Modularity and robustness of frontal cortical networks.

Neural activity underlying short-term memory is maintained by interconnected networks of brain regions. It remains unknown how brain regions interact to maintain persistent activity while exhibiting robustness to corrupt information in parts of the network. We simultaneously measured activity in large neuronal populations across mouse frontal hemispheres to probe interactions between brain regions. Activity across hemispheres was coordinated to maintain coherent short-term memory. Across mice, we uncovered individual variability in the organization of frontal cortical networks. A modular organization was required for the robustness of persistent activity to perturbations: each hemisphere retained persistent activity during perturbations of the other hemisphere, thus preventing local perturbations from spreading. A dynamic gating mechanism allowed hemispheres to coordinate coherent information while gating out corrupt information. Our results show that robust short-term memory is mediated by redundant modular representations across brain regions. Redundant modular representations naturally emerge in neural network models that learned robust dynamics.

A Map-like Micro-Organization of Grid Cells in the Medial Entorhinal Cortex.

How the topography of neural circuits relates to their function remains unclear. Although topographic maps exist for sensory and motor variables, they are rarely observed for cognitive variables. Using calcium imaging during virtual navigation, we investigated the relationship between the anatomical organization and functional properties of grid cells, which represent a cognitive code for location during navigation. We found a substantial degree of grid cell micro-organization in mouse medial entorhinal cortex: grid cells and modules all clustered anatomically. Within a module, the layout of grid cells was a noisy two-dimensional lattice in which the anatomical distribution of grid cells largely matched their spatial tuning phases. This micro-arrangement of phases demonstrates the existence of a topographical map encoding a cognitive variable in rodents. It contributes to a foundation for evaluating circuit models of the grid cell network and is consistent with continuous attractor models as the mechanism of grid formation.

Whole-Cell Models and Simulations in Molecular Detail.

Comprehensive data about the composition and structure of cellular components have enabled the construction of quantitative whole-cell models. While kinetic network-type models have been established, it is also becoming possible to build physical, molecular-level models of cellular environments. This review outlines challenges in constructing and simulating such models and discusses near- and long-term opportunities for developing physical whole-cell models that can connect molecular structure with biological function.

Large-Scale Mechanistic Models of Brain Circuits with Biophysically and Morphologically Detailed Neurons.

Understanding the brain requires studying its multiscale interactions from molecules to networks. The increasing availability of large-scale datasets detailing brain circuit composition, connectivity, and activity is transforming neuroscience. However, integrating and interpreting this data remains challenging. Concurrently, advances in supercomputing and sophisticated modeling tools now enable the development of highly detailed, large-scale biophysical circuit models. These mechanistic multiscale models offer a method to systematically integrate experimental data, facilitating investigations into brain structure, function, and disease. This review, based on a Society for Neuroscience 2024 MiniSymposium, aims to disseminate recent advances in large-scale mechanistic modeling to the broader community. It highlights (1) examples of current models for various brain regions developed through experimental data integration; (2) their predictive capabilities regarding cellular and circuit mechanisms underlying experimental recordings (e.g., membrane voltage, spikes, local-field potential, electroencephalography/magnetoencephalography) and brain function; and (3) their use in simulating biomarkers for brain diseases like epilepsy, depression, schizophrenia, and Parkinson's, aiding in understanding their biophysical underpinnings and developing novel treatments. The review showcases state-of-the-art models covering hippocampus, somatosensory, visual, motor, auditory cortical, and thalamic circuits across species. These models predict neural activity at multiple scales and provide insights into the biophysical mechanisms underlying sensation, motor behavior, brain signals, neural coding, disease, pharmacological interventions, and neural stimulation. Collaboration with experimental neuroscientists and clinicians is essential for the development and validation of these models, particularly as datasets grow. Hence, this review aims to foster interest in detailed brain circuit models, leading to cross-disciplinary collaborations that accelerate brain research.

Reused Protein Segments Linked to Functional Dynamics.

Protein space is characterized by extensive recurrence, or "reuse," of parts, suggesting that new proteins and domains can evolve by mixing-and-matching of existing segments. From an evolutionary perspective, for a given combination to persist, the protein segments should presumably not only match geometrically but also dynamically communicate with each other to allow concerted motions that are key to function. Evidence from protein space supports the premise that domains indeed combine in this manner; we explore whether a similar phenomenon can be observed at the sub-domain level. To this end, we use Gaussian Network Models (GNMs) to calculate the so-called soft modes, or low-frequency modes of motion for a dataset of 150 protein domains. Modes of motion can be used to decompose a domain into segments of consecutive amino acids that we call "dynamic elements", each of which belongs to one of two parts that move in opposite senses. We find that, in many cases, the dynamic elements, detected based on GNM analysis, correspond to established "themes": Sub-domain-level segments that have been shown to recur in protein space, and which were detected in previous research using sequence similarity alone (i.e. completely independently of the GNM analysis). This statistically significant correlation hints at the importance of dynamics in evolution. Overall, the results are consistent with an evolutionary scenario where proteins have emerged from themes that need to match each other both geometrically and dynamically, e.g. to facilitate allosteric regulation.

AD-Syn-Net: systematic identification of Alzheimer's disease-associated mutation and co-mutation vulnerabilities via deep learning.

Alzheimer's disease (AD) is one of the most challenging neurodegenerative diseases because of its complicated and progressive mechanisms, and multiple risk factors. Increasing research evidence demonstrates that genetics may be a key factor responsible for the occurrence of the disease. Although previous reports identified quite a few AD-associated genes, they were mostly limited owing to patient sample size and selection bias. There is a lack of comprehensive research aimed to identify AD-associated risk mutations systematically. To address this challenge, we hereby construct a large-scale AD mutation and co-mutation framework ('AD-Syn-Net'), and propose deep learning models named Deep-SMCI and Deep-CMCI configured with fully connected layers that are capable of predicting cognitive impairment of subjects effectively based on genetic mutation and co-mutation profiles. Next, we apply the customized frameworks to data sets to evaluate the importance scores of the mutations and identified mutation effectors and co-mutation combination vulnerabilities contributing to cognitive impairment. Furthermore, we evaluate the influence of mutation pairs on the network architecture to dissect the genetic organization of AD and identify novel co-mutations that could be responsible for dementia, laying a solid foundation for proposing future targeted therapy for AD precision medicine. Our deep learning model codes are available open access here: https://github.com/Pan-Bio/AD-mutation-effectors.

Enhancing schizophrenia phenotype prediction from genotype data through knowledge-driven deep neural network models.

This article explores deep learning model design, drawing inspiration from the omnigenic model and genetic heterogeneity concepts, to improve schizophrenia prediction using genotype data. It introduces an innovative three-step approach leveraging neural networks' capabilities to efficiently handle genetic interactions. A locally connected network initially routes input data from variants to their corresponding genes. The second step employs an Encoder-Decoder to capture relationships among identified genes. The final model integrates knowledge from the first two and incorporates a parallel component to consider the effects of additional genes. This expansion enhances prediction scores by considering a larger number of genes. Trained models achieved an average AUC of 0.83, surpassing other genotype-trained models and matching gene expression dataset-based approaches. Additionally, tests on held-out sets reported an average sensitivity of 0.72 and an accuracy of 0.76, aligning with schizophrenia heritability predictions. Moreover, the study addresses genetic heterogeneity challenges by considering diverse population subsets.

Disease spreading modeling and analysis: a survey.

MOTIVATION: The control of the diffusion of diseases is a critical subject of a broad research area, which involves both clinical and political aspects. It makes wide use of computational tools, such as ordinary differential equations, stochastic simulation frameworks and graph theory, and interaction data, from molecular to social granularity levels, to model the ways diseases arise and spread. The coronavirus disease 2019 (COVID-19) is a perfect testbench example to show how these models may help avoid severe lockdown by suggesting, for instance, the best strategies of vaccine prioritization. RESULTS: Here, we focus on and discuss some graph-based epidemiological models and show how their use may significantly improve the disease spreading control. We offer some examples related to the recent COVID-19 pandemic and discuss how to generalize them to other diseases.

Modeling State Firearm Law Adoption Using Temporal Network Models.

Policy Points Promoting healthy public policies is a national priority, but state policy adoption is driven by a complex set of internal and external factors. This study employs new social network methods to identify underlying connections among states and to predict the likelihood of new firearm-related policy adoption given changes to this interstate network. This approach could be used to assess the likelihood that a given state will adopt a specific new firearm-related law and to identify points of influence that could either inhibit or promote wider diffusion of specific laws. CONTEXT: US states are largely responsible for the regulation of firearms within their borders. Each state has developed a different legal environment with regard to firearms based on different values and beliefs of citizens, legislators, governors, and other stakeholders. Predicting the types of firearm laws that states may adopt is therefore challenging. METHODS: We propose a parsimonious model for this complex process and provide credible predictions of state firearm laws by estimating the likelihood they will be passed in the future. We employ a temporal exponential-family random graph model to capture the bipartite state law-state network data over time, allowing for complex interdependencies and their temporal evolution. Using data on all state firearm laws over the period 1979-2020, we estimate these models' parameters while controlling for factors associated with firearm law adoption, including internal and external state characteristics. Predictions of future firearm law passage are then calculated based on a number of scenarios to assess the effects of a given type of firearm law being passed in the future by a given state. FINDINGS: Results show that a set of internal state factors are important predictors of firearm law adoption, but the actions of neighboring states may be just as important. Analysis of scenarios provide insights into the mechanics of how adoption of laws by specific states (or groups of states) may perturb the rest of the network structure and alter the likelihood that new laws would become more (or less) likely to continue to diffuse to other states. CONCLUSIONS: The methods used here outperform standard approaches for policy diffusion studies and afford predictions that are superior to those of an ensemble of machine learning tools. The proposed framework could have applications for the study of policy diffusion in other domains.

Modelling animal social networks: New solutions and future directions.

Research Highlight: Ross, C. T., McElreath, R., & Redhead, D. (2023). Modelling animal network data in R using STRAND. Journal of Animal Ecology. https://doi.org/10.1111/1365-2656.14021. One of the most important insights in ecology over the past decade has been that the social connections among animals affect a wide range of ecological and evolutionary processes. However, despite over 20 years of study effort on this topic, generating knowledge from data on social associations and interactions remains fraught with problems. Redhead et al. present an R package-STRAND-that extends the current animal social network analysis toolbox in two ways. First, they provide a simple R interfaces to implement generative network models, which are an alternative to regression approaches that draw inference by simulating the data-generating process. Second, they implement these models in a Bayesian framework, allowing uncertainty in the observation process to be carried through to hypothesis testing. STRAND therefore fills an important gap for hypothesis testing using network data. However, major challenges remain, and while STRAND represents an important advance, generating robust results continues to require careful study design, considerations in terms of statistical methods and a plurality of approaches.

Convolutional neural network for brachial plexus segmentation at the interscalene level.

BACKGROUND: Regional anesthesia with ultrasound-guided brachial plexus block is widely used for patients undergoing shoulder and upper limb surgery, but needle misplacement can result in complications. The purpose of this study was to develop and validate a convolutional neural network (CNN) model for segmentation of the brachial plexus at the interscalene level. METHODS: This prospective study included patients who underwent ultrasound-guided brachial plexus block in the Anesthesiology Department of Beijing Jishuitan Hospital between October 2019 and June 2022. A Unet semantic segmentation model was developed to train the CNN to identify the brachial plexus features in the ultrasound images. The degree of overlap between the predicted segmentation and ground truth segmentation (manually drawn by experienced clinicians) was evaluated by calculation of the Dice index and Jaccard index. RESULTS: The final analysis included 502 images from 127 patients aged 41 ± 14 years-old (72 men, 56.7%). The mean Dice index was 0.748 ± 0.190, which was extremely close to the threshold level of 0.75 for good overlap between the predicted and ground truth segregations. The Jaccard index was 0.630 ± 0.213, which exceeded the threshold value of 0.5 for a good overlap. CONCLUSION: The CNN performed well at segregating the brachial plexus at the interscalene level. Further development could allow the CNN to be used to facilitate real-time identification of the brachial plexus during interscalene block administration. CLINICAL TRIAL REGISTRATION: The trial was registered prior to patient enrollment at the Chinese Clinical Trial Registry (ChiCTR2200055591), the site url is https://www.chictr.org.cn/ . The date of trial registration and patient enrollment is 14/01/2022.

Advancing maxillofacial prosthodontics by using pre-trained convolutional neural networks: Image-based classification of the maxilla.

PURPOSE: The study aimed to compare the performance of four pre-trained convolutional neural networks in recognizing seven distinct prosthodontic scenarios involving the maxilla, as a preliminary step in developing an artificial intelligence (AI)-powered prosthesis design system. MATERIALS AND METHODS: Seven distinct classes, including cleft palate, dentulous maxillectomy, edentulous maxillectomy, reconstructed maxillectomy, completely dentulous, partially edentulous, and completely edentulous, were considered for recognition. Utilizing transfer learning and fine-tuned hyperparameters, four AI models (VGG16, Inception-ResNet-V2, DenseNet-201, and Xception) were employed. The dataset, consisting of 3541 preprocessed intraoral occlusal images, was divided into training, validation, and test sets. Model performance metrics encompassed accuracy, precision, recall, F1 score, area under the receiver operating characteristic curve (AUC), and confusion matrix. RESULTS: VGG16, Inception-ResNet-V2, DenseNet-201, and Xception demonstrated comparable performance, with maximum test accuracies of 0.92, 0.90, 0.94, and 0.95, respectively. Xception and DenseNet-201 slightly outperformed the other models, particularly compared with InceptionResNet-V2. Precision, recall, and F1 scores exceeded 90% for most classes in Xception and DenseNet-201 and the average AUC values for all models ranged between 0.98 and 1.00. CONCLUSIONS: While DenseNet-201 and Xception demonstrated superior performance, all models consistently achieved diagnostic accuracy exceeding 90%, highlighting their potential in dental image analysis. This AI application could help work assignments based on difficulty levels and enable the development of an automated diagnosis system at patient admission. It also facilitates prosthesis designing by integrating necessary prosthesis morphology, oral function, and treatment difficulty. Furthermore, it tackles dataset size challenges in model optimization, providing valuable insights for future research.

The influence of inter-regional delays in generating large-scale brain networks of phase synchronization.

Large-scale networks of phase synchronization are considered to regulate the communication between brain regions fundamental to cognitive function, but the mapping to their structural substrates, i.e., the structure-function relationship, remains poorly understood. Biophysical Network Models (BNMs) have demonstrated the influences of local oscillatory activity and inter-regional anatomical connections in generating alpha-band (8-12 Hz) networks of phase synchronization observed with Electroencephalography (EEG) and Magnetoencephalography (MEG). Yet, the influence of inter-regional conduction delays remains unknown. In this study, we compared a BNM with standard "distance-dependent delays", which assumes constant conduction velocity, to BNMs with delays specified by two alternative methods accounting for spatially varying conduction velocities, "isochronous delays" and "mixed delays". We followed the Approximate Bayesian Computation (ABC) workflow, i) specifying neurophysiologically informed prior distributions of BNM parameters, ii) verifying the suitability of the prior distributions with Prior Predictive Checks, iii) fitting each of the three BNMs to alpha-band MEG resting-state data (N = 75) with Bayesian optimization for Likelihood-Free Inference (BOLFI), and iv) choosing between the fitted BNMs with ABC model comparison on a separate MEG dataset (N = 30). Prior Predictive Checks revealed the range of dynamics generated by each of the BNMs to encompass those seen in the MEG data, suggesting the suitability of the prior distributions. Fitting the models to MEG data yielded reliable posterior distributions of the parameters of each of the BNMs. Finally, model comparison revealed the BNM with "distance-dependent delays", as the most probable to describe the generation of alpha-band networks of phase synchronization seen in MEG. These findings suggest that distance-dependent delays might contribute to the neocortical architecture of human alpha-band networks of phase synchronization. Hence, our study illuminates the role of inter-regional delays in generating the large-scale networks of phase synchronization that might subserve the communication between regions vital to cognition.

Estimating co-extinction threats in terrestrial ecosystems.

The biosphere is changing rapidly due to human endeavour. Because ecological communities underlie networks of interacting species, changes that directly affect some species can have indirect effects on others. Accurate tools to predict these direct and indirect effects are therefore required to guide conservation strategies. However, most extinction-risk studies only consider the direct effects of global change-such as predicting which species will breach their thermal limits under different warming scenarios-with predictions of trophic cascades and co-extinction risks remaining mostly speculative. To predict the potential indirect effects of primary extinctions, data describing community interactions and network modelling can estimate how extinctions cascade through communities. While theoretical studies have demonstrated the usefulness of models in predicting how communities react to threats like climate change, few have applied such methods to real-world communities. This gap partly reflects challenges in constructing trophic network models of real-world food webs, highlighting the need to develop approaches for quantifying co-extinction risk more accurately. We propose a framework for constructing ecological network models representing real-world food webs in terrestrial ecosystems and subjecting these models to co-extinction scenarios triggered by probable future environmental perturbations. Adopting our framework will improve estimates of how environmental perturbations affect whole ecological communities. Identifying species at risk of co-extinction (or those that might trigger co-extinctions) will also guide conservation interventions aiming to reduce the probability of co-extinction cascades and additional species losses.

Longitudinal symptomatic interactions in long-standing schizophrenia: a novel five-point analysis based on directed acyclic graphs.

BACKGROUND: Recent network models propose that mutual interaction between symptoms has an important bearing on the onset of schizophrenic disorder. In particular, cross-sectional studies suggest that affective symptoms may influence the emergence of psychotic symptoms. However, longitudinal analysis offers a more compelling test for causation: the European Schizophrenia Cohort (EuroSC) provides data suitable for this purpose. We predicted that the persistence of psychotic symptoms would be driven by the continuing presence of affective disturbance. METHODS: EuroSC included 1208 patients randomly sampled from outpatient services in France, Germany and the UK. Initial measures of psychotic and affective symptoms were repeated four times at 6-month intervals, thereby furnishing five time-points. To examine interactions between symptoms both within and between time-slices, we adopted a novel technique for modelling longitudinal data in psychiatry. This was a form of Bayesian network analysis that involved learning dynamic directed acyclic graphs (DAGs). RESULTS: Our DAG analysis suggests that the main drivers of symptoms in this long-term sample were delusions and paranoid thinking. These led to affective disturbance, not vice versa as we initially predicted. The enduring relationship between symptoms was unaffected by whether patients were receiving first- or second-generation antipsychotic medication. CONCLUSIONS: In this cohort of people with chronic schizophrenia treated with medication, symptoms were essentially stable over long periods. However, affective symptoms appeared driven by the persistence of delusions and persecutory thinking, a finding not previously reported. Although our findings as ever remain hostage to unmeasured confounders, these enduring psychotic symptoms might nevertheless be appropriate candidates for directly targeted psychological interventions.

Network modeling of major depressive disorder symptoms in adult women.

BACKGROUND: Major depressive disorder (MDD) is one of the growing human mental health challenges facing the global health care system. In this study, the structural connectivity between symptoms of MDD is explored using two different network modeling approaches. METHODS: Data are from 'the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders (VATSPSUD)'. A cohort of N = 2163 American Caucasian female-female twins was assessed as part of the VATSPSUD study. MDD symptoms were assessed using personal structured clinical interviews. Two network analyses were conducted. First, an undirected network model was estimated to explore the connectivity between the MDD symptoms. Then, using a Bayesian network, we computed a directed acyclic graph (DAG) to investigate possible directional relationships between symptoms. RESULTS: Based on the results of the undirected network, the depressed mood symptom had the highest centrality value, indicating its importance in the overall network of MDD symptoms. Bayesian network analysis indicated that depressed mood emerged as a plausible driving symptom for activating other symptoms. These results are consistent with DSM-5 guidelines for MDD. Also, somatic weight and appetite symptoms appeared as the strongest connections in both networks. CONCLUSIONS: We discuss how the findings of our study might help future research to detect clinically relevant symptoms and possible directional relationships between MDD symptoms defining major depression episodes, which would help identify potential tailored interventions. This is the first study to investigate the network structure of VATSPSUD data using both undirected and directed network models.

A hybrid neural network based model for blood donation forecasting.

OBJECTIVE: To develop a hybrid neural network-based blood donation prediction method, via this predictive model, we can obtain the best estimate of whole blood in Beijing Tongzhou District Central Blood Station and help managers smoothly solve the allocation problem under fluctuating hospital demand and limited resources. METHOD: Inspired by the practical problems faced by blood stations providing transfusion services to several hospitals, a hybrid model based on a time-series prediction method and neural network, SARIMAX-TCN-LSTM is proposed for the prediction of daily whole blood donations. The experiment was performed at the central blood station in Tongzhou district, where we used whole blood donations from January 1, 2015, to November 14, 2021, as the subject, supplemented by meteorological and epidemic factors affecting blood donation, to predict daily blood donations for the next two weeks. RESULT: The hybrid model significantly outperformed the traditional time series forecasting method on multiple regression metrics, with twice as effective fitting as the baseline and a 33% reduction in Root Mean Squared Error (RMSE). Results indicate that the proposed model can improve the prediction accuracy of daily blood donations, and the co-validity of the structure was evidenced in an ablation experiment. CONCLUSION: Development and evaluation of a hybrid neural network-based model structure improve the prediction of daily blood donations. This intelligent forecasting method can help managers to overcome the challenges of sudden blood demand and contribute to the optimization of resource allocation tasks.

Higher-order brain regions show shifts in structural covariance in adolescent marmosets.

Substantial progress has been made studying morphological changes in brain regions during adolescence, but less is known of network-level changes in their relationship. Here, we compare covariance networks constructed from the correlation of morphometric volumes across 135 brain regions of marmoset monkeys in early adolescence and adulthood. Substantial shifts are identified in the topology of structural covariance networks in the prefrontal cortex (PFC) and temporal lobe. PFC regions become more structurally differentiated and segregated within their own local network, hypothesized to reflect increased specialization after maturation. In contrast, temporal regions show increased inter-hemispheric covariances that may underlie the establishment of distributed networks. Regionally selective coupling of structural and maturational covariance is revealed, with relatively weak coupling in transmodal association areas. The latter may be a consequence of continued maturation within adulthood, but also environmental factors, for example, family size, affecting brain morphology. Advancing our understanding of how morphological relationships within higher-order brain areas mature in adolescence deepens our knowledge of the developing brain's organizing principles.

On Graphical Models and Convex Geometry.

A mixture-model of beta distributions framework is introduced to identify significant correlations among P features when P is large. The method relies on theorems in convex geometry, which are used to show how to control the error rate of edge detection in graphical models. The proposed 'betaMix' method does not require any assumptions about the network structure, nor does it assume that the network is sparse. The results hold for a wide class of data-generating distributions that include light-tailed and heavy-tailed spherically symmetric distributions. The results are robust for sufficiently large sample sizes and hold for non-elliptically-symmetric distributions.

Heterogeneity in Individual Network Analysis: Reality or Illusion?

The use of idiographic research techniques has gained popularity within psychological research and network analysis in particular. Idiographic research has been proposed as a promising avenue for future research, with differences between idiographic results highlighting evidence for radical heterogeneity. However, in the quest to address the individual in psychology, some classic statistical problems, such as those arising from sampling variation and power limitations, should not be overlooked. This article aims to determine to what extent current tools to compare idiographic networks are suited to disentangle true from illusory heterogeneity in the presence of sampling error. To this end, we investigate the performance of tools to inspect heterogeneity (visual inspection, comparison of centrality measures, investigating standard deviations of random effects, and GIMME) through simulations. Results show that power limitations hamper the validity of conclusions regarding heterogeneity and that the power required to assess heterogeneity adequately is often not realized in current research practice. Of the tools investigated, inspecting standard deviations of random effects and GIMME proved the most suited. However, all tools evaluated leave the door wide open to misinterpret all observed variability in terms of individual differences. Hence, the current paper calls for caution in the use and interpretation of new time-series techniques when it comes to heterogeneity.