Effective connectivity based on functional magnetic resonance imaging (fMRI) allows assessing directions of interaction between brain regions. For real-time fMRI, we compared models of positive social emotion regulation based on a network involving the bilateral amygdala, dorsomedial prefrontal, and subgenual anterior cingulate cortex. The top-down regulation model implied modulation of the dorsomedial prefrontal cortex exerted onto other regions, while the bottom-up model implied the inverse modulation. The validity of model calculations was tested using the data from three healthy volunteers who imagined positive interactions with people in presented photos (stimuli). We confirmed the dominance of the top-down model and evaluated the number and duration of iterations required for model estimations. The study shows the applicability of the four-node effective connectivity models for regulation of positive social emotions using real-time fMRI, e.g ., for neurofeedback applications.

The purpose of this study is to highlight the modern possibilities of magnetic resonance as a unique method for assessing and visualizing living systems from the standpoint of chemistry and physics, in particular, from the standpoint of biochemistry and biophysics of metabolism: circulation and mass transfer of protons as a part of water and macromolecules due to flow, diffusion, and perfusion effects in tissues. The main sections of the review are devoted to the use of the mapping method of the macromolecular proton fraction for the determination of the biochemical composition of tissues, evaluation of free diffusion of molecules based on diffusion-tensor and diffusion-kurtosis magnetic resonance tomography (MRI), analysis of the mass transfer of protons in human body fluids due to the flow (circulation) and perfusion effects in the permeable tubular structures (vessels), as well as in complex multicomponent life support systems of the human central nervous system. The effects of oxy- and deoxyhemoglobin conversions during cognitive disorders are specially considered. The results obtained by the listed MRI techniques are used in the construction of models of proton, macromolecular, cellular, and system interactions in living systems.

There are more than 30 inherited human disorders connected with repeat expansion (myotonic dystrophy type I, Huntington's disease, Fragile X syndrome). Fragile X syndrome is the most common reason for inherited intellectual disability in the human population. The ways of the expansion development remain unclear. An important feature of expanded repeats is the ability to form stable alternative DNA secondary structures. There are hypotheses about the nature of repeat instability. It is proposed that these DNA secondary structures can block various stages of DNA metabolism processes, such as replication, repair and recombination and it is considered as the source of repeat instability. However, none of the hypotheses is fully confirmed or is the only valid one. Here, an experimental system for studying (CGG)n repeat expansion associated with transcription and TCR-NER is proposed. It is noteworthy that the aberrations of transcription are a poorly studied mechanism of (CGG)n instability. However, the proposed systems take into account the contribution of other processes of DNA metabolism and, therefore, the developed systems are universal and applicable for various studies. Transgenic cell lines carrying a repeat of normal or premutant length under the control of an inducible promoter were established and a method for repeat instability quantification was developed. One type of the cell lines contains an exogenous repeat integrated into the genome by the Sleeping Beauty transposon; in another cell line, the vector is maintained as an episome due to the SV40 origin of replication. These experimental systems can serve for finding the causes of instability and the development of therapeutic agents. In addition, a criterion was developed for the quantification of exogenous (CGG)n repeat instability in the transgenic cell lines' genome.Существует ряд наследственных заболеваний человека, причиной которых является экспансия тандемных повторов. К ним относятся миотоническая дистрофия первого типа, болезнь Хантингтона, заболевания, ассоциированные с ломкой Х-хромосомой. Синдром ломкой Х-хромосомы – наиболее распространенная причина наследственной умственной отсталости у человека. На сегодняшний день причины развития экспансии остаются неисследованными. Важная особенность протяженных повторов – их способность формировать альтернативные вторичные структуры ДНК. Существуют гипотезы, объясняющие природу нестабильности повторов, однако все они предполагают возникновение устойчивых вторичных структур ДНК на различных этапах клеточного цикла. Источником нестабильности считаются нарушения в различных процессах метаболизма ДНК (репликация, репарация и рекомбинация), вызванные образованием вторичных структур. Однако ни одна из гипотез до конца не подтверждена и, видимо, не является единственно верной. Вероятно, в различных типах клеток и на определенных стадиях клеточного цикла источником нестабильности выступает множество процессов. В настоящей работе мы предлагаем экспериментальную систему для изучения вклада транскрипции и ассоциированной с ней репарации в нестабильность повтора (CGG)n, поскольку это наименее изученный механизм возникновения нестабильности. Однако предложенные модели могут учитывать вклад и других процессов метаболизма ДНК, например репликации, что делает полученные системы универсальными и применимыми в разных исследованиях. Нами были созданы трансгенные клеточные линии, несущие повтор нормальной и премутантной длины под тетрациклин-индуцируемым промотором. Один тип линий содержит плазмиду с экзогенным повтором, интегрированным в геном посредством транспозона Sleeping Beauty, в другой клеточной линии вектор поддерживается в виде эписомы благодаря ориджину репликации SV40. Такие трансгенные клеточные линии могут служить экспериментальной системой для поиска причин нестабильности и создания терапевтических средств. Кроме того, был разработан критерий для оценки нестабильности экзогенного (CGG)n повтора в геноме трансгенных клеточных линий, расчет которого не зависит от эффективности синтеза протяженных повторов.

This article discusses the contribution of fMRI- and fMRI-EEG-neurofeedback into recovery of motor function in two subacute stroke patients during the early post-stroke period. Premotor and supplementary motor zones of the cortex were chosen as the targets of voluntary control. Patient 1 received 6 sessions of motor imagery-based fMRI neurofeedback of secondary motor areas activity and Patient 2 received a similar course with the addition of μ- and β-EEG activity suppression. Both reduced the motor deficit severity, improved on the quality of life, and increased the C3/C4 coherence to other central leads within EEG μ-band. Patient 1 reliably increased the fMRI signal in target areas and improved on the strength and speed of hand movements. Patient 2 (fMRI-EEG) mastered the EEG activity regulation to a greater degree. The authors conclude that pure fMRI neurofeedback and bi-modal fMRI-EEG neurofeedback produce different clinical effects in motor rehabilitation, which confirms the prospect of the closed-loop stroke treatment.

We performed a fMRI study during which 18 healthy subjects passively viewed abstract images and tried to name them. The images were geometric primitives, impossible images (Penrose images), and ambiguous images (Rorschach inkblots). Activation and deactivation areas were revealed for each task. The results of psychological assessment of ambiguity tolerance according to MSTAT-I inventory were used as regressors. Deactivation of the precuneus (Brodmann area 7) and neighboring structures (especially when observing geometric primitives and inventing names for them) and in the fronto-temporal areas was associated with high ambiguity tolerance. Similar links were observed for both activation and deactivation (depending on the certain contrast) of the occipito-cerebellar area.

Interaction of EEG and BOLD brain activity was studied in subjects during EEG-biofeedback training course (20 sessions). Healthy male subjects aged 20-35 underwent a training course of sound-reinforced upregulation of alpha- (20 participants) or beta-activity (9 participants). Pretraining, intermediate (after 10 sessions), and post-training fMRI-EEG recordings were conducted in resting state and during the participants' attempts to upregulate the power of target EEG activity. Regression analysis was carried out on three sessions in total; the main changes in BOLD signal connected with alpha rhythm power were related to the subjects who performed alpha training "good enough" (were able to increase alpha power at least at one stage). Maximum changes in BOLD response connected with alpha rhythm power were observed in the form of deactivation at T8 lead in the right hemisphere, and at F7 in the left hemisphere, and involved middle frontal gyrus, triangular part of inferior frontal gyrus, superior temporal gyrus, parietal lobule, and insula. The identified areas correspond to the executive control network (ECN) and anterior salience network (ASN).

Synchronous fMRI-EEG mapping of cerebral activity in stroke patients made it possible to implement neurofeedback, a novel and promising therapeutic technology. This method integrates a real-time monitoring of cerebral activity by EEG and fMRI signals and training of the patients to control this activity simultaneously or alternatively via neurofeedback. The targets of such cerebral stimulation are cortical regions controlling arbitrary movements (Brodmann area 4), whereas its aim is optimization of activity in these regions in order to achieve better rehabilitation of stroke patients. The paper discusses the methodical details, advantages, and promise of bimodal neurofeedback treatment.

A course of interactive stimulation of primary motor cortex (Brodmann area 4) in the brain of a stroke patient resulted in recovery of locomotion volume in the paretic extremities and in improvement of general health accompanied with diverse changes in cerebral activity. During the training course, the magnitude of response in the visual fields of Brodmann areas 17 and 18 decreased; in parallel, the motor areas were supplemented with other ones such as area 24 (the ventral surface of anterior cingulate gyrus responsible for self-regulation of human brain activity and implicated into synthesis of tactile and special information) in company with Brodmann areas 40, 41, 43, 44, and 45. EEG data showed that neurofeedback sessions persistently increased the θ rhythm power in Brodmann areas 7, 39, 40, and 47, while the corresponding powers progressively decreased during a real motion. Both real motion and its virtual sibling constructed by interactive stimulation via neurofeedback were characterized with decreasing powers of the EEG β rhythm in Brodmann areas 6 and 8. The neurofeedback course decreased the coherence between the left Brodmann area 6 and some other ones examined in α and θ ranges. In the context of real motions, the coherence assessed in the EEG β range generally increased. Overall, the EEG and fMRI parameters attest to growing similarity between the moieties of functional communications effected in real and imaginary movements during neurofeedback course. The data open the vista for interactive stimulation to rehabilitate stroke patients; they highlight the important role of Brodmann areas in rearrangement of the brain in such patients; finally, the present results revealed the "common nervous pathway" that can be used to restore the capability for imaginary and real movements by a neurofeedback course after stroke.

The connections between large neuronal networks were analyzed in 12 patients with ischemic or hemorrhagic strokes and hemiparesis included in the course of the interactive brain stimulation in the area of the primary motor cortex by the analysis of independent components of fMRI. The results obtained in 3 patients are presented. Desynchronization of the visual networks with each other and with the motor networks as well as positive dynamics in Rankin scale and box and blocks test were observed in the patients. These data attest to a decrease in the importance of visual control during movements and probably on partial restoration of prioperception. The important role of interactive brain stimulation and network analysis of fMRI data in neurology are discussed.

In depressed patients, changes in spontaneous brain activity, in particular, the strength of functional connectivity between different regions are observed. The data on changes in the synchrony of different regions of interest in the brain can serve as markers of depressive symptoms and as the targets for the corresponding therapy. The study involved 21 patients with mild depression and 21 healthy volunteers; by the time of second fMRI scanning, 15 and 19 subjects, respectively). The subjects underwent two 4-min sessions of resting state fMRI with 2-4 months interval between the recordings; on the basis of these data, functional connectivity between regions of interest was assessed. During the first session, depressed patients demonstrated more pronounced connection between the right frontal eye field and cerebellar area III. When the sample was restricted to subjects who underwent both fMRI sessions, depressed patients demonstrated closer relations of the right parietal operculum and cerebellar vermis area VIII. During the second recording, healthy subjects showed stronger connectivity between more than 20 frontal, temporal, and subcortical regions of interest and cerebellum area II. In healthy participants, brainstem functional interactions increased from the first to the second fMRI-recording. In depressed subjects a number of cortical areas split from left intraparietal sulcus, but the left temporal cortex became more intra-connected. The results confirm the differences in functional connectivity between depressed and healthy subjects. At the same time, attention should be paid to the variability of the data obtained.

Depressive disorders can be associated with changes in not only interaction between neural networks, but also in their composition. Resting state fMRI scanning was performed for 4 min twice for each subject and the results of patients with mild depression ( N =15) and healthy subjects ( N =19) were analyzed. The fMRI signal was reduced into the independent components and the contrasts between the groups and between the first and second records were constructed for each component. During the first scanning, the auditory network of individuals with depression involved greater volume in the left insular region and lower volume in the right hemisphere. In record 2, depression patients were characterized by expansion of the executive network in the left hemisphere in the region of the middle and inferior frontal cortex. In healthy people, from record 1 to record 2, representation of the dorsal default mode network (DMN) increased in the left medial prefrontal area, the precuneus network expanded in the left hemisphere, and presentation of the ventral DMN in the right precuneus decreased. In the depression group, the auditory network lost some part of the left temporo-insular cortex; the sensorimotor network expanded in the left hemisphere to the cerebellum or to the central parietal region depending on the evaluation method, and the visuospatial network included or excluded a cluster in the left parietal lobe (in different points). Our findings indicate that connection of the auditory network with the left insular cortex could be a possible depression marker and also demonstrate a possibility of evaluating the composition of cerebral networks in intergroup comparisons and in dynamics without interventions.

Patients with mild depression and apparently healthy individuals were presented images and asked to sort them into "pleasant" and "unpleasant" subsets. In both groups, the main differences between brain activation patterns during presentation of pleasant and unpleasant images were localized in the motor regions (precentral and postcentral gyrus) and in the cerebellum (p < 0.05 with FWE correction). Most likely, these clusters are associated with motion (pressing a button in accordance with the instruction). According to the data of intergroup contrasts, patients with depression had less pronounced activation of frontal structures (middle frontal gyrus and other areas, including the white matter) in response to both positive and negative images (p < 0.001). In healthy subjects, the response of the temporo-occipital areas (lingual and fusiform gyrus) to unpleasant stimuli was more intensive than in patients (p < 0.001). This can be due to differences in the semantic image processing. Thus, in case of mild depression, the response of the amygdaloid complex, the key structure in the development in affective disorder, was not always observed. At the same time, the response of frontal and temporo-occipital regions has a certain potential as a biomarker of mild depression, although the reliability of the obtained data requires additional confirmation.

fMRI markers of mild depression were revealed using standard emotional test. Patients with mild depression and healthy volunteers were asked to determine gender of subjects in photographs with different emotional expressions (neutral, surprise, disgust, confusion, anger, sadness, fear, and joy). The pattern of response to different emotions was universal in both groups and included the largest clusters in the occipital region, as well as a certain volume in the parietal lobes and posterior lateral frontal cortex. In depression group, a lack of activation in the middle cingulate gyrus (bilaterally) and in the postcentral and inferior parietal gyrus (left) in response to presentation of sad faces. For other emotion, no large clusters of intergroup contrasts significant at p<0.05 with FWE correction were revealed. The response of the middle cingulate gyrus and the left inferior parietal lobe can be considered as a potential diagnostic marker of depressive disorders and as the target for neurofeedback.

Depression is associated with changes in the pattern of interaction of cerebral networks, which can reflect both existing symptoms and compensatory processes. The study is based on analysis of resting state fMRI data from 15 patients with mild depression and 19 conventionally healthy individuals. From fMRI signal recorded at rest for 4 min, the independent components were reconstructed. The intergroup differences and dynamics of functional connectivity from the first to the second recording were analyzed. Initially, depressive patients demonstrated weaker connectivity between cerebellar declive network (CN) and left central executive network (CEN) and also sensorimotor network (SMN); left CEN and primary visual network (PVN). During the second recording, the patients demonstrated more intensive reciprocal connection of the dorsal domain of default mode network (DMN) and auditory network (AN). In healthy subjects, positive correlations of the dorsal DMN and left CEN, right CEN and CN, and negative correlation of dorsal DMN and visuospatial network weakened from the first to second record. In the depression group, the interaction of AN with PVN, the right CEN with the anterior salience network and with ventral DMN weakened. At the same time, the connectivity between SMN and CN were strengthened. The results can be interpreted as spontaneous normalization of brain activity, but no direct evidence for their relation to the improvement of depression symptoms was found.

A study of a child with intellectual disability revealed an enlarged p-arm in chromosome 13 and amplified rDNA. qRT-PCR showed an approximately 6-fold increased level of rRNA in the patient’s blood samples. fMRI study revealed changes in uncinate fasciculus. His father is a carrier of the same chromosome, healthy and has a normal level of rRNA.

Biocontrol based on fMRI signals from the motor area of the cortex is a potential approach to restoring motor functions in poststroke states and Parkinson’s disease. The region of interest in most studies is in the secondary motor areas and the strength of the magnetic field is 3 T. We report here our studies on biocontrol using the fMRI signal from an area of the primary motor cortex associated with the operation of the right hand obtained using a 1.5-T tomograph and settings optimal for obtaining optimal images at this magnetic field strength. Subjects were 16 healthy subjects who took part in 30-min fMRI recording including 1) individual localization of the region of interest (rhythmic fist clenching test) and attempts to control its activity using 2) imaginary movements and 3) any cognitive strategy of the participant’s choice. Attempts to carry out self-control in both cases led to activation of the precentral, anterior cingulate, superior frontal, and inferior parietal gyri and Brodmann zone 6. fMRI signal maps for these tasks did not show any statistically significant differences and the activation zones showed little if any overlap with the region of interest, evidencing lack of success of sessions. The limitations of the experiments are discussed, as are factors with adverse influences on the effectiveness of biocontrol.

Some aspects of resting-state fMRI signal can be the key markers of depression. fMRI was recoded over 4 min in evidently healthy persons ( N =21) and in patients with mild depression ( N =21). The data were separated into the independent spatial components, and the strength of their association with established brain networks was analyzed. The patients with mild depression were characterized with greater correlations between the components representing the ventral and dorsal subdivisions of default mode network (DMN), whereas correlations between the components relating to cerebellum and to the left hemisphere language system were less pronounced. The data revealed a significant role of DMN in the development of affective abnormalities and importance of its functional state as a probable marker of mild depression.