[Dual-tasks is an indicator of cognitive deficit specificity in patients after traumatic brain injury]. / Dvoinye zadachi - indikator osobennostei kognitivnogo defitsita u patsientov posle cherepno-mozgovoi travmy.

AIM: To investigate the brain activity impairment in patients after traumatic brain injury (TBI) during dual-tasks in comparison with the normal ranges. MATERIAL AND METHODS: Electroencephalographic (EEG), stabilographic and clinical study was performed in 9 patients (mean age 25±1.2 years) for up to 3 months after a mild traumatic brain injury (TBI) in comparison with 18 healthy subjects (mean age 26.6±0.07 years). All participants of the study performed two motor tasks and two cognitive tasks that were carried out in isolation, and simultaneously (dual-tasks). RESULTS: Clinical examination revealed cognitive deficit in TBI patients with safety of postural control. The EEG data demonstrated a pronounced decrease in the coherence for slow rhythms in the left hemisphere and frontal areas during cognitive tasks performance. In healthy subjects, an increase in EEG coherence for slow spectral bands was observed in these brain areas. CONCLUSION: Dual-tasks are an informative method for estimation of predominant cognitive deficit after mild TBI and the use of this approach for rehabilitation contributes to positive clinical dynamics.

[Regression of post-stroke aphasia and associated non-speech syndromes caused by a course of restorative treatment including intensive speech therapy]. / Regress postinsul'tnoi afazii i soputstvuiushchikh nerechevykh sindromov, obuslovlennyi kursom vosstanovitel'nogo lecheniia, vkliuchaiushchim intensivnuiu rechevuiu terapiiu.

AIM: To analyze clinical and fMRI indicators related with the therapeutic effectiveness of complex restorative treatment including intensive speech therapy in various clinical forms and severity of the aphasia syndrome. MATERIAL AND METHODS: The study included 40 right-handed patients with aphasia syndrome after the first hemispheric ischemic stroke. Patients were studied 3 month after disease onset. Patients were examined before and after rehabilitation treatment (4.7 weeks) including intensive speech therapy (15 hours of exercise per week). Evaluation of the effectiveness of treatment was carried out based on the dynamics of the results of neuropsychological, neurological and neuroimaging examinations of patients before and after treatment. The degree of recovery of speech and non-speech cognitive functions (based on the 10-point cognitive assessment, the dynamics of focal neurological deficit (NIHSS) and functional recovery of patients (Barthel index, modified Rankin scale) were assessed. Neuroimaging methods included structural MRI and two fMRI methods: fMRI resting state and fMRI equivalent of the evoked potentials of mismatch negativity (HP), using a sequence of standard and deviant sounds (Russian phonemes) to obtain the equivalent of HP. For statistical calculations, the program in Python version 3.6.0 was used. RESULTS: The maximum efficacy of restorative treatment (≥15% improvement in the scores of 10-point quantifying) was detected in 28 (70%) cases: 18 patients with initially severe and 10 patients with moderate aphasia, regardless of the clinical form of aphasia, and 11 patients with isolated sensory aphasia. Regression of speech and non-speech cognitive impairments in sensory aphasia was accompanied by a pronounced activation of intact speech homologues of the right hemisphere and the appearance of a small temporal and parietal region, which was small in volume and weak in intensity, similar in the localization to the norm. Regardless of the clinical form of aphasia, maximum therapeutic efficacy was accompanied by a reorganization of the speech neuronal rest network, which includes enhancement of both intra- and interhemispheric functional connectivity, with the predominance of amplification of the intra-hemispheric interactions of the posterior speech zones to the left while reducing their interhemispheric connectivity. Significant improvement in motor and sensory functions was detected in 9 (22%) patients with moderate contralateral spastic hemiparesis (p≤0.00) and did not correlate with the degree of regression of speech and non-speech focal cognitive impairments. A slight therapeutic effect was observed in 12 (30%) patients with mild to moderate speech and non-speech cognitive impairment. This effect was not correlated with a specific clinical form of aphasia. CONCLUSION: The maximum effectiveness of the 4.7 week restorative inpatient treatment, including intensive speech therapy (15 sessions per week), was obtained mainly with severe aphasia, and also with a specific clinical form - isolated sensory aphasia. According to the fMRI data, various compensatory reorganization of the neural speech network was detected, which probably reflects post stroke neuroplasticity associated with both the severity of aphasia and its specific clinical form.

[The prognosis for post-stroke aphasia]. / Prognoz postinsul'tnoi afazii.

AIM: To determine risk factors and factors of favorable prognosis for regression of post-stroke aphasia in the early recovery period of ischemic stroke (IS). MATERIAL AND METHODS: A cohort study was undertaken with 40 patients with different clinical forms of aphasia. The duration of study was 3-4 months of the disease. The regression of speech and non-speech cognitive impairment was assessed by the Method of a 10-point evaluation of higher mental functions. The method involves a comprehensive assessment of all mental functions with more than 90 subtests at the beginning and at the end of rehabilitation course and the calculation of the difference in the scoring of each mental function as a measure of treatment efficacy. Using logistic regression and odds ratio estimation, significance of the influence and the prognostic relationship of symptoms related to IS, and a number of biological and social factors (sex, age, and education) were studied. RESULTS: An independent prognostic value for the aphasia regression on the third month of disease has the severity of neurologic symptomatology (NIHSS score) for the first day of stroke (OR 3,27 95% CI 1,02-9,77) and the third month of the disease (p=0,005, OR 4,6, 95% CI [1,39-15,11]) and the decrease in daily activity assessed by the total score of the Barthel index (p=0,004, OR 3,92, 95% CI [1,01-15,21]). A number of MRI signs (localization of post-stroke changes in the left angular gyrus, frontal-temporal region and focal volume) had a significant effect on the dynamics of non-verbal cognitive impairment. Neuropsychological examination revealed a significant improvement of speech in patients with initially severe forms of aphasias, in particular, sensory and sensorimotor. A direct relationship between age and certain clinical forms of aphasia as well as a significant positive effect of duration (ß=1,91, p≤0,01) and level of education (ß=1,68, p≤0,007) on aphasia regression were determined. CONCLUSION: The severity of neurologic symptoms, in particular motor and sensory deficits, both in the acute and in the recovery period of the disease is one of the pathogenetic factors worsening the processes of functional reorganization of neuronal speech networks. The positive dynamics of the recovery of speech function is associated with the initial severity and clinical form of aphasia. The level and duration of education are related to factors positively affecting post-stroke neuroplasticity.

Neural mechanisms of two different verbal working memory tasks: A VLSM study.

Currently, a distributed bilateral network of frontal-parietal areas is regarded as the neural substrate of working memory (WM), with the verbal WM network being more left-lateralized. This conclusion is based primarily on functional magnetic resonance imaging (fMRI) data that provides correlational evidence for brain regions involved in a task. However, fMRI cannot differentiate the areas that are fundamentally required for performing a task. These data can only come from brain-injured individuals who fail the task after the loss of specific brain areas. In addition to the lack of complimentary data, is the issue of the variety in the WM tasks used to assess verbal WM. When different tasks are assumed to measure the same behavior, this may mask the contributions of different brain regions. Here, we investigated the neural substrate of WM by using voxel-based lesion symptom mapping (VLSM) in 49 individuals with stroke-induced left hemisphere brain injuries. These participants completed two different verbal WM tasks: complex listening span and a word 2-back task. Behavioral results indicated that the two tasks were only slightly related, while the VLSM analysis revealed different critical regions associated with each task. Specifically, significant detriments in performance on the complex span task were found with lesions in the inferior frontal gyrus, while for the 2-back task, significant deficits were seen after injury to the superior and middle temporal gyri. Thus, the two tasks depend on the structural integrity of different, non-overlapping frontal and temporal brain regions, suggesting distinct neural and cognitive mechanisms triggered by the two tasks: rehearsal and cue-dependent selection in the complex span task, versus updating/auditory recognition in the 2-back task. These findings call into question the common practice of using these two tasks interchangeably in verbal WM research and undermine the legitimacy of aggregating data from studies with different WM tasks. Thus, the present study points out the importance of lesion studies in complementing functional neuroimaging findings and highlights the need to consider task demands in neuroimaging and neuropsychological investigations of WM.

[The Futures of Auditory Passive Perception While Listening to Sounds in Healthy Persons of Young or Advanced Age (ERP and Psychology Tests Analysis).]

The study analyzed ERPs in 37 healthy right handed subjects without neurological and psychiatric disorders. Young age group consisted of 18 persons aged 18 to 27; advanced age group included 19 persons aged 32 to 59. ERPs were recorded by 32 scalp electrodes according to 10-20% system. Two toned addball paradigm including standard and target tones was used for ERP-recording. The sound sequence was given to examinees without any preliminary instruction. Complex psychology testing included Stroop color and word test for the attention and interference assessment, and Wisconsin card sorting test. Significantly larger amplitude of N200 was detected in young persons in comparison to ones of advantage age. Wavelet-analysis revealed stronger wavelet-connections in frontal-central area on the time range of P300 in persons of advanced age vs. younger ones. The correlation of data of psychological tests examining executive functions was detected with latency of P300 in young examinees and with amplitude of P300 in advanced age ones. Obtained data suggests that switching from one activity to another is prevalence in young persons and focusing on a current activity in advanced age persons.

[FMRI study of visual task switching in healthy individuals].

The present study was aimed, first, at developing a visual switching task for fMRI research and, second, at identification of the brain regions involved in task switching. Forty eight healthy individuals (from 21 to 56 years of age) participated in the study. The designed visual switching task was relatively short, it consisted of an easy stimulus set and involved a simple condition, in which participants had to shift their attention between two task conditions (classifying figures according to their form or number). Thus, this developed testing procedure can further be used to assess special populations, including patients with brain damage who cannot do monotonous tasks for a long period of time and have language impairments. The results of this testing technique revealed that task switching is carried out by an interconnected neuronal network, consisting of dorsolateral prefrontal cortex, inferior parietal area, secondary visual area, supplementary motor area and cerebellum cortex of both hemispheres.

[Sex Differences in Visual Task Switching (an fMRI Study)].

Executive functions are an important ability of human brain to program, regulate and control various cognitive processes; one of these processes is the voluntary task switching. However, the sex differences in this process are poorly studied. In our study, these differences were investigated in 70 healthy subjects (36 men and 34 women) aged 21-48 years by means of functional magnetic resonance imaging (fMRI) and neuropsychological examination. During the fM RI study, the subjects had to shift their attention between two tasks (classifying figures according to their form or number). During neuropsychological examination, the subjects completed a series of visual attention, task switching and memory tests. The results of fMRI study showed that visual task switching in women is carried out by a neuronal network, consisting of dorsolateral prefrontal cortex, inferior parietal areas, secondary visual areas of both hemispheres and cerebellum cortex. Task switching in men involved the same areas and, in addition, right supplementary motor area, right insula and left thalamus. As compared with women, the rate of activation of prefrontal cortex, left parietal lobe and right insula in men was significantly higher. The results of neuropsychological tests showed that men completed the tasks with attention switching, searching and arranging of stimuli significantly slower than women. The data demonstrate the differences in the organization of task switching processes in men and women.

[Electroencephalograpic Parameters of Healthy Persons with Different Successfulness of Dual-Task Performance (Postural Control and Calculation)].

Complex electroencephalographic (EEG), stabilographic and psychological study was executed during the number dual tasks performance--postural control and calculation in 25 healthy volunteers (age 25 ± 0.7). Successful performances of dual tasks required a high usage of cognitive resources, such as memory and attention as well as good motor command and low level of anxiety. Two EEG-markers of successful dual tasks performance were revealed. An increase of EEG coherence for long diagonal pairs of leads between frontal and parieto-occipital areas was observed. Additionally a decrease of EEG coherence for short pairs of leads was revealed. The poor performance of dual tasks was accompanied by an increase of EEG coherence between local pairs of leads for different spectral bands.

Processing lexical ambiguity in sentential context: Eye-tracking data from brain-damaged and non-brain-damaged individuals.

The purpose of the present study was to identify general and syndrome-specific deficits in the lexical processing of individuals with non-fluent and fluent aphasia compared to individuals without cognitive, neurological or language impairments. The time course of lexical access, as well as lexical selection and integration was studied using a visual-world paradigm in three groups of Russian speakers: 36 individuals in the control group, 15 individuals with non-fluent aphasia and eight individuals with fluent aphasia. Participants listened to temporarily ambiguous sentences wherein the context biased the interpretation of an ambiguous word toward one of its two meanings. In half of the experimental sentences, a reanalysis was needed upon encountering the disambiguating phrase. The effect of the length of the intervening material between the ambiguous word and the disambiguation point was additionally monitored. All groups of participants showed intact lexical access under slowed speech rate, but non-fluent participants experienced difficulties with timely activation of multiple referents. At later stages of lexical processing, they additionally demonstrated a specific impairment of reanalysis. The deficit in participants with fluent aphasia was not focalized at any specific stage of lexical processing. Rather, the breakdown of lexical processes in fluent aphasia was likely related to difficulties with the inhibition of irrelevant lexical activation, which is further supported by the finding that increased phonological distance between the ambiguous word and ambiguity resolution was influential to the offline performance in this group.

[The comparative analysis of changes of short pieces of EEG at perception of music on the basis of the event-related synchronization/desynchronization and wavelet-synchrony].

The going of present pilot study is an analysis of features changes of EEG short pieces registered from 32 sites, at perception of musical melodies healthy examinees depending on logic (cognizance) and emotional (it was pleasant it was not pleasant) melody estimations. For this purpose changes of event-related synchronization/desynchronization, and also wavelet-synchrony of EEG-responses at 31 healthy examinees at the age from 18 till 60 years were compared. It is shown that at a logic estimation of music the melody cognizance is accompanied the event-related desynchronization in the left fronto-parietal-temporal area. At an emotional estimation of a melody the event-related synchronization in left fronto - temporal area for the pleasant melodies, desynchronization in temporal area for not pleasant and desynchronization in occipital area for the melodies which are not causing the emotional response is typical. At the analysis of wavelet-synchrony of EEG characterizing jet changes of interaction of cortical zones, it is revealed that the most distinct topographical distinctions concern type of processing of the heard music: logic (has learned-hasn't learned) or emotional (it was pleasant-it was not pleasant). If at an emotional estimation changes interhemispheric communications between associative cortical zones (central, frontal, temporal), are more expressed at logic - between inter - and intrahemispheric communications of projective zones of the acoustic analyzer (temporal area). It is supposed that the revealed event-related synchronization/desynhronization reflects, most likely, an activation component of an estimation of musical fragments whereas the wavelet-analysis provides guidance on character of processing of musical stimulus.

[Features of dual--postural and calculation--task performance in patients with consequences of traumatic brain injury].

Dual tasks with voluntary postural control and calculation have been done by 14 patients (25.7 +/- 4.7 yo.) after traumatic brain injury and 40 healthy volunteers (29.8 +/- 2.5 y.o.). Complex clinical (MMSE, FIM, MPAI-3 and Berg scales) and stabilographic evaluation has been performed. According to clinical evaluation 8 patients were included into group 1 with less severe functional deficit and 6 patients formed group 2 with more severe deficit. Parameters of motor and especially cognitive sub-tasks in patients were lower than in healthy subjects in both separate and dual tasks. In group 2 these parameters were lower than in group 1. Certain types of dual task where the quality of sub-tasks, especially of the motor-one increased in healthy subjects and patients of the first group were revealed. The complex of stabilographic parameters which could be used for estimation of quality of sub-tasks performance has been revealed. Dual tasks could be an additional method of evaluation of patients' adaptive possibilities and certain type of dual task could become a promising approach to recovery at late period of rehabilitation.

[Higher mental functions and cognitive auditory event-related potentials impairment in liquidators of Chernobyl accident].

An integrated neuropsychological study and analysis of cognitive auditory event-related potentials (ERP) using the three-stimulus oddball paradigm was performed in ten subjects who participated in the liquidation of Chernobyl accident and ten healthy subjects. Impairment of higher mental functions, including aspontaneity, fatigability, a decrease in the auditory-verbal and visual memories, and higher motor function deficiency was shown in liquidators. A decrease of amplitude in all components of ERP (N1, N2 and P3) was found in liquidators for all stimuli in both experimental situations (audition of all stimuli and counting of deviant stimuli) compared to healthy subjects. The latent period (LP) of ERP in liquidators was decreased for N1 and N2 components and increased for P3. The largest between-group differences in the LP were revealed in the frontal areas for N1 and P3 in the left hemisphere and for N2 - in the right one. The correlation analysis between the ERP and a neuropsychological study had shown that changes in the LP of N1 are correlated to the impairment of short-term memory and pose praxis of the right hand while changes in the N2 were correlated to the impairment of long-term memory and pose praxis of the left hand. The changes in LP of P3 were correlated to complex cognitive processing disorders. Thus, the complex study identified the deceleration of perception, processing, and analysis of information combined with the weakened inhibition and "uneconomical" type of reactivity which led to the impairment of higher mental functions in liquidators compared to healthy subjects of the same age. The changes found in liquidators are similar to those observed in elderly people and support the hypotheses on accelerated brain ageing caused by low dose irradiation.

[Features of cognitive audiory evoked potentials changes at participants of liquidation of chernobyl accident consequences the message II. the analysis of late component P300].

At 10 participants of liquidation of consequences of Chernobyl accident (middle age 50.5 +/- 4.0 years) and at 10 healthy persons (middle age 47.0 +/- 6.0 years) are performed complex neuropsychological examination and registration acoustical cognitive evoked potentials (EP) using odd-ball paradigms. Neuropsyhological research has revealed at liquidators disorders of the higher mental functions, such as aspontanity, decrease speech and a visual memory, and also deficit of higher motor functions. According to the analysis of amplitude-time characteristics of component P300 acoustical cognitive EP a decrease in amplitude of this component at liquidators in all areas of the brain, for both experimental situations for all stimulus in comparison with healthy persons the same age was revealed. At the analysis of latent period (LP) P300 at liquidators the most distinct increase was revealed in a situation of passive listening for all kinds of stimulus. The analysis of reactivity of LP in different experimental situations has shown that at healthy persons during passive listening had similar values for all kinds of stimulus, and an account situation the maximum values--for significant stimulus. For liquidators the type of reaction in the form of increase in LP values at the majority of stimulus in both experimental situations. The analysis of regional LP changes of component P300 has found out the maximum distinctions between groups in frontal area of the left hemisphere. Along with it at liquidators the type the reactions similar for all shown stimulus without dependence from their importance in comparison with norm is revealed "uneconomical, superfluous". It can testify about decreasing of attention and memory reserves and to promote disorder of the higher mental functions. The described of amplitude-time characteristics of component P300 of acoustical EP at liquidators EP can testify to delay of perception, processing and the information analysis in a combination to easing of inhibitory processes leading to the higher mental dysfunctions. The obtained data have similarity to people of old age, supporting a hypothesis about the accelerated ageing of a brain, and also about pathological development of processes of ageing as a result of influence of low doses of radiation.

[Specificity of auditory evoked potencials changes in participants of Chernobyl accident consequences: I. Analysis of early N1 component].

Amplitude-time characteristics analysis of the N1 component of auditory cognitive evoked potentials (EP) was made in 10 persons who had participated in the cleanup of the Chenobyl Accident - liquidators (mean age 50.5 +/- 4.0 years old) and in 10 healthy subjects (mean age 47 +/- 6.0 years old). Comparison of amplitude features of the N1 auditory EP component in liquidators of the Chernobyl Accident found a decrease in all areas of the cortex with the maximum decrease in the central and frontal leads, and also an inversion in reactive changes to stimuli of different significance in comparison to healthy subjects of the same age. The most distinct differences between the healthy subjects and liquidators of the Chernobyl Accident were found for time characteristics of the N1 component. They show a significantly smaller value of latent period (LP) for all stimuli and for all experimental tasks in comparison with healthy subjects and more distinct for a significant stimulus when persons counted these stimuli. Analysis of regional changes in LP of the N1 component found that liquidators, in comparison with healthy subjects, have maximal differences in the frontal area of the left hemisphere which were accompanied with inversion asymmetry of LP in this component. Less distinct changes were observed in the central area with relatively little damage in the parietal area. Detected changes in the amplitude-time characteristics of the N1 component of the auditory cognitive EP in liquidators of Chernobyl Accident can show an abnormality in primary attention and its reserves due to weakened inhibitory processes in comparison with healthy subjects, which has similarities of old age. The obtained data supports the hypothesis about the accelerated brain aging in liquidators of Chernobyl Accident as a result of low dosage radiation effects; however, it also allows the pathological development of the brain ageing due to the effects of radiation.

[Polymer coatings with immobilized thrombin and peptides: preparation and use for wound healing]. / Polimernye pokrytiia s immobilizovannymi v nikh trombinom ili peptidami: poluchenie i primenenie dlia ranozazhivleniia.

Polymer dressings with encapsulated thrombin or synthetic peptides which can mimic thrombin action are employed for wound healing. Paper describes the method for preparation of these hydrogel composites of PVCL-CaAlg [poly(N-vinyl caprolactam-calcium alginate). The effect of encapsulated thrombin/peptides on tissue repair process have beet investigatat in vivo experiments using a mouse model of wound healing. The developed dressings accelerated wound healing: thascan be used as a basis for creation of novel formulations with controlled drug release for wound therapy.

[Thrombin--a regulator of reparative processes in wound healing]. / Trombin--reguliator reparativnikh protsessov pri zazhivlenii ran.

Thrombin, binding to receptors of the protease activated receptor (PAR) family, is involved in wound healing by inducing the reparation processes and regulating the activity of mast cells, which secrete mediators of inflammation. Using thrombin receptor agonist peptide (TRAP-6) for the activation of rat mast cells, effect of several receptors, including PAR-1, on mast cells was demonstrated. It was shown that TRAP increases the concentration of Ca2+ in the cytoplasm of mast cells and regulates cell degranulation, while releasing nitrogen oxide. Thrombin encapsulated in poly(N-vinyl caprolactam)-calcium alginate (PVCL-Ca-Alg) hydrogel films promotes wound healing in rats as demonstrated by the acceleration of fibroblast proliferation and neovascularization.

Stabilization of proteases by entrapment in a new composite hydrogel.

A new one-step procedure for entrapping proteases into a polymeric composite calcium alginate-poly(N-vinyl caprolactam) hydrogel was developed that provided 75-90% retention of the activity of entrapped enzymes compared to soluble ones. Properties of entrapped carboxypeptidase B, trypsin, and thrombin were investigated. The immobilized enzymes were active within a wide pH range. The temperature optima of entrapped trypsin and carboxypeptidase B were approx 25 degrees C higher than that of the soluble enzymes, and the resistance to heating was also increased. The effects of various polar and nonpolar organic solvents on the entrapped proteases were investigated. The immobilized enzymes retained their activity within a wide concentration range (up to 90%) of organic solvents. Gel-entrapped trypsin and carboxypeptidase (CPB) were successfully used for obtaining human insulin from recombinant proinsulin. The developed stabilization method can be used to catalyze various reactions proceeding within wide pH and temperature ranges.