Possibilities of Applying Non-invasive Multichannel Electrical

Stimulation Technology for Treatment Neuropsychiatric Diseases

Timur S. Petrenko

, Vladimir S. Kublanov

, Konstantin Ju. Retyunskiy

and Roman A. Sherstobitov

Ural Federal University, Yekaterinburg, Russian Federation

Ural State Medical University, Yekaterinburg, Russian Federation

Keywords: Neuroelectrstimulation, Neuropsychiatric Diseases, Autonomic Nervous System.

Abstract: The article discusses some of the mechanisms of clinical effects when using the technology of non-invasive

multichannel electrical stimulation of the neural formations of the neck in patients with diseases of the central

nervous system of the neuropsychiatric profile. When implementing this technology in all clinical examples,

"SYMPATHOCOR-01" device was used, which provides stimulation of neural formations of the neck using

a spatially distributed field of monopolar current pulses.

1 INTRODUCTION

The rapid spread throughout the world of diseases of

the central and peripheral nervous system determines

the relevance of the search for effective

pathophysiologically-based therapeutic and

rehabilitation approaches to their correction. In most

cases, the pathogenetic links of such diseases are

realized through dysregulation of the autonomic

nervous system (Licznerski, Duman, 2013).

Particularly relevant today are diseases associated

with organic damage to the central nervous system.

Existing methods of treatment of central nervous

system diseases suggest the use of pharmacological

agents with high risks of unwanted and side effects

(Watanabe et al, 2010). An alternative approach may

be to stimulate the structures of the central and

peripheral nervous system using multi-electrode

systems of neuroelectrostimulation . The activation of

different parts of the nervous system in this way

allows you to get a variety of clinical effects,

including may affect somatic processes in the body

(Danilov et al, 2015).

To create effective medical technologies in the

treatment of neuropsychiatric disorders, it is

https://orcid.org/0000-0001-7328-9894

https://orcid.org/0000-0001-6584-4544

https://orcid.org/0000-0003-1302-483X

https://orcid.org/0000-0002-090-407X

necessary to understand the physiological

mechanisms of the formation of the clinical result,

depending on the therapeutic agents used.

This work presents the results of studies of

medical technologies in which the therapeutic effect

is achieved through the use of a

neuroelectrostimulator "SYMPATHOCOR-01"

device (Kublanov, Babich, Petrenko, 2018)

2 RESULTS OF CLINICAL

STUDIES

2.1 Attention Deficit Hyperactivity

Disorder (ADHD)

In the period from 2007 to 2014, we conducted a

study for children with ADHD. Participated 90

children of both gender and ages from 4 to 10 years

that have clinic features of the ADHD syndrome

(according to the ICD-10). The degree of the ADHD

symptoms was estimated by the psychometric scale

ADHD-RS-IV (Attention-Deficit Hyperactivity

Disorders Rating Scale IV). The attention level was

estimated by means of the psycho-physiological test

Petrenko, T., Kublanov, V., Retyunskiy, K. and Sherstobitov, R.

Possibilities of Applying Non-invasive Multichannel Electrical Stimulation Technology for Treatment Neuropsychiatric Diseases.

DOI: 10.5220/0009377304210426

In Proceedings of the 13th International Joint Conference on Biomedical Engineering Systems and Technologies (BIOSTEC 2020) - Volume 1: BIODEVICES, pages 421-426

ISBN: 978-989-758-398-8; ISSN: 2184-4305

421

T.O.V.A. (the Test Of Variability Of Attention).

Impairments of the brain bioelectric activity (of

children with the ADHD) were verified by the

electro-encephalographic investigation. In such

children, increasing the theta- and delta-activity was

observed and/or impairment of the main (alpha)

rhythm under the loading tests. For treating children,

a complex therapy was applied: in group I (of 37

participants), neuromethabolic remedies were used;

in group II (of 55 participants), neuromethabolic was

used together with the neurostimulation device.

The best result has been achieved in the second

group of children, in which during the treating

process, both the complex medicated therapy and

neurostimulation were used. The dynamic of ADHD

overall score was: in I group from 2.11±0.34 to

1.88±0.11; in II group from 2.08±0.45 to 1.22±0.17.

The dynamic of attention level by TOVA was: for

omission error in I group from 28.5±4.3 to 21.1±2.5

and in II group from 32.5±4.3 to 8.7±2.7; for

commission error in I group from 19.2±4.9 to

18.8±2.2 and in II group from 23.5±4.3 to 8.7±3.1.

Catamnesis observation after children of the second

group has proved stability of the achieved results two

years later from the treatment beginning (Kublanov,

Petrenko, Retyunskiy, 2016).

2.2 Psychosomatic Disorders

In 2018 we conducted study for children with

psychosomatic disorders. Participated 83 children of

both sexes from 5 to 14 years old with following

diagnosis: bronchial asthma (n = 34), atopic

dermatitis (n = 27), gastroesophageal reflux disease

(n = 22). Data on relevant diseases were evaluated by

clinical methods. Baseline ANS was assessed by the

heart rate variability (HRV). All children were

randomly divided into two groups (n1 = 41; n2 = 42).

The entire observation period was 21 days. Both

groups received standard medical therapy prescribed

by a pediatrician. The second group was given

additional neurostimulation daily therapy for 2

weeks. Evaluation of the state of children after the

observation period was carried out according to the

same criteria as the original one.

Clinical trials showed that most children (78%)

had increased baseline ANS activity, which

correlated with the severity of somatic

manifestations. After two weeks of complex therapy

improving the clinical condition was observed in

most children in the group with

neuroelectrostimulation device. This is consistent

with the HRV analysis: LF/HF ratio for the first group

changed from 7.71±4.54 to 5.82±6.28; for the second

group – significantly decreases from 8.21±5.82 to

2.12±4.53.

Adding non-invasive correction of ANS to

standard medical therapy allows reducing the

condition of children with psychosomatic diseases

(Petrenko, 2019).

2.3 Anxiety Disorder

In 2015 we have investigated the effectiveness of

the method of dynamic correction of activity of the

sympathetic nerves system by using neurostimulation

device in comparison of standard medications

approach in patients with panic disorder.

The study included 40 patients from clinical base

of the Department of Psychiatry of Ural State Medical

University with diagnosed ‘panic disorder’. All

patients were randomly divided into two equal group.

Patients from the first group received antidepressant

– escitalopram 10mg once daily. Patients from the

second received a course of ten procedures of

neuroelectrostimulation. The period of therapy and

dynamic follow-up was six weeks. The Hamilton

(HAM-A) and Sheehan (SPRAS) anxiety scales were

used to determine changes in state of patients.

For patients from the first group were follow

changes by scales for the six-weeks period: HAM-A

(from 26.35±7.53 to 15.35±4.20), SPRAS (from

72.83±21.41 to 39.27±8.13). For patients from the

second group: HAM-A (from 27.49±7.32 to

7.30±2.05), SPRAS (from 74.33±23.42 to

24.22±5.29).

The neurostimulation therapy in comparison

antidepressant was a faster onset of the therapeutic

effect, a faster reduction quantity and severity of

panic attacks during the whole period of observation

(Petrenko, Retjunskiy, Kublanov, 2018).

2.4 Organic Amnestic Syndrome

In 2016 we conducted study for patient with organic

amnesic syndrome. Three patients with clinical

organic amnestic syndrome resulting of brain damage

(poisoning, alcohol and trauma) held inpatient

treatment for at least 12 months in the neurology or

psychiatry department without a significantly

improvement.

Patients were assessed using the clinical method,

neuropsychological scales: Frontal Assessment

Batter (FAB), Montreal Cognitive Assessmnet

(MCA), Mini-Mental State (MMSE), MRI, EEG,

Heart rate variability (HRV). The initial clinical state

of the patients was severe, with structural damage on

MRI and low rates of neuropsychological tests. As a

NDNSNT 2020 - Special Session on Non-invasive Diagnosis and Neuro-stimulation in Neurorehabilitation Tasks

422

result of seven Neurostimulation procedures

improved significantly neuropsychological

assessments: FAB (from 5,7±3,1 to 12±4,0); MCA

(from 11,3±3,0 to 16,3±4,0); MMSE (from 15,3±6,2

to 21,3±8,3). EEG comparison analysis showed an

increase in power of Alpha waves and power

reduction of Delta waves on all leads. HRV

comparison analysis showed an increase total power

and the change in autonomic balance (Retyunskiy,

2017).

Thus, the resulting clinical effects in the described

cases required a thorough study of the mechanisms of

action of multichannel electrical stimulation of the

nerve formations of the neck. We conducted

experimental studies on laboratory animals, as well as

fundamental clinical studies using neuroimaging

technologies.

3 EXPERIMENTAL RESEARCH

To study changes at the cellular and tissue levels, as

well as behavioral functions in 2009-2010. We

conducted experimental studies of the effectiveness

of stimulation using the above field of current pulses

in laboratory rats to correct disorders caused by

immobilization stress and ischemia of the leg

muscles. For stimulation, the "SYMPATHOCOR-

01V" device was used, the parameters of which were

modified taking into account the difference in the

blood supply system of a laboratory rat with respect

to humans (Kublanov et al, 2010).

After exposure to immobilization stress, rats were

less likely to switch between elements of an open

field polygon, consisting of 25 elements and equipped

with a vision system. This was manifested by a

decrease in the length of the trajectories of movement

and a decrease in the motor activity of rats. The

application of the electrical stimulation procedure

after immobilization stress was accompanied by the

restoration of these characteristics.

Also, stress parameters were noted by blood

biochemical parameters (AST, ALT, LDH, MSM),

which corresponds to the state of endogenous

intoxication. After exposure to current pulses by the

field, blood biochemical parameters returned to the

level of intact animals.

When studying the morphological picture of

sections of ischemic muscle of rats, it was noted that

after exposure to electrical stimulation of the cervical

ganglia there is a rapid restoration of blood supply

due to the growth of capillaries of collateral arterial

systems.

Thus, neuroelectrostimulation helps to reduce the

negative effects of immobilization stress and

ischemic muscle damage, which is accompanied by:

1) at the molecular-cellular level - by a decrease

in metabolites and endogenous intoxication products

characteristic of stress, which the body does not

manage to utilize during immobilization stress and

ischemic muscle damage;

2) at the tissue level - stimulation of angiogenesis,

restoration of blood supply and contractile apparatus

in the ischemic muscle tissue of the hind tibia of rats;

3) at the level of the body - a change in the

behavioral reaction, manifested in increased

adaptation to immobilization stress (Kublanov et al,

2010).

4 FUNDAMENTAL RESEARCH

Obtaining new knowledge about the mechanisms for

implementing the clinical effects of

neuroelectrostimulation essentially belongs to the

category of basic research. In our case, the studies

were performed in the form of clinical cases with a

detailed study of the results of functional

neuroimaging.

4.1 Study of SPECT and EEG in

Patients with Incurable Forms of

Epilepsy

Confirmation of nonspecific changes in brain tissue

after dynamic correction of the activity of the

sympathetic nervous system using the

"SYMPATHOCOR-01" device is the result of

changes in single-photon emission computed

tomography (SPECT) and electroencephalogram

(EEG) in patients suffering from epilepsy.

To illustrate, the data of the clinical case of patient

D., 20 years old, suffering from a cryptogenic

temporomandibular form of epilepsy are presented.

Before treatment in patient D., the number of

epileptic seizures was 12–16 per month. Before

treatment, according to SPECT, the asymmetry of the

perfusion marker accumulation between different

regions of the cerebral cortex was determined up to

20%. According to the EEG, epileptiform activity in

the form of sharp waves and spikes in the

frontotemporal regions of variable lateralization,

more often on the right. After 5 treatment procedures,

patient D. did not have epilepsy attacks for three

weeks, and three attacks in the following weeks.

Subjective well-being was noted (headaches

Possibilities of Applying Non-invasive Multichannel Electrical Stimulation Technology for Treatment Neuropsychiatric Diseases

423

disappeared, sleep improved, appetite, the level of

anxiety and aggressiveness decreased). According to

SPECT, in cross sections, the asymmetry of perfusion

marker accumulation is up to 6%. According to EEG

data, moderate diffuse changes in BEA with signs of

increased synchronizing effects of mid-stem

structures, epileptiform activity in the form of sharp

waves and spikes in the lateral regions of variable

lateralization in the left hemisphere, epileptiform

activity of the previous localization, but

quantitatively less (Kublanov et al, 2004).

4.2 Study of RS-fMRI and

Multichannel EEG in Patients with

Depressive Disorder

We conducted pilot studies of changes in the

functioning of the basic working network of the brain

according to functional magnetic resonance imaging

of resting state (RS-fMRI). The study involved 10

patients with established depressive disorder. The use

of neuroelectrostimulation with the

"SYMPATHOCOR-01" device in addition to

pharmacotherapy prescribed by a doctor turned out to

be more effective according to clinical data (self-test

of symptoms of Beck depression, Hamilton

depression scale) compared with patients who did not

receive electrical stimulation.

According to the analysis of fMRI data after 5

days of neuroelectrostimulation, a significant

improvement in the functional connections of the

medial prefrontal cortex with other brain regions was

noted. This indicates an improvement in connectivity,

especially due to the activation of the premotor zones

of the cerebral cortex.

The results of an electrophysiological study

according to multichannel EEG are consistent with

the results of the analysis of functional connectivity.

In all clinical cases, after a course of

neuroelectrostimulation, a change in the asymmetry

of the power distribution of the main EEG rhythms in

the direction of harmonization was noted; expansion

of variability of activation zones; improving

bioelectric synchronization of various parts of the

cortex (Kublanov, Petrenko, Efimcev, 2019).

Thus, the results of experimental and fundamental

studies made it possible to formulate a theoretical

justification for the selection of stimulation targets.

5 THEORETICAL

SUBSTANTIATION OF THE

CHOICE OF TARGETS OF

NEUROELECTRIC

STIMULATION

The regulation of many physiological processes in the

human body is carried out by the central nervous

system (CNS) and the autonomic nervous system

(ANS). Centers for the regulation of vital functions

are represented by the nuclei of the brain stem,

midbrain, bridge and cerebellum, as well as the

vegetative nuclei of the spinal cord and brain. Most

of the pathways of these centers are located in the

neck.

Somatic innervation of the neck is carried out by

the cervical spinal nerves, which form a massive

cervical plexus, located on the anterolateral surface of

the deep muscles of the neck. Front and side, it is

covered by the sternocleidomastoid muscle.

The composition of the spinal nerves includes

efferent and afferent fibers. Efferent fibers begin from

the nuclei of the anterior horns of the spinal cord.

Afferent fibers pass through the posterior horns of the

spinal cord and end in the sensitive nuclei of the brain

stem and reticular formation. The reticular formation

is involved in the processing of sensory information:

it has a selective activating effect on the cerebral

cortex or an inhibitory effect on spinal cord motor

neurons, delaying habitual or repeated impulses.

Using this mechanism, somatomotor and self-

sensitive control, neuroendocrine transduction and

coordination of the work of different centers of the

brain stem are carried out.

On the deep muscles of the neck is the cervical

sympathetic trunk, which is represented by three

nodes. Nerve fibers approach the cervical nodes from

the autonomic nuclei of the lateral substance of the

thoracic spinal cord. Seven main branches departing

from the upper cervical node, containing

postganglionic fibers and propagating along the

external and internal carotid arteries, as part of the

fibers of the glossopharyngeal, vagal and sublingual

nerves. Thus, the sympathetic innervation of the

vessels of the head and neck, the parotid and thyroid

glands is carried out (Netter, Frank, 2014).

The middle cervical node (intermittent), located at

the level of the VI cervical vertebra at the intersection

of the lower thyroid and common carotid arteries. The

lower cervical (stellate) node is located above the

subclavian artery and behind the vertebral artery.

These nodes provide sympathetic innervation of the

vessels of the shoulder girdle, spine and meninges of

NDNSNT 2020 - Special Session on Non-invasive Diagnosis and Neuro-stimulation in Neurorehabilitation Tasks

424

the spinal cord. Cardiac nerves participating in the

formation of the cardiac plexus depart from the

cervical nodes. From the upper node - the upper

cardiac nerve, is involved in the formation of the

superficial cardiac plexus. From the middle and lower

nodes - the middle and lower cardiac nerves,

respectively, involved in the formation of the deep

cardiac plexus. With the help of these plexuses,

sympathetic regulation of cardiac activity is carried

out (Netter, Frank, 2014).

In the course of the internal jugular vein, first the

internal carotid, and then the common carotid artery,

the vagus nerve is located, forming a neurovascular

bundle of the neck. The vagus nerve, being mixed,

originates from the motor, sensory and

parasympathetic nuclei of the brain stem. The motor

nucleus (nucleus ambiguous), common with the

glossopharyngeal and accessory nerves, has motor

axons that innervate the muscles of the soft palate,

pharynx, and larynx.

The dorsal nucleus (nucleus dorsalis) has

parasympathetic fibers. Afferent impulses in this

nucleus come from the hypothalamus, olfactory

system, and autonomic centers of the reticular

formation. The efferent impulses of the dorsal

nucleus travel through the postganglionic fibers to the

smooth muscles of the lungs, heart, and

gastrointestinal tract. Thus, parasympathetic

regulation of respiration, palpitations and digestion is

carried out.

In the area of bifurcation of the common carotid

artery, there is a carotid glomerulus, which is a

capillary clot with a large number of chemo- and

baroreceptors. Impulses from these receptors are

transmitted along the glossopharyngeal nerve to the

nucleus of the single pathway (nucleus tractus

solitarii), common to the facial, glossopharyngeal and

vagus nerves. Similar chemoreceptors are located on

the aortic arch and transmit their impulses in the

composition of afferent fibers of the vagus nerve

along the same path. Thus, the regulation of blood

pressure and oxygen tension in the blood is carried

out (Moore, 2013)

Nerve formations in the neck are closely

connected with the brain stem, through which they

have bilateral connections with the bridge, midbrain,

cerebellum, thalamus, hypothalamus and cerebral

cortex. The presence of these connections ensures the

participation of nerve formations of the neck in the

analysis of sensory irritations, regulation of muscle

tone, autonomic and higher integrative functions.

Based on the foregoing, the cervical ganglia of the

sympathetic trunk, the cervical plexus of the spinal

nerves, the branches of the X and XI cranial nerves

and the nerve structures that enter them can act as

targets of stimulation, which significantly expands

the possibilities of neurostimulation of various

processes in the brain tissue. The neck area as a

“target” of neurostimulation seems to be a very

interesting and promising choice.

6 DISCUSSION

Thus, as a result of experimental and fundamental

studies, the main hypotheses were formulated for

realizing the clinical effectiveness of the technology

of multichannel neuroelectrostimulation of neural

formations of the neck in the treatment of

neuropsychiatric disorders.

Due to the impact on the nodes of the sympathetic

trunk and the internal carotid plexus, neurogenic

regulation of cerebral blood flow is performed due to

a change in the tone of the cerebral vessels of various

calibers: from the main arteries to the

microvasculature. The leading role in this process

belongs to the superior cervical stellate ganglion.

The impact of a focused field of electrical

impulses in the neck spreads in the form of electrical

impulses to the sublingual, glossopharyngeal and

vagus nerves, rise to the corresponding nuclei of the

brain stem, reaching the cerebellum, bridge and

frontal cortex. Thus, deep stimulation of the mid-stem

structures of the brain is performed with the release

of a large number of neurotransmitters. Under such

conditions, synoptic transmission and the

construction of new neural and glial networks are

greatly facilitated, metabolic processes both in

neurons and in neuroglia are improved. The

destruction of stagnant neural networks, as well as

pathological determinants and systems, is facilitated.

In clinical practice, multichannel

neuroelectrostimulation technology can be used not

only in the treatment of diseases of the

neuropsychiatric profile, but also in the treatment of

vegetative-vascular dystonia, headaches of various

origins, including migraine, hypertension,

sensorineural hearing loss, degenerative diseases of

the eye, neuropathies of various origins,

hyperhidrosis syndrome, orthostatic hypotension

syndrome and postural tachycardia, vestibulopathic

syndrome, as well as in the rehabilitation of patients

after stroke that one.

Possibilities of Applying Non-invasive Multichannel Electrical Stimulation Technology for Treatment Neuropsychiatric Diseases

425

7 CONCLUSIONS

Thus, further research is needed on the technology of

multichannel electrostimulation of neck neural

structure by means functional neuroimaging to

expand the scope of the medical devices created on its

basis. The success of such tasks can be achieved

through the interaction of biologists, specialists in the

field of medical physics, doctors and engineers.

ACKNOWLEDGEMENTS

The reported study was funded by RFBR according

to the research project № 18-29-02052 and supported

by Act 211 Government of the Russian Federation,

contract № 02.A03.21.0006.

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