Lower Functional Integration Research Articles

Evidence of shared and distinct functional and structural brain signatures in schizophrenia and autism spectrum disorder

Schizophrenia (SZ) and autism spectrum disorder (ASD) share considerable clinical features and intertwined historical roots. It is greatly needed to explore their similarities and differences in pathophysiologic mechanisms. We assembled a large sample size of neuroimaging data (about 600 SZ patients, 1000 ASD patients, and 1700 healthy controls) to study the shared and unique brain abnormality of the two illnesses. We analyzed multi-scale brain functional connectivity among functional networks and brain regions, intra-network connectivity, and cerebral gray matter density and volume. Both SZ and ASD showed lower functional integration within default mode and sensorimotor domains, but increased interaction between cognitive control and default mode domains. The shared abnormalties in intra-network connectivity involved default mode, sensorimotor, and cognitive control networks. Reduced gray matter volume and density in the occipital gyrus and cerebellum were observed in both illnesses. Interestingly, ASD had overall weaker changes than SZ in the shared abnormalities. Interaction between visual and cognitive regions showed disorder-unique deficits. In summary, we provide strong neuroimaging evidence of the convergent and divergent changes in SZ and ASD that correlated with clinical features.

Interindividual variability of functional connectome in schizophrenia

Schizophrenia is a complex psychiatric disorder that displays an outstanding interindividual variability in clinical manifestation and neurobiological substrates. A better characterization and quantification of this heterogeneity could guide the search for both common abnormalities (linked to lower intersubject variability) and the presence of biological subtypes (leading to a greater heterogeneity across subjects). In the current study, we address interindividual variability in functional connectome by means of resting-state fMRI in a large sample of patients with schizophrenia and healthy controls. Among the different metrics of distance/dissimilarity used to assess variability, geodesic distance showed robust results to head motion. The main findings of the current study point to (i) a higher between subject heterogeneity in the functional connectome of patients, (ii) variable levels of heterogeneity throughout the cortex, with greater variability in frontoparietal and default mode networks, and lower variability in the salience network, and (iii) an association of whole-brain variability with levels of clinical symptom severity and with topological properties of brain networks, suggesting that the average functional connectome overrepresents those patients with lower functional integration and with more severe clinical symptoms. Moreover, after performing a graph theoretical analysis of brain networks, we found that patients with more severe clinical symptoms had decreased connectivity at both whole-brain level and within the salience network, and that patients with higher negative symptoms had large-scale functional integration deficits.

The Relationship Between Air Pollution and Cognitive Functions in Children and Adolescents: A Systematic Review.

Air pollution has a negative impact on one's health and on the central nervous system. We decided to assess studies that evaluated the relationship between air pollution and cognitive functions in children and adolescents by reviewing studies that had been published between January 2009 and May 2019. We searched three major databases for original works (26 studies) and for studies using brain imaging methods based on MRI (six studies). Adverse effects of air pollutants on selected cognitive or psychomotor functions were found in all of the studies. Exposure to nitrogen dioxide, for example, was linked to impaired working memory, general cognitive functions, and psychomotor functions; particulate matter 2.5 was linked to difficulties in working memory, short-term memory, attention, processing speed, and fine motor function; black carbon was linked to poor verbal intelligence, nonverbal intelligence, and working memory; airborne copper was linked to impaired attentiveness and fine motor skills; isophorone was linked to lower mathematical skills; and polycyclic aromatic hydrocarbons in fetal life were linked to lower intelligence scores. The studies using MRI showed that high concentrations of air pollutants were linked to changes in the brain's white matter or lower functional integration and segregation in children's brain networks. In view of the global increase in air pollution, there is a need for further research to elucidate the relationship between air pollution and cognitive and motor development in children. According to some studies, neuroinflammation, the e4 allele of the apolipoprotein E gene, and gutathione-S-transferase gene polymorphism processes may play a role.

The Research on MEMS S&A Device with Metal-Silicon Composite Structure

MEMS Safety-and-Arming device is the new generation of S&A device, which integrates the mechanism of actuation and barrier. Fabricated by Micro-Nano processing, its minimized structure and easy integration make it indispensable support to the development of weapon miniaturization, integration and intelligence. Confined by the material and fabrication process, the current MEMS S&A device displays such problems as the tiny output displacement, weak structural strength and low functional integration. In order to solve these technical difficulties, the silicon based MEMS S&A device with metal enhanced structure is proposed in this paper. The process of bulk micromachining and electroplating are integrated together. Based on the SOI substrate, the fabrication of movable structure can be realized. This novel combination equips the device with the qualities of high structural strength and miniaturization. With specific control signal, the MEMS S&A device can generate 1 mm output displacement, and change the device status smoothly (safe to armed, or armed to safe). The micro detonator has been integrated in the system. Stimulated by the surge voltage (1400 V), the flyer can be accelerated to the speed of 1370 m/s. The safety and armed function is validated by the high pressure sensor. The test results show that the metal enhanced layer can stay intact after being stroked by the flyer, and the collision pressure has decreased almost 21.4 times (from 13.5 GPa to 632 MPa). [2019-0184]

Pre‐natal brain development as a target for urban air pollution

Air pollution is the main urban-related environmental hazard and one of the major contributors to the global burden of disease based on its cardiovascular-respiratory impacts. In children, exposure to urban air pollution is associated, among others, with decelerated neurodevelopment early in life and increased risk of neurodevelopmental problems such as attention-deficit hyperactivity disorder, autism spectrum disorders, academic failure and the start of Alzheimer's pathogenesis. However, the evidence of the effects of air pollution on brain development is still inadequate, mainly due to the limitations in (a) characterizing brain development (most studies were based on subjective tools such as questionnaires or neuropsychological tests) and (b) air pollution exposure (most studies only used residential levels based on geographical modelling and also overlooking the variation in the mixture of air pollutants as well as the composition and hence toxicity of particulate pollutants in different settings), (c) the lack of studies during the most vulnerable stages of brain development (foetal and early life (first two years post-natally)) and (d) the lack of structural and functional imaging data underlying these effects. In mice, in utero exposure to fine particles was linked to structural brain changes and there is a need to establish the generalizability of these findings in human beings. Though scarce, current evidence in children supports the importance of the pre-natal period as a susceptible window of exposure. Two studies in schoolchildren found that pre-natal air pollution exposure might damage brain structure while exposure during childhood was not linked to any structural alteration. Another study showed that children with higher traffic-related air pollution at school had lower functional integration in key brain networks, but no changes in brain structure, possibly partly because of the time window of air pollution exposure (in utero versus childhood exposure). A key development is to discover the windows of greatest sensitivity of structural brain changes to air pollution exposure by incorporating the recent advances in non-invasive imaging to characterize natal and post-natal brain development and exploring whether and to what extend placental dysfunction could mediate such an association. Studying pre-natal life is important because effects at this time are of a potentially irreversible nature and because the largest preventive opportunities occur during these periods.

Resting-state network connectivity and metastability predict clinical symptoms in schizophrenia

BackgroundThe functional architecture of resting-state networks (RSNs) is defined by their connectivity and metastability. Disrupted RSN connectivity has been amply demonstrated in schizophrenia while the role of metastability remains poorly defined. Here, we undertake a comprehensive characterisation of RSN organization in schizophrenia and test its contribution to the clinical profile of this disorder. MethodsWe extracted RSNs representing the default mode (DMN), central executive (CEN), salience (SAL), language (LAN), sensorimotor (SMN), auditory (AN) and visual (VN) networks from resting-state functional magnetic resonance imaging data obtained from patients with schizophrenia (n = 85) and healthy individuals (n = 48). For each network, we computed its functional cohesiveness and integration and used the Kuramoto order parameter to compute metastability. We used stepwise multiple regression analyses to test these RSN features as predictors of symptom severity in patients. ResultsRSN features respectively explained 14%, 17%, 12% and 5% of the variance in positive, negative, anxious/depressive and agitation/disorganization symptoms. Lower functional integration between the DMN, CEN and SMN primarily contributed to positive symptoms. The functional properties of the SAL network were key predictors of all other symptom dimensions; specifically, lower cohesiveness of the SAL, lower integration of this network with the LAN and higher integration with the CEN respectively contributed to negative, anxious/depressive and disorganization symptoms. Increased SAL metastability was associated with negative symptoms. ConclusionsThese results confirm the primacy of the SAL network for schizophrenia and demonstrate that abnormalities in RSN connectivity and metastability are significant predictors of schizophrenia-related psychopathology.

Altered Functional Connectivity in Sickle Cell Disease Exists at Rest and During Acute Pain Challenge.

Sickle cell disease (SCD) is a chronic pain disorder in which abnormally shaped red blood cells obstruct microcirculation causing ischemia and pain. The lack of SCD responsiveness to analgesics has led many to propose that nociceptive neural systems engaged when detecting pain become sensitized, resulting in an enhancement of pain response. Individuals with SCD and non-SCD controls were exposed to a painful stimuli of varying intensity using a pressure algometer and underwent several neuroimaging tasks. This study identified and characterized the neural correlates of possible central sensitization in SCD. We found functional connectivity abnormalities in individuals with SCD in the brain's somatosensory network, salience network, and default mode network during both an unstructured resting state and paradigm involving acute pain challenge. There was evidence for both increased and decreased connectivity which is consistent with findings in other chronic pain disorders. Preliminary evidence was found that subcortical brain regions might contribute to neurodevelopmental abnormalities in chronic pain. The results support a model in which SCD pain sensitization involves abnormally low functional integration of brain regions that make use of nociceptive information to plan movements, and hyperconnectivity of various frontal and parietal lobe regions that direct attention to or represent higher-order abstractions within circuits involved with either nocioceptive processing or detection of abnormally salient environmental stimuli.

Urban air pollution affects structural and functional processes of brain maturation in children

Introduction From conception to young adulthood, the human brain undergoes dynamic changes in both its structural and functional organization. This period of life is particularly vulnerable to environmental insults that may interfere with the cascade of neurodevelopmental processes. Exposure to urban air pollution has been associated with poorer cognitive performance, which is thought to be a result of direct interference with brain maturation. We aimed to assess the extent of such potential effects of urban pollution exposure during the prenatal period and the childhood. Methods A group of 263 children, aged 8 to 12 years, underwent magnetic resonance imaging to quantify regional brain volumes and functional connectivity in major neural networks and activation / deactivation dynamics during a sensory task. Prenatal NO2 exposure was estimated using both the mothers address during pregnancy and the data from an urban background monitoring station. A combined measurement of elemental carbon and NO2 in the school environment was used to assess urban air pollution exposure during the childhood period. Results While the children exposed to low prenatal NO2 levels showed an increase in white matter volume (WMV) with advancing age, no WMV progression was observed in the children exposed to higher prenatal levels. Similarly, in the opposite effect to that of age, a higher content of pollutants in the school environment was associated with lower functional integration and segregation in key brain networks relevant to both inner mental processes (the default mode network) and stimulus-driven mental operations. Conclusion Both prenatal and postnatal air pollution exposure appear to adversely affect the structural and functional brain maturation. Further research is needed to determine to what extent these disruptions in the brain maturation process are involved in the poor cognitive performance previously observed in children exposed to air pollution.

Traffic pollution exposure is associated with altered brain connectivity in school children

Children are more vulnerable to the effects of environmental elements due to their active developmental processes. Exposure to urban air pollution has been associated with poorer cognitive performance, which is thought to be a result of direct interference with brain maturation. We aimed to assess the extent of such potential effects of urban pollution on child brain maturation using general indicators of vehicle exhaust measured in the school environment and a comprehensive imaging evaluation. A group of 263 children, aged 8 to 12years, underwent MRI to quantify regional brain volumes, tissue composition, myelination, cortical thickness, neural tract architecture, membrane metabolites, functional connectivity in major neural networks and activation/deactivation dynamics during a sensory task. A combined measurement of elemental carbon and NO2 was used as a putative marker of vehicle exhaust. Air pollution exposure was associated with brain changes of a functional nature, with no evident effect on brain anatomy, structure or membrane metabolites. Specifically, a higher content of pollutants was associated with lower functional integration and segregation in key brain networks relevant to both inner mental processes (the default mode network) and stimulus-driven mental operations. Age and performance (motor response speed) both showed the opposite effect to that of pollution, thus indicating that higher exposure is associated with slower brain maturation. In conclusion, urban air pollution appears to adversely affect brain maturation in a critical age with changes specifically concerning the functional domain.

Synaptic Integration of Adult-Born Hippocampal Neurons Is Locally Controlled by Astrocytes

Adult neurogenesis is regulated by the neurogenic niche, through mechanisms that remain poorly defined. Here, we investigated whether niche-constituting astrocytes influence the maturation of adult-born hippocampal neurons using two independent transgenic approaches to block vesicular release from astrocytes. In these models, adult-born neurons but not mature neurons showed reduced glutamatergic synaptic input and dendritic spine density that was accompanied with lower functional integration and cell survival. By taking advantage of the mosaic expression of transgenes in astrocytes, we found that spine density was reduced exclusively in segments intersecting blocked astrocytes, revealing an extrinsic, local control of spine formation. Defects in NMDA receptor (NMDAR)-mediated synaptic transmission and dendrite maturation were partially restored by exogenous D-serine, whose extracellular level was decreased in transgenic models. Together, these results reveal a critical role for adult astrocytes in local dendritic spine maturation, which is necessary for the NMDAR-dependent functional integration of newborn neurons.

A model of functional integration and conflict

Purpose – The purpose of this article is to generate theory on how functional integration and conflict interrelate by studying the interface between production and purchasing. Design/methodology/approach – An interpretive single case research methodology is adopted. The authors rely on in-depth interviewing of managers in the production and purchasing functions of a construction company, as well as by its suppliers. Findings – Given low functional integration, antagonistic reasoning within each function and resultant conflicting behaviors are allowed to develop in a negative cycle, escalating the conflict between purchasing and production. This process leads to the creation of two opposing functional sourcing models that serve as blueprints for behavior. Research limitations/implications – The single case methodology was chosen to maximize depth and detail and form an ideal foundation for theory building. Future qualitative and quantitative studies should inquire further into the studied phenomenon to increase analytical and statistical generalizability of the proposed model. Practical implications – The findings can help managers understand how poor integration between functions can develop into cross-functional conflict. Facing a conflicting functional relationship, managers must resort to conflict resolution methods, instead of attempting to integrate, as several integrative devices are not appropriate in conflicting interfaces. Originality/value – The proposed model contributes by connecting the constructs of integration, group reasoning, and conflict, thereby generating knowledge on conflict development processes in cross-functional interfaces. Furthermore, the article contributes by uncovering the difficulties associated with implementing spend consolidation, a prevailing sourcing strategy.