Comparative analysis of resting-state EEG functional connectivity in depression and obsessive-compulsive disorder.

Major depressive disorder (MDD) and obsessive-compulsive disorder (OCD) are psychiatric disorders that often co-occur. We aimed to investigate whether their high comorbidity could be traced not only by clinical manifestations, but also at the level of functional brain activity. In this paper, we examined the differences in functional connectivity (FC) at the whole-brain level and within the default mode network (DMN). Resting-state EEG was obtained from 43 controls, 26 OCD patients, and 34 MDD patients. FC was analyzed between 68 cortical sources, and between-group differences in the 4-30 Hz range were assessed via the Network Based Statistic method. The strength of DMN intra-connectivity was compared between groups in the theta, alpha and beta frequency bands. A cluster of 67 connections distinguished the OCD, MDD and control groups. The majority of the connections, 8 of which correlated with depressive symptom severity, were found to be weaker in the clinical groups. Only 3 connections differed between the clinical groups, and one of them correlated with OCD severity. The DMN strength was reduced in the clinical groups in the alpha and beta bands. It can be concluded that the high comorbidity of OCD and MDD can be traced at the level of FC.

Electrophysiological signatures of spelling sensitivity development from primary school age to adulthood.

Recognizing spelling errors is important for correct writing and reading, and develops over an extended period. The neural bases of the development of orthographic sensitivity remain poorly understood. We investigated event-related potentials (ERPs) associated with spelling error recognition when performing the orthographic decision task with correctly spelled and misspelled words in children aged 8-10 years old, early adolescents aged 11-14 years old, and adults. Spelling processing in adults included an early stage associated with the initial recognition of conflict between orthography and phonology (reflected in the N400 time window) and a later stage (reflected in the P600 time window) related to re-checking the spelling. In children 8-10 years old, there were no differences in ERPs to correct and misspelled words; in addition, their behavioral scores were worse than those of early adolescents, implying that the ability to quickly recognize the correct spelling is just beginning to develop at this age. In early adolescents, spelling recognition was reflected only at the later stage, corresponding to the P600 component. At the behavioral level, they were worse than adults at recognizing misspelled words. Our data suggest that orthographic sensitivity can develop beyond 14 years.

The Dynamics of Resting-State EEG and Salivary Trace Elements in Patients with Obsessive-Compulsive Disorder.

The study of salivary microelements and their neurophysiological and behavioral correlates in patients with obsessive-compulsive disorder (OCD) is a pressing issue in modern psychiatry, which, however, lacks adequate research at this time. In this study, we tested the dynamics of behavioral parameters, resting-state electroencephalogram (EEG), and salivary iron, copper, manganese, magnesium, and zinc in 30 healthy volunteers and 30 individuals with OCD before and after an emotional antisaccade task. The eye-movement data served as a measure of behavioral performance. Our research revealed consistently higher manganese concentrations in the OCD group compared to healthy volunteers associated with a higher EEG ratio of amplitude transformation and symptom severity. The dynamics of salivary microelements and resting-state EEG, possibly influenced by cognitive and emotional load during the anticsaccade task, differed between groups. In healthy volunteers, there was a decrease in salivary iron level with an increase in high-frequency power spectral density of EEG. The OCD group showed a decrease in salivary copper with an increased Hjorth mobility of EEG.

Long-range temporal correlations in resting state alpha oscillations in major depressive disorder and obsessive-compulsive disorder.

Introduction: Mental disorders are a significant concern in contemporary society, with a pressing need to identify biological markers. Long-range temporal correlations (LRTC) of brain rhythms have been widespread in clinical cohort studies, especially in major depressive disorder (MDD). However, research on LRTC in obsessive-compulsive disorder (OCD) is severely limited. Given the high co-occurrence of OCD and MDD, we conducted a comparative LRTC investigation. We assumed that the LRTC patterns will allow us to compare measures of brain cortical balance of excitation and inhibition in OCD and MDD, which will be useful in the area of differential diagnosis. Methods: In this study, we used the 64-channel resting state EEG of 29 MDD participants, 26 OCD participants, and a control group of 37 volunteers. Detrended fluctuation analyzes was used to assess LRTC. Results: Our results indicate that all scaling exponents of the three subject groups exhibited persistent LRTC of EEG oscillations. There was a tendency for LRTC to be higher in disorders than in controls, but statistically significant differences were found between the OCD and control groups in the entire frontal and left parietal occipital areas, and between the MDD and OCD groups in the middle and right frontal areas. Discussion: We believe that these results indicate abnormalities in the inhibitory and excitatory neurotransmitter systems, predominantly affecting areas related to executive functions.

Detecting cognitive traits and occupational proficiency using EEG and statistical inference.

Machine learning (ML) is widely used in classification tasks aimed at detecting various cognitive states or neurological diseases using noninvasive electroencephalogram (EEG) time series. However, successfully detecting specific cognitive skills in a healthy population, independent of subject, remains challenging. This study compared the subject-independent classification performance of three different pipelines: supervised and Riemann projections with logistic regression and handcrafted power spectral features with light gradient boosting machine (LightGBM). 128-channel EEGs were recorded from 26 healthy volunteers while they solved arithmetic, logical, and verbal tasks. The participants were divided into two groups based on their higher education and occupation: specialists in mathematics and humanities. The balanced accuracy of the education type was significantly above chance for all pipelines: 0.84-0.89, 0.85-0.88, and 0.86-0.88 for each type of task, respectively. All three pipelines allowed us to distinguish mathematical proficiency based on learning experience with different trade-offs between performance and explainability. Our results suggest that ML approaches could also be effective for recognizing individual cognitive traits using EEG.

Temporal dynamics of autonomic nervous system responses under cognitive-emotional workload in obsessive-compulsive disorder.

Dysregulation of the autonomic nervous system (ANS) is commonly observed in various mental disorders, particularly when individuals engage in prolonged cognitive-emotional tasks that require ANS adjustment to workload. Although the understanding of the temporal dynamics of sympathetic and parasympathetic tones in obsessive-compulsive disorder (OCD) is limited, analyzing ANS reactions to cognitive-emotional workload could provide valuable insights into one of the underlying causes of OCD. This study investigated the temporal dynamics of heart rate (HR) and pupil area (PA) while participants with OCD and healthy volunteers solved antisaccade tasks, with affective pictures serving as central fixation stimuli. The data of 31 individuals with OCD and 30 healthy volunteers were included in the study, comprising three separate blocks, each lasting approximately 8 min. The results revealed an increase in sympathetic tone in the OCD group, with the most noticeable rise occurring during the middle part of each block, particularly during the presentation of negative stimuli. Healthy volunteers demonstrated adaptive temporal dynamics of HR and PA from the first block to the last block of tasks, whereas individuals with OCD exhibited fewer changes over time, suggesting a reduced adaptation of the ANS sympathetic tone to cognitive-emotional workload in OCD.

Increased error rate and delayed response to negative emotional stimuli in antisaccade task in obsessive-compulsive disorder.

Ample evidence links impaired inhibitory control, attentional distortions, emotional dysregulation, and obsessive-compulsive disorder (OCD). However, it remains unclear what underlies the deficit that triggers the OCD cycle. The present study used an antisaccade paradigm with emotional valences to compare eye movement patterns reflecting inhibitory control and attention switching in OCD and healthy control groups. Thirty-two patients with OCD and thirty healthy controls performed the antisaccade task with neutral, positive, and negative visual images served as fixation stimuli. Presentation of the fixation stimulus overlapped with target stimuli appearance for 200 ms. The OCD group showed more errors to negative stimuli than the control group and they also performed antisaccades more slowly to negative and neutral stimuli than positive ones. Other patterns, including mean gaze velocity of correct antisaccades did not differ between groups. The mean gaze velocity of correct antisaccades was higher for negative and positive stimuli than for neutral stimuli in both groups. The peak velocity parameter did not show any differences either between groups or between valences. The findings support a hypothesis that an attentional bias toward negative stimuli interferes with inhibitory control in OCD.

Abnormal spectral and scale-free properties of resting-state EEG in girls with Rett syndrome.

Spontaneous EEG contains important information about neuronal network properties that is valuable for understanding different neurological and psychiatric conditions. Rett syndrome (RTT) is a rare neurodevelopmental disorder, caused by mutation in the MECP2 gene. RTT is characterized by severe motor impairments that prevent adequate assessment of cognitive functions. Here we probe EEG parameters obtained in no visual input condition from a 28-channels system in 23 patients with Rett Syndrome and 38 their typically developing peers aged 3-17 years old. Confirming previous results, RTT showed a fronto-central theta power (4-6.25 Hz) increase that correlates with a progression of the disease. Alpha power (6.75-11.75 Hz) across multiple regions was, on the contrary, decreased in RTT, also corresponding to general background slowing reported previously. Among novel results we found an increase in gamma power (31-39.5 Hz) across frontal, central and temporal electrodes, suggesting elevated excitation/inhibition ratio. Long-range temporal correlation measured by detrended fluctuation analysis within 6-13 Hz was also increased, pointing to a more predictable oscillation pattern in RTT. Overall measured EEG parameters allow to differentiate groups with high accuracy, ROC AUC value of 0.92 ± 0.08, indicating clinical relevance.

Top-down modulation of brain responses in spelling error recognition.

The task being undertaken can influence orthographic, phonological and semantic processes. In linguistic research, two tasks are most often used: a task requiring a decision in relation to the presented word and a passive reading task which does not require a decision regarding the presented word. The results of studies using these different tasks are not always consistent. This study aimed to explore brain responses associated with the process of recognition of spelling errors, as well as the influence of the task on this process. Event-related potentials (ERPs) were recorded in 40 adults during an orthographic decision task to determine correctly spelled words and words written with errors that did not change the phonology and during the passive reading. During spelling recognition, the early stages up to 100 ms after the stimulus were automatic and did not depend on the requirements of the task. The amplitude of the N1 component (90-160 ms) was greater in the orthographic decision task, but did not depend on the correct spelling of the word. Late word recognition after 350-500 ms was task dependent, but spelling effects were similar across the two tasks: misspelled words evoked an increase in the amplitude of the N400 component related to lexical and semantic processing regardless of the task. In addition, the orthographic decision task modulated spelling effects, this was reflected in an increase in the amplitude of the P2 component (180-260 ms) for correctly spelled words compared with misspelled words. Thus, our results show that spelling recognition involves general lexico-semantic processes independent of the task. Simultaneously, the orthographic decision task modulates the spelling-specific processes necessary to quickly detect conflicts between orthographic and phonological representations of words in memory.

Salivary Antioxidant Capacity and Magnesium in Generalized Anxiety Disorder.

Generalized anxiety disorder (GAD) is a prevalent disorder. The search for biomarkers may contribute to new knowledge about molecular pathogenesis and treatment. Since oxidative stress and micronutrient imbalance play a key role in the development of mental disorders, we aimed to study salivary antioxidant capacity and magnesium in patients with GAD in an anxiety model of solving problems with increasing complexity. The study subgroup consisted of 15 patients with GAD, and 17 healthy volunteers of the same age made up the control subgroup. Participants took a test with six levels of difficulty, which included false feedback. In this test, the participants were asked to remember the colors of balloons and react when the color changed. The reaction time, the number of correct answers, as well as biochemical parameters such as the antioxidant capacity of saliva and salivary magnesium, were assessed. There was no difference in the results of the quest between the subgroups; however, anxious participants spent more time at the moment of experimental frustration due to incorrect feedback and additional negative psycho-emotional load. Antioxidant capacity did not differ between the subgroups both before and after the experimental session. Average antioxidant capacity also did not change significantly at the endpoint of the experiment. However, the endpoint antioxidant capacity correlated negatively with the reaction time in anxious patients in the second block (where the false feedback as a frustrating factor appeared). Magnesium was initially significantly higher in the group of anxious participants and decreased at the experiment endpoint; in healthy patients, there were no changes in salivary magnesium at the endpoint. In conclusion, the compensatory potential of oxidative metabolism and magnesium in patients with GAD was spent with additional psycho-emotional stress, in contrast to healthy individuals, but it was sufficient to avoid exhaustion during experimental frustrating exposure.

Frequency Effects on Spelling Error Recognition: An ERP Study.

Spelling errors are ubiquitous in all writing systems. Most studies exploring spelling errors focused on the phonological plausibility of errors. However, unlike typical pseudohomophones, spelling errors occur in naturally produced written language. We investigated the time course of recognition of the most frequent orthographic errors in Russian (error in an unstressed vowel in the root) and the effect of word frequency on this process. During event-related potentials (ERP) recording, 26 native Russian speakers silently read high-frequency correctly spelled words, low-frequency correctly spelled words, high-frequency words with errors, and low-frequency words with errors. The amplitude of P200 was more positive for correctly spelled words than for misspelled words and did not depend on the frequency of the words. In addition, in the 350-500-ms time window, we found a more negative response for misspelled words than for correctly spelled words in parietal-temporal-occipital regions regardless of word frequency. Considering our results in the context of a dual-route model, we concluded that recognizing misspelled high-frequency and low-frequency words involves common orthographic and phonological processes associated with P200 and N400 components such as whole word orthography processing and activation of phonological representations correspondingly. However, at the 500-700 ms stage (associated with lexical-semantic access in our study), error recognition depends on the word frequency. One possible explanation for these differences could be that at the 500-700 ms stage recognition of high-frequency misspelled and correctly spelled words shifts from phonological to orthographic processes, while low-frequency misspelled words are accompanied by more prolonged phonological activation. We believe these processes may be associated with different ERP components P300 and N400, reflecting a temporal overlap between categorization processes based on orthographic properties for high-frequency words and phonological processes for low-frequency words. Therefore, our results complement existing reading models and demonstrate that the neuronal underpinnings of spelling error recognition during reading may depend on word frequency.

Electrophysiological and Behavioral Evidence for Hyper- and Hyposensitivity in Rare Genetic Syndromes Associated with Autism.

Our study reviewed abnormalities in spontaneous, as well as event-related, brain activity in syndromes with a known genetic underpinning that are associated with autistic symptomatology. Based on behavioral and neurophysiological evidence, we tentatively subdivided the syndromes on primarily hyper-sensitive (Fragile X, Angelman) and hypo-sensitive (Phelan-McDermid, Rett, Tuberous Sclerosis, Neurofibromatosis 1), pointing to the way of segregation of heterogeneous idiopathic ASD, that includes both hyper-sensitive and hypo-sensitive individuals. This segmentation links abnormalities in different genes, such as FMR1, UBE3A, GABRB3, GABRA5, GABRG3, SHANK3, MECP2, TSC1, TSC2, and NF1, that are causative to the above-mentioned syndromes and associated with synaptic transmission and cell growth, as well as with translational and transcriptional regulation and with sensory sensitivity. Excitation/inhibition imbalance related to GABAergic signaling, and the interplay of tonic and phasic inhibition in different brain regions might underlie this relationship. However, more research is needed. As most genetic syndromes are very rare, future investigations in this field will benefit from multi-site collaboration with a common protocol for electrophysiological and event-related potential (EEG/ERP) research that should include an investigation into all modalities and stages of sensory processing, as well as potential biomarkers of GABAergic signaling (such as 40-Hz ASSR).

Implicit auditory perception of local and global irregularities in passive listening condition.

The auditory system detects differences in sounds at an implicit level, but data on this difference might not be sufficient to make explicit discrimination. The biomarkers of implicit auditory memory of ambiguous stimuli could shed light on unconscious auditory processing and implicit auditory learning. Mismatch negativity (MMN) and P3a, components of event-related potentials (ERPs) reflecting stimuli discrimination without direct attention, were previously detected in response to the local (short-term) irregularity in the auditory sequence even in an unconscious state. At the same time, P3b was elicited only in case of direct attention in response to the global (long-term) irregularity. In this study, we applied the local-global auditory paradigm to obtain possible electrophysiological signatures of implicit detection of hardly distinguishable auditory stimuli. ERPs were recorded from 20 healthy volunteers during active discrimination of deviant sounds in the old-ball sequence and passive listening of the same sounds in the sequence with local-global irregularity. The discrimination task consisted of two blocks with different deviant sounds targeted to respond. The sound discrimination accuracy was at an average of 40%, implying the difficulty of explicit sound recognition. Comparing ERPs to standard and deviant sounds, we found posterior negativity in ERP around 450-600 ms in response to targeted deviant sounds. MMN was significant only in response to non-target deviants. In the passive local-global paradigm, we observed an anterior positivity (284-412 ms), compatible with P3a, in response to a violation of local regularity. Violation of global regularity elicited an anterior negative response (228-586 ms), resembling the N400 component of ERPs. Importantly, the other indexes of auditory discrimination, such as MMN and P3b, were insignificant in ERPs to both regularity violations. The observed P3a and N400 components of ERPs may reflect prediction error signals in the implicit perception of sound patterns even if behavioral recognition was poor.

The ages of zone of proximal development for retrospective time assessment and anticipation of time event.

From childhood to adulthood, an individual's ability to estimate and anticipate the timing of events changes continuously. This study investigated the ability of 287 children aged 5-14 years to estimate the duration of prior events and anticipate the timing of future events for determination of the age at which children improve their timing skills. The Luria neuropsychological assessment battery and the Wechsler Intelligence Scale for Children (WISC-IV) were applied to find correlations between timing skills and the development of cognitive functions. The findings demonstrated that retrospective estimation of duration has a zone of proximal development in children between the ages of six to eight; in these children, the accuracy of time assessment significantly improved after receiving the prompt. However, improvement in time estimation was significantly lower in those children who achieved lower results in the attention and memory tests and demonstrated reduced spatial and verbal reasoning skills. The zone of proximal development for the ability to anticipate the timing of future events was demonstrated in children between the ages of nine to eleven years. The improvement of time anticipation was negatively correlated with the number of mistakes made during the dynamic praxis test.

A Toolbox and Crowdsourcing Platform for Automatic Labeling of Independent Components in Electroencephalography.

Independent Component Analysis (ICA) is a conventional approach to exclude non-brain signals such as eye movements and muscle artifacts from electroencephalography (EEG). A rejection of independent components (ICs) is usually performed in semiautomatic mode and requires experts' involvement. As also revealed by our study, experts' opinions about the nature of a component often disagree, highlighting the need to develop a robust and sustainable automatic system for EEG ICs classification. The current article presents a toolbox and crowdsourcing platform for Automatic Labeling of Independent Components in Electroencephalography (ALICE) available via link http://alice.adase.org/. The ALICE toolbox aims to build a sustainable algorithm to remove artifacts and find specific patterns in EEG signals using ICA decomposition based on accumulated experts' knowledge. The difference from previous toolboxes is that the ALICE project will accumulate different benchmarks based on crowdsourced visual labeling of ICs collected from publicly available and in-house EEG recordings. The choice of labeling is based on the estimation of IC time-series, IC amplitude topography, and spectral power distribution. The platform allows supervised machine learning (ML) model training and re-training on available data subsamples for better performance in specific tasks (i.e., movement artifact detection in healthy or autistic children). Also, current research implements the novel strategy for consentient labeling of ICs by several experts. The provided baseline model could detect noisy IC and components related to the functional brain oscillations such as alpha and mu rhythm. The ALICE project implies the creation and constant replenishment of the IC database, which will improve ML algorithms for automatic labeling and extraction of non-brain signals from EEG. The toolbox and current dataset are open-source and freely available to the researcher community.

The Deficit of Multimodal Perception of Congruent and Non-Congruent Fearful Expressions in Patients with Schizophrenia: The ERP Study.

Emotional dysfunction, including flat affect and emotional perception deficits, is a specific symptom of schizophrenia disorder. We used a modified multimodal odd-ball paradigm with fearful facial expressions accompanied by congruent and non-congruent emotional vocalizations (sounds of women screaming and laughing) to investigate the impairment of emotional perception and reactions to other people's emotions in schizophrenia. We compared subjective ratings of emotional state and event-related potentials (EPPs) in response to congruent and non-congruent stimuli in patients with schizophrenia and healthy controls. The results showed the altered multimodal perception of fearful stimuli in patients with schizophrenia. The amplitude of N50 was significantly higher for non-congruent stimuli than congruent ones in the control group and did not differ in patients. The P100 and N200 amplitudes were higher in response to non-congruent stimuli in patients than in controls, implying impaired sensory gating in schizophrenia. The observed decrease of P3a and P3b amplitudes in patients could be associated with less attention, less emotional arousal, or incorrect interpretation of emotional valence, as patients differed from healthy controls in the emotion scores of non-congruent stimuli. The difficulties in identifying the incoherence of facial and audial components of emotional expression could be significant in understanding the psychopathology of schizophrenia.

Cross-frequency phase coupling of brain oscillations and relevance attribution as saliency detection in abstract reasoning.

reasoning is associated with the ability to detect relations among objects, ideas, events. It underlies the understanding of other individuals' thoughts and intentions. In natural settings, individuals have to infer relevant associations that have proven to be reliable or precise predictors. Salience theory suggests that the attribution of meaning to stimulus depends on their contingency, saliency, and relevance to adaptation. So far, subjective estimates of relevance have mostly been explored in motivation and implicit learning. Mechanisms underlying formation of associations in abstract thinking with regard to their subjective relevance, or salience, are not clear. Applying novel computational methods, we investigated relevance detection in categorization tasks in 17 healthy individuals. Two models of relevance detection were developed: a conventional one with nouns from the same semantic category, an aberrant one based on an insignificant common feature. Control condition introduced non-related words. The participants were to detect either a relevant principle or an insignificant feature to group presented words. In control condition they inferred that the stimuli were irrelevant to any grouping idea. Cross-frequency phase coupling analysis revealed statistically distinct patterns of synchronization representing search and decision in the models of normal and aberrant relevance detection. Significantly distinct frontotemporal functional networks with central and parietal components in the theta and alpha frequency bands may reflect differences in relevance detection.

Variance and Scale-Free Properties of Resting-State Blood Oxygenation Level-Dependent Signal After Fear Memory Acquisition and Extinction.

Recently, the dynamic properties of brain activity rather than its stationary values have attracted more interest in clinical applications. It has been shown that brain signals exhibit scale-free dynamics or long-range temporal correlations (LRTC) that differ between rest and cognitive tasks in healthy controls and clinical groups. Little is known about how fear-inducing tasks may influence dispersion and the LRTC of subsequent resting-state brain activity. In this study, we aimed to explore the changes in the variance and scale-free properties of the brain's blood oxygenation level-dependent (BOLD) signal during the resting-state sessions before and after fear learning and fear memory extinction. During a 1-h break between magnetic resonance imaging (MRI) scanning, 23 healthy, right-handed volunteers experienced a fear extinction procedure, followed by Pavlovian fear conditioning that included partial reinforcement using mild electrical stimulation. We extracted the average time course of the BOLD signal from 245 regions of interest (ROIs) taken from the resting-state functional atlas. The variance of the BOLD signal and the Hurst exponent (H), which reflects the scale-free dynamic, were compared in the resting states before and after fear learning and fear memory extinction. After fear extinction, six ROIs showed a difference in H at the uncorrected level of significance, including areas associated with fear processing. H decreased during fear extinction but then became higher than before fear learning, specifically in areas related to the fear extinction network (FEN). However, activity in the other ROIs restored the H to its initial level. The variance of the BOLD signal in six ROIs demonstrated a significant increase from initial rest to the post-task rest. A limited number of ROIs showed changes in both H and variance. Our results imply that the variability and scale-free properties of the BOLD signal might serve as additional indicators of changes in spontaneous brain activity related to recent experience.

Brain Oscillatory Activity during Tactile Stimulation Correlates with Cortical Thickness of Intact Areas and Predicts Outcome in Post-Traumatic Comatose Patients.

In this study, we have reported a correlation between structural brain changes and electroencephalography (EEG) in response to tactile stimulation in ten comatose patients after severe traumatic brain injury (TBI). Structural morphometry showed a decrease in whole-brain cortical thickness, cortical gray matter volume, and subcortical structures in ten comatose patients compared to fifteen healthy controls. The observed decrease in gray matter volume indicated brain atrophy in coma patients induced by TBI. In resting-state EEG, the power of slow-wave activity was significantly higher (2-6 Hz), and the power of alpha and beta rhythms was lower in coma patients than in controls. During tactile stimulation, coma patients' theta rhythm power significantly decreased compared to that in the resting state. This decrease was not observed in the control group and correlated positively with better coma outcome and the volume of whole-brain gray matter, the right putamen, and the insula. It correlated negatively with the volume of damaged brain tissue. During tactile stimulation, an increase in beta rhythm power correlated with the thickness of patients' somatosensory cortex. Our results showed that slow-wave desynchronization, as a nonspecific response to tactile stimulation, may serve as a sensitive index of coma outcome and morphometric changes after brain injury.

Retinoprotective Effect of 2-Ethyl-3-hydroxy-6-methylpyridine Nicotinate.

An important task of pharmacology is to find effective agents to improve retinal microcirculation and resistance to ischemia. The purpose of the study is to pharmacologically evaluate the retinoprotective effect of 2-ethyl-3-hydroxy-6-methylpyridine nicotinate in a rat model of retinal ischemia-reperfusion. A retinal ischemia-reperfusion model was used, in which an increase in intraocular pressure (IOP) to 110 mmHg was carried out within 30 min. The retinoprotective effect of 2-ethyl-3-hydroxy-6-methylpyridine nicotinate at a dose of 3.8 mg/kg, in comparison with nicotinic acid at a dose of 2 mg/kg and emoxipine at a dose of 2 mg/kg, was estimated by the changes in the eye fundus during ophthalmoscopy, the retinal microcirculation level with laser Doppler flowmetry (LDF), and electroretinography (ERG) after 72 h of reperfusion. The use of 2-ethyl-3-hydroxy-6-methylpyridine nicotinate prevented the development of ischemic injuries in the fundus and led to an increase in the retinal microcirculation level to 747 (median) (lower and upper quartiles: 693;760) perfusion units (p = 0.0002) in comparison with the group that underwent no treatment. In the group with the studied substance, the b-wave amplitude increased significantly (p = 0.0022), and the b/a coefficient increased reliably (p = 0.0002) in comparison with the group with no treatment. Thus, 2-ethyl-3-hydroxy-6-methylpyridine nicotinate has established itself as a potential retinoprotector.