Multiscale examination of cytoarchitectonic similarity and human brain connectivity

The human brain comprises an efficient communication network, with its macroscale connectome organization argued to be directly associated with the underlying microscale organization of the cortex. Here, we further examine this link in the human brain cortex by using the ultrahigh-resolution BigBrain dataset; 11,660 BigBrain profiles of laminar cell structure were extracted from the BigBrain data and mapped to the MRI based Desikan–Killiany atlas used for macroscale connectome reconstruction. Macroscale brain connectivity was reconstructed based on the diffusion-weighted imaging dataset from the Human Connectome Project and cross-correlated to the similarity of laminar profiles. We showed that the BigBrain profile similarity between interconnected cortical regions was significantly higher than those between nonconnected regions. The pattern of BigBrain profile similarity across the entire cortex was also found to be strongly correlated with the pattern of cortico-cortical connectivity at the macroscale. Our findings suggest that cortical regions with higher similarity in the laminar cytoarchitectonic patterns have a higher chance of being connected, extending the evidence for the linkage between macroscale connectome organization and microscale cytoarchitecture. The human brain connectome organization has been suggested to associate with cytoarchitecture similarity. Here, we utilize the state-of-the-art ultrahigh-resolution BigBrain dataset and diffusion-weighted imaging dataset to examine this association. Our results show that cortical regions with higher cytoarchitecture similarity are more likely to be connected, as well as connected by stronger white matter tracts. This work further extends our understanding of the interaction between macroscale cortico-cortical connectivity organization and microscale cortical cytoarchitecture

The association of maternal-infant interactive behavior, dyadic frontal alpha asymmetry, and maternal anxiety in a smartphone-adapted still face paradigm

Mother-infant interactions form a strong basis for emotion regulation development in infants. These interactions can be affected by various factors, including maternal postnatal anxiety. Electroencephalography (EEG) hyperscanning allows for simultaneous assessment of mother-infant brain-to-behavior association during stressful events, such as the still-face paradigm (SFP). This study aimed at investigating dyadic interactive behavior and brain-to-behavior association across SFP and identifying neural correlates of mother-infant interactions in the context of maternal postnatal anxiety. We measured frontal alpha asymmetry (FAA), a physiological correlate of emotion regulation and a potential marker of risk for psychopathology. To emulate real-life interactions, EEG and behavioral data were collected from 38 mother-infant dyads during a smartphone-adapted dual-SFP. Although the behavioral data showed a clear still-face effect for the smartphone-adapted SFP, this was not reflected in the infant or maternal FAA. Brain-to-behavior data showed higher infant negative affect being associated with more infant leftward FAA during the still-face episodes. Finally, mothers with higher postnatal anxiety showed more right FAA during the first still-face episode, suggesting negative affectivity and a need to withdraw from the situation. Our results form a baseline for further research assessing the effects of maternal postnatal anxiety on infants' FAA and dyadic interactive behavior

The type I interferon signature in leukocyte subsets from peripheral blood of patients with early arthritis: a major contribution by granulocytes

The type I interferon (IFN) signature in rheumatoid arthritis (RA) has shown clinical relevance in relation to disease onset and therapeutic response. Identification of the cell type(s) contributing to this IFN signature could provide insight into the signature's functional consequences. The aim of this study was to investigate the contribution of peripheral leukocyte subsets to the IFN signature in early arthritis. Blood was collected from 26 patients with early arthritis and lysed directly or separated into peripheral blood mononuclear cells (PBMCs) and polymorphonuclear granulocytes (PMNs). PBMCs were sorted into CD4(+) T cells, CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes by flow cytometry. Messenger RNA expression of three interferon response genes (IRGs RSAD2, IFI44L, and MX1) and type I interferon receptors (IFNAR1 and IFNAR2) was determined in whole blood and blood cell subsets by quantitative polymerase chain reaction. IRG expression was averaged to calculate an IFN score for each sample. Patients were designated "IFN(high)" (n = 8) or "IFN(low)" (n = 18) on the basis of an IFN score cutoff in whole peripheral blood from healthy control subjects. The difference in IFN score between IFN(high) and IFN(low) patients was remarkably large for the PMN fraction (mean 25-fold) compared with the other subsets (mean 6- to 9-fold), indicating that PMNs are the main inducers of IRGs. Moreover, the relative contribution of the PMN fraction to the whole-blood IFN score was threefold higher than expected from its abundance in blood (p = 0.008), whereas it was three- to sixfold lower for the other subsets (p ≤ 0.063), implying that the PMNs are most sensitive to IFN signaling. Concordantly, IFNAR1 and IFNAR2 were upregulated compared with healthy controls selectively in patient PMNs (p ≤ 0.0077) but not in PBMCs. PMNs are the main contributors to the whole-blood type I IFN signature in patients with early arthritis, which seems due to increased sensitivity of these cells to type I IFN signaling. Considering the well-established role of neutrophils in the pathology of arthritis, this suggests a role of type I IFN activity in the disease as wel

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Figure S3. Line plot of the absolute number of cells per lymphocyte subset in 68 non-converting and 17 converting patients with arthralgia. The non-converting patients are depicted from the time point of inclusion. The converting patients are depicted from the time point of conversion and the time before conversion. (TIF 1784 kb

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

A blueprint of the developing mind

Brain development during pregnancy is characterized by tremendous brain growth and the construction of connections between communicating brain regions (brain networks). This makes the fetal period essential for normal development and perturbations to these processes render the brain at risk for neurodevelopmental deficits. Mapping and understanding global fetal and neonatal brain growth in vivo are great challenges, data is sparse and multimodal approaches are needed to fill the gap in our knowledge on neuroimaging interpretation. Recent advances in MRI now enable longitudinal study of the fetal and neonatal brain making detailed measurements of brain growth possible. For our studies, we used data from different resources including the first Dutch cohort of healthy pregnant participants that underwent MRI (YOUth study). The main aims of this thesis are: 1) to map the tremendous structural transformation and maturation of the developing brain in utero and neonatal period, both in healthy individuals and preterm born infants; 2) to reveal its functional blueprint in the second half of pregnancy. Different findings on fetal and neonatal MRI are discussed, with a focus on connectome (brain networks) development. Using fetal fMRI, this work shows a large overlap of fetal and adult functional networks, revealing that the blueprint of our brain is established before birth. Other findings on novel baby-brain MRI analyzing techniques, cortical chemoarchitecture and functional connectivity, cortical expansion and the association with gene expression patterns, will be discussed as well

Connectomics in Schizophrenia: From Early Pioneers to Recent Brain Network Findings

Schizophrenia has been conceptualized as a brain network disorder. The historical roots of connectomics in schizophrenia go back to the late 19th century, when influential scholars such as Theodor Meynert, Carl Wernicke, Emil Kraepelin, and Eugen Bleuler worked on a theoretical understanding of the multifaceted syndrome that is currently referred to as schizophrenia. Their work contributed to the understanding that symptoms such as psychosis and cognitive disorganization might stem from abnormal integration or dissociation due to disruptions in the brain's association fibers. As methods to test this hypothesis were long lacking, the claims of these early pioneers remained unsupported by empirical evidence for almost a century. In this review, we revisit and pay tribute to the old masters and, discussing recent findings from the developing field of disease connectomics, we examine how their pioneering hypotheses hold up in light of current evidence

Cortical chemoarchitecture shapes macroscale effective functional connectivity patterns in macaque cerebral cortex

The mammalian cortex is a complex system of-at the microscale level-interconnected neurons and-at the macroscale level-interconnected areas, forming the infrastructure for local and global neural processing and information integration. While the effects of regional chemoarchitecture on local cortical activity are well known, the effect of local neurotransmitter receptor organization on the emergence of large scale region-to-region functional interactions remains poorly understood. Here, we examined reports of effective functional connectivity-as measured by the action of strychnine administration acting on the chemical balance of cortical areas-in relation to underlying regional variation in microscale neurotransmitter receptor density levels in the macaque cortex. Linking cortical variation in microscale receptor density levels to collated information on macroscale functional connectivity of the macaque cortex, we show macroscale patterns of effective corticocortical functional interactions-and in particular, the strength of connectivity of efferent macroscale pathways-to be related to the ratio of excitatory and inhibitory neurotransmitter receptor densities of cortical areas. Our findings provide evidence for the microscale chemoarchitecture of cortical areas to have a direct stimulating influence on the emergence of macroscale functional connectivity patterns in the mammalian brain

Multiscale examination of cytoarchitectonic similarity and human brain connectivity

The human brain comprises an efficient communication network, with its macroscale connectome organization argued to be directly associated with the underlying microscale organization of the cortex. Here, we further examine this link in the human brain cortex by using the ultrahigh-resolution BigBrain dataset; 11,660 BigBrain profiles of laminar cell structure were extracted from the BigBrain data and mapped to the MRI based Desikan– Killiany atlas used for macroscale connectome reconstruction. Macroscale brain connectivity was reconstructed based on the diffusion-weighted imaging dataset from the Human Connectome Project and cross-correlated to the similarity of laminar profiles. We showed that the BigBrain profile similarity between interconnected cortical regions was significantly higher than those between nonconnected regions. The pattern of BigBrain profile similarity across the entire cortex was also found to be strongly correlated with the pattern of corticocortical connectivity at the macroscale. Our findings suggest that cortical regions with higher similarity in the laminar cytoarchitectonic patterns have a higher chance of being connected, extending the evidence for the linkage between macroscale connectome organization and microscale cytoarchitecture

In sync with your child: The potential of parent–child electroencephalography in developmental research

Funding Information: This work was financially supported by the Dutch Scientific Council (NWO; VI.Veni.191G.025; PI: van den Heuvel) and the Sara van Dam z.l. Foundation, Royal Netherlands Academy of Arts and Sciences (PIs: van den Heuvel, Levy). Publisher Copyright: © 2022 Wiley Periodicals LLCHealthy interaction between parent and child is foundational for the child's socioemotional development. Recently, an innovative paradigm shift in electroencephalography (EEG) research has enabled the simultaneous measurement of neural activity in caregiver and child. This dual-EEG or hyperscanning approach, termed parent–child dual-EEG, combines the strength of both behavioral observations and EEG methods. In this review, we aim to inform on the potential of dual-EEG in parents and children (0–6 years) for developmental researchers. We first provide a general overview of the dual-EEG technique and continue by reviewing the first empirical work on the emerging field of parent–child dual-EEG, discussing the limited but fascinating findings on parent–child brain-to-behavior and brain-to-brain synchrony. We then continue by providing an overview of dual-EEG analysis techniques, including the technical challenges and solutions one may encounter. We finish by discussing the potential of parent–child dual-EEG for the future of developmental research. The analysis of multiple EEG data is technical and challenging, but when performed well, parent–child EEG may transform the way we understand how caregiver and child connect on a neurobiological level. Importantly, studying objective physiological measures of parent–child interactions could lead to the identification of novel brain-to-brain synchrony markers of interaction quality.Peer reviewe