol W and atomic number 74. Tungsten is a rare metal found naturally on Earth almost exclusively as compounds with other elements. It was identified as a new element in 1781 and first isolat ...
microwire, iridium microwires, and sputtered or electrodeposited Platinum-iridium alloy microelectrodes are the examples of microelectrode used in DBS.[ ]Silicon carbide
Silicon carbide (SiC), also known as carborundum (), is a hard chemical compound containing silicon and carbon. A semiconductor, it occurs in nature as the extremely rare mineral moissanite, but has been mass-produced as a powder and crystal sin ...
is a potential interesting material for realizing biocompatible semiconductor devices.
History
The primary findings about neurostimulation originated from the idea to stimulate nerves for therapeutic purposes. The 1st recorded use of electrical stimulation for pain relief goes back to 46 AD, when Scribonius Largus
Scribonius Largus (c. 1-c. 50) was the court physician to the Roman emperor Claudius.
About 47 AD, at the request of Gaius Julius Callistus, the emperor's freedman, he drew up a list of 271 prescriptions (''Compositiones''), most of them his own, ...
used torpedo fish (electric ray) for relieving headaches. In the late 18th century, Luigi Galvani
Luigi Galvani (, also ; ; la, Aloysius Galvanus; 9 September 1737 – 4 December 1798) was an Italian physician, physicist, biologist and philosopher, who studied animal electricity. In 1780, he discovered that the muscles of dead frogs' legs ...
discovered that the muscles of dead frog legs twitched when struck by direct current on the nervous system. The modulation of the brain
A brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals. It is located in the head, usually close to the sensory organs for senses such as vision. It is the most complex organ in a v ...
activity by electrical stimulation of the motor cortex in dogs was shown in 1870 that resulted in limb movement. From the late 18th century to today many milestones have been developed. Nowadays, sensory prosthetic devices, such as visual implants, cochlear implants, auditory midbrain implants, and spinal cord stimulators and also motor prosthetic devices, such as deep brain stimulators, Bion microstimulators, the brain control and sensing interface, and cardiac electro-stimulation devices are widely used.
In 2013 the British pharmaceutical company GlaxoSmithKline
GSK plc, formerly GlaxoSmithKline plc, is a British multinational pharmaceutical and biotechnology company with global headquarters in London, England. Established in 2000 by a merger of Glaxo Wellcome and SmithKline Beecham. GSK is the ten ...
(GSK) coined the term "electroceutical" to broadly encompass medical devices
A medical device is any device intended to be used for medical purposes. Significant potential for hazards are inherent when using a device for medical purposes and thus medical devices must be proved safe and effective with reasonable assura ...
that use electrical, mechanical, or light stimulation to affect electrical signaling in relevant tissue types.[ Clinical neural implants such as ]cochlear implant
A cochlear implant (CI) is a surgically implanted neuroprosthesis that provides a person who has moderate-to-profound sensorineural hearing loss with sound perception. With the help of therapy, cochlear implants may allow for improved speech und ...
s to restore hearing, retinal implant
Retinal prostheses for restoration of sight to patients blinded by retinal degeneration are being developed by a number of private companies and research institutions worldwide. The system is meant to partially restore useful vision to people who ...
s to restore sight, spinal cord stimulator
A spinal cord stimulator (SCS) or dorsal column stimulator (DCS) is a type of implantable neuromodulation device (sometimes called a "pain pacemaker") that is used to send electrical signals to select areas of the spinal cord (dorsal columns) for ...
s for pain relief or cardiac pacemakers
350px, Image showing the cardiac pacemaker or SA node, the primary pacemaker within the electrical_conduction_system_of_the_heart">SA_node,_the_primary_pacemaker_within_the_electrical_conduction_system_of_the_heart.
The_muscle_contraction.htm ...
and implantable defibrillator
Defibrillation is a treatment for life-threatening cardiac arrhythmias, specifically ventricular fibrillation (V-Fib) and non-perfusing ventricular tachycardia (V-Tach). A defibrillator delivers a dose of electric current (often called a ''coun ...
s are proposed examples of electroceuticals. GSK formed a venture fund
Venture capital (often abbreviated as VC) is a form of private equity financing that is provided by venture capital firms or funds to startups, early-stage, and emerging companies that have been deemed to have high growth potential or which hav ...
and said it would host a conference in 2013 to lay out a research agenda for the field. A 2016 review of research on interactions between the nervous and immune systems in autoimmune disorders
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
mentioned "electroceuticals" in passing and quotation marks, referring to neurostimulation devices in development for conditions like arthritis.
Research
In addition to the enormous usage of neurostimulation for clinical applications, it is also used widely in laboratories started dates back to 1920s by people like Delgado who used stimulation as an experimental manipulation to study basics of how the brain works. The primary works were on the reward center of the brain in which stimulation of those structures led to pleasure that requested more stimulation. Another most recent example is the electrical stimulation of the MT area of primary visual cortex to bias perception. In particular, the directionality of motion is represented in a regular way in the MT area. They presented monkeys with moving images on screen and monkey throughput was to determine what the direction is. They found that by systematically introducing some errors to the monkey's responses, by stimulating the MT area which is responsible for perceiving the motion in another direction, the monkey responded to somewhere in between the actual motion and the stimulated one. This was an elegant use of stimulation to show that MT area is essential in the actual perception of motion. Within the memory
Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembered, ...
field, stimulation is used very frequently to test the strength of the connection between one bundle of cells to another by applying a small current in one cell which results in the release of neurotransmitters and measuring the postsynaptic potential
Postsynaptic potentials are changes in the membrane potential of the postsynaptic terminal of a chemical synapse. Postsynaptic potentials are graded potentials, and should not be confused with action potentials although their function is to ini ...
.
Generally, a short but high-frequency current in the range of 100 Hz helps strengthening the connection known as long-term potentiation
In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neurons ...
. However, longer but low-frequency current tends to weaken the connections known as long-term depression.[Interview with Dr. J. Manns, Emory University, Oct. 2010]
See also
* Non-invasive cerebellar stimulation
References
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Neurostimulation,
Neurotechnology
Electrotherapy
Medical devices