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CLOSED-LOOP METHODS OF NON-INVASIVE BRAIN STIMULATION IN THE DIAGNOSIS AND CORRECTION OF COGNITIVE IMPAIRMENTS
A.A. Zemlyanaya1, S.B. Parin2, S.A. Polevaya2, A.I. Fedotchevi*
1 Moscow Research Institute of Psychiatry - a branch of the Serbsky National Medical Research Center for Psychiatry and Narcology, Ministry of Health of Russia, 3 Poteshnaya St., Building 10, Moscow, 107076, Russia;
2 National Research Lobachevsky State University of Nizhny Novgorod, 23 Prospekt Gagarina, Nizhny Novgorod, 603950, Russia;
3 Institute of Cell Biophysics of the Russian Academy of Sciences, 3 Institutskaya St., Pushchino, Moscow region, 142290, Russia.
* Corresponding author: [email protected]
Abstract. Cognitive impairments are among the most common types of neurological disorders that require the creation of reliable diagnostic and correction tools. Along with the development of effective drugs, in recent years a line of research has been actively developing, in which various methods of non-invasive brain stimulation with feedback from the current physiological parameters of a person, and primarily from the rhythmic components of the electroencephalogram (EEG), are successfully used to diagnose and correct cognitive impairments. The purpose of the presented work is to analyze recent publications, consider the achievements of this line of research and highlight the most promising directions for its further development. Studies using transcranial magnetic and electrical stimulation, as well as sensory types of stimulation - acoustic, photic and audiovisual stimulations, in which non-invasive stimulation is carried out on the basis of feedback signals from the patient's own bioelectrical processes, are considered. The advantages of EEG-guided light-music stimulation, developed by the authors for the correction of various cognitive disorders, are demonstrated.
Keywords: cognitive impairment, correction, non-invasive brain stimulation, transcranial magnetic and electrical stimulation, sensory stimulation, feedback, electroencephalogram (EEG), EEG-guided light-music stimulation.
List of Abbreviations
EEG - electroencephalogram
LED - light-emitting diode
The development and adequate use of reliable diagnostic and correction tools for cognitive impairment is a relevant area of modern neurological research. Its significance and relevance are determined by the following circumstances. Cognitive impairment is one of the most common types of neurological disorders encountered in the practice of both neurologists and doctors of other specialties (Lokshina et al., 2023). Cognitive deficit has a negative impact on the quality of life of the patient and his environment, largely hindering the possibility of returning to full social and professional recovery (Bogolepova & Levin, 2020). Therefore, early detection and treatment of diseases of the nervous system accompanied by cognitive impairment are among the most significant tasks of modern clinical neurology (Emelin, 2020).
When considering the basic principles of therapy for cognitive impairment, an unambiguous conclusion is made that it should be comprehensive and include not only drug-based methods of improving cognitive functions, but also non-drug-based methods - cognitive training, cognitive stimulation and cognitive rehabilitation (Parfenov, 2023). In this regard, of interest is the line of research that has been actively developing in recent years (Polevaya et al. , 2024), in which various methods of non-invasive brain stimulation with feedback from a person's current physiological parameters, which control stimulation in real time, are used to diagnose and correct cognitive impairment (Farkhondeh et al., 2022). Such interventions take into account the individual dynamics of micro- and macrostates of the brain (Khanna et al., 2015; Dick & Nozdrachev, 2020) and achieve high personalization and effectiveness, acquiring the character of physiologically informed adaptive neuromodulation (Wendt et
al., 2022). Among the most popular types of non-invasive stimulation are transcranial electrical and magnetic stimulation, as well as sensory types of stimulation - acoustic, light and audiovisual interventions (Polevaya et al., 2024). The basic mechanism of action of the stimulation procedures used is considered to be the activation of neuroplasticity processes (Piradov et al., 2018), due to which impaired cognitive functions such as perception, memory, attention, speech and others are restored (Kalantarova et al., 2020).
The analysis of literature shows that the number of publications on this topic has been exponentially increasing in recent years, as has the range of conditions for the successful use of different types of noninvasive brain stimulation with feedback in the diagnosis and correction of cognitive disorders. The purpose of this paper is to analyze recent publications, review the achievements of this line of research, and identify the most promising areas for its further development. The paper reviews studies using transcranial magnetic and electrical stimulation, as well as sensory types of stimulation-acoustic, light, and audiovisual interventions, in which noninvasive stimulation is carried out based on feedback signals from the patient's own bioelectric processes. The paper demonstrates the advantages of EEG-guided light and music stimulation developed by the authors to correct various cognitive disorders.
Transcranial magnetic and electrical stimulation in the correction of cognitive functions
Transcranial magnetic and electrical stimulations are widely used in cognitive neuroscience. This is due to their ability to modulate the activity of the stimulated area of the brain and neural networks through neuroplasticity mechanisms to clarify the role of individual areas of the cerebral cortex in ensuring perception, memory, attention, speech and other cognitive functions (Bakulin et al., 2020).
The most popular and actively developing methods of adaptive neurostimulation are those using feedback from the patient's EEG. This is due to the advantages of EEG such as ease of
use, non-invasiveness, high temporal resolution, and the ability to extract data in real time (Koenig et al., 2020).
A number of studies have shown that non-invasive sensory stimulation synchronized with certain current EEG parameters can improve sleep quality, enhance cognitive functions, and memory consolidation processes (Choi et al., 2020; Barnes et al., 2023). For example, after a session of transcranial electrical stimulation controlled by slow-wave EEG components, a significant increase in memory consolidation was recorded, which manifested itself in improved processes of recognition and reproduction of information (Ketz et al., 2018). High efficiency has also been demonstrated for tran-scranial magnetic stimulation synchronized with certain phases of EEG oscillations (Ding et al., 2022).
It is also known that rhythmic transcranial magnetic stimulation under the EEG control is a highly effective treatment for cognitive disorders (Poydasheva et al., 2021). It is emphasized that oscillations induced in the cerebral cortex by rhythmic stimulation in older people help restore natural frequencies of neural activity to those frequency characteristic of a younger and healthier brain (Qiao et al., 2022).
EEG-controlled sensory stimulation in the correction of cognitive functions
Recent studies have demonstrated the possibility of significantly improving sleep quality and memory consolidation processes using acoustic stimulation controlled by feedback signals from slow-wave EEG components (Ruch et al., 2022) or sleep EEG spindles (Ngo et al., 2019). Successful elimination of anxiety and depression states was observed with audiovisual stimulation automatically controlled by feedback signals from narrow-band spectral components of the EEG (Pino, 2022).
Another option for non-invasive brain stimulation with feedback is the computer transformation of current EEG parameters into therapeutic sensory stimulation. For example, pronounced positive effects in the correction of cognitive functions have been recorded with
rhythmic photic stimuli automatically generated in real time based on the digitized values of the native EEG (Fedotchev, 2019). Also worthy of attention is the bioacoustic correction method, which consists in presenting a person with acoustic signals obtained by computer transformation of the current EEG (Konstanti-nov et al., 2014). The method allows person to "hear" the work of the brain in real time and has been successfully used to restore such cognitive functions as executive functions, perception, reading and mental arithmetic in patients with focal brain lesions (Tereshin et al., 2019) and in the cognitive rehabilitation of patients with the consequences of transient cerebrovascular disorders (Shchegolkov et al., 2022).
EEG-controlled acoustic stimulation is also effectively used in a number of clinical applications. Thus, the presentation of acoustic stimuli generated in real time by software-controlled transformation of the subject's dominant EEG rhythms into a sound sequence causes a clinically significant reduction in post-traumatic stress symptoms and an improvement in cognitive functions (Tegeler et al., 2017; Shaltout et al., 2018; Tegeler et al.., 2023). According to the authors, the on-line updating of one's own EEG patterns and the resonance between audible acoustic signals and oscillatory brain networks provide the body with the opportunity for autocalibration, relaxation, and overcoming stable pathological conditions (Tegeler et al., 2020).
EEG-guided light-music stimulation in the correction of cognitive impairments
Computer transformation of current EEG parameters into therapeutic sensory stimuli was also used in our studies. A musical neural interface was developed in which the current values of the dominant spectral EEG components (EEG oscillators) of the subject are transformed into music-like signals, reminiscent of flute sounds in timbre, smoothly varying in pitch and intensity. This neural interface was successfully used in the correction of stress-induced disturbances (Fedotchev et al., 2018) and in the cognitive rehabilitation of the elderly (Fedotchev et al. , 2020). The described method of EEG-
guided musical stimulation was improved by adding a second feedback loop, in which rhythmic light stimuli formed on the basis of the patient's native EEG are presented simultaneously with music-like stimulation (Fedotchev et al., 2019; Fedotchev et al., 2022). The created method of light-music stimulation with double feedback from EEG was successfully applied to eliminate the risks of reliability of high-tech specialists (Fedotchev, 2022), as well as for cognitive rehabilitation of patients with stroke (Mukhina et al., 2021).
Our studies also outlined a promising approach to increasing the effectiveness of EEG-guided sensory stimulation. This approach involves the use of resonance scanning, or LED rhythmic photostimulation with a gradually increasing frequency in the range of the main EEG rhythms (Savchuk et al., 2022). It has been experimentally shown that resonance scanning can serve as a kind of preliminary tuning of the brain, causing the activation of potential resonators in the EEG spectrum and increasing the brain's response to subsequent EEG-controlled adaptive neurostimulation (Fedotchev et al., 2023). It is important to emphasize that the possibility of enhancing cognitive activity and improving well-being in general through the interaction of endogenous and exogenous oscillations has been proven in model studies (Nuidel et al., 2019). When combining resonance scanning with EEG-controlled adaptive neurostimulation, significant positive effects in the treatment of patients with post-COVID syndrome were recorded after just one combined exposure (Polevaya et al., 2022).
The data reviewed are summarized taking into account the conditions, type of stimulation and feedback parameter (Table 1).
The data in the table show that the range of conditions for the successful use of non-invasive brain stimulation in the correction of cognitive impairments is quite wide, as are the specific characteristics of the applied therapeutic stimulation. In addition, the arrangement of publications in chronological order allows one to note the annual increase in their number, which indicates the prospects of this area of research.
Table 1
Dynamics of studies successfully using non-invasive brain stimulation with feedback in the correction of cognitive impairments
Purpose/condition of the study Type of stimulation Feedback parameter Reference
Bioacoustic correction of the functional state EEG-controlled acoustic stimulation Frontal and occipital EEG Konstantinov et al., 2014
Enhancing of cognitive control under stress Acoustic stimulation Dominant EEG rhythms Tegeler et al., 2017
Elimination of stress-induced cognitive impairments Music-acoustic stimulation Narrow-band EEG oscillators Fedotchev et al., 2018
Enhancing of memory consolidation Transcranial electrical stimulation Slow wave EEG components Ketz et al., 2018
Optimization of cognitive functions Acoustic stimulation Dominant EEG rhythms Shaltout et al., 2018
Enhancing of cognitive control under stress Rhythmic light stimulation Digitized native EEG Fedotchev, 2019
Strengthening of memory consolidation Acoustic stimulation Sleep spindles on EEG Ngo et al., 2019
Restoration of cognitive functions EEG-controlled acoustic stimulation Frontal and occipital EEG Tereshin et al., 2019
Enhancing of cognitive control Acoustic stimulation Dominant EEG rhythms Tegeler et al., 2020
Cognitive rehabilitation of the elderly Music-like stimulation Alpha EEG oscillators Fedotchev et al., 2020
Therapy for cognitive disorders Transcranial magnetic stimulation Total EEG Poydasheva et al., 2021
Cognitive rehabilitation of stroke patients EEG-guided light-music stimulation Alpha EEG oscillators + native EEG Mukhina et al., 2021
Correction of psychogenic cognitive disturbances Audiovisual stimulation Spectral EEG components Pino, 2022
Cognitive rehabilitation in post-covid syndrome EEG-guided light-music stimulation Alpha EEG oscillators + native EEG Polevaya et al., 2022
Restoration of cognitive functions EEG-controlled acoustic stimulation Frontal and occipital EEG Shchegolkov et al., 2022
Enhancing of memory consolidation Acoustic stimulation Slow wave EEG components Ruch et al., 2022
Cognitive rehabilitation of high tech specialists EEG-guided light-music stimulation Alpha EEG oscillators + native EEG Fedotchev, 2022
Improving sleepy, activation of cognitive functions Acoustic stimulation Dominant EEG rhythms Tegeler et al., 2023
Cognitive rehabilitation of university students EEG-guided light-music stimulation Alpha EEG oscillators + native EEG Fedotchev et al., 2023
Conclusions
The presented data allow one to conclude that the development and improvement of approaches to the correction of cognitive impairments using non-invasive brain stimulation
with feedback is an actively developing and promising area of neurophysiology. Judging by the publications reviewed, the greatest development and efficiency are demonstrated by technologies using automatic modulation of non-in-
vasive sensory stimulation by feedback signals from rhythmic components of the EEG. Feedback from these components ensures the involvement of the mechanisms of multisensory integration, neuroplasticity and resonance mechanisms of the brain in the processes of correction of cognitive impairments. Due to the use of control signals from the EEG, such non-invasive stimulation, by taking into account the dynamics of brain microstates, achieves high personalization and efficiency of therapeutic procedures. Automatic control of therapeutic sensory stimulation makes it possible to use these technologies in conditions that do not require conscious efforts of the subjects, which is
especially important when conducting therapeutic sessions with children and with patients who are characterized by altered mental states or drug therapy is contraindicated.
The above advantages of the considered technologies open up prospects for their application in rehabilitation activities of a wide profile, in military and sports medicine, disaster medicine, and scientific research.
Acknowledgements
This research was funded by the Russian Scientific Foundation, grant No. 22-18-20075.
The authors declare that there is no conflict of interest.
References
BAKULIN IS., POYDASHEVA AG., MEDYNTSEV A.A., SUPONEVA N.A. & PIRADOV M.A. (2020): Transcranial magnetic stimulation in cognitive neuroscience: methodological foundations and safety. Russian Journal of Cognitive Science 7(3), 25-44. doi: 10.47010/20.3.2.
BARNES C.M., GUARANA C., LEE J. & KAUR E. (2023): Using wearable technology (closed loop acoustic stimulation) to improve sleep quality and work outcomes. J Appl Psychol. 108(8), 1391-1407. doi: 10.1037/apl0001077.
BOGOLEPOVA A.N., OSINOVSKAYA N.A., KOVALENKO E.A. & MAKHNOVICH E.V. (2021): Fatigue and cognitive impairment in post-COVID syndrome: possible treatment approaches. Nevrologiya, Neiropsikhiatriya, Psikhosomatika 13(4), 88-93. doi: 10.17116/jnevro2020120041115.
CHOI J., KWON M. & JUN S.C. (2020): A Systematic Review of Closed-Loop Feedback Techniques in Sleep Studies-Related Issues and Future Directions. Sensors (Basel) 20(10), E2770. doi: 10.3390/s20102770.
DIK O.E. & NOZDRACHEV A.D. (2020): Dynamics of patterns of electrical activity of the brain in violations of its functional state. Advances in Physiol. Sciences 51(2), 68-87. doi: 10.31857/S0301179820020046.
DING Z., WANG Y., LI J. & LI X. (2022): Closed-loop TMS-EEG reactivity with occipital alpha-phase synchronized. J Neural Eng. 19(5), 056027. doi: 10.1088/1741-2552/ac9432.
EMELIN A.YU. (2020): Possibilities of diagnostics and treatment of cognitive impairment at non-dementia stages. Neurology, Neuropsychiatry, Psychosomatics 12(5), 78-83. doi: 10.14412/2074-2711-2020-578-83.
FARKHONDEH TNF., HEYSIEATTALAB S., RAMANATHAN D.S., RAOUFY MR. & NAZARI M.A. (2022): Closed-loop Modulation of the Self-regulating Brain: A Review on Approaches, Emerging Paradigms, and Experimental Designs. Neuroscience 483, 104-126. doi: 10.1016/j.neurosci-ence.2021.12.004.
FEDOTCHEV A.I. (2019): Effects of photostimulation controlled by human EEG. Biophysics 64(2), 358-361. doi: 10.1134/S0006302919020157.
FEDOTCHEV A.I. (2022): Closed-loop adaptive neurostimulation technologies in cognitive rehabilitation of high-tech specialists. Sovremennye tehnologii v medicine 14(4), 34-43. doi: 10.17691/stm2022.14.4.04.
FEDOTCHEV A., PARIN S. & POLEVAYA S. (2023): Resonance scanning as an efficiency enhancer for EEG-guided adaptive neurostimulation. Life 13(620), 1-9. doi: 10.3390/life13030620.
FEDOTCHEV A., PARIN S., POLEVAYA S. & ZEMLIANAIA A. (2022): EEG-based musical neurointerfaces in the correction of stress-induced states. Brain Comput. Interfaces 9, 1-6. doi: 10.1080/2326263X2021.1964874.
FEDOTCHEV A.I., RADCHENKO G.S. & ZEMLYANAYA A.A. (2018): On one approach to health protection: music of the brain. J. Integr. Neurosci. 17(3-4), 309-315. doi: 10.3233/JIN-170053.
FEDOTCHEV A.I., ZEMLYANAYA A.A., PARIN S B., POLEVAYA S.A. & SILANTYEVA O.M. (2020): Cognitive rehabilitation of the elderly using a musical neurointerface. Preventive Medicine 23(2), 42-46. doi: 10.17116/profmed20202302142.
FEDOTCHEV A.I., ZEMLYANAYA A.A., SAVCHUK L.V. & POLEVAYA S.A. (2019): Neurointerface with dual feedback from EEG in the correction of stress-induced disorders. Sovremennye tehnologii v medicine 11(1), 150-154. doi: 10.17691/stm2019.11.1.17.
KALANTAROVA M.V. ZAVALIY L.B., BORISONIK E.V., SUBOTIC M.I., GRECHKO A.V., SHCHELKUNOVA I.G. & PETRIKOV S.S. (2020): Digital technologies in cognitive rehabilitation of patients with focal brain lesions. Counseling Psychology and Psychotherapy 28(3), 122-141. doi: 10.17759/cpp.2020280308.
KETZ N., JONES A.P., BRYANT N.B., CLARK V P. & PILLY P.K. (2018): Closed-Loop Slow-Wave tACS Improves Sleep-Dependent Long-Term Memory Generalization by Modulating Endogenous Oscillations. J Neurosci. 38(33), 7314-7326. doi: 10.1523/JNEUROSCI.0273-18.2018.
KHANNA A., PASCUAL-LEONE A., MICHEL CM. & FARZAN F. (2015): Microstates in resting-state EEG: current status and future directions. Neurosci Biobehav Rev. 49, 105-113. doi: 10.1016/j.neubio-rev.2014.12.010.
KOENIG T., SMAILOVIC U. & JELIC V. (2020): Past, present and future EEG in the clinical workup of dementias. Psychiatry Res Neuroimaging 306: 111182. doi: 10.1016/j.pscychresns.2020.111182.
KONSTANTINOV K.V., LEONOVA ML., MIROSHNIKOV D.B. & KLIMENKO V.M. (2014): Features of perception of the acoustic image of one's own bioelectrical activity of the brain. Rus. Physiol. Zhurn. im. I.M. Sechenov 100(6), 710-721.
LOKSHINA A.B., ZAKHAROV V.V. & VAKHNINA N.V. (2023): Modern aspects of diagnostics and treatment of cognitive impairment. Neurology, Neuropsychiatry, Psychosomatics 15(1), 83-89. doi: 10.14412/2074-2711-2023-1-83-89.
MUKHINA E.A., POLEVAYA S.A., PARIN S B. & FEDOTCHEV A.I. (2021): Cognitive rehabilitation of patients with acute cerebrovascular accident using EEG-guided adaptive neurostimulation. Opera Med Physiol. 8(4), 90-96. doi: 10.24412/2500-2295-2021-4-90-96.
NGO H.V., SEIBOLD M., BOCHE D C., MOLLE M. & BORN J. (2019): Insights on auditory closed-loop stimulation targeting sleep spindles in slow oscillation up-states. J Neurosci Methods 316, 117-124. doi: 10.1016/j .jneumeth.2018.09.006.
NUIDEL I.V., KOLOSOV A V., DEMAREVA V.A. & YAKHNO V.G. (2019): Application of a phenome-nological mathematical model to reproduce the effect of interaction of endogenous and exogenous oscillations in neurobiofeedback. Sovremennye tehnologii v medicine 11(1), 103-108. doi: 10.17691/stm2019.11.1.12.
PARFENOV V.A. (2023): Management of patients with cognitive impairment. Neurology, Neuropsychiatry, Psychosomatics 15(1), 97-102. doi: 10.14412/2074-2711-2023-1-97-102.
PINO O. (2022): A randomized controlled trial (RCT) to explore the effect of audio-visual entrainment among psychological disorders. Acta Biomed. 92(6), e2021408. doi: 10.23750/abm.v92i6.12089.
PIRADOV M.A., CHERNIKOVA L A. & SUPONEVA N.A. (2018): Brain plasticity and modern technologies of neurorehabilitation. Bulletin of the Russian Academy of Sciences 88(4), 299-312. doi: 10.7868/S0869587318040023.
POLEVAYA S.A., PARIN S B. & FEDOTCHEV A.I. (2024): Current trends and prospects for development of non-invasive brain stimulation. Opera Med Physiol. 11(1), 147-155. doi: 10.24412/2500-2295-20241-147-155.
POLEVAYA S.A., PARIN S B., ZEMLYANAYA A.A. & FEDOTCHEV A.I. (2022): Dynamics of EEG reactions under combination of resonance scanning and adaptive neurostimulation in patients with post-COVID syndrome. Opera Med Physiol. 9(2), 103-109. doi: 10.24412/2500-2295-2022-2-103-109.
QIAO J., WANG Y. & WANG S. (2022): Natural frequencies of neural activities and cognitions may serve as precise targets of rhythmic interventions to the aging brain. Front Aging Neurosci. 14, 988193. doi: 10.3389/fnagi.2022.988193.
RUCH S., SCHMIDIG F.J., KNUSEL L. & HENKE K. (2022): Closed-loop modulation of local slow oscillations in human NREM sleep. Neuroimage 264, 119682. doi: 10.1016/j.neuroimage.2022.119682.
SAVCHUK L.V., POLEVAYA S.A., PARIN S.B., BONDAR AT. & FEDOTCHEV A.I. (2022): Resonance scanning and EEG analysis in determining the maturity of cortical rhythms in primary school children. Biophysics 67(2), 354-361. doi: 10.31857/S0006302922020181.
SHCHEGOLKOV A.M., ALEKHNOVICH A.V., TIMERGAZINA E.Z. ET AL (2022): The influence of bioacoustic correction on the process of medical rehabilitation of patients with consequences of transient cerebrovascular disorders. Hospital medicine: science and practice 5(4): 46-49. doi: 10.34852/GM3CVKG.2022.17.46.009.
SHALTOUT H.A., LEE S.W., TEGELER C.L. ET AL. (2018): Improvements in Heart Rate Variability, Baroreflex Sensitivity, and Sleep After Use of Closed-Loop Allostatic Neurotechnology by a Heterogeneous Cohort. Front Public Health 6, 116. doi: 10.3389/fpubh.2018.00116.
TEGELER C.L., GERDES L., SHALTOUT H.A. ET AL. (2017): Successful use of closed-loop allostatic neurotechnology for post-traumatic stress symptoms in military personnel: self-reported and autonomic improvements. Mil Med Res. 4(1), 38. doi: 10.1186/s40779-017-0147-0.
TEGELER C.L., MUNGER CLARY H., SHALTOUT H.A. ET AL. (2023): Cereset Research Standard Operating Procedures for Insomnia: A Randomized, Controlled Clinical Trial. Glob Adv Integr Med Health 12, 27536130221147475.doi: 10.1177/27536130221147475.
TEGELER C.L., SHALTOUT H.A., LEE S.W. ET AL. (2020): Pilot Trial of a Noninvasive Closed-Loop Neurotechnology for Stress-Related Symptoms in Law Enforcement: Improvements in Self-Reported Symptoms and Autonomic Function. Glob Adv Health Med. 9, 2164956120923288. doi: 10.1177/2164956120923288.
TERESHIN A.E., KIRYANOVA V.V., KONSTANTINOV K.V. ET AL. (2022): Bioacoustic correction in cognitive rehabilitation of patients with focal brain lesions. Bulletin of Restorative Medicine 5(93): 47-56.
WENDT K., DENISON T., FOSTER G. ET AL. (2022): Physiologically informed neuromodulation. J Neurol Sci. 434, 120121. doi: 10.1016/j.jns.2021.120121.
