Non-invasive Multichannel Electrostimulation of Neck Nerve

Structures for the Treatment of Patients with Anxiety Disorders

Timur Petrenko

1,2

, Mikhail Shalyagin

, Konstantin Retjunskiy

Vladimir Kublanov

and Mikhail Babich

Ural Federal University, Mira 19, Yekaterinburg, Russian Federation

Ural State Medical University, Repina 3, Yekaterinburg, Russian Federation

Keywords: Anxiety Disorders, Neurostimulation, Autonomic Nervous System.

Abstract: The efficiency of non-invasive multichannel neuro-electrostimulation device (‘SYMPATHOCOR-01’) for

treatment of anxiety disorders against the standard antidepressant medication is presented in article. Forty

patients from psychiatric clinic with diagnosed 'panic disorder' were treated and followed-up during six weeks.

The Hamilton (HAM-A) and Sheehan (SPRAS) anxiety scales were used to determine changes in state of

patients. Electrostimulation has helped patients quickly overcome symptoms of anxiety and better control

panic attacks. There was a significant difference in the final psychometric assessment of anxiety among

groups on the Hamilton (HAM-A) and Sheehan (SPRAS) scales almost twice.

1 INTRODUCTION

Anxiety disorder is one of the most common among

all mental disorders. According to the data of Russian

and foreign scientists panic disorder occurs in 1,5-3,0

% of the adult population, and its subthreshold forms

are diagnosed among 9-10 % of adult population in

the developed countries (NIMH, 2017; Schmidt et al.,

2003).

Contemporary neurophysiological studies have

revealed that panic disorder develops in the midst of

the increasing dysfunction of the autonomic nervous

system (ANS) (Stahl and Moore, 2013). In the

beginning, the ANS dysfunction is permanent and

subtle. Then, it intensifies and becomes a paroxysmal

one, fully defining the clinical symptoms of the panic

attack (Kar and Sarkar, 2016). If the dysfunction of

ANS stayed for a considerable time, it would cause

irreversible changes in the blood vessels walls. This,

in turn increases the risk of the vascular disorders

development, which could result in stroke or heart

attack (Kar and Sarkar, 2016). Autonomic disorders

in different countries occurs in 25-80 % of the adult

population (Schmidt et al., 1999). More than half of

these people have a risk of the paroxysmal anxiety

disorders.

Negative impact of the panic disorder on quality

of life and social adaptation defines the relevance of

the search for novel treatment approaches (Schmidt et

al., 1999). At the same time, the effectiveness of the

medicamentous approaches stays quite low

(Starcevic, 2009).

Contemporary approaches of the anxiety

disorders therapy imply psychotropic medication –

antidepressants. These drugs increase exchange of the

serotonin and other neuromediators in structures of

the central nervous system (CNS), which are

responsible for the emotions. This increases the role

of the inhibitor mechanisms in the conscious control

of the fear and anxiety emotions (Stahl and Moore,

2013).

However, the medicamentous approach is

effective only among the one third of the patients. In

most cases, the life-long drug regimen is implied,

which is accompanied by the numerous side effects.

Essentially, the medicamentous approach is just a

substitution therapy and does not treat the disorder

itself (Stahl and Moore, 2013).

Combination of the medicamentous therapy with

the psychotherapy allows to increase effectiveness up

to 50 % (Weaver et al., 2009). However, this

approach implies life-long psychotropic drug

regimen and daily psychiatrist appointments. Many

patients cannot afford such expenses. In 20 % the

disorder can become a malignant one. In that case, the

known approaches become inefficient (Stahl and

Moore, 2013).

Petrenko T., Shalyagin M., Retyunsky K., Kublanov V. and Babich M.

Non-invasive Multichannel Electrostimulation of Neck Nerve Structures for the Treatment of Patients with Anxiety Disorders.

DOI: 10.5220/0006592603450350

Recently, the methods of neuro-electrostimulation

for treatment of the depressive and anxiety disorders

are being actively developed (White and Tavakoli,

2015). The highest effectiveness was reported for the

transcranial magnetic stimulation and invasive

stimulation of the vagus nerve (Sarkar and Cohen

Kadosh, 2016). The anti-depressive and anti-anxiety

effects are associated with the stimulation of the

brainstem nucleus and midline brain structures,

which, in turn leads to the massive emission of the

neurotransmitters and reconstructions of the neural

networks (White and Tavakoli, 2015).

In current study, we have investigated the

effectiveness of the dynamic correction of activity of

the sympathetic nervous system (DCASNS) approach

in comparison with standard medicamentous

approaches. The DCASNS approach is realized by

the medical device ‘SYMPATHOCOR-01’

(Kublanov et al., 2014).

2 NECK NERVE STRUCTURES

Centres for regulation of the life-important functions

are placed in nucleuses of the brain stem, middle

brain, the bridge, and cerebellum, and also, in the

vegetative nucleuses of the neuraxis and cerebrum.

Many of the conducting paths of these centers are

located in the neck. The neck somatic innervation is

provided by the neck neuraxis nerves that forms the

massive cervical interlacing on its back surface. The

afferent nerve fibers pass through the neuraxis back

horns and end in the sensitive nucleuses of the brain

stem and reticular formation. The reticular formation

participates in processing the sensors’ information

and, additionally, makes activating impact onto the

brain-cortex. By this way, the formation controls the

neuraxis activity.

This mechanism implements the tonus control of

the skeletal muscles and moreover, of the human

vegetative functions. The ganglia of the sympathetic

stem are placed in deep muscles of the neck. These

ganglia are formed by the nerve stems of the

vegetative ones of the neuraxis nervous offshoots.

The upper, middle, and lower (stellular) sympathetic

ganglia have multiple branches that perform

sympathetic innervation of glands, brain involucres,

and vessels of the neck, head and vertebra. The vagus

nerve is located abreast the main neck arteries. Its

ganglia are placed in the brain stem and are common

with the tong-pharyngeal nerve. They have wide

connections with the hypothalamus, rhinal system,

and reticular formation. The pair of IX and X cranial

nervous branches jointly implements para-

sympathetic innervation of the majority of human

organs. Together with branches of vagus nerve, ones

of the neck part of the sympathetic stem form several

nervous interlacings in the heart region. By this, the

vegetative regulation of the heart activity is

implemented. The nervous formations of neck area

are tightly joined with brain stem, middle brain,

cerebellum, thalamus, hypothalamus, and the large

brain cortex. Presence of these connections provides

participation of the neck nervous formations in

analysis of irritations from sensors and in regulation

of the muscle tonus, vegetative and the highest

integrative functions (Moore et al., 2013; Netter,

2014). Taking into account the mentioned facts, it is

perspective to use the neck neuraxis nervous

interlacing and the X and IX cranial nerves as a target

for electro-stimulation. It will allow one to stimulate

(through the afferent paths) the grey matter of the

brain stem. Through the reticular formation, this

action can propagate onto the thalamic structures and

the cerebrum cortex. Stimulation of the neck ganglia

of the sympathetic stem will permit to affect onto both

the vascular tonus of the brain arteries and onto the

vegetative ganglia of the neuraxis. Thus, the neuro

electro-stimulation system (under developing) is

completely able to modulate the vegetative processes

and affect onto the sensori-motor control and

cognitive functions.

3 MATERIALS AND METHODS

3.1 Multichannel

Neuro-electrostimulation Device

The group of scientists and engineers from the Ural

Federal University developed the portable corrector

of activity of the sympathetic nervous system

(‘SYMPATHOCOR-01’) is an electrical pulse

generator that delivers the spatially-distributed field

of the carefully-controlled current pulses in the neck

(Kublanov, 2008).

The device is included in the register of medical

equipment products of the Russian Federation

(registration certificate № FCR 2007/00757) and has

the Certificate of correspondence to the requirements

of the regulations GOST R 50444-92.

The spatially-distributed field of the current

pulses is formed between two multi-element

electrodes of the device. Each multi-element

electrode comprises a cluster of thirteen partial

current-conducting elements. The multi-element

electrodes are arranged on the neck into left and right

sides. In the working state, one element of one multi-

element electrode performs the role of the anode.

Elements on the other side become the cathodes. If it

is necessary, the arrangement can be reversed in

opposite direction.

Placing the multi-element electrodes on the

subject neck, the centre elements of multi-element

electrodes have to be located in projections of the

neck ganglia of the sympathetic nervous system

(Fig. 1).

Figure 1: Scheme of the partial current-conducting

elements of the multi-element electrodes location.

Note the following basic bio-tropic characteristics

of the field: the current partial pulses duration τ is

from 15 to 60 usec. The number of partial pulses in

the period (pulse group) is 12. The frequency f of

pulses group is from 5 to 150 Hz. Pulses group period

is named as T

and calculated as T

=1/f. The cathode

elements are switched accordingly to each given rule

(for example, a pseudo-random with the clockwise or

counterclockwise direction of switching, and so on).

The used anode is set depending on the stimulation

target. The duration of the anode connection varies

from 30 seconds to several minutes and is controlled

by the doctor. The current pulses amplitude can be up

to 15 mA.

Elements connection timing diagram is shown in

Fig. 2.

Figure 2: Elements connection timing diagram.

Before starting the stimulation, the generator

connects the positive pole of the built-in current

source to the element used as the anode. During

stimulation process, the generator sequentially

switches elements used as cathodes to the negative

pole of the current source in accordance with

switching order used. Cathodes and anodes

connections are performed by the built-in multi-

channel switches.

Depending on pathogenesis of the peripheral or

central dysfunctions of the ANS, the dynamic

correction of the activity sympathetic nervous system

(DCASNS) algorithm has two different branches.

Decision of which branch should be executed is based

on nature of the ANS dysfunction. The bio-tropic

parameters of the implemented current pulse field

(the field structure, pulses amplitude, frequency, and

duration) are calculated from the analysis of the heart

rhythm variability. In particular, in the case of the

abnormal hyperactivity of sympathetic innervation, it

is necessary to block or suppress the activity of the

sympathetic nervous system. In contrast, sympathetic

innervation should be increased, if the hyperactivity

of the parasympathetic 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.

In clinic practice, the ‘SYMPATHOCOR-01’

device and DCASNS algorithm were efficiently

applied for treatment of various diseases including

organic and/or functional disorders of the CNS and/or

the ANS: consequences of brain trauma or stroke,

epilepsy, chronic headache, somatoform disorders,

anxiety and depressive spectrum disorders, attention-

deficit hyperactivity disorder, disorders involving

cognitive impairments (Kublanov et al., 2017).

In transistory paths of the nervous system of the

neck region, there are both myelinated fiber and non-

myelinated fiber. The rate of excitation propagation

in the myelinated fibers is significantly larger than in

the non-myelinated ones. To provide participation in

stimulation of structures of various formations, it is

necessary that the length of the partial spatially

distributed pulses is matched with the rate of

excitation propagation in the myelinated fibers, and

the length of the spatially concentrated pulses’

structure is matched with the rate of excitation

propagation in the non- myelinated ones.

Block diagram of the engineering feasibility of

multi-channel neurostimulation system is shown in

Fig. 3.

Figure 3: Block diagram of the engineering feasibility of

multi-channel neurostimulation system.

The detailed technical description of the

‘SYMPATHOCOR-01’ device and the algorithm of

the DCASNS approaches were presented in

(Kublanov, et al., 2008) and (Kublanov, et al., 2017).

3.2 Clinical Data

The study on the clinical basis of the Department of

Psychiatry at the State Medical University was

conducted. The study has an approval of the Local

Ethics committee (protocol 2 from 16.03.2007). The

study included 40 outpatients with a newly diagnosed

"panic disorder" (“ICD-10,” 2010). All participants

have signed the informed consent of participation in

the study. Among the participants, there were 20 male

and 20 female patients. Average age of the

participants was 28,5 years. On average the disorder

has lasted for 7,6 months.

The following patients were excluded from the study:

 patients, having clinically significant disease,

which can prevent the therapy evaluation and

which can affect safety of the therapy;

 patients, suffering from the paroxysmal anxiety

within other mental disorders (bipolar disorder,

schizophrenia disorder, eating disorder,

obsessive-compulsive disorder, dependence on

psychoactive substances);

 patients, taking psycho-pharmacological

medicine prior to the study;

 female patients during pregnancy and lactation.

The period of therapy and dynamic follow-up was

6 weeks for each patient. All patients were randomly

divided into two equal groups (20 patients each). In

the first group (to be referred as AD), patients

received drug therapy with antidepressant –

escitalopram, 10 mg once daily, during whole study.

In the second group (to be referred as SCR), patients

were treated by means of the device

‘SYMPATHOCOR-01’. The treatment course

consisted of daily 15-minute long procedures, for 10

days in a row. It was allowed to take a break for a

single day once during the course. After 10-day

course the patients did not take any additional

treatment for the rest of the study.

The medical examination was performed by the

psychiatric doctor in all groups of patients initially (to

be referred as T0), on the 4-th day of therapy (to be

referred as T1), and then on 7-th, 10-th, 14-th, 21-st,

28-th, 35-th and 42-nd days (to be referred as T2, T3,

T4, T5, T6, T7, T8 respectively). In order to evaluate

effectiveness of the therapy during each visit (T0-T8)

the following scales were used to estimate anxiety

level and anxiety symptoms reduction degree:

 Hamilton anxiety rating scale (HAM-A)

(Hamilton, 1959);

 Sheehan anxiety rating scale (SPRAS)

(Schmidt et al., 2003);

 Quality-of-life index (QLI) (Katschnig, 2006);

 Global clinical impression – Severity scale

(CGI-S) (Busner and Targum, 2007).

The statistical analysis was performed by the

software ‘STATISTICA 12’. Analysis of variance

was used to find the inter-group differences.

4 RESULTS

Figures 4 – 7 show that the group of patients with

neuro-electrostimulation therapy (SCR) has a faster

reduction of the anxiety symptoms, evaluated by the

generally accepted tests, in comparison with the

antidepressant therapy group (AD).

Figure 4: HAM-A dynamic for two patient’s groups.

Data on Fig. 4 shows that after 4 days of treatment

the DCASNS method has a greater effectiveness than

medicamentous approach. After three weeks, the

anxiety evaluation for patients in second group is as

for healthy people (less than 10). The DCASNS

method effect stays until the end of the study.

Figure 5: SPRAS dynamic for two patient’s groups.

Fig. 5 shows that after the first days the DCASNS

method significantly suppresses the medicamentous

treatment. After 10 days of treatment the subjective

evaluation of the patients is comparable to those of

healthy people (less than 40 points). It can be seen,

that the effect is stable until the end of the study (day

42).

Figure 6: QLI dynamic for two patient’s groups.

Plots on Fig. 6 show that patients’ evaluation of

quality of life significantly changes for two groups

after the first therapy days. After first two weeks, the

QLI evaluation for patients ingroup with neuro-

electrostimulation therapy reaches an acceptable level

(more than 60).

Figure 7: CGI-S dynamic for two patient’s groups.

Data on Fig. 7 shows that after 14 days of

treatment the DCASNS method has a greater

effectiveness than medicamentous approach. After

five weeks, the global clinical impression about

patients in second group is as for healthy people (less

than 2).

5 CONCLUSIONS

Clinical effect of the non-invasive multi-electrode

neuro-electrostimulation based on the DCASNS

approach for patients with panic disorder shows high

effectiveness in comparison with the medicamentous

therapy. This is confirmed by the psychometric study

using generally accepted scales HAM-A, SPRAS,

QLI and CGI-S. The effect is most likely associated

with the stimulation of the neurotransmitters emission

in the stem structures of the CNS and reconstruction

of the existing neural networks for most efficient

functioning. This enhances the achieved clinical

effect. However, this assumption needs confirmation

by long-term clinical studies involving technologies

of the neuroimaging. The results can be considered as

a model for treating the anxiety and depression

diseases.

In the future, we plan functional neuroimaging

study of neuroplasticity changes after proposed

neuro-electrostimulation method in patients with

anxiety and depressive disorders.

Success of this technology development depends

on interaction and collaboration of various

specialists: engineers, physicians, physiologists, and

biologists.

ACKNOWLEDGEMENTS

The work was supported by Act 211 Government of

the Russian Federation, contract № 02.A03.21.0006.

REFERENCES

Busner, J., Targum, S.D., 2007. The Clinical Global

Impressions Scale. Psychiatry Edgmont 4, 28–37.

Hamilton, M., 1959. The assessment of anxiety states by

rating. Br. J. Med. Psychol. 32, 50–55.

ICD-10 [WWW Document], 2010. URL

http://apps.who.int/classifications/icd10/browse/2010/

en (accessed 9.5.17).

Kar, S.K., Sarkar, S., 2016. Neuro-stimulation Techniques

for the Management of Anxiety Disorders: An Update.

Clin. Psychopharmacol. Neurosci. 14, 330–337.

doi:10.9758/cpn.2016.14.4.330.

Katschnig, H., 2006. Quality of life in mental disorders:

challenges for research and clinical practice. World

Psychiatry Off. J. World Psychiatr. Assoc. WPA 5, 139–

145.

Kublanov, V., Babich, M., Dolganov, A., 2017. Principles

of Organization and Control of the New

Implementation of the “SYMPATHOCOR-01” Neuro-

electrostimulation Device. Presented at the Special

Session on Neuro-electrostimulation in

Neurorehabilitation Tasks, pp. 276–282.

Kublanov, V., Shmirev, V., Shershever, A., Kazakov, Y.,

Porshnev, S., Vasilev, A., 2014. About innovative

possibilities of the device SIMPATOCOR in

management of functional disorders of vegetative and

central nervous system in neurology. Kremljovskaya

Med. 1, 60–64.

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

diagnosis and correction of autonomic dysfunctions.

Biomed. Eng. 42, 206–212.

Moore, K.L., Agur, A.M.R., Dalley, A.F., 2013. Clinically

Oriented Anatomy, 7th edition. ed. LWW, Philadelphia.

Netter, F., 2014. Atlas of Human Anatomy: Including

Student Consult Interactive Ancillaries and Guides, 6e,

6 edition. ed. Saunders, Philadelphia, PA.

NIMH, 2017. Anxiety Disorders [WWW Document]. URL

https://www.nimh.nih.gov/health/topics/anxiety-

disorders/index.shtml (accessed 9.5.17).

Sarkar, A., Cohen Kadosh, R., 2016. Transcranial electrical

stimulation and numerical cognition. Can. J. Exp.

Psychol. Can. Psychol. Expérimentale 70, 41–58.

doi:10.1037/cep0000064.

Schmidt, N.B., Joiner, T.E., Staab, J.P., Williams, F.M.,

2003. Health perceptions and anxiety sensitivity in

patients with panic disorder. J. Psychopathol. Behav.

Assess. 25, 139–145.

Schmidt, N.B., Lerew, D.R., Jackson, R.J., 1999.

Prospective evaluation of anxiety sensitivity in the

pathogenesis of panic: replication and extension. J.

Abnorm. Psychol. 108, 532–537.

Stahl, S.M., Moore, B.A. (Eds.), 2013. Anxiety Disorders:

A Guide for Integrating Psychopharmacology and

Psychotherapy, 1 edition. ed. Routledge, New York.

Starcevic, V., 2009. Anxiety Disorders in Adults A Clinical

Guide, 2 edition. ed. Oxford University Press, Oxford ;

New York.

Weaver, F.M., Follett, K., Stern, M., Hur, K., Harris, C.,

Marks, W.J., Rothlind, J., Sagher, O., Reda, D., Moy,

C.S., Pahwa, R., Burchiel, K., Hogarth, P., Lai, E.C.,

Duda, J.E., Holloway, K., Samii, A., Horn, S.,

Bronstein, J., Stoner, G., Heemskerk, J., Huang, G.D.,

CSP 468 Study Group, 2009. Bilateral deep brain

stimulation vs best medical therapy for patients with

advanced Parkinson disease: a randomized controlled

trial. JAMA 301, 63–73. doi:10.1001/jama.2008.929.

White, D., Tavakoli, S., 2015. Repetitive transcranial

magnetic stimulation for treatment of major depressive

disorder with comorbid generalized anxiety disorder.

Ann. Clin. Psychiatry Off. J. Am. Acad. Clin.

Psychiatr. 27, 192–196.