NEUROPHYSIOLOGICAL BASIS OF THE COMBINED EFFECTS OF ACUTE STRESS AND LOW DOSES OF IONIZING RADIATION ON HUMAN BRAIN. / НЕЙРОФІЗІОЛОГІЧНИЙ БАЗИС КОМБІНОВАНИХ ЕФЕКТІВ ГОСТРОГО СТРЕСУ ТА МАЛИХ ДОЗ ІОНІЗУЮЧОГО ВИПРОМІНЮВАННЯ НА ГОЛОВНИЙ МОЗОК ЛЮДИНИ.

OBJECTIVE: to study the clinical and neurophysiological features in the Chornobyl clean-up workers with a verified chronic cerebrovascular disease/cerebral small vessels disease (SVD) exposed to low doses of ionizing radiation (IR), employees of the Chornobyl Nuclear Power Plant (SSE ChNPP), who were exposed to the stress factor of a full-scale war as a result of being held captive by the Russian military at their workplaces, and individuals of the non-irradiated comparison group.Design, object and methods. A cross-sectional clinical study with parallel external control groups. We studied and carried out an expert statistical analysis of the clinical and neurophysiological characteristics of 62 male subjects, from which three examination groups were formed: 1) a randomized sample from the Clinical Epidemiological Register (CER) of the State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine¼ (NRCRM) of 22 Chornobyl clean-up workers ('Chornobyl liquidators') in 1986-1990,examined during 2020-2021, aged 50-68 years at the time of examination (M ± SD: (58.1 ± 5.2) years) with a documented external radiation dose of 0.03-2.30 Sv; 2) 24 SSE ChNPP employees exposed to the stress factor impact of a full-scale war as a result of being held captive by the Russian military at their workplaces. The average age of the examined was (54.5 ± 5.8) years (range 46-71 years). 3) Comparison group - 16 non-exposed men with verified chronic cerebrovascular disease/cerebral small vessels disease (SVD). The average age of the examined was (57.8 ± 5.6) years (range 50-70 years). RESULTS: Neurophysiological studies confirm the presence of the pronounced dysfunction of the cortico-limbic system of the left dominant hemisphere of the brain with special involvement of the hippocampus in the Chornobyl clean-up workers. In the SSE ChNPP group, for the first time, the disorders of cerebral neurodynamics were detected in the form of functional hypofrontality and hyperfunction of the cortico-limbic system with lateralization to the right hemisphere. CONCLUSIONS: Today there exists a long-term thorough methodological and evidence base for a possible neurophysiological diagnosis and differential diagnosis of the combined cerebral effects of IR and psycho-emotional stress associated with the conditions of military conflicts. Neurophysiological technologies can be used in the objective professional and qualification selection of employees in a number of professions that require quick and responsible decision-making. Employees of SSE ChNPP need further medical and psychological support due to an increased risk of developing mental health disorders.

BRAIN AND EYE AS POTENTIAL TARGETS FOR IONIZING RADIATION IMPACT: PART II - RADIATION CEREBRO/OPHTALMIC EFFECTS IN CHILDREN, PERSONS EXPOSED IN UTERO, ASTRONAUTS AND INTERVENTIONAL RADIOLOGISTS. / GOLOVNYI MOZOK TA ORGAN ZORU IaK POTENTsIINI MIShENI DLIa VPLYVU IONIZUIuChOGO VYPROMINIuVANNIa: ChASTYNA II ­ RADIATsIINI TsEREBROOFTAL'MOLOGIChNI EFEKTY U DITEI, OSIB, EKSPONOVANYKh VNUTRIShN'O/UTROBNO, ASTRONAVTIV TA INTERVENTsIINYKh RADIOLOGIV.

BACKGROUND: Ionizing radiation (IR) can affect the brain and the visual organ even at low doses, while provoking cognitive, emotional, behavioral, and visual disorders. We proposed to consider the brain and the visual organ as potential targets for the influence of IR with the definition of cerebro-ophthalmic relationships as the «eye-brain axis¼. OBJECTIVE: The present work is a narrative review of current experimental, epidemiological and clinical data on radiation cerebro-ophthalmic effects in children, individuals exposed in utero, astronauts and interventional radiologists. MATERIALS AND METHODS: The review was performed according to PRISMA guidelines by searching the abstract and scientometric databases PubMed/MEDLINE, Scopus, Web of Science, Embase, PsycINFO, Google Scholar, published from 1998 to 2021, as well as the results of manual search of peer-reviewed publications. RESULTS: Epidemiological data on the effects of low doses of IR on neurodevelopment are quite contradictory, while data on clinical, neuropsychological and neurophysiological on cognitive and cerebral disorders, especially in the left, dominant hemisphere of the brain, are nore consistent. Cataracts (congenital - after in utero irradiation) and retinal angiopathy are more common in prenatally-exposed people and children. Astronauts, who carry out longterm space missions outside the protection of the Earth's magnetosphere, will be exposed to galactic cosmic radiation (heavy ions, protons), which leads to cerebro-ophthalmic disorders, primarily cognitive and behavioral disorders and cataracts. Interventional radiologists are a special risk group for cerebro-ophthalmic pathology - cognitivedeficits, mainly due to dysfunction of the dominant and more radiosensitive left hemisphere of the brain, andcataracts, as well as early atherosclerosis and accelerated aging. CONCLUSIONS: Results of current studies indicate the high radiosensitivity of the brain and eye in different contingents of irradiated persons. Further research is needed to clarify the nature of cerebro-ophthalmic disorders in different exposure scenarios, to determine the molecular biological mechanisms of these disorders, reliable dosimetric support and taking into account the influence of non-radiation risk factors.

BRAIN AND EYE AS POTENTIAL TARGETS FOR IONIZING RADIATION IMPACT. PART III / FEATURES MORPHOMETRIC RETINAL PARAMETERS, AMPLITUDE AND LATENCY COMPONENTS OF VISUAL EVOKED POTENTIAL IN RADIATION EXPOSED IN UTERO. / GOLOVNYI MOZOK TA ORGAN ZORU IaK POTENTsIINI MIShENI DLIa VPLYVU IONIZUIuChOGO VYPROMINIuVANNIa: ChASTYNA III ­ OSOBLYVOSTI MORFOMETRYChNYKh PARAMETRIV SITChASTOÏ OBOLONKY TA AMPLITUDA I LATENTNIST' KOMPONENTIV ZOROVYKh VYKLYKANYKh POTENTsIALIV U OPROMINENYKh VNUTRIShN'OUTROBNO OSIB.

One of the current problems of modern radiobiology is determine the characteristics of the manifestation of radiation-induced effects not only at different dose loads, but also at different stages of development of the organism. In previous reports, we have summarized available evidence that at certain ages there is a comparative acceleration of radiation-induced pathological changes in the eye and brain, and the study and assessment of the risk of possible ophthalmic and neurological pathology in remote periods after contamination of radioactive areas. Data of irradiated in utero individuals are possible on the basis of observation of the state of the visual analyzer in persons who underwent intrauterine irradiation in 1986. Therefore, a parallel study of retinal morphometric parameters, amplitude and latency of components of evoked visual potentials in irradiated in utero individuals was performed. OBJECTIVE: to evaluate the retinal morphometric parameters, amplitude and latency components of the evoked visual potentials in intrauterine irradiated persons. MATERIALS AND METHODS: The results of surveys of 16 people irradiated in utero in the aftermath of the Chornobyl disaster were used; the comparison group were residents of Kyiv of the corresponding age (25 people). Optical coherence tomography was performed on a Cirrus HD-OCT, Macular Cube 512x128 study technique was used. At the same time, the study of visual evoked potentials on the inverted pattern was performed, and occipital leads wereanalyzed. Visual evoked potentials were recorded on a reversible chess pattern (VEP) - an electrophysiological test, which is a visual response to a sharp change in image contrast when presenting a reversible image of a chessboard. RESULTS: In those irradiated in utero at the age of 22-25 years, there was a probable increase in retinal thickness in the fovea, there was a tendency to increase the thickness of the retina in the areas around the fovea. When recording visual evoked potentials on a reversible chess pattern in this group, there was a tendency to decrease the amplitudes of components (N75, P100, N145, P200) in the right and left parieto-occipital areas and asymmetric changes in latency of these components. CONCLUSIONS: Early changes of fovea recorded in OCT and decreasing amplitudes of components of visual evoked potentials on the reversible chess pattern at the age of 22 25 years may indicate a risk of development in patients irradiated in utero, early age-related macular degeneration, as well as increased risk and increased risk structures of the visual analyzer.

BRAIN AND EYE AS POTENTIAL TARGETS FOR IONIZING RADIATION IMPACT. Part І. THE CONSEQUENCES OF IRRADIATION OF THE PARTICIPANTS OF THE LIQUIDATION OF THE CHORNOBYL ACCIDENT. / GOLOVNYI MOZOK TA ORGAN ZORU IaK POTENTsIINI MIShENI DLIa VPLYVU IONIZUIuChOGO VYPROMINIuVANNIa. Chastyna I. TsEREBROOFTAL'MOLOGIChNI EFEKTY OPROMINENNIa V UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChAES.

BACKGROUND: Exposure to ionizing radiation could affect the brain and eyes leading to cognitive and vision impairment, behavior disorders and performance decrement during professional irradiation at medical radiology, includinginterventional radiological procedures, long-term space flights, and radiation accidents. OBJECTIVE: The objective was to analyze the current experimental, epidemiological, and clinical data on the radiation cerebro-ophthalmic effects. MATERIALS AND METHODS: In our analytical review peer-reviewed publications via the bibliographic and scientometric bases PubMed / MEDLINE, Scopus, Web of Science, and selected papers from the library catalog of NRCRM - theleading institution in the field of studying the medical effects of ionizing radiation - were used. RESULTS: The probable radiation-induced cerebro-ophthalmic effects in human adults comprise radiation cataracts,radiation glaucoma, radiation-induced optic neuropathy, retinopathies, angiopathies as well as specific neurocognitive deficit in the various neuropsychiatric pathology including cerebrovascular pathology and neurodegenerativediseases. Specific attention is paid to the likely stochastic nature of many of those effects. Those prenatally and inchildhood exposed are a particular target group with a higher risk for possible radiation effects and neurodegenerative diseases. CONCLUSIONS: The experimental, clinical, epidemiological, anatomical and pathophysiological rationale for visualsystem and central nervous system (CNS) radiosensitivity is given. The necessity for further international studieswith adequate dosimetric support and the follow-up medical and biophysical monitoring of high radiation riskcohorts is justified. The first part of the study currently being published presents the results of the study of theeffects of irradiation in the participants of emergency works at the Chornobyl Nuclear Power Plant (ChNPP).

DIFFUSION TENSOR MAGNETIC RESONANCE IMAGING IN EARLY DIAGNOSIS OF STRUCTURAL CHANGES IN BRAIN WHITE MATTER IN SMALL VESSEL DISEASE ASSOCIATED WITH ARTERIAL HYPERTENSION AND IONIZING RADIATION. / DYFUZIINO-TENZORNA MRT U RANNII DIAGNOSTYTsI STRUKTURNYKh ZMIN BILOÏ REChOVYNY GOLOVNOGO MOZKU PRY ASOTsIIOVANII Z ARTERIAL'NOIu GIPERTENZIIeIu TA IONIZUIuChYM VYPROMINIuVANNIaM KhVOROBI MALYKh SUDYN.

OBJECTIVE: to determine the early signs of structural changes in brain white matter in small vessel disease associated with arterial hypertension and exposure to ionizing radiation using DTI-MRI. MATERIALS AND METHODS: 45 patients (mean age (57.56 ± 6.34) years) with small vessel disease (SVD) associatedwith arterial hypertension (AH) were examined: group I - 20 patients, participants of liquidation of the accident atthe Chornobyl nuclear power plant (Chornobyl clean-up workers); group II - 25 patients not exposed to ionizingradiation. MRI was performed on an Ingenia 3T tomograph («Philips¼). The fractional anisotropy (FA) was determined in the main associative and commissural pathways, periventricular prefrontal areas (fasciculus fronto-occipitalis superior / anterior - f. FO ant., corona radiata anterior - CR ant.) and semioval centers (SC). RESULTS: No signs of cerebral cortex or brain white matter (WM) atrophy, intracerebral microhemorrhages, and widespread areas of leukoaraiosis consolidation were observed in the examined patients. In the Chornobyl clean-up workers a larger number of foci of subcortical leukoaraiosis was visualized (80 %) on MRI images including multiple -8 (40 %), > 0.5 cm - 10 (50 %), with signs of consolidation - 5 (25 %). The results of the FA analysis in semiovalcenters showed its significant decrease in the patients of groups I and II (p < 0,007), regardless of the presence orabsence of visual signs of subcortical leukoaraiosis (ScLA) (III gr.: 253-317, p < 0.00001; IV gr.: 287- 375,p < 0.001). FA indicators in f. FO ant. and CR ant. in the patients of groups I and II differed insignificantly but weresubstantially lower than controls (p < 0.05). FA was significantly lower, compared to reference levels, in visuallyunchanged f. FO ant. (0.389-0.425; p = 0.015) and CR ant. (0.335-0.403; p = 0.05). In patients with AH-associated SVD of middle age, regardless of the effects of ionizing radiation, no significant changes in FA in the mainWM associative and commissural pathways were found (p > 0.05). CONCLUSIONS: DTI-MRI allows to detect early signs of structural changes in the white matter of the brain - a significant decrease in fractional anisotropy indicators in visually unchanged periventricular and subcortical areas. Themain associative and commissural pathways of the brain remain intact in the absence of widespread consolidatedfoci of leukoaraiosis and lacunar infarctions. The negative impact of ionizing radiation on the course of SVD associated with arterial hypertension is manifested by more active processes of WM disorganization: the prevalence andtendency to the consolidation of periventricular and subcortical leukoaraiosis foci, a significant FA decrease in semioval centers.

NEUROPSYCHOBIOLOGICAL MECHANISMS OF AFFECTIVE AND COGNITIVE DISORDERS IN THE CHORNOBYL CLEAN-UP WORKERS TAKING INTO ACCOUNT THE SPECIFIC GENE POLYMORPHISMS. / NEIROPSYKhOBIOLOGIChNI MEKhANIZMY AFEKTYVNYKh I KOGNITYVNYKh ROZLADIV V UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChORNOBYL'S'KII AES Z URAKhUVANNIaM POLIMORFIZMU GENIV.

Relevance of the present work is determined by the considerable prevalence of both affective and cognitive disor-ders in the victims due to the Chornobyl accident, the pathogenesis of which is insufficiently studied.Objective is to identify the neuropsychiobiological mechanisms of the formation of the remote affective and cog-nitive disorders following exposure to ionizing radiation taking into account the specific gene polymorphisms.Design, object and methods of research. The retrospective and prospective cohort study with the external andinternal control groups. The randomized sample of the male participants in liquidation of the consequences of theaccident (Chornobyl clean-up workers, liquidators) at the Chornobyl nuclear power plant (ChNPP) in 1986-1987(n = 198) recruited from the Clinico-epidemiological registry (CER) of NRCRM aged 39-87 (M ± SD: 60.0-8.5 years)with the external irradiation dose ranged 0.6-5900.0 mSv (M ± SD: 456.0 ± 760.0 mSv) was examined. The compar-ison group (n = 110) consisted of the unexposed patients of the Radiation Psychoneurology Department with thecorresponding age and sex (the external control group). The internal control group included the liquidators irradi-ated at doses < 50.0 mSv (n = 42). The standard diagnostic neuropsychiatric scales, psychodiagnostic questionnairesand tests, neuropsychological methods (including the Wechsler Adult Intelligence Scale (WAIS) with premorbid IQ(pre-IQ) assessment), neuropsychiatric and psychophysiological methods (quantitative EEG (qEEG) and the audito-ry cognitive evoked potentials (Event-Related Potentials, ERP) were applied. The genotypes of the serotonin trans-porter gene SLC6A4 were determined by the 5_HTTLPR and rs25531 polymorphisms. The methods of descriptive and vari-ation statistics, non-parametric criteria, regression-correlation analysis, survival analysis by Kaplan - Meier and riskanalysis were used.Results. Cerebrovascular diseases, organic mental and depressive disorders, mainly of radiation-stress-relatednature, prevail among the liquidators. The overall risk of neuropsychiatric pathology increases (Pv < 0.001) with theirradiation dose. The verbal memory and learning are impaired, as well as the full IQ is reduced at the expense of theverbal one. The frequency of both mild cognitive impairment and dementia is risen. The cognitive impairment atdoses > 0.3 Sv is dose-dependent (r = 0.4-0.7; p = 0.03-0.003). Affective disorders (depression) and neurocogni-tive deficit are more severe at higher doses of irradiation (> 50 mSv). In the left posterior temporal region(Wernicke's area) the qEEG indices changes become dose-dependent at doses greater than 0.25-0.3 Sv. The dis-turbed brain information processes lateralized to the Wernicke's area are observed even at doses > 50 mSv. The car-riers of intermediate and low-level genotypes (LА/S, LА/LG, LG/LG, LG/S, S/S) of the serotonin transporter gene SLC6A4have more depressive disorders, especially severe ones, and tend to have more frequent and severe cognitive andstress-related disorders.The debut of depressive disorders in the carriers of the intermediate and low-activity genotypes occurs much earli-er (Log-Rank Test = 4.43, p = 0.035) in comparison with the carriers of the high-performance genotype LА/ LА.Conclusions. The radiation-induced dysfunction of the cortico-limbic system in the left dominant hemisphere ofthe human brain with a specific involvement of the hippocampus is considered to be the key cerebral basis of post-radiation organic brain damage. The association of genotypes by 5_HTTLPR and rs25531 polymorphisms of the SLC6A4gene with affective and cognitive disorders suggests the presence of neuropsychobiological features of these dis-orders associated with ionizing radiation depending on the certain gene polymorphisms.

Cognitive evoked potentials P300 after radiation exposure. / KOGNITYVNI VYKLYKANI POTENTsIALY P300 PISLIa OPROMINENNIa.

OBJECTIVE: The study was aimed at evaluating features of brain information processes and cognitive functioning in the remote period after irradiation due to the Chornobyl accident by using cognitive evoked potentials P300. MATERIALS AND METHODS: The study included 128 people, 112 male Chornobyl clean up workers in 1986-1987 with the records of radiation doses available in Clinical and Epidemiological Registry (CER) of State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine¼ (NRCRM) (study group) and 16 unexposed persons due to the Chornobyl disaster (control group). At the time of the survey the average age of clean up workers (M ± SD) was (57.3 ± 5.9) years, range 44-65 years, and of unex posed persons was (57.3 ± 6.5) years, range 44-65 years. Radiation doses were within the range 0.0002-1.23 Gy, with the arithmetic mean dose (M ± SD) of (0.2 ± 0.2) Gy and the geometric mean dose of 0.1 Gy. RESULTS: The radiocerebral effect in the projection of the left posterior superior temporal gyrus (Wernicke's area) proportionally to the radiation dose with the possible threshold of 0.05 Gy of total irradiation was revealed, with increasing radiation dose cognitive component P300 amplitude reduces and its latency period (LP) increases, espe cially at doses > 0.3-0.5 Gy. At doses > 0.5 Gy the functional relationship with the radiation dose for LP P300 increase in the projection of Wernicke's area (r = 0.9; p = 0.027) has been found. CONCLUSIONS: The neurophysiological features detected are fully consistent with hypotheses both on radiosensitiv ity of human central nervous system and accelerated aging of the brain under the influence of small doses of ioniz ing radiation, and have questioned the feasibility of long term manned space flights (including Mars) until the development of adequate radiation hygiene standardization for space crews and invention of means for radiation protection of space flights. Further dynamic clinical and neurophysiological monitoring of individuals exposed to ionizing radiation is necessary. To identify the neurophysiological biological markers of ionizing radiation further international researches with adequate dosimetry support are needed.