Non-invasive Multi-channel Neuro-stimulators in Treatment

of the Nervous System Disorders

Y. P. Danilov

, V. S. Kublanov

, K. Ju Retjunskij

, T. S. Petrenko

and M. V. Babich

Tactile Communication and Neuromodulation Laboratory, Biomedical Engineering Department,

University of Wisconsin-Madison, 1550 Engineering Drive, Madison, WI, 52706, U.S.A.

Research Medical and Biological Engineering Center of High Technologies,

Institute of Radio Engineering and Information Technology, Ural Federal University,

Mira Str., 32, Yekaterinburg, 620002, Russia

Keywords: Neurostimulation, Neurorehabilitation, Non-invasive, Medical Device.

Abstract: Approaches of non-invasive neuromodulation organization for rehabilitation brain injuries outcomes and

psycho-emotional disorders are discussed. One of technologies based on electrocutaneous stimulation of the

tongue (CN-NINM), and other technology based on transcutaneous stimulation of the neck

(SYMPATHOCORRECTION). Currently, two portable devices were developed and introduced in clinical

practice: PoNS

and SYMPATHOCOR. Both technologies are complement each other and demonstrate

perspectives in various applications for purpose of neurorehabilitation and neurological symptoms

management in such difficult for rehabilitation areas, as traumatic brain injury, stroke, Parkinson’s disease,

multiple sclerosis and many other neurological disorders.

1 INTRODUCTION

The brain injuries and psycho-emotional disorders

are among the leading causes of severe human

neurological disabilities and high mortality rate. The

most common approach to treat such disorders is the

neuroprotective therapy. Indeed, such a therapy

facilitates, in some extent, the normalization and

strengthening the physiological activity of the brain

tissues. It is also can help to repair the system

damages inflicted by various kinds of pathogenic

impacts (traumatic, inflectional, inflammatory,

vascular, degenerative, etc.).

In general, the neuro-protective therapy is based

on the combinations of drug therapy with another

kind of therapies (physical, cognitive, speech, etc.)

that oriented on different symptoms, have an impact

on different mechanisms and affect various

physiological mechanisms and biochemical

pathways. Eventually, all these means affect various

components of a pathogenic process under treating

(Greenberg, 2009).

Recently, the low effectiveness of the traditional

methods has stimulated the development of new

approaches and methods of the neuroprotection,

which should be less dangerous, more effective and

non-invasive. During last decade, the whole family

of such methods have been discovered, based on

various forms of physical impact on the neural

system. All these methods were called the

neurostimulation methods. Multiple studies

demonstrate the efficiency of such neurostimulation

methods and the perspective in use of non-invasive

technologies for rehabilitation of the full spectrum of

neural disorders. It has become especially important

for age-related disorders, considering the growth of

the human life span and the wave of retirement of

“baby-boomers” generation.

2 PATHOPHYSIOLOGICAL

PECULIARITIES OF THE

NERVOUS SYSTEM

DISORDERS

Any damage of the central nervous system leads to

many pathological processes and affects numerous

structural parts, pathways and physiological

mechanisms. In clinics, these phenomena appear in

multiple neurological, psychological, vegetative, and

regulatory damages. The “multidimensional”

P. Danilov Y., S. Kublanov V., Ju Retjunskij K., S. Petrenko T. and V. Babich M..

Non-invasive Multi-channel Neuro-stimulators in Treatment of the Nervous System Disorders.

DOI: 10.5220/0005200000880094

In Proceedings of the International Conference on Biomedical Electronics and Devices (BIODEVICES-2015), pages 88-94

ISBN: 978-989-758-071-0

 2015 SCITEPRESS (Science and Technology Publications, Lda.)

damage needs the “multidimensional” treatment.

Apparently, instead of one "universal," fit-for-all"

medical mean, the complex therapy should be

applied, as a combination of different methods and

technologies that applied simultaneously can

facilitate each other.

However, in case of drugs, such combination can

become very dangerous, because simultaneous use

of several medications can lead to summation of

drug side-effects, lead to the increasing adverse

effects. In this case, the positive treatment effects

become slower. The treatment becomes ineffective

and even harmful for the patient’s life.

This situation becomes even more dangerous

when the treatment interferes with the natural

regulatory and adaptive processes of the nervous

system, and, essentially, these interventions become

the stress factors. As a result, the corresponding

systems are reacting properly, initiating the stress

adaptation mechanisms. It is initiating a composite

regulatory complex that plays the main role in

activation and coordination of all changes in the

patient’s organism in a response to the stress.

Such system, so-called stress-system, is based on

mechanisms both self-regulation and outer-

regulation. The self-regulation of the stress-releasing

system is built on the feedback principle, where the

main role is played by the adrenal-corticotrophin

hormone, cortisol, and several other components of

the brain (Davis, 2008). The outer-regulation

mechanisms are released by the so-called stress-

limiting system that limits activity of the stress-

system and excessive stress-reaction on the central

and periphery levels. The central levels are consisted

of the GABA-ergic, opioid-ergic, and serotonin-

ergic systems. The peripheral level includes the

adenosine, prostaglandins, and antioxidant systems,

and, additionally, the nitrate-oxide generation

system (Stahl, 2008).

Moreover, there are also other factors that play

an important role in the stress-reaction regulation.

Those are the endogenous neuropeptides (the

substance P), the brain growth factors, and some

others (Dupont, 1981; Rothman, 2012). Therefore,

the organization of complicated multi-phase

adaptation reaction (during the stress) is provided by

complex neurohumoral mechanisms of interaction

between the stress-releasing and stress-limiting

systems (Holaday, 1983; Knapman, 2012).

Considering, that the stress is caused by both the

disease itself and the combination of direct and side

effects of several applied drugs, there is a high

probability of the immune system damages that can

lead to, so called, secondary immune-deficit state,

abnormal condition of the neurogenic origin

(Turnbull and Rivier, 1999; Kronfol, 2000).

If adaptation performance of the neural

regulation is exceeded the natural limits, then the

central regulatory mechanisms should be initiated. It

includes the direct control of the endocrine, immune,

cardio-vascular, and digestive systems. This new

level of activation is implemented by complex

communication networks, including the

neurohumoral interactions, hormones,

neuromediators, and immunotoxic agents (McEwen,

2009; Dedovic, 2009).

Such natural basic and fundamental regulation

systems eventually become the primary target for

development of new neurostimulation methods.

3 SPECIFICITY OF

NEUROSTIMULATION

SYSTEMS

The non-medication methods of neuro-stimulation

can be classified by the following key features:

Depending on the part of nervous system involved in

activation, different clinical effects of the

neurostimulation can be obtained. Therefore, the

non-medication neurostimulation can modulate

various processes in the human body.

In contrast to the traditional pharmacotherapy,

the neurostimulation methods do not change directly

the balance of neurochemical and molecular

compounds in the regulatory, biochemical, and

immune processes in the organism. As a result, the

non-invasive neurostimulation (if applied properly)

does not have unwanted side effects and do not

cause evident additional stress-reaction of the

organism. It is an open wide spectrum of application

of the neurostimulation methods in the rehabilitation

of many kinds of pathologies.

To solve particular medical problems, it is

necessary to find the appropriate “targets” and

conditions for technical implementation of adequate

neurostimulation, based on the pathophysiology of

disorder and the knowledge of anatomy and

physiology of the CNS and pattern of innervation of

affected organs and systems.

In our investigations, the specific regions of the

neck and the dorsal surface of the tongue were

chosen as new targets for the transcutaneous

electrical neurostimulation.

There are several reasons why these areas were

selected as perspective targets:

Both the neck and tongue regions are located in

Non-invasiveMulti-channelNeuro-stimulatorsinTreatmentoftheNervousSystemDisorders

the close proximity of the major structures of the

CNS (brainstem, cerebellum and cranial nerve

ganglia) and its main sensory, motor and autonomic

control systems, i.e., close to structures of the

vegetative nervous system (VNS, both the

sympathetic and parasympathetic) on the level of its

over-segmental and segmental sections.

Regulating and controlling many functions of the

organism, these structures of the VNS essentially

control intimate mechanisms of compensation and

adaptation to various damaging factors of the outer

and internal environment. This determines

importance of the VNS in creating the prerequisites

and development of disorders. Therefore, the

malfunctioning in the work of the VNS can be

represented by its own nosologic forms, and at the

same time. The abnormal functions of VNS can go

together with many wide-spread disorders.

Considering, that even the treatment of pathological

processes in the VNS itself is rather problematic, it

is not surprising, that the vegetative disorders as

accompanied symptoms frequently are not the

targets of the major treatment at all.

Indeed, during stimulation of the neck and

tongue regions it is possible to impacts both the

parasympathetic and sympathetic structures of the

VNS and to affect the ascending afferent conductive

pathways, and correspond centers in the brainstem,

subcortical and cortical areas of the brain.

The neck section of the sympathetic stem

consists of three nodes and inter-node connection

branches that are located in the deep neck muscles

behind the pre-spinal plate of the neck fascia.

Incoming afferent fibers are coming from the

vegetative cores of the lateral intermediate (gray)

substance of the eighth neck and six-seven upper

pectoral segments of the spinal cord through the

inter-node branches of the pectoral section of the

sympathetic stem.

The efferent branches (coming out of the neck

node) contain the post-ganglion sympathetic fibers

passing close to the upper nerves of spinal cord and

cranial nerves (glossopharyngeal, vagal, additional,

and hypoglossal) and next to the outer and internal

carotid arteries and other near located blood vessels.

The parasympathetic nervous system in the neck

region is represented by components of the

pneumogastric or vagal nerve. Moreover, on the

neck level from this nerve came out pharyngeal,

laryngeal, and heart branches that participate in

innervations and regulations of muscles and mucous

membrane of the pharynx, larynx, trachea,

esophagus, tongue root, thyroid and near-thyroid

glands, thymus, myocardium, and lungs (by creating

the lung plexus).

The oral cavity, including the tongue, is

intensively innerved by the motor, sensory, and

secretion control fibers. The motor, sensory, and

taste fibers are parts of the cranial nerve system. The

multiple glands of oral cavity are controlled by VNS

fibers divided into sympathetic and parasympathetic

ones. In total, five out of twelve cerebral nerves

participate in innervations of the tongue and oral

cavity. Those are the following nerves: trigeminal,

facial, hypoglossal, glossopharyngeal and

pharyngeal ones. The mentioned above five nerves

(that innerve the walls and organs in the oral cavity)

have nuclei in the brainstem just under the rhomboid

fossa. These cores are divided into motor, sensory,

and vegetative (autonomic) ones.

Both non-invasive multichannel

neurostimulation methods allow directly affect VNS

for purpose of neurorehabilitation. It is well known,

that in control of complex objects, the effectiveness

of control is increasing proportionally to degree of

freedom of the control system (McEwen, 2009).

Considering the neuro-stimulation problems, this

rule can be applied by extension of the control

abilities by increasing the number of specific ways

of the neural structure's activation. The stimulation

effectiveness can be also improved by using bio-

tropic parameters of stimulation signals similar to

parameters of internal processes.

In neurostimulation systems, the application of

low-frequency impulse series of one polarity current

seems to be perspective, especially in combination

of the multi-channel neuro-stimulation with

computerized process control.

Figure 1: Block diagram of the engineering feasibility of

multi-channel neurostimulation systems.

In this article, we are presenting two original

BIODEVICES2015-InternationalConferenceonBiomedicalElectronicsandDevices

multi-channel portable systems for noninvasive

stimulation of the tongue (PoNS device) and the

neck area (SYMPATHOCOR device) for purpose of

neurorehabilitation of sensory, motor and autonomic

functions.

Block diagram of the engineering feasibility of

multi-channel neurostimulation systems is shown in

Fig.1.

3.1 CN-NINM Technology

The portable neuromodulation stimulator (PoNS™)

is an electrical pulse generator that delivers

carefully-controlled electrical stimulation to the

tongue. The pulses are generated and controlled by

commercially available counter, timer, and wave-

shaping electronic components. The components are

mounted on a single printed circuit board (Fig. 2).

The circuit board contains 143 gold-plated

electrodes that contact the tongue. A rechargeable

lithium-polymer battery with built-in charge safety

circuitry provides the power.

Figure 2: PoNS device.

The PoNS

device is placed in the mouth and

has been investigated in conjunction with physical

therapy for treatment of balance and gait disorders

caused by a variety of etiologies, including the

traumatic brain injury, multiple sclerosis, central and

peripheral vestibular disorder, migraine-related

balance disorder, chronic Meniere’s disease,

spinocerebellar ataxia, gentamicin ototoxicity,

idiopathic cerebellar ataxia, idiopathic vestibular

disorder, and cerebellar infarction (Danilov, 2007;

Wildenberg, 2010; Tyler, 2014).

The device is easily held at the place by the lips

and teeth around the neck of the tab that goes into

the mouth and rests on the anterior superior part of

the tongue. The paddle-shaped tab of the device has

a hexagonally patterned array of 143 gold-plated

circular electrodes (1.50 mm diameter, on 2.34 mm

centers). The array is created by a photolithograph

process used to make printed circuit boards. It uses

the low-level electrical current to stimulate the

lingual branch projections of at least two cranial

nerves in the tongue anterior through the gold-plated

electrodes. Device function is user-controlled by

four buttons: On, Off, Intensity 'Up', and Intensity

'Down'. The system delivers triplets of 0.4 – 60 µs

wide pulses at 5 ms intervals (i.e., of 200 Hz) every

20 ms (50 Hz) that has been designed to achieve a

balance of stimulus dynamic range and sensation

quality. The sensation produced by the array is

similar to the feeling of drinking a carbonated

beverage. The system has operational limits of 19V

(max) on the tongue (a nominal 5–7 kOhm load).

The biphasic waveform is specifically designed to

ensure zero net DC current to minimize the potential

for the tissue irritation.

The current hypothesis for the underlying

mechanism by which the PoNS™ Cranial Nerve

Noninvasive Neuromodulation (CN-NINM)

stimulation leads to sustained neuromodulation (and

subsequent therapeutic effect) comes from previous

FMRI studies using optokinetic visual stimulation to

activate regions involved in processing balance

information (Wildenberg, 2010). Cortical procession

of the motion is performed primarily by the motion

sensitive visual cortex (hMT+).

Previous work from our group investigating

network behavior after the CN-NINM (Cranial

Nerve Noninvasive Neuromodulation) showed

hypersensitivity of the balance-processing network

in individuals with balance dysfunction compared to

healthy controls. The network behavior normalized

after the CN-NINM therapy. A high-resolution study

of activity within the brainstem suggested that the

trigeminal nucleus, the point at which afferents from

the tongue enter the central nervous system, had

altered neural responses to motion in the visual field

after stimulation.

We hypothesize that spatio-temporal trains of

spikes induced in the trigeminal and facial nerves by

electrical stimulation of the tongue produce changes

of activity in corresponding nuclei of the brainstem,

namely, at least in the sensory and spinal nuclei of

trigeminal nuclei complex (the largest nuclei in the

brainstem, extending from the midbrain to the nuclei

of the descending spinal tracts), and in the nucleus

tractus solitarius where both stimulated nerves have

direct projections. We postulate that intensive

activation of these structures initiates a sequential

cascade of changes in neighboring and/or connected

nuclei by direct collaterals, interneuron circuitry, or

passive transmission of biochemical compounds in

Non-invasiveMulti-channelNeuro-stimulatorsinTreatmentoftheNervousSystemDisorders

the intercellular space. Accordingly, electrotactile

stimulation of cranial nerve endings, particularly in

the lingual tract of the trigeminal and the facial

nerve, initiate activity in the corresponding nuclei

similar to long-term potentiation/inhibition, which,

in the turn, increases the receptivity of multiple

neural circuitries and/or affect internal mechanisms

of homeostatic regulation.

This, in the turn, causes radiating therapeutic

neurochemical and neurophysiological changes

affecting both neural and glial networks affecting

information processing of afferent and efferent

neural signals involved in the motion control,

including the cerebellum and nuclei of spinal motor

pathways. PET scans study on the blind subjects

before and after training with the visual sensory

substitution system via the tongue stimulation

(electrotactile feedback) system demonstrates

massive activation in cortical and subcortical levels

of the brain (Kronfol, 2000). It may also increase the

receptivity of multiple neural circuitries and/or

affect internal mechanisms of homeostatic regulation

according to the contemporary concept of synaptic

plasticity. We as well cannot exclude also that this

induces simultaneous activation of serotoninergic

and noradrenalinergic regulation systems

components located in the brainstem.

In the course of testing and training numerous

persons having a primary indication of balance and

gait disorder using the balance recovery therapeutic

method we developed, we observed therapeutic

benefits well beyond balance (attention, memory,

multitasking, vision, fine motor control, sleep,

tremor, tinnitus) regardless of their etiology

(peripheral vestibular, central or idiopathic

vestibular loss, cerebellar stroke, Meniere's,

Parkinson's, MS).

3.2 SYMPATHOCORRECTION

Technology

The portable corrector of activity of the sympathetic

nervous system (SYMPATHOCOR) is an electrical

pulse generator that delivers the spatially-distributed

field of the carefully-controlled current pulses in the

neck (Kublanov, 2008). The general view of the

SYMPATHOCOR device is presented in Fig. 3.

The spatially-distributed field of the current

impulses in the SYMPATHOCOR device is formed

between two multi-element electrodes. Each

electrode comprises a cluster of thirteen partial

current-conducting elements with galvanic isolation

of each other. The multi-element electrodes are

arranged on the neck into left and right arrays. In the

working state, the central element of one array plays

the role of the anode. Electrodes on the other side

become the cathodes. If it is necessary, the

arrangement can be reversed in opposite direction.

Figure 3: The general view of the SYMPATHOCOR

device.

Placing the multi-element electrodes on the

subject neck, the anodes have to be located in

projections of the neck ganglia of the sympathetic

nervous system (Fig.4).

Figure 4: Scheme of location (on the patient ‘neck) for the

partial current-conducting elements of the multi-element

electrodes.

The electric current impulses are delivered to the

partial elements of the multi-element array from the

processor through the multi-channel switch. At each

instant moment, the impulse of current is formed

only between only one partial cathode element and

the anode partial element on the opposite side of the

neck. Therefore, the current flows between the

opposite multi-element electrodes across the neck.

The spatio-temporal pattern of stimulation is

controlled by processor, using specially developed

software. Such control provides the necessary input

BIODEVICES2015-InternationalConferenceonBiomedicalElectronicsandDevices

information on variation of structure of the spatially-

distributed field of the current and implements pre-

calculated pattern for activation the partial cathodes.

Pre-calculated pattern was designed to manipulate

continuously changing vectors of the current and

provide the maximum current density (onto the

volume unit) in the active anode zone.

Note the following basic bio-tropic

characteristics of the field: the current partial

impulse length is from 20 to 60 -sec. The number of

partial impulses in the period (impulse group) is 12.

The frequency of impulse group is from 10 to 150

Hz. The partial electrodes are switched accordingly

to each given rule (for example, a pseudo-random

with the clockwise or counterclockwise direction of

switching, and so on). The current impulse

amplitude can be up to 20 mA.

SYMPATHOCORRECTION Technology is a

method of the dynamic correction of the activity

sympathetic nervous system is used for the neck

neuro-stimulation in limits of the “homeostatic

corridor," under which the vegetative regulation is

not violated (Kublanov, 2010).

Depending on pathogenesis of the peripheral or

central dysfunctions of the vegetative nervous

system, the dynamic correction of the activity

sympathetic nervous system algorithm has two

different branches. Decision of which branch should

be executed is based on nature of the VNS

dysfunction. The bio-tropic parameters of the

implemented current impulse field (the field

structure, impulse amplitude, frequency, and length)

are calculated from the analysis of the heart rhythm

variability. In particular, in the case of the abnormal

hyperactivity of sympathic innervation, it is

necessary to block or suppress the activity of the

sympathetic nervous system. In contrast, sympathic

innervation should be increased, if the hyperactivity

of the parasympathic innervation is observed.

In case of central dysfunctions, the bio-tropic

parameters of the stimulation field are calculated,

based on analysis of the main activity rhythms of the

cerebral cortex and its deviation from the norm.

The first model of the SYMPATHOCOR unit is

certified for fabrication, marketing, and application

on the Russian Federation territory. In clinic

practice, the SYMPATHOCOR device and the

dynamic correction of the activity sympathetic

nervous system technology are efficiently applied to

treatment (Kublanov, 2010):

 Diseases involving organic and / or functional

disorders of the CNS and / or the VNS:

consequences of trauma or stroke, epilepsy,

chronic headache, somatoform disorders, anxiety

and depressive spectrum disorders, attention-

deficit hyperactivity and tic disorder,

consequences of alcoholism, disorders of

autonomic nervous system, hypertension and its

consequences;

 Diseases associated with impaired visual,

auditory and vestibular function.

4 CONCLUSIONS

Analysis of topological structures of the neural

network of the neck and tongue shows that the

structures affected by neurostimulation are

organized in the similar way. The primary activation

targets have several common components (e.g.

solitary nucleus) and spectrums of observed effects

for both neurostimulation systems are significantly

overlapped. Therefore, both presented technologies

are complimentary to each other. The CN-NINM

technology primarily affects sensory-motor

integration in CNS and partially autonomic system.

The DCASNS technology is affecting primarily

VNS and partially sensory-motor integration. Both

technologies can affect cognitive (memory,

attention) and psychosocial (depression and anxiety)

functions as well.

Considering the complimentary nature of both

systems, the results of pilot research and experience

in the clinical applications of the PoNS and

SYMPATHOCOR units, we can recommend the

parallel use of the neck and tongue neurostimulation

in the rehabilitation process. It has become

especially important in cases of the brain polytrauma

or multiple functional damage after stroke, moderate

traumatic brain injury or in advanced stage of

multiple sclerosis. Moreover, it can be the only way,

non-invasively, to recover various autonomic

functions – bladder and bowl control, GI motility,

hypertension, etc.

The result of this transcutaneous non-invasive

neurostimulation is essentially brain plasticity on

demand, i.e., a priming or up-regulating of targeted

neural structures to develop new working pathway

that is the goal of neurorehabilitation and a primary

means of functional recovery from permanent

physical damage caused by a stroke or trauma, by

neurodevelopmental or by neurodegenerative

disorders.

We believe on the theoretical grounds that both

neurostimulation systems activate and synchronizes

several large brainstem nuclei and the cerebellum,

neck ganglia and VNS centers enabling the

beneficial neuroplastic changes in multiple CNS and

Non-invasiveMulti-channelNeuro-stimulatorsinTreatmentoftheNervousSystemDisorders

VNS control circuitries. We envision the application

of these technologies to functional recovery to the

broad range of sensory, motor, cognitive, autonomic

and mood disorders.

REFERENCES

Danilov, Y. P., Tyler, M. E., Skinner, K. L., Hogle, R. A.,

Bach-y-Rita, P., 2007. Efficacy of electrotactile

vestibular substitution in patients with peripheral and

central vestibular loss. Journal Vestibular Research.

17(2-3), 119-130.

Davis, M. C., Zautra, A. J., Younger, J., Motivala, S. J.,

Attrep, J., Irwin, M. R., 2008. Chronic Stress and

Regulation of Cellular Markers of Inflammation in

Rheumatoid Arthritis: Implications for Fatigue. Brain,

Behavior, and Immunity. 22 (1), 24-32.

Dedovic, K., Duchesne, A., Andrews, J., Engert, V.,

Pruessner, J.C., 2009. The Brain and the Stress Axis:

The Neural Correlates of Cortisol Regulation in

Response to Stress. Neuroimage. 47(3), 864-871.

Dupont, A., Sabord, P., Merand, G., et al., 1981. Age-

related changes in central nervous system eukephalins

substance P. Life Science. 29 (22), 2317-2322.

Greenberg, D. A., Aminoff, M. J., Simon, R. P., 2009.

Clinical Neurology, Seventh Edition (LANGE Clinical

Medicine). – McGraw-Hill Professional Publishing.

Holaday, J. W., 1983. Cardiovascular Сonsequences of

Endogenous Opiate Antagonism. Biochemical

Pharmacology. 32, 573-585.

Knapman, A., Kaltwasser, S.F., Martins-de-Souza, D.,

Holsboer, F., Landgraf, R., Turck, C.W., Czisch, M.,

Touma, C, 2012. Increased Stress Reactivity is

Associated with Reduced Hippocampal Activity and

Neuronal Integrity Along with Changes in Energy

Metabolism. European Journal of Neuroscience. 35,

412-422.

Kronfol, Z., Remick, D. G., 2000. Cytokines and the

Brain: Implications for Clinical Psychiatry. The

American Journal of Psychiatry. 157 (5), 683-694.

Kublanov, V. S., 2008. A hardware-software system for

diagnosis and correction of autonomic dysfunctions.

Biomedical Engineering. 42 (4), 206-212.

Kublanov, V. S., Danilova, I. G., Goette, I. F., et al, 2010.

Application of Spatially Distributed Field of Electric

Impulses for Correction of Angiogenesis in Ischemic

Muscular Tissue. International Journal of

Biomedical Science 2010, Vol. 6, Issue 4, 310-315.

Kublanov, V. S., Shmirev, V. I., Shershever, A. S.,

Kazakov, Ya. E., Porshnev, S. V., Vasilijev, A. S.,

2010. About innovative possibilities of the device

“SIMPATOCOR” in management of functional

disorders of vegetative and central nervous system in

neurology. Kremljovskaya Medicina. Clinichesky

Vestnik. 4, 60-64.

McEwen, B. S., 2009. The Brain is the Central Organ of

Stress and Adaptation. Neuroimage. 47 (3), 911-913.

Rothman, S. M., Griffioen, K. J., Wan, R., Mattson, M. P.,

2012. Brain-derived Neurotrophic Factor as a

Regulator of Systemic and Brain Energy Metabolism

and Cardiovascular Health. Annals of the New York

Academy of Science. 1264, 49–63.

Stahl, S. M., Wise, D. D., 2008. The Potential Role of a

Corticotropin-Releasing Factor Receptor-1 Antagonist

in Psychiatric Disorders. CNS Spectrums. 13 (6), 467-

483.

Turnbul,l A. V., Rivier, C. L., 1999. Regulation of the

Hypothalamic-Pituitary-Adrenal Axis by Cytokines:

Actions and Mechanisms of Action. Physiological

Reviews. 79 (1), 1-71.

Tyler, M. E., Kaczmarek, K. A., Rust, K. L., Subbotin, A.

M., Skinner, K. L., Danilov, Y. P., 2014. Non-invasive

neuromodulation to improve gait in chronic multiple

sclerosis: A randomized double blind controlled pilot

trial. Journal of NeuroEngineering and Rehabilitation.

11 (1), Article number 79.

Wildenberg, J. C., Tyler, M. E., Danilov, Y. P.,

Kaczmarek, K. A., Meyerand, M. E., 2010. Sustained

cortical and subcortical neuromodulation induced by

electrical tongue stimulation. Brain Imaging and

Behavior. 4, 199-211.

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