Recovery of the Cognitive Function by the Non-Invasive

Multichannel Neuro-Electrostimulation

for Patients with Amnesic Syndrome

Vladimir Kublanov

, Timur Petrenko

1,2

, Mikhail Babich

, Anna Petrenko

and Konstantin Retyunskiy

Research and Development Medical and Biological Engineering Centre of High Technologies, Ural Federal University,

Mira 19, 620002, Yekaterinburg, Russian Federation

Department of Psychiatry, Ural State Medical University, Repina 3, 620028, Yekaterinburg, Russian Federation

Keywords: SYMPATHOCOR-01 Device, Biofeedback, Neuromodulation, Autonomic Balance Correction,

Neurorehabilitation, Neuro-Electrostimulation, Amnesic Syndrome.

Abstract: The efficiency of non-invasive multichannel neuro-electrostimulation device for recovery of cognitive

functions is presented in article. The article contain description of the structural schematic and algorithm of

the microcontroller execution program of “SYMPATHOCOR-01” device. The possibility of the

“SYMPATHOCOR-01” application for the cognitive disorders treatment is justified. As the example, results

are presented that involved five middle-aged men with signs of pronounced organic amnesic syndrome,

previously held specialized treatment in hospital. As a result, the stimulation rate during the three weeks of

recovery could achieve stable fixing of memory and other cognitive functions in all the patients according to

clinical observation and methods of neuropsychological assessments FAB, MoCA and MMSE. A significant

positive trend noted by the results of the data analysis of EEG and heart rate variability. A hypothesis

mechanism for clinical effect is formulated.

1 INTRODUCTION

Nowadays, population ageing, more complex

technosphere and rapid growth of social stressors

define importance of cognitive disorders, caused by

organic injuries of the Central nervous system (CNS).

The memory is one of the most important cognitive

function. Severe disorders of memory are observed

for patients with organic amnesic syndrome. The

amnesic syndrome arises as a result of the severe

cerebral injury or the intoxication of the brain

(Kopelman, 2002). Neuromodulation, which is a

technology shown to induce neuroplasticity changes,

is the alternative to the traditional pharmacological

methods of the cognitive function recovery (Doidge,

2010). However, contemporary elaborations of the

neuro-electrostimulators applicable to this task in

medicine have a number of the significant drawback

that reduce efficiency of the exposure. For example,

the quick adaptation of the nervous system to

exposure to the external electric fields results in a

decreased reaction when the exposure is continuous.

2 SYMPATHOCOR-01 DEVICE

Group of scientists and engineers from the Ural

Federal University developed the

“SYMPATHOCOR-01” device. 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. Block diagram of

the “SYMPATHOCOR-01” device is shown in Fig.

1. The device includes neuro-electrostimulation

subsystem, electrocardiogram (ECG) registration

subsystem, microcontroller and a control unit.

Neuro-electrostimulation subsystem is used to

create spatially distributed field of current impulses,

which allows correcting the ANS activity. ECG

registration subsystem is used for ECG registration in

the first limb lead scheme for the consequent ECG

analysis, heart rate variability acquisition and

decision making for the structural changes of the

neuro-electrostimulation field. Microcontroller is

Kublanov, V., Petrenko, T., Babich, M., Petrenko, A. and Retyunskiy, K.

Recovery of the Cognitive Function by the Non-Invasive Multichannel Neuro-Electrostimulation for Patients with Amnesic Syndrome.

DOI: 10.5220/0006074400250030

In Proceedings of the 4th International Congress on Neurotechnology, Electronics and Informatics (NEUROTECHNIX 2016), pages 25-30

ISBN: 978-989-758-204-2

used to receive and to process commands from the

control unit, neuro-electrostimulation subsystem and

the ECG registration subsystem, and to coordinate

subsystems.

Figure 1: Block diagram of the neuro-electrostimulation

device.

In order to display information about current

neuro-electrostimulation device state, microcon-

troller cyclically poll the neuro-electrostimulation

subsystem and ECG registration subsystem, pack

information about these subsystem states into

information messages and transmit packets to the

control unit. Current ECG data, received from the

ECG registration subsystem are buffered, packed into

information messages and transmitted to the control

unit for the further processing.

The control unit is used by the doctor to control

neuro-electrostimulation procedure, to process and to

analyze ECG signal, to alter neuro-electrostimuila-

tion field of current impulses characteristics, depen-

ding on neuro-electrostimulation program and results

of the ECG signal analysis. A personal computer or a

mobile device can be used as the control unit.

The “SYMPATHOCOR-01” device implemented

as a mobile unit and has dimensions of 90.0 x 50.0 x

18.5 mm. The “SYMPATHOCOR-01” device

general view is shown in Fig. 2. The

“SYMPATHOCOR-01” device main printed circuit

board is shown in Fig. 3.

Neuro-electrostimulation susbsystem consists of:

 two multi-element electrodes, first performs

anodes function, and second – cathodes

function

 voltage controlled current source (VCCS)

 anodes multiplexer, which connects one of the

partial anodes to the positive pole of VCCS

 cathodes multiplexer, which connects one of

the partial cathodes to the negative pole of

VCCS

Figure 2: The “SYMPATHOCOR-01” device view.

Figure 3: The “SYMPATHOCOR-01” device main printed

circuit board view.

During neuro-electrostimulation procedure,

microcontroller executes program implemented in

accordance with the algorithm, that shown in Fig. 4.

Alteration of the neuro-electrostimulation field of

current impulses state is possible only at discrete time

points. These discrete time points are determined by

the formula:

∗∗,

(1)

where a

∈

N, N – set of all natural numbers,

T – impulses “packets” repeat interval,

∈,0,

(2)

where K – number of partial cathodes, involved in

neuro-electrstimulation procedure, τ – duration of the

partial impulses.

NEUROTECHNIX 2016 - 4th International Congress on Neurotechnology, Electronics and Informatics

Figure 4: Neuro-electrostimulation microcontroller

algorithm.

The frequency

ν1

⁄

(3)

is called a frequency of the impulses “packets”.

At the discrete time point microcontroller

performs several steps:

 Turns off the previous connected cathode and

turns on following cathode according to the

neuro-electrostimulation program. If the

previous connected cathode is the latest

cathode in accordance to the neuro-

electrostimulation procedure than turning on of

the following cathode does not occurs.

 After change of the partial cathode, if change

of the anodes is required in accordance with the

neuro-electrostimulation program or by doctor

command, received from the control unit,

microcontroller disconnects the current

connected anode and connects new anode.

 If the current amplitude and temporal

characteristics of field of current impulses

(such as impulses “packets” repeat interval,

partial impulse duration, impulse amplitude) is

different from the target characteristics, set by

neuro-electrostimulation program or set by the

control unit, the current field characteristics are

changed in accordance with the following

equations:











,











∆







∆







∆













∆







∆









(4)











,







∆







∆



,



∆











∆



,



∆







(5)







,τ



τ



∆





∆



,τ



∆



τ





∆



,τ



∆



τ



,

(6)

where A

– the partial current impulses amplitude at i

discrete time point, A

target

– the target partial current

impulses amplitude, Δ

– the maximum current

impulses amplitude increment, T

– the impulses

“packets” repeat interval at i discrete time point, T

target

– the impulses “packets” repeat interval, Δ

– the

maximum impulses “packets” repeat interval

increment, τ

– partial impulse duration at i discrete

time point, τ

target

– target partial impulse duration, Δ

– the maximum partial impulse duration increment.

Rapid amplitude and temporal characteristic

changes during neuro-stimulation procedure cause

Recovery of the Cognitive Function by the Non-Invasive Multichannel Neuro-Electrostimulation for Patients with Amnesic Syndrome

pain. Therefore, microcontroller limit amplitude and

temporal characteristics of field of current impulses

growth rate using amplitude and temporal

characteristics increments.

Subsequent switch of the partial cathodes at the

neck area forms spatially centered current structure.

Maximum of the current density in this structure is

located in the center of the anode. Ability to switch

operating anode allows one to move the maximum

current density point of the spatially centered current

structure. This leads to neuro-electrostimulation

improvements due to increase of the local neuro-

electrostimulation targets number in the neck area.

Improvements of the neuro-electrostimulation

efficiency is achieved through involvement in the

regulatory process brain structures responsible for

motor, visual, auditory, vestibular functions, in

addition to the ANS.

The neuro-electrostimulation subsystem is based

on Analog Devices ADG5408 8-channel multiplexor

chips. These chips perform partial cathodes and

anodes commutation to the VCCS. At the current

version of the neuro-electrostimulation devices four

ADG-5408 chips are used, that allows to connect up

to 16 partial cathodes and 16 anodes for the neuro-

electrostimulation procedure. VCCS is formed by a

current mirror with two BC807 and one BC817

bipolar transistors.

Microcontroller with built-in 12-bit digital-to-

analog converter (DAC) generates control voltage.

Current mirror resistor values are calculated in a way

that the current source can generate a current in the

range 0 to 15 mA with a load from 0 to 2 kOhms.

The ECG registration subsystem obtain signals

from the first limb lead. The signal electrode 1 and

the signal electrode 2 are located on the patient’s

hands. The RLD electrode may be on placed either on

the right leg of the patient or on the any hands of the

patient, if the case of the short circuiting is avoided.

Standard disposable adhesive electrodes for ECG are

used.

The ECG registration subsystem is based on the

usage of the analog interface for ECG applications

ADS1292 chip. The ADS1292 consists of a

differential amplifier with the programmable

amplification factor, 24-bit delta-sigma analog-to-

digital converter (ADC), the device for the down

sampling and digital low-pass filtration, the SPI

interface, the Right Leg Drive (RLD) amplifier.

The first step of the ECG registration is filtration

of the impulse interferences on the patient by a low-

pass RC-filter with the 2 kHz cut-off frequency. The

second step of the conversation is gain of the ECG

signal by a differential amplifier, the amplified signal

is supplied to the ADC and the RLD amplifier. The

RLD amplifier compares the constant component of

the ECG signal with the half supply voltage, amplifies

the difference of signals and uses amplified difference

as RLD signal. Thus, the RLD signal applied to the

patient fluctuates around the half supply voltage

value, which provides chip normal operation.

Delta-sigma ADC operates at 8kSPS sampling

frequency, but further digital signal is filtered with

help of digital low-pass filter and decimated in

accordance with chip configuration. The ECG

registration subsystem signal sampling rate after

decimation is 500 SPS, with 131 Hz cut-off frequency

of the digital low-pass filter. This frequency range is

sufficient to assess the characteristics of the ANS.

The filtered digital signal is sent to the

microcontroller using the modified SPI protocol. In

addition to the standard SPI protocol lines such as

MOSI, MISO, SCLK, additional lines Data Ready

(DRDY) and Conversation Start are used. DRDY

signal is used by the ADS1292 to notify the

microcontroller about the conversion end of the

current data sample. Conversation Start signal is used

for forced start of the ADC.

Usage of the ADS1292 significantly reduces

devices size and improves patients comfort during

neuro-electrsotimulation compared with the case,

when the ECG registration subsystem is implemented

using multiple chips.

3 TREATMENT OF PATIENTS

WITH AMNESIC SYNDROM

Models of cognitive disorders are not sufficiently

formed at the moment. So, researchers and clinicians

encounter with various difficulties in development of

effective approaches for neuro-rehabilitation.

The experimental studies on the laboratory

animals confirmed the efficiency of the developed

technology application for the restoration of the blood

flow after artificial ischemia of the muscle tissue and

for the normalization of the behaviour patterns after

adjustment disorder (Kublanov et al., 2010). Clinical

trials of the patients with epilepsy after application of

the neuromodulation showed non-specific changes of

the neurometabolism based on the data of the single-

photon emission computed tomography (SPECT) in

the cerebral cortex. The global decrease of the activity

of the epileptic areas was shown by the

electroencephalography features (Kublanov, 1999).

The goal of the present study is to define

possibilities of the dynamic correction of the neck

NEUROTECHNIX 2016 - 4th International Congress on Neurotechnology, Electronics and Informatics

nerve structures conduction activity for the recovery

of the cognitive function for the patients with the

organic amnesic syndrome. The study was approved

by USMU ethics committee (protocol #8 from

16.10.2015)

Design of serious clinical studies will be produced

based on the results of this project.

3.1 Objectives and Methods

For this pilot study five male patients with clinical

manifestation of the organic amnesic syndrome, as a

result of brain damage caused by different

pathological factors (traumatic brain injury, chronic

alcohol intoxication, poisoning by household toxins)

were investigated at the department of psychiatry of

the Ural state medical university. All patients prior to

the investigation held specialized treatment in

psychological and/or neurological hospital without

significant improvement. The duration of the disease

varied from 12 to 24 months. Patients age varied from

33 to 48 years.

Neuromodulation with the “SYMPATHOCOR-

01” device was used as the treatment course. The

dynamic correction of the neck nerve structures

conduction activity technique allowed affection on

the processes of the autonomic regulation (through

the autonomic ganglia) and stimulation of the brain

stem neuronal centres (through the nerve pathways of

the neck). The treatment course consisted of the 15

procedures on the span of the 3 weeks. There was no

additional pharmacological treatment, except for

designated previously.

Clinical data and psychometric test were used for

the initial and the following evaluation of the

patient’s cognitive skills: Frontal Assessment Batter

(FAB) (Dubois et al., 2000), Montreal Cognitive

Assessment (MoCA) (Nasreddine et al., 2005), Mini-

Mental State Examination (MMSE) (Folstein et al.,

1975). Instrumental diagnostics was performed with

“Encephalan-EEGR-19/26 Medicom Ltd” complex

and included quantitate analysis of the

electroencephalograms (EEG), spectral analysis of

the heart rate variability (HRV) based on

electrocardiogram. The analysed features of the

biomedical signals: power of the main EEG rhythms,

total power of the HRV spectrum (TP), low-

frequency component of the HRV spectrum (6,5-25

s) (LF), high-frequency component of the HRV

spectrum (2,5-6,5 s) (HF). Clinical and instrumental

evaluation was carried out by independent experts.

3.2 Results

The initial state of the patient reflected symptoms of

the severe CNS damage: rough disturbance of

orientation by the amnesic type, rough disturbance of

the fixation amnesia, rapid exhaustion of attention,

lack of cognitive efficiency, phenomena of emotional

incontinence, complacency. Pronounced decrease of

cognitive status and cognitive skills was defined

according to the data of psychometric test.

Pronounced diffusion disorganization of the main

rhythms with signs of the epileptization were defined

by the EEG signals analysis. HRV signals analysis

revealed pronounced signs of autonomic

dysregulation.

The sessions of the dynamic correction of the neck

nerve structures conduction activity resulted in rather

quick positive dynamic. After clinical studies patients

become more active. The fatiguability and attention

disorders reduced, attention and acumen significantly

increase, the cognitive processes and memory

improved.

The recovery of spatial and constructive activity,

dynamic praxis and reciprocal coordination were

noted according to the psychometric tests. The results

proves recovery of the intracerebral connections. The

Table 1 present summary data of the psychometric

tests.

Table 1: Data of the psychometric tests prior and after

treatment.

Psychometric test

Mean values of the scoring

prior treatment after treatment

FAB 5,7 ± 3,1 12,0 ± 4,0*

MoCA 11,3 ± 3,0 16,3 ± 4,0*

MMSE 15,3 ± 6,2 21,3 ± 8,3*

* - significance of the difference of data after treatment

from data prior treatment, P<0,05.

The comparative analysis of the EEG quantitative

features prior and after neuro-electrostimulation

showed recovery with the increase of the alpha-

rhythm power, suppression of the diffusion delta-

activity and paroxysmal patterns “acute-slow wave”.

Results of EEG signals analysis concludes significant

normalization of functional processes in the CNS.

The comparative analysis of the HRV signals

prior and after neuro-electrostimulation noted the

increase of the total power of the HRV and change of

the autonomic balance, defined by the LF/HF ratio.

The autonomic balance became normal. That

concludes normalization of the autonomic regulation

Recovery of the Cognitive Function by the Non-Invasive Multichannel Neuro-Electrostimulation for Patients with Amnesic Syndrome

processes which in turn provide conditions for the

recovery of the lost functions. The Table 2 presents

data of the HRV spectrum features changes.

Table 2: Data of the HRV spectrum features prior and after

treatment.

HRV spectrum

features

Mean values of the spectrum

features

prior treatment after treatment

LF/HF 6,39 ± 2,4 2,2 ± 0,7*

* - significance of the difference of data after treatment

from data prior treatment, P<0,05.

4 CONCLUSIONS

The results of the study demonstrated high potential

of the dynamic correction of the neck nerve structures

conduction activity technique to recovery of the

cognitive functions. Apparently, the technique is

capable to activate neuroplasticity processes and

recover of the autonomic regulation in the whole

organism.

Analysis of the recorded data allows one to

formulate hypothesis about the formation

mechanisms of the clinical effects for the developed

neuromodulation method. The main ideas of the

hypothesis:

• cerebral blood flow is modulated due to the

regulation of the arteries tone of the small and

medium calibre;

• suppression of the sympathetic department of the

ANS;

• stimulation of the neurotransmitters production in

the brain stem nucleus;

• suppression of the pathological hypergenerator

areas in the cortex;

The mentioned mechanisms provide condition for

the recovery of the intracerebral connections, which

certainly increase overall adaptive possibilities of the

organism.

It requires full clinical trial according to the GСP

rules to confirm these hypotheses.

P. K. Anochin formulated theory of the afferent

syntheses. According to this theory, the proposed

neuromodulation technique might be the factor which

starts afferentation. The afferentation helps to limits

of the systems activity freedom in order to stabilize

its functions (Anokhin, 1974). However, this

hypothesis needs additional verification.

The obtained results confirm efficiency of the

hardware non-invasive multichannel neuromodula-

tion for the recovery of the cognitive impairment as

the result of the organic damage of the CNS. The

proximate perspectives of the developed technique

are the treatment of the neurodegenerative diseases

and affective disorders. The following development

of the non-invasive multichannel neuromodulation

technique of the nervous formations for the recovery

of the cognitive functions will be defined by the

reliability of the knowledge about plasticity

mechanisms. Biophysicist, radiophysicist, physiolo-

gists, doctors, engineers – all must take part in the

reliable knowledge formation.

ACKNOWLEDGEMENTS

The work was supported by Act 211 Government of

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

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NEUROTECHNIX 2016 - 4th International Congress on Neurotechnology, Electronics and Informatics