Immunoinflammatory Profile in Patients with Episodic and Continuous Paranoid Schizophrenia.

Introduction: Associations of disturbances in innate and adaptive immunity during the clinical course of schizophrenia have been found in a number of studies. Yet, the relationship of immune parameters and systemic inflammation in relation to the clinical course of the disease and its prognosis, remains poorly understood, which highlights an interesting topic for further research. The goal of this study was to research the immuno-inflammatory changes in patients with clinical continuous and episodic paranoid schizophrenia, to assess the pathogenetic significance of these changes. Methods: Thirty-six patients with paranoid schizophrenia, of which 20 had episodic symptoms and 16 had continuous symptoms, consented to participate in the study, together with 30 healthy volunteers. In the study we assessed the parameters of innate immune response (serum levels of key pro-inflammatory and anti-inflammatory cytokines, C-reactive protein) and the adaptive immune response, including humoral-mediated immunity (serum immunoglobulins IgA, IgM, IgG, circulating immune complexes), as well as the cell link of adaptive immunity (key lymphocyte subpopulations). Positive and negative symptoms were assessed with the positive and negative symptoms scale; frontal dysfunction was assessed by Frontal Assessment Battery (FAB). Results: Both patient groups had higher than normal levels of C-reactive protein and IL-8. There was a significant elevation of circulating immune complexes among patients with continuous symptoms of schizophrenia, compared to patients with episodic symptoms and healthy controls. Levels of CD45+CD3+ lymphocytes (T-cells) differed between clinical groups, with higher values identified among patients with episodic symptoms and lower values among those with continuous symptoms. In addition, patients with episodic symptoms had significantly increased levels of CD45+CD3+CD4+CD25+CD127- regulatory T-cells. Finally, the level of CD45+CD3-CD19+ B-cells was significantly higher among patients with continuous symptoms vs. patients with episodic symptoms and the control groups. Markers of activation of humoral immunity were associated with the severity of frontal disorders in these patients. Discussion: Comprehensive data on the serum level of cytokines and the parameters of adaptive immunity among individuals with continuous schizophrenia, by comparison with patients with episodic schizophrenia, are practically absent in the literature. We have shown that among those with continuous schizophrenia, there are signs of systemic inflammation and chronic activation of the adaptive humoral immune response, while among patients with episodic symptoms of the disease, there are signs of systemic inflammation and certain activation of cell-mediated immunity, without significant changes in the humoral link of adaptive immunity. Conclusion: More studies are needed, but the data obtained in this study are important for subsequent clinical studies of new treatment methods, based on various immunophenotypes of schizophrenia.

Asymmetry of amygdala resting-state functional connectivity in healthy human brain.

Lateral asymmetry is one of the fundamental properties of the functional anatomy of the human brain. Amygdala (AMYG) asymmetry was also reported in clinical studies of resting-state functional connectivity (rsFC) but rarely in healthy groups. To explore this issue, we investigated the reproducibility of the data on rsFC of the left and right AMYG using functional MRI twice a week in 20 healthy volunteers with mild-to-moderate anxiety. We found a resting-state network of the AMYG, which included regions involved in emotional processing and several other brain areas associated with memory and motor inhibition. The AMYG network was stable in time and within subjects, but the right AMYG had more significant connections with anatomical brain regions. The rsFC values of the right AMYG were also more sustained across the week than the left AMYG rsFC. Subjective ratings of anxiety did not correlate significantly with the patterns of seed-based AMYG connectivity. Our findings indicate that, for healthy subjects, rsFC may differ for the right and left AMYG. Moreover, the AMYG functional connectivity is variable in short-term observations, which may also influence the results of longitude studies.

Consciousness in a multilevel architecture: What causes the lateralization of effective connectivity under resting state?

Here we present our answers to a critical commentary by Elkhonon Goldberg on our recent publication (Velichkovsky et al., 2018). To avoid discussions about novelty effects in the human brain activity and memory processes, we narrowed down this response to a reanalysis of our data along the lines proposed in the commentary, namely to comparing the effective links between symmetrical brain structures during the first and the last parts of a prolonged resting-state fMRI experiment. We also tested for sex differences in our results and checked for a stability of top-down interactions during the course of experiment because learning is often expressed in the weakening of upper level control over low-level mechanisms. Our attempts to test the predictions based on the novelty hypothesis has led to mixed results suggesting that the discovered right-to-left dominance of causal connections at rest may have a deeper origin than supposed in the Goldberg's commentary.

Consciousness in a multilevel architecture: Evidence from the right side of the brain.

By taking into account Bruce Bridgeman's interest in an evolutionary framing of human cognition, we examine effective (cause-and-effect) connectivity among cortical structures related to different parts of the triune phylogenetic stratification: archicortex, paleocortex and neocortex. Using resting-state functional magnetic resonance imaging data from 25 healthy subjects and spectral Dynamic Causal Modeling, we report interactions among 10 symmetrical left and right brain areas. Our results testify to general rightward and top-down biases in excitatory interactions of these structures during resting state, when self-related contemplation prevails over more objectified conceptual thinking. The right hippocampus is the only structure that shows bottom-up excitatory influences extending to the frontopolar cortex. The right ventrolateral cortex also plays a prominent role as it interacts with the majority of nodes within and between evolutionary distinct brain subdivisions. These results suggest the existence of several levels of cognitive-affective organization in the human brain and their profound lateralization.

Effective Connectivity within the Default Mode Network: Dynamic Causal Modeling of Resting-State fMRI Data.

The Default Mode Network (DMN) is a brain system that mediates internal modes of cognitive activity, showing higher neural activation when one is at rest. Nowadays, there is a lot of interest in assessing functional interactions between its key regions, but in the majority of studies only association of Blood-oxygen-level dependent (BOLD) activation patterns is measured, so it is impossible to identify causal influences. There are some studies of causal interactions (i.e., effective connectivity), however often with inconsistent results. The aim of the current work is to find a stable pattern of connectivity between four DMN key regions: the medial prefrontal cortex (mPFC), the posterior cingulate cortex (PCC), left and right intraparietal cortex (LIPC and RIPC). For this purpose functional magnetic resonance imaging (fMRI) data from 30 healthy subjects (1000 time points from each one) was acquired and spectral dynamic causal modeling (DCM) on a resting-state fMRI data was performed. The endogenous brain fluctuations were explicitly modeled by Discrete Cosine Set at the low frequency band of 0.0078-0.1 Hz. The best model at the group level is the one where connections from both bilateral IPC to mPFC and PCC are significant and symmetrical in strength (p < 0.05). Connections between mPFC and PCC are bidirectional, significant in the group and weaker than connections originating from bilateral IPC. In general, all connections from LIPC/RIPC to other DMN regions are much stronger. One can assume that these regions have a driving role within the DMN. Our results replicate some data from earlier works on effective connectivity within the DMN as well as provide new insights on internal DMN relationships and brain's functioning at resting state.

Network activity of mirror neurons depends on experience.

In this work, the investigation of network activity of mirror neurons systems in animal brains depending on experience (existence or absence performance of the shown actions) was carried out. It carried out the research of mirror neurons network in the C57/BL6 line mice in the supervision task of swimming mice-demonstrators in Morris water maze. It showed the presence of mirror neurons systems in the motor cortex M1, M2, cingular cortex, hippocampus in mice groups, having experience of the swimming and without it. The conclusion is drawn about the possibility of the new functional network systems formation by means of mirror neurons systems and the acquisition of new knowledge through supervision by the animals in non-specific tasks.