Effective Connectivity of the Bilateral Amygdala, Dorsomedial Prefrontal, and Subgenual Anterior Cingulate Cortices: Feasibility of Positive Social Emotion Regulation Models for Real-Time Functional Magnetic Resonance Imaging.

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.

fMRI Brain Response in Patients with Depression at the Time of Control of the Severity of Positive Social Emotions and Analysis of Behavioral Factors.

The study presents functional magnetic resonance imaging (fMRI) data on the brain activity in depression and psycho-diagnostic indicators that characterize cognitive activity strategies of positive social emotion regulation. It was shown that fMRI activity of the brain during viewing of emotionally neutral and moderately positive images and searching for an optimal self-regulation strategy was associated with changes in activation in the dorsomedial prefrontal cortex. Analysis of behavioral factors showed that strategies of searching for the optimal way of emotional self-regulation were closely related to the general style of behavior, level of uncertainty tolerance, and commitment. The integration of psycho-diagnostic and neuroimaging data allows deeper understanding of the mechanisms of emotions regulation that contributes to the optimization of protocols for the diagnosis and treatment of depressive disorders.

Diffusional Characteristics of Brain Matter after Stroke.

We analyzed characteristics of diffusion and its kurtosis obtained using diffusion-kurtosis MRI in the hemisphere contralateral to the one affected by acute cerebrovascular accident. Diffusion characteristics in the white and gray matter were compared using analysis of covariance (ANCOVA) in healthy subjects and stroke patients with consideration for the age and sex factors. Significant differences between the groups were revealed for apparent diffusion coefficient and mean kurtosis in the white matter. Age dependence was studied using regression analysis and, according to the results of ANCOVA, this factor was found to be significant for apparent diffusion coefficient and diffusion kurtosis in the white matter. Metrics are proposed that can be used to determine the risk of stroke.

Application of fMRI and Simultaneous fMRI-EEG Neurofeedback in Post-Stroke Motor Rehabilitation.

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 ß-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.

The Relationships Between Cortical Activity while Observing Images Featuring Different Degrees of Ambiguity and Ambiguity Tolerance.

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.

EEG Alpha-Rhythm-Related Changes in BOLD fMRI Signal in Neurofeedback Training.

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).

Prospects of Synchronous fMRI-EEG Recording as the Basis for Neurofeedback (Exemplified on Patient with Stroke Sequelae).

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.

Dynamics of fMRI and EEG Parameters in a Stroke Patient Assessed during a Neurofeedback Course Focused on Brodmann Area 4 (M1).

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 ß 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 ß 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.

Dynamics of Interactions between Cerebral Networks Derived from fMRI Data and Motor Rehabilitation during Stokes.

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.

Functional Connectivity of Brain Regions According to Resting State fMRI: Differences between Healthy and Depressed Subjects and Variability of the Results.

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.

fMRI Response of Parietal Brain Areas to Sad Facial Stimuli in Mild Depression.

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.

Spontaneous Changes in Functional Connectivity of Independent Components of fMRI Signal in Healthy Volunteers at Rest and in Subjects with Mild Depression.

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.

fMRI Responses in Healthy Individuals and in Patients with Mild Depression to Presentation of Pleasant and Unpleasant Images.

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.

Peculiarities in Interaction of Independent Components of Resting-State fMRI Signal in Patients with Mild Depressions.

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.

Dynamics of Interaction of Neural Networks in the Course of EEG Alpha Biofeedback.

Brain EEG-fMRI activity was studied in subjects, who had successfully completed the EEG alpha stimulating training course (20 sessions): for 14 healthy men (20-35 years) three records were obtained in the feedback loop (biofeedback with EEG alpha rhythm with sound reinforcement): in the beginning, middle and at the end of the course. During alpha training, increased functional connectivity was revealed between precuneus network and anterior salience network, left executive control network, default mode network, primary visual network; anterior salience network and executive control network, visual-spatial network. The most prominent changes were found for precuneus network and anterior salience network, which could be due to their key role in the biofeedback phenomenon. Significant changes in functional connectivity were recorded for anterior salience network and precuneus network (synchronicity increased from the first to the third trial) and right and left executive control networks (weakening from the first to the second session.

[Real Time Fuctional Magnetic Resonance Imaging Biofeedback: a New Generation of Neurotherapy].

The review summarizes the data related to the potential of the real time fMRI biofeedback (the rt-fMRI), a novel technology implementing instructing patients to modify the neural activity in the certain brain regions related to the disordered function. The recent positive results were gained for a treatment of the post-stroke impairments, the Parkinson disease, the pain syndrome, the tinnitus, the alcohol and nicotine abuse, the major depression, and phobias of contamination and spiders. The intervention Was found to be less promising for schizophrenia and nearly ineffective for the criminal antisocial personality disorder. The reliability of the results is mostly poor due to suboptimal study designs, lack of the control groups, and insufficient sample sizes. The article deals with biological basis of the technology, its current applications and perspectives; and also its method- ologicdl and methodical problems.

[Experience of the Continuous Real Time fMRI Biofeedback of the Primary Motor Cortex Using a 1.5 T MR Scanner].

The neurofeedback based on the motor areas fMRI signal may be a promising treatment for improving motor impairment in post-stroke conditions and Parkinson's disease. In the majority of the studies has been conducted using the 3 T MR machines, and the region of interest has been placed to the secondary motor areas. The current study attempted to perform an fMRI neurofeeback based on response of the right hand projection locus within primary motor cortex utilizing the 1.5 T MR scanner and using the optimal parameters for the named magnetic field strength. The subjects were 16 healthy participants who underwent a 30-minute imaging session comprised 1) individual func- tional localization of the region of interest (using the hand clinging task) and attempts to control its activity with 2) motor imagery and 3) any cognitive strategy chosen by participant. In both self-regulation conditions subjects activated G. precentralis, G. cinguli anterior, G. frontalis superior, G. parietalis inferior, and 6-th Brodman area. Activation maps for these two tasks didn't differ one from another significantly, and the involved area had only a few overlays with the region of interest map which signifies that training was unsucessful. The limitations of the study and factors influenc- ing the biofeedback efficacy negatively are discussed.

EEG-fMRI Study of Alpha-Stimulation Neurobiofeedback Training Course.

fMRI-EEG dynamics of brain activity in volunteers was studied during the course of EEG alpha-stimulation training (20 sessions). Twenty-three healthy men (20-35 years) were subjected to 3-fold mapping in a feedback loop (EEG alpha-rhythm biofeedback with acoustic reinforcement). This procedure was performed at the beginning, middle, and end of the course. During the first neurofeedback training session, deactivation (p<0.001) was found in the right angular gyrus, supramarginal, and superior temporal gyri, Brodmann area 39, and cerebellum. Activation (p<0.001) was observed in the medial frontal and cingulate gyri, motor areas of both hemispheres, and Brodmann area 32. During final (third) neurofeedback training session, we observed strong deactivation (p<0.05 with FDR) of zones responsible for spatial thinking and motor functions: left medial frontal and left medial temporal gyri; right postcentral, lingual, and superior frontal gyri; insula and right side of the cerebellum; and precuneus and cuneus (Brodmann areas 6, 9, 7, 31, 8, 13, and 22). Changes in the alpha wave power were most pronounced in the primary and secondary somatosensory cortex of the left hemisphere (Brodmann areas 2L and 5L).

Raven's Progressive Matrices in the Lexicon of Dynamic Mapping of the Brain (MRI).

Using functional magnetic resonance imaging, we studied intracerebral dynamics during completion of Raven's Progressive Matrices test. Solving the test organized in sets of progressively increasing difficulty cause changes in cerebellar activation functionally related to cognitive activities and operations. As the tasks became more complicated, we observed gradual suppression of the activity of default mode network (DMN). The most pronounced changes in cerebral activation patterns occurred the second set of the test and involved associative somatosensory area and Wernicke's area that is known to play an important role in cognitive processes associated with synthesis and analysis of information.

Sirt1 Regulates p53 Stability and Expression of Its Target S100B during Long-Term Potentiation in Rat Hippocampus.

Induction of long-term potentiation in rat hippocampus was followed by short-term activation of transcription factor p53 and its subsequent degradation. We studied the effects of EX-527 (inhibitor of deacetylase Sirt1, a negative regulator of p53) and pifi thrin-ß (inhibitor of p53-dependent transcription) on the levels of p53 protein and mRNA of its target gene S100B during long-term potentiation. Pifi thrin-ß limited the increase in S100B mRNA content after tetanization, which confi rmed signifi cant contribution of p53 in the regulation of S100B during long-term potentiation. EX-527 completely prevented p53 degradation and increased S100B expression induced by tetanization. Thus, Str1 regulates stability of p53 and expression of its target gene S100B in rat hippocampus during long-term potentiation.