Brain Architecture Research Articles

Around the moving image

The article is devoted to the analysis of the "moving image" as a phenomenon of noospheric significance, a phenomenon of historically unavoidable, existential-authentic, extremely objective symbolic fixation of the temporal-spatial processuality of the world. It was found out that this "moving image" put an end to the polemic presented by the German educator Lessing in his treatise "Laokoon, or on the limits of painting and poetry", outlining the boundaries between "spatial arts" that reflect "space, objects in it" and poetry (properly language art), which embodies first of all time, and in this way connected Time and Space in its very structure. A very specific interaction of spatial and temporal information in the very architecture of the human brain has been established, in which the left hemisphere forms language-speech, and the right hemisphere forms spatial representationsformations, and the human brain itself "films" the surrounding world in the same way as a movie camera, but in full awareness.

The Impact of the COVID-19 Pandemic on Mental Health Among the General Population: A Narrative Review

The Coronavirus Disease-2019 (COVID-19) has infected millions of people worldwide, resulting in a global burden for long-term care of sufferers. The impact of COVID-19 has affected the mental health of innumerable people. Emotional, psychological, and social well-being are all parts of our mental health, influencing our thoughts, emotions, and behaviours. Additionally, it affects how people respond to stress and make good decisions. For instance, depression raises the risk of a wide range of physical health issues, especially chronic illnesses like diabetes, heart disease, and stroke. The COVID-19 pandemic has infected millions worldwide, leaving a global burden for the long-term care of COVID-19 survivors. Therefore, it is imperative to study the shortterm (post-COVID) and long-term effects of COVID-19, specifically as the local and systemic pathophysiological outcomes of other coronavirus-related diseases (such as Middle East Respiratory Syndrome - MERS and Severe Acute Respiratory Syndrome Coronavirus 2 - SARS-CoV-2) have been well-documented. Mental health was evaluated using four psychological measurement scales to assess fear of COVID-19, depression, general anxiety, and post-traumatic stress. The worldwide social and economic upheaval has resulted in the worst recession since the Great Depression. The Impact of Event Scale-Revised and the Depression, Anxiety, and Stress Scale can be used to evaluate the psychological impact and mental health status. The main themes include the biology of stress and the effect of infection on the brain. Adversity can cause anatomical and functional changes in the brain. Although cortisol, for example, can alter brain architecture, tolerable stress is mitigated by protective systems and interpersonal connections that promote adaptive coping. The risk of physical and mental illness, as well as cognitive decline, may increase due to toxic stress, which is often caused by prolonged activation. From a behavioural standpoint, it is essential to understand burnout, compassion fatigue, grief, and other psychological processes and strategies in the context of the COVID-19 pandemic. COVID-19 has adversely affected the mental states of people. The COVID-19 pandemic is associated with significantly high levels of psychological distress that meet the threshold for clinical relevance. Mitigating the harmful effects of COVID-19 on mental health is an international public health priority

The role of combined oral contraceptive use on the serotonin 2A receptor brain architecture in healthy women

The role of combined oral contraceptive use on the serotonin 2A receptor brain architecture in healthy women

Protruding cantilever microelectrode array to monitor the inner electrical activity of cerebral organoids.

Stem cell-derived cerebral organoids are artificially grown miniature organ-like structures mimicking embryonic brain architecture. They are composed of multiple neural cell types with 3D cell layer organization exhibiting local field potential. Measuring the extracellular electrical activity by means of conventional planar microelectrode arrays is particularly challenging due to the 3D architecture of organoids. In order to monitor the intra-organoid electrical activity of thick spheroid-shaped samples, we developed long protruding microelectrode arrays able to penetrate the inner regions of cerebral organoids to measure the local potential of neurons within the organoids. A new microfabrication process has been developed which, thanks to the relaxation of internal stresses of a stack of materials deposited over a sacrificial layer, allows one to build a protruding cantilever microelectrode array placed at the apex of beams which rise vertically, over two hundred microns. These slender beams inserted deeply into the organoids give access to the recording of local field potential from neurons buried inside the organoid. This novel device shall provide valuable tools to study neural functions in greater detail.

The Correlation Between Knowledge of Family Development Tasks and the Application of Developmental Stimulation in Pre-School Aged Children

The development of a child is a fundamental part of human development; this emphasizes the architecture of a person's brain formed at the beginning of life, which comes from genetic and environmental influences. There are two important factors that influence a child's development, namely genetic factor and environmental stimulation factor. Stimulation has an important role in the growth and development of children because the child's brain develops very quickly when it is stimulated. The main task of a family that determines the child's ability is on the task of family in every stage of family development. This study aims to determine the correlation between knowledge of family development tasks and the application of developmental stimulation in preschool-aged children. The research design used was quantitative research with a correlational descriptive method and a cross sectional study approach. The data obtained from 242 respondens and then analyzed using bivariate analysis (chi-square test). After analyzing the data, the results showed that the value of p=0.000 (<α 0.05). Hence, there is a significant correlation between knowledge of family development tasks and the application of developmental stimulation in pre-school-aged children. Families who have good knowledge of family development tasks have the ability to perform developmental stimulation 22.6 times greater than families who have less knowledge. Family knowledge about good family development tasks will have an impact on meeting children's needs. The children who get good stimulation could have a better impact on their development. The result of this study is expected to be the basis for Community Nurses who work in primary health services to be able to carry out promotive and preventive efforts with a family approach.

Brain structure and stroke risk score in subjects without a history of atrial fibrillation

CHA2DS2-VASc score system aids in clinical decision-making in subjects with atrial fibrillation (AF). Little is known on the association between CHA2DS2-VASc scores and brain structure in patients without cardiac arrhythmia. Detailed brain architecture analysis was performed. Assessment of bivariate correlation between the volume of segmented brain structures and Z-scores of CHA2DS2-VASc showed that higher risk scores correlated negatively and significantly with various brain framework. Our study confirms that a cluster of risk factors incorporated in a well-established risk score correlated with brain tissue volume independently of the presence of an arrhythmia.

Hippocampus and Prefrontal Cortex Following the Use of Anti-Retroviral Therapy in Adult Wistar Rats: Therapeutic Role of Epigallocatechin Gallate.

The contribution of prefrontal-hippocampal interactions to brain function of people infected with HIV may be aggravated by toxicities due to long-term use of antiretroviral agents. This study was designed to investigate the curative potential of Epigallotatechin gallate (EGCG) in the treatment of neurodegenerative disorders as a possible consequence of antiretroviral toxicity. Twenty-four adult male Wistar rats, weighing 80~100g, were divided into four groups and treated as follows: control A (distilled water), B (HAART), C (EGCG 2.5mg/kg), D (EGCG 2.5mg/kg) + HAART) Brain histology, immunohistochemistry, and oxidative stress markers such as superoxide dismutase (SOD), glutathione (GSH),catalase (CAT) and malondialdehyde (MDA) were examined. The use of highly active antiretroviral therapy (HAART) showed extensive architectural deformation with pyknotic neuronal cells and obliterated neurons in the hippocampus and prefrontal cortex. Expression of inflammasome cells was also evident in this group. MDA levels increased significantly with a significant reduction in the levels of GSH, as well as antioxidant enzyme (SOD and CAT) activities compared to other treatment groups. Treatment with EGCG resulted in partial neuronal restoration of histopathological alterations, and modulation of NLRP3 inflammasome in the hippocampus and prefrontal cortex. EGCG also showed significant improvements in terms of increased antioxidant levels of SOD, GSH, CAT and a reduced MDA level and well-preserved brain architecture. Epigallocatechin gallate improves brain morphology and function with a reversal of HAART-induced alterations.

Direct modulation index: A measure of phase amplitude coupling for neurophysiology data.

Neural communication across different spatial and temporal scales is a topic of great interest in clinical and basic science. Phase-amplitude coupling (PAC) has attracted particular interest due to its functional role in a wide range of cognitive and motor functions. Here, we introduce a novel measure termed the direct modulation index (dMI). Based on the classical modulation index, dMI provides an estimate of PAC that is (1) bound to an absolute interval between 0 and +1, (2) resistant against noise, and (3) reliable even for small amounts of data. To highlight the properties of this newly-proposed measure, we evaluated dMI by comparing it to the classical modulation index, mean vector length, and phase-locking value using simulated data. We ascertained that dMI provides a more accurate estimate of PAC than the existing methods and that is resilient to varying noise levels and signal lengths. As such, dMI permits a reliable investigation of PAC, which may reveal insights crucial to our understanding of functional brain architecture in key contexts such as behaviour and cognition. A Python toolbox that implements dMI and other measures of PAC is freely available at https://github.com/neurophysiological-analysis/FiNN.

Functional Coherence in Intrinsic Frontal Executive Networks Predicts Cognitive Impairments in Alcohol Use Disorder.

Growing evidence highlights the potential of innovative rehabilitative interventions such as cognitive remediation and neuromodulation, aimed at reducing relapses in Alcohol Use Disorder (AUD). Enhancing their effectiveness requires a thorough description of the neural correlates of cognitive alterations in AUD. Past related attempts, however, were limited by the focus on selected neuro-cognitive variables. We aimed to fill this gap by combining, in 22 AUD patients and 18 controls, an extensive neuro-cognitive evaluation and metrics of intrinsic connectivity as highlighted by resting-state brain activity. We addressed an inherent property of intrinsic activity such as intra-network coherence, the temporal correlation of the slow synchronous fluctuations within resting-state networks, representing an early biomarker of alterations in the functional brain architecture underlying cognitive functioning. AUD patients displayed executive impairments involving working-memory, attention and visuomotor speed, reflecting abnormal coherence of activity and grey matter atrophy within default mode, in addition to the attentional and the executive networks. The stronger relationship between fronto-lateral coherent activity and executive performance in patients than controls highlighted possible compensatory mechanisms counterbalancing the decreased functionality of networks driving the switch from automatic to controlled behavior. These results provide novel insights into AUD patients' cognitive impairments, their neural bases, and possible targets of rehabilitative interventions.

Differences in the functional brain architecture of sustained attention and working memory in youth and adults.

Sustained attention (SA) and working memory (WM) are critical processes, but the brain networks supporting these abilities in development are unknown. We characterized the functional brain architecture of SA and WM in 9- to 11-year-old children and adults. First, we found that adult network predictors of SA generalized to predict individual differences and fluctuations in SA in youth. A WM model predicted WM performance both across and within children-and captured individual differences in later recognition memory-but underperformed in youth relative to adults. We next characterized functional connections differentially related to SA and WM in youth compared to adults. Results revealed 2 network configurations: a dominant architecture predicting performance in both age groups and a secondary architecture, more prominent for WM than SA, predicting performance in each age group differently. Thus, functional connectivity (FC) predicts SA and WM in youth, with networks predicting WM performance differing more between youths and adults than those predicting SA.

Flexibility of in vitro cortical circuits influences resilience from microtrauma.

Small clusters comprising hundreds to thousands of neurons are an important level of brain architecture that correlates single neuronal properties to fulfill brain function, but the specific mechanisms through which this scaling occurs are not well understood. In this study, we developed an in vitro experimental platform of small neuronal circuits (islands) to probe the importance of structural properties for their development, physiology, and response to microtrauma. Primary cortical neurons were plated on a substrate patterned to promote attachment in clusters of hundreds of cells (islands), transduced with GCaMP6f, allowed to mature until 10-13 days in vitro (DIV), and monitored with Ca2+ as a non-invasive proxy for electrical activity. We adjusted two structural factors-island size and cellular density-to evaluate their role in guiding spontaneous activity and network formation in neuronal islands. We found cellular density, but not island size, regulates of circuit activity and network function in this system. Low cellular density islands can achieve many states of activity, while high cellular density biases islands towards a limited regime characterized by low rates of activity and high synchronization, a property we summarized as "flexibility." The injury severity required for an island to lose activity in 50% of its population was significantly higher in low-density, high flexibility islands. Together, these studies demonstrate flexible living cortical circuits are more resilient to microtrauma, providing the first evidence that initial circuit state may be a key factor to consider when evaluating the consequences of trauma to the cortex.

Salix subserrata Bark Extract-Loaded Chitosan Nanoparticles Attenuate Neurotoxicity Induced by Sodium Arsenate in Rats in Relation with HPLC–PDA-ESI–MS/MS Profile

Pollution is a worldwide environmental risk. Arsenic (As) is an environmental pollutant with a major health concern due to its toxic effects on multiple body organs, including the brain. Humans are exposed to As through eating contaminated food and water or via skin contact. Salix species (willow) are plants with medicinal efficacy. Salix subserrata Willd bark extract-loaded chitosan nanoparticles (SBE.CNPs) was formulated, characterized, and evaluated against As-induced neurotoxicity. The stem bark was selected for nanoparticle formulation based on HPLC–PDA-ESI–MS/MS profiling and in vitro antioxidant assessment using free radical scavenging activity. SBE.CNPs demonstrated an average un-hydrated diameter of 193.4 ± 24.5 nm and zeta potential of + 39.6 ± 0.4 mV with an encapsulation efficiency of 83.7 ± 4.3%. Compared to As-intoxicated rats, SBE.CNP-treated rats exhibited anxiolytic activity and memory-boosting as evidenced in open field test, light–dark activity box, and Y-maze. Also, it increased the antioxidant biomarkers, including superoxide dismutase and glutathione peroxidase associated with reducing the malondialdehyde levels and apoptotic activity. Besides this, SBE.CNPs maintained the brain architecture and downregulated both nuclear factor-kappa B and heme oxygenase-1 expression. These results suggest that SBE.CNP administration showed promising potent neuroprotective and antioxidative efficiencies against arsenic-induced oxidative threats.

Fine-tuning of mTOR signaling by the UBE4B-KLHL22 E3 ubiquitin ligase cascade in brain development.

Spatiotemporal regulation of the mechanistic target of rapamycin (mTOR) pathway is pivotal for establishment of brain architecture. Dysregulation of mTOR signaling is associated with a variety of neurodevelopmental disorders. Here, we demonstrate that the UBE4B-KLHL22 E3 ubiquitin ligase cascade regulates mTOR activity in neurodevelopment. In a mouse model with UBE4B conditionally deleted in the nervous system, animals display severe growth defects, spontaneous seizures and premature death. Loss of UBE4B in the brains of mutant mice results in depletion of neural precursor cells and impairment of neurogenesis. Mechanistically, UBE4B polyubiquitylates and degrades KLHL22, an E3 ligase previously shown to degrade the GATOR1 component DEPDC5. Deletion of UBE4B causes upregulation of KLHL22 and hyperactivation of mTOR, leading to defective proliferation and differentiation of neural precursor cells. Suppression of KLHL22 expression reverses the elevated activity of mTOR caused by acute local deletion of UBE4B. Prenatal treatment with the mTOR inhibitor rapamycin rescues neurogenesis defects in Ube4b mutant mice. Taken together, these findings demonstrate that UBE4B and KLHL22 are essential for maintenance and differentiation of the precursor pool through fine-tuning of mTOR activity.

Artificial intelligence system for verification of schizophrenia via theta-EEG rhythm

Schizophrenia (SZ) is an illness of the mind. Electroencephalogram (EEG) is an excellent notion of forecasting abnormalities and cognitive tasks as part of the study of mental illness. This scholarly research aimed to develop an Artificial Intelligence System (AIS) to research and classify the EEG signal features of healthy and Schizophrenia patients. The developed AIS was utilized to assess a 19-channel EEG signal collected from normal and Schizophrenia patients. The EEG signal is decomposed using Multi-level Discrete Wavelet Transformation (MDWT) into distinct EEG rhythms, specifically theta, alpha, beta, and gamma. Eight statistical feature extraction was then implemented to calculate 2128 features of healthy and 2128 features of schizophrenia patients from the Theta-EEG rhythm. And finally, ten machine-learning state-of-the-art classifiers are stacked together to classify the 4256 statistical features with different kernels. The experimental outcomes; the performance of (a) the Ada-Boost Classifier with Central electrodes is 85.71%, (b) the Gradient-Boosting Classifier with Parietal-Occipital electrodes is 80.00%, (c) the Decision-Tree Classifier & Ada-Boost Classifier with Frontal-Prefrontal electrodes is 76.67%, and (d) the XGBoost Classifier with the combination of the Central, Parietal-Occipital and Frontal-Prefrontal electrodes is 78.75%. The research achievement; (A) “In 10–20 Electrodes system of the brain architecture, Central electrodes are the better choice as compared to the Parietal-Occipital, and Frontal-Prefrontal electrodes for the EEG-based investigation of SZ,” (B) “Parietal-Occipital electrodes are the better choice as compared to the Frontal-Prefrontal electrodes for the EEG-based investigation of SZ,” (C) “Theta-EEG rhythm is the most relevant EEG rhythm for the diagnosis of SZ.”

Neuromorphic Functional Modules of a Spiking Neural Network

In the current era, the design and development of artificial neural networks exploiting the architecture of the human brain have evolved rapidly. Artificial neural networks (ANN) effectively solve a wide range of common artificial-intelligence tasks involving data classification and recognition, prediction, forecasting and adaptive control of the behavior of an object. The biologically inspired underlying principles of ANN operation have certain advantages over the conventional von Neumann architecture including unsupervised learning, architectural flexibility and adaptability to environmental change and high performance under significantly reduced power consumption due to large parallel and asynchronous data processing. In this paper, we present a circuit design of main functional blocks (neurons and synapses) intended for the hardware implementation of a perceptron-based feedforward spiking neural network. As the third generation of artificial neural networks, spiking neural networks perform data processing utilizing spikes, which are discrete events (or functions) that take place at points in time. Neurons in spiking neural networks initiate precisely timed spikes and communicate with each other via spikes transmitted through synaptic connections or synapses with adaptable scalable weight. One of the prospective approaches to emulating synaptic behavior in hardware implemented spiking neural networks is to use nonvolatile-memory devices with analog conduction modulation (or memristive structures). Here we propose a circuit design for functional analogues of memristive structures to mimic synaptic plasticity, pre- and postsynaptic neurons which could be used for developing a circuit design of spiking-neural-network architectures with different training algorithms including the spike-timing-dependent-plasticity learning rule. Two different circuits of an electrical synapse are developed. The first one is an analog synapse with a photoresistor optocoupler used to ensure the tunable conductivity for synaptic-plasticity emulation. While the second one is a digital synapse, in which the synaptic weight is stored in a digital code with its direct conversion into conductivity (without a digital-to-analog converter and photoresistor optocoupler). The results of prototyping the developed circuits for electronic analogs of synapses, pre- and postsynaptic neurons and the study of transient processes are presented. The developed approach could provide a basis for the ASIC (application-specific integrated circuit) design of spiking neural networks based on CMOS (complementary metal—oxide–semiconductor) design technology.

Situating tau pathology and neuroinflammation along the principal gradients of brain organisation in Alzheimer’s disease

AbstractBackgroundThe spread of abnormal tau along connectivity‐based networks is a hallmark of Alzheimer’s disease (AD). In addition, activated microglia was shown to affect tau spread across networks. However, traditional network approaches using atlas‐defined regions suffer from assuming within‐region homogenous connectivity, as well as abrupt and linear connectivity changes between the regions; while, in fact, brain structure and function exist as complex overlapping axes of connectivity variation. Here, we studied smooth/continuous spatial transitions or ‘gradients’ of connectivity and their link to gradients of pathology in AD. This work provides novel insights into brain architecture driving pathology spread.MethodWe enrolled 220 individuals including 106 cognitively normal Aβ‐negative (A‐) and 37 A+, and 77 MCI/AD A+ (TRIAD). From diffusion‐weighted MRI and fMRI data, we estimated region‐to‐region fiber count and correlated timeseries, respectively, and averaged subject‐wise connectivity matrices to create structural and functional ‘template connectomes’. From 18F‐MK6240 and 11C‐PBR28 PET data, we extracted regional tau and neuroinflammation SUVR values, respectively, and created covariance matrices for each disease stage. Next, the template connectomes/covariance matrices were subjected to non‐linear dimensionality reduction to extract embedded components (‘gradients’). We correlated the primary gradients of functional or structural connectivity (G1FC/G1SC) with the primary and secondary gradients of tau or neuroinflammation (G1TAU/G2TAU; G1INFLAM/G2INFLAM). We employed three brain atlases for validation: high‐resolution customized Glasser‐atlas (1332 equally‐sized subregions), DKT, and Schaefer‐100.ResultG1FC replicated the previously reported ‘uni‐to‐transmodal’ functional gradient (Margulies 2016) and correlated strongly with G1TAU in cognitively impaired A+ (Fig.1 A); illustrating a common topographic variation in tau spread and functional connectivity in symptomatic stages. Conversely, G1SC ran between medial‐temporal‐lobe (MTL)/posterior and frontal/anterior regions, and correlated strongly with both G2TAU (Fig.1 B) and G1INFLAM (Fig.1 C) in cognitively (un)impaired A+; illustrating a common topographic variation in tau/microglia and structural connectivity already present at early disease stages. Different brain atlases led to similar results.ConclusionWe identified two gradients of continuous topographic variation in tau and neuroinflammation, potentially reflecting heterogeneity of AD‐subgroups. While microglial activation and early‐stage tau propagation may be largely dominated by structural organisation, later‐stage tau propagation may be more heterogeneously associated with variation in structural and particularly functional connectivity.

Coenzyme Q10 prevented Trypanosoma brucei rhodesiense-mediated breach of the blood brain barrier, inflammation and organ damage in late stage of Human African Trypanosomiasis.

During the late stage of Human African Trypanosomiasis (HAT), there is severe cytokine-driven inflammation, oxidative stress and organ damage. Controlling inflammation and oxidative damage presents unique therapeutic opportunities to improve treatment outcome. The current study sought to determine the putative impact of Coenzyme-Q10 (Co-Q10), a potent antioxidant and anti-inflammatory, on adverse inflammatory and oxidative events during Trypanosoma brucei rhodesiense (T.b.r) infection. Group one constituted the control; the second group was infected with T.b.r; the third group was orally administered with 200mg/kg Co-Q10 for two weeks; thereafter, Co-Q10 administration continued after infection with T.b.r. Co-Q10 improved the survival rate of infected mice and prevented full blown parasite driven splenomegaly and hepatomegaly. Co-Q10 prevented characteristic T.b.r-driven breach of the blood brain barrier and improved neurological integrity among T.b.r infected mice. Co-Q10 protected from T.b.r-induced microcytic hypochromic anaemia and thrombocytopenia. T.b.r-induced oxidative stress in the vital organs was assuaged following exposure to Co-Q10. Co-Q10 blocked T.b.r-induced derangement of high density lipoprotein and triglyceride levels. Co-Q10 significantly abrogated T.b.r-driven elevation of serum TNF-α and IFN-γ levels. Moreover, T.b.r-induced kidney and liver damage was assuaged by Co-Q10 administration. Co-Q10 administration downregulated T.b.r-induced elevation of uric acid and C-reactive protein. Likewise, T.b.r infected mice receiving Co-Q10 exhibited normal brain architecture. In conclusion, treatment with Co-Q10 may be useful in protecting against T.b.r-mediated organ injury, lethal inflammation and oxidative stress commonly present in severe late stage HAT; and presents unique opportunities for an adjunct therapy for late stage HAT.

Illuminating links between cis-regulators and trans-acting variants in the human prefrontal cortex

BackgroundNeuropsychiatric disorders afflict a large portion of the global population and constitute a significant source of disability worldwide. Although Genome-wide Association Studies (GWAS) have identified many disorder-associated variants, the underlying regulatory mechanisms linking them to disorders remain elusive, especially those involving distant genomic elements. Expression quantitative trait loci (eQTLs) constitute a powerful means of providing this missing link. However, most eQTL studies in human brains have focused exclusively on cis-eQTLs, which link variants to nearby genes (i.e., those within 1 Mb of a variant). A complete understanding of disease etiology requires a clearer understanding of trans-regulatory mechanisms, which, in turn, entails a detailed analysis of the relationships between variants and expression changes in distant genes.MethodsBy leveraging large datasets from the PsychENCODE consortium, we conducted a genome-wide survey of trans-eQTLs in the human dorsolateral prefrontal cortex. We also performed colocalization and mediation analyses to identify mediators in trans-regulation and use trans-eQTLs to link GWAS loci to schizophrenia risk genes.ResultsWe identified ~80,000 candidate trans-eQTLs (at FDR<0.25) that influence the expression of ~10K target genes (i.e., “trans-eGenes”). We found that many variants associated with these candidate trans-eQTLs overlap with known cis-eQTLs. Moreover, for >60% of these variants (by colocalization), the cis-eQTL’s target gene acts as a mediator for the trans-eQTL SNP's effect on the trans-eGene, highlighting examples of cis-mediation as essential for trans-regulation. Furthermore, many of these colocalized variants fall into a discernable pattern wherein cis-eQTL’s target is a transcription factor or RNA-binding protein, which, in turn, targets the gene associated with the candidate trans-eQTL. Finally, we show that trans-regulatory mechanisms provide valuable insights into psychiatric disorders: beyond what had been possible using only cis-eQTLs, we link an additional 23 GWAS loci and 90 risk genes (using colocalization between candidate trans-eQTLs and schizophrenia GWAS loci).ConclusionsWe demonstrate that the transcriptional architecture of the human brain is orchestrated by both cis- and trans-regulatory variants and found that trans-eQTLs provide insights into brain-disease biology.

Expectant mothers and fathers' knowledge of nurturing care in a developing country.

The Nurturing Care Framework (NCF), which has been emphasized by the World Health Organization (WHO) in recent years and is among the United Nations Sustainable Development Goals (SDGs), expresses the conditions created to promote early childhood development (ECD). These conditions aim to provide opportunities for children in the Good Health, Adequate Nutrition, Responsive Caregiving, Security and Safety, and Opportunities for Early Learning (5 Components) by caregivers, primarily from low and middle-income countries (LMICs). The aim of this study is to examine the knowledge and awareness of expectant mothers and fathers in Turkey, about the NCF. In this study, a cross-sectional, analytical research design was used. Nurturing Care (NC) knowledge and awareness levels of expectant mothers and fathers in the 2nd and 3rd trimesters of pregnancy were determined via the online form of "The Knowledge of Nurturing Care Inventory (KNCI)" prepared by the researchers. This form consists of 60 questions describing the 5 components mentioned above. The sample contains a total of 103 people, 91 (88.3%) women, and 12 (11.7%) men. Among the findings, the highest mean of knowledge level (13.76 ± 1.22) was found in Responsive Caregiving, and the lowest mean of knowledge level (4.35 ± 1.83) was found in Opportunities for Early Learning. The general level of knowledge on NC was found to vary statistically significantly depending on gender in favor of the women [t(101) = 3.27, p < .05], depending on educational status in favor of those with university and graduate education [F(2, 100) = 3.481, p < .05], depending on participation in pregnancy school training in favor of those who attended [t(101) = 2.349, p < .05], and depending on knowledge on how to support development in favor of those who know how to support [t(101) = 2.370, p < .05]. As a result, expectant parents need information and support about the period when children can acquire the basic developmental milestones and about the developmental risk indicators. More research is needed to implement the NCF starting from the preconception period, especially in LMICs, so that the opportunities in early childhood (which is the time period when the brain architecture is shaped, and development is the fastest) are not missed.

The low dimensionality of post-stroke cognitive deficits: it's the lesion anatomy!

For years, dissociation studies on neurological single-case patients with brain lesions were the dominant method to infer fundamental cognitive functions in neuropsychology. In contrast, the association between deficits was considered to be of less epistemological value. Still, associational computational methods for dimensionality reduction-such as principal component analysis or factor analysis-became popular for the identification of fundamental cognitive functions and to understand human cognitive brain architecture from post-stroke neuropsychological profiles. In the present in silico study with lesion imaging of 300 stroke patients, we investigated the dimensionality of artificial simulated neuropsychological profiles that exclusively contained independent fundamental cognitive functions without any underlying low-dimensional cognitive architecture. Still, the anatomy of stroke lesions alone was sufficient to create a dependence between variables that allowed a low-dimensional description of the data with principal component analysis. All criteria that we used to estimate the dimensionality of data, including the Kaiser criterion, were strongly affected by lesion anatomy, while the Joliffe criterion provided the least affected estimates. The dimensionality of profiles was reduced by 62-70% for the Kaiser criterion, up to the degree that is commonly found in neuropsychological studies on actual cognitive measures. The interpretability of such low-dimensional factors as deficits of fundamental cognitive functions and their provided insights into human cognitive architecture thus seem to be severely limited, and the heavy focus of current cognitive neuroscience on group studies and associations calls for improvements. We suggest that qualitative criteria and dissociation patterns could be used to refine estimates for the dimensionality of the cognitive architecture behind post-stroke deficits. Further, given the strong impact of lesion anatomy on the associational structure of data, we see the need for further optimization of interpretation strategies of computational factors in post-stroke lesion studies of cognitive deficits.