Neurotherapy

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Neurotherapy is 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. [1] [2] [3]

Contents

Definition

A consensus in the academic community considers this notion within limitations of the contemporary meaning of neuromodulation, [4] which 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" (see Neuromodulation). While neurotherapy may have a broader meaning, its modern definition focuses exclusively on technological methods that exert an energy-based impact on the development of the balanced nervous system in order to address symptom control and cure several conditions. [3] The definition of neurotherapy relies on evolving scientific concepts from different fields of knowledge, ranging from physics to neuroscience. Four central concepts that underlie the knowledge of neurotherapy are defined here:

Energy stimulus

Energy, as the ability to do work, cannot be created or destroyed; it can only be transformed from one form to another (the law of conservation of energy). There are different form of energy. Such forms of energy as radiant energy carried by electromagnetic radiation, electrical energy and magnetic energy, [5] are of interest to neurotherapy. Medical devices for neuromodulation exert electrical, magnetic, and/or electromagnetic energy to treat mental and physical health disorders in patients.

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 and dependent on the events that influence them such as experience or neuromodulation. [6]

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. [6]

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. [7]

Medical uses

According to the International Neuromodulation Society, neuromodulation-based therapy "addresses symptom control through nerve stimulation" in the following condition categories: [3]

Types

Neurotherapy, as many medical therapy, is based on knowledge from conventional medicine, relying on 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") [8] 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

Magnetic energy

Electromagnetic radiation

Mechanisms

Origins behind the way that an external energy stimulus alters neuronal activity and stimulates neuroplasticity during various artificial neurostimulation techniques are still under discussion. It is important to note that electrical and magnetic energy are two forms of energy that are closely interconnected: a moving charge induces electrical and magnetic fields. Electrical current creates a magnetic field, and a magnetic field induces an electrical charge movement. Neurons are electrically active cells. [16] Neuronal oscillations have a dual role in synapsis: they are affected by spiking inputs and, in turn, impact the timing of spike outputs. [17] Because of the above facts, both electrical and magnetic fields may induce electrical currents in neuronal circuits. [18] Therefore, similar mechanisms of altered neuronal activity may underlie different neuromodulation techniques that use electrical, magnetic, or electromagnetic energy in treatment. [14]

A variety of hypotheses try to explain the mechanisms that contribute to synaptic activity during neurostimulation. According to an influential position, electrical and magnetic fields may alter Ca2+ and Na+ channel activity. [19] [20] [21] [22] [23] The voltage-gated Ca2+ channels are the primary conduits for the Ca2+ ions that cause a confluence of neurotransmitter-containing vesicles with the presynaptic membrane. [23] The altered activity of Ca2+ and Na+ channel changes the timing and strength of synaptic output, contributing to neuronal excitability. [23]

Another perspective hypothesis stands that electromagnetic fields increase in adenosine receptors release that facilitates neuronal communication. [24] Because A(2A) adenosine receptors control the release of other neurotransmitters (e.g., glutamate and dopamine), this contributes to adjusting neuronal functions. [24]

According to the natural neurostimulation hypothesis, energy stimuli induce mitochondrial stress and micro vascular vasodilation. These promote increasing Adenosine triphosphate (ATP) protein and oxygenation, inducing synaptic strength. [14] This position explains neuromodulation from different scale levels: from interpersonal dynamics to nonlocal neuronal coupling. [14] According to natural neurostimulation, the innate natural mechanism of physical interactions between the mother and embryo ensures the balanced development of the embryonic nervous system. [14] The drivers of these interactions, the electromagnetic properties of the mother's heart, enable brain waves to interact between the mother's and fetal nervous systems. [14] The electromagnetic and acoustic oscillations of the mother's heart converge the neuronal activity of both nervous systems in an ensemble, shaping harmony from a cacophony of separate oscillations. [14] These interactions synchronize brain oscillations, influencing neuroplasticity in the fetus. [14] During the mother's intentional actions with her environment, these interchanges provide hints to the fetus's nervous system, binding synaptic activity with relevant stimuli. [14] This hypothesis posits that the physiological processes of mitochondrial stress induction (affecting neuronal plasticity) and vasodilation, which cooperatively increase microvascular blood flow and tissue oxygenation, are the basis of the natural neurostimulation. It is also thought to be a foundation of many non-invasive artificial neuromodulation techniques. [14] [25] Because if the mother-fetus interactions allow the child's nervous system to grow with adequate biological sentience, similar (while scaling) environmental interactions can heal the damaged nervous system in adults.

History

While neurotherapy is a relatively young medical treatment in conventional Western biomedicine (that relies on a scientific approach and evidence-based practice), [26] different age-old cultural practices of traditional Indian, Egyptian, and Chinese medicine have been using neuromodulation elements thousands of years ago. Before the basic processes of neurotherapy were scientifically studied, humans used the electrical properties of animals for therapeutic purposes. The Egyptians used the Nile catfish (Synodontis batensoda and Malapterurus electricus) to stimulate tissue electrically, according to an interpretation of frescoes in the tomb of the architect Ti at Saqqara, Egypt. The first documented use of electrical stimulation for pain relief dates back to 46 AD when Scribonius Largus of the ancient Roman Empire used the electric properties of torpedo fish to relieve headaches. [27]

Scientific studies of neuromodulation began in 1745, when German physician De Haen published “a number of cases of spasmodic, paralytic and other nervous affections cured by electricity”. [28]

The first implementation of electrocutical apparatus in hospital medical treatment recorded in Middlesex Hospital of London in 1767. [28] In 1870, German physicians Gustav Fritsch and Eduard Hitzig reported the modulation of brain activity in dogs by electrical stimulation of the motor cortex. [29]

In 1924, the German psychiatrist Hans Berger attached electrodes to the scalp and detected small currents in the brain. [4]

In the mid-20th century, the scientific study of neuromodulation in humans expanded significantly. Neurologist Professor Spiegel and neurosurgeon Professor Weissys of Temple University presented a stereotactic device to perform "ablation procedures" in humans; "intraoperative electrical stimulation" was introduced to test the brain's target zone before surgery in 1947. In the 1950s, Professor Heath reported about subcortical stimulation with precise descriptions of behavioral changes. [30] In 1967, Dr. Norm Shealy from Western Reserve Medical School presented “the first dorsal column stimulator for pain control”. It was developed based on the Gate Theory of Wall and Melzack, [31] which stated that pain transmissions from tiny nerve fibers would be blocked if competing transmissions were made along larger sensory nerve fibers. [32]

In 1987, the team of neurosurgeons/neurologists Professor Benabid and Professor Pollak and their colleagues (Grenoble, France) published results on this topic about thalamic Deep Brain Stimulation. [33]

See also

Related Research Articles

<span class="mw-page-title-main">Neurology</span> Medical specialty dealing with disorders of the nervous system

Neurology is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the spinal cord and the peripheral nerves. Neurological practice relies heavily on the field of neuroscience, the scientific study of the nervous system, using various techniques of neurotherapy.

<span class="mw-page-title-main">Nervous system</span> Part of an animal that coordinates actions and senses

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 that impact the body, then works in tandem with the endocrine system to respond to such events. Nervous tissue first arose in wormlike organisms about 550 to 600 million years ago. In vertebrates, it consists of two main parts, the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS consists of the brain and spinal cord. The PNS consists mainly of nerves, which are enclosed bundles of the long fibers, or axons, that connect the CNS to every other part of the body. Nerves that transmit signals from the brain are called motor nerves (efferent), while those nerves that transmit information from the body to the CNS are called sensory nerves (afferent). The PNS is divided into two separate subsystems, the somatic and autonomic, nervous systems. The autonomic nervous system is further subdivided into the sympathetic, parasympathetic and enteric nervous systems. The sympathetic nervous system is activated in cases of emergencies to mobilize energy, while the parasympathetic nervous system is activated when organisms are in a relaxed state. The enteric nervous system functions to control the gastrointestinal system. Nerves that exit from the brain are called cranial nerves while those exiting from the spinal cord are called spinal nerves.

<span class="mw-page-title-main">Cognitive neuroscience</span> Scientific field

Cognitive neuroscience is the scientific field that is concerned with the study of the biological processes and aspects that underlie cognition, with a specific focus on the neural connections in the brain which are involved in mental processes. It addresses the questions of how cognitive activities are affected or controlled by neural circuits in the brain. Cognitive neuroscience is a branch of both neuroscience and psychology, overlapping with disciplines such as behavioral neuroscience, cognitive psychology, physiological psychology and affective neuroscience. Cognitive neuroscience relies upon theories in cognitive science coupled with evidence from neurobiology, and computational modeling.

<span class="mw-page-title-main">Transcranial magnetic stimulation</span> Brain stimulation using magnetic fields

Transcranial magnetic stimulation (TMS) is a noninvasive neurotherapy, a 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 generator, or stimulator, is connected to a magnetic coil connected to the scalp. The stimulator generates a changing electric current within the coil which creates a varying magnetic field, inducing a current within a region in the brain itself.

Neurotechnology encompasses any method or electronic device which interfaces with the nervous system to monitor or modulate neural activity.

Neural engineering is a discipline within biomedical engineering that uses engineering techniques to understand, repair, replace, or enhance neural systems. Neural engineers are uniquely qualified to solve design problems at the interface of living neural tissue and non-living constructs.

<span class="mw-page-title-main">Neuromodulation</span> Regulation of neurons by neurotransmitters

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 messenger signaling cascade that induces a broad, long-lasting signal. This modulation can last for hundreds of milliseconds to several minutes. Some of the effects of neuromodulators include altering intrinsic firing activity, increasing or decreasing voltage-dependent currents, altering synaptic efficacy, increasing bursting activity and reconfiguring synaptic connectivity.

<span class="mw-page-title-main">Transcranial direct-current stimulation</span> Technique of brain electric stimulation therapy

Transcranial direct current stimulation (tDCS) is a form of neuromodulation that uses constant, low direct current delivered via electrodes on the head. This type of neurotherapy was originally developed to help patients with brain injuries or neuropsychiatric conditions such as major depressive disorder. It can be contrasted with cranial electrotherapy stimulation, which generally uses alternating current the same way, as well as transcranial magnetic stimulation.

<span class="mw-page-title-main">Responsive neurostimulation device</span> Category of medical devices that respond to signals in a patients body to treat disease

Responsive neurostimulation device is a medical device that senses changes in a person's body and uses neurostimulation to respond in the treatment of disease. The FDA has approved devices for use in the United States in the treatment of epileptic seizures and chronic pain conditions. Devices are being studied for use in the treatment of essential tremor, Parkinson's disease, Tourette's syndrome, depression, obesity, and post-traumatic stress disorder.

Connectomics is the production and study of connectomes: comprehensive maps of connections within an organism's nervous system. More generally, it can be thought of as the study of neuronal wiring diagrams with a focus on how structural connectivity, individual synapses, cellular morphology, and cellular ultrastructure contribute to the make up of a network. The nervous system is a network made of up to billions of connections and these connections are responsible for our thoughts, emotions, actions, memories, function and dysfunction. Therefore, the study of connectomics aims to advance our understanding of mental health and cognition by understanding how cells in the nervous system are connected and communicate. Because these structures are extremely complex, methods within this field use a high-throughput application of functional and structural neural imaging, most commonly magnetic resonance imaging (MRI), electron microscopy, and histological techniques in order to increase the speed, efficiency, and resolution of these nervous system maps. To date, tens of large scale datasets have been collected spanning the nervous system including the various areas of cortex, cerebellum, the retina, the peripheral nervous system and neuromuscular junctions.

<span class="mw-page-title-main">Electrical brain stimulation</span> Form of electrotherapy

Electrical brain stimulation (EBS), also referred to as focal brain stimulation (FBS), is a form of electrotherapy and neurotherapy used as a technique in research and clinical neurobiology to stimulate a neuron or neural network in the brain through the direct or indirect excitation of its cell membrane by using an electric current. EBS is used for research or for therapeutic purposes.

<span class="mw-page-title-main">Pulsed electromagnetic field therapy</span> Attempted medical therapy using electromagnetic fields

Pulsed electromagnetic field therapy, also known as low field magnetic stimulation (LFMS) is the use of electromagnetic fields in an attempt to heal non-union fractures and depression. By 2007 the FDA had cleared several such stimulation devices.

Neurostimulation is the purposeful modulation of the nervous system's activity using invasive or non-invasive means. Neurostimulation usually refers to the electromagnetic approaches to neuromodulation.

<span class="mw-page-title-main">Restorative neurology</span> Medical intervention

Restorative neurology is a branch of neurology dedicated to improving functions of the impaired nervous system through selective structural or functional modification of abnormal neurocontrol according to underlying mechanisms and clinically unrecognized residual functions. When impaired, the body naturally reconstructs new neurological pathways and redirects activity. The field of restorative neurology works to accentuate these new pathways and primarily focuses on the theory of the plasticity of an impaired nervous system. Its main goal is to take a broken down and disordered nervous system and return it to a state of normal function. Certain treatment strategies are used to augment instead of fully replace any performance of surviving and also improving the potential of motor neuron functions. This rehabilitation of motor neurons allows patients a therapeutic approach to recovery opposed to physical structural reconstruction. It is applied in a wide range of disorders of the nervous system, including upper motor neuron dysfunctions like spinal cord injury, cerebral palsy, multiple sclerosis and acquired brain injury including stroke, and neuromuscular diseases as well as for control of pain and spasticity. Instead of applying a reconstructive neurobiological approach, i.e. structural modifications, restorative neurology relies on improving residual function. While subspecialties like neurosurgery and pharmacology exist and are useful in diagnosing and treating conditions of the nervous system, restorative neurology takes a pathophysiological approach. Instead of heavily relying on neurochemistry or perhaps an anatomical discipline, restorative neurology encompasses many fields and blends them together.

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 instilled directly in the subdural space. 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.

Transcranial pulsed ultrasound (TPU) uses low intensity, low frequency ultrasound (LILFU) to stimulate the brain. In 2002, Dr. Alexander Bystritsky first proposed the idea that this methodology contained therapeutic benefits. Beginning in 2008, Dr. William Tyler and his research team from Arizona State University began an investigation and development of this alternative neuromodulation without the harmful effects and risks of invasive surgery. They discovered that this low-power ultrasound is able to stimulate high neuron activity which allows for the manipulation of the brain waves through an external source. Unlike deep brain stimulation or Vagus nerve stimulation, which use implants and electrical impulses, TPU is a noninvasive and focused procedure that does not require the implantation of electrodes that could damage the nervous tissue. Its use is applicable in the various fields including but not limited to medical and military science. Although this technology holds great potential to introducing new and beneficial alternatives to conventional brain manipulation, it is a relatively young science and has certain obstructions to its full development such as a lack of complete understanding and control of every safety measure.

<span class="mw-page-title-main">Non-invasive procedure</span> Medical procedure involving no break in skin

A medical procedure is defined as non-invasive when no break in the skin is created and there is no contact with the mucosa, or skin break, or internal body cavity beyond a natural or artificial body orifice. For example, deep palpation and percussion are non-invasive but a rectal examination is invasive. Likewise, examination of the ear-drum or inside the nose or a wound dressing change all fall outside the definition of non-invasive procedure. There are many non-invasive procedures, ranging from simple observation, to specialised forms of surgery, such as radiosurgery. Extracorporeal shock wave lithotripsy is a non-invasive treatment of stones in the kidney, gallbladder or liver, using an acoustic pulse. For centuries, physicians have employed many simple non-invasive methods based on physical parameters in order to assess body function in health and disease, such as pulse-taking, the auscultation of heart sounds and lung sounds, temperature examination, respiratory examination, peripheral vascular examination, oral examination, abdominal examination, external percussion and palpation, blood pressure measurement, change in body volumes, audiometry, eye examination, and many others.

Magnetogenetics is a medical research technique whereby magnetic fields are used to affect cell function.

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 showed that by using an alternate current along with random amplitude and frequency in healthy subjects, the motor cortex excitability increased for up to 60 minutes after 10 minutes of stimulation. The study included all the frequencies up to half of the sampling rate i.e. 640 Hz, however the positive effect was limited only to higher frequencies. Although tRNS has shown positive effects in various studies the optimal parameters, as well as the potential clinical effects of this technique, remain unclear.

Non-invasive cerebellar stimulation is the application of non-invasive neurostimulation techniques on the cerebellum to modify its electrical activity. Techniques such as transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) can be used. The cerebellum is a high potential target for neuromodulation of neurological and psychiatric disorders due to the high density of neurons in its superficial layer, its electrical properties, and its participation in numerous closed-loop circuits involved in motor, cognitive, and emotional functions.

References

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