Parkinsons disease (PD) alters cortical neural dynamics, yet reliable non-invasive electrophysiological biomarkers remain elusive. This study examined whether interpretable EEG features capturing complementary aspects of neural dynamics can discriminate Parkinsonian neural states. A comprehensive set of interpretable features was extracted and grouped into Standard descriptors (spectral power, phase synchronization, time-domain statistics) and Dynamical descriptors (aperiodic activity, cross-frequency coupling, scale-free dynamics, neuronal avalanche statistics, and instantaneous frequency measures). A multi-head attention transformer classifier was trained using strict LOSO validation. Group-level comparisons were performed to identify electrophysiological differences associated with disease and medication state. Standard feature sets achieved strongest performance in discriminating medication states (PDoff vs PDon), whereas Dynamical performed competitively in contrasts between PD patients and healthy controls. Random feature ablation analyses indicated that Dynamical descriptors provide complementary information distributed across features while correlation analysis revealed low redundancy within both feature sets. Group-level comparisons revealed medication-sensitive reductions in delta power and voltage variance, modulation of neuronal avalanche statistics, persistent increases in theta phase synchronization in PD patients, and disease-related alterations in cross-frequency interactions. Traditional spectral and synchronization features primarily reflect medication-related neural modulation, whereas dynamical descriptors reveal broader alterations in cortical network organization associated with disease but also with medication. These findings support multivariate EEG representations as a promising framework for developing non-invasive biomarkers of PD.
Accurately predicting individual neurons' responses and spatial functional properties in complex visual tasks remains a key challenge in understanding neural computation. Existing whole-brain connectome models of Drosophila often rely on parameter assumptions or deep learning approaches, yet remain limited in their ability to reliably predict dynamic neuronal responses. We introduce a Multi-Path Aggregation (MPA) framework, based on neural network steady-state theory, to build a whole-brain Visual Function Profiles (VFP) of Drosophila neurons and predict their responses under diverse visual tasks. Unlike conventional methods relying on redundant parameters, MPA combines visual input features with the whole-brain connectome topology. It uses adjacency matrix powers and finite-path optimization to efficiently predict neuronal function, including ON/OFF polarity, direction selectivity, and responses to complex visual stimuli. Our model achieves a Pearson correlation of 0.84+/-0.12 for ON/OFF responses, outperforming existing methods (0.33+/-0.59), and accurately captures neuron functional properties, including luminance and direction preferences, while allowing single-neuron or population-level blockade simulations. Replacing CNN modules with VFP-derived Lobula Columnar(LC) population responses in a Drosophila simulation enables successful navigation and obstacle avoidance, demonstrating the model's effectiveness in guiding embodied behavior. This study establishes a "connectome-functional profile-behavior" framework, offering a whole-brain quantitative tool to study Drosophila visual computation and a neuron-level guide for brain-inspired intelligence.
Aim: This in silico study sought to identify specific biomarkers for mild traumatic brain injury (mTBI) through the analysis of publicly available gene and miRNA databases, hypothesizing their influence on neuronal structure, axonal integrity, and regeneration. Methods: This study implemented a three-step process: (1) Data searching for mTBI-related genes in Gene and MalaCard databases and literature review ; (2) Data analysis involved performing functional annotation through GO and KEGG, identifying hub genes using Cytoscape, mapping protein-protein interactions via DAVID and STRING, and predicting miRNA targets using miRSystem, miRWalk2.0, and mirDIP (3) RNA-sequencing analysis applied to the mTBI dataset GSE123336. Results: Eleven candidate hub genes associated with mTBI outcome were identified: APOE, S100B, GFAP, BDNF, AQP4, COMT, MBP, UCHL1, DRD2, ASIC1, and CACNA1A. Enrichment analysis linked these genes to neuron projection regeneration and synaptic plasticity. miRNAs linked to the mTBI candidate genes were hsa-miR-9-5p, hsa-miR-204-5p, hsa-miR-1908-5p, hsa-miR-16-5p, hsa-miR-10a-5p, has-miR-218-5p, has-miR-34a-5p, and has-miR-199b-5p. The RNA sequencing revealed 2664 differentially expressed miRNAs post-mTBI, with 17 showing significant changes at the time of injury and 48 hours post-injury. Two miRNAs were positively correlated with direct head hits. Conclusion: Our study indicates that specific genes and miRNAs, particularly hsa-miR-10a-5p, may influence mTBI outcomes. Our research may guide future mTBI diagnostics, emphasizing the need to measure and track these specific genes and miRNAs in diverse cohorts.
This contribution challenges the authenticity of 23 June 1835 as the actual founding day of Durban. The origins of this seaport are traced, with reference to the role played by the founders, the indigenous inhabitants on the Bluff, the British settlers and the Voortrekkers. The author concludes that the original settlement of Henry Francis Fynn and Francis Farewell during May and June 1824 was the nucleus that developed into the present city. This implies that in 1988 Durban should be celebrating its 164th anniversary and not its 153rd anniversary.
Tiantian He, Elinor Thompson, Anna Schroder
et al.
Computational models of neurodegeneration aim to emulate the evolving pattern of pathology in the brain during neurodegenerative disease, such as Alzheimer's disease. Previous studies have made specific choices on the mechanisms of pathology production and diffusion, or assume that all the subjects lie on the same disease progression trajectory. However, the complexity and heterogeneity of neurodegenerative pathology suggests that multiple mechanisms may contribute synergistically with complex interactions, meanwhile the degree of contribution of each mechanism may vary among individuals. We thus put forward a coupled-mechanisms modelling framework which non-linearly combines the network-topology-informed pathology appearance with the process of pathology spreading within a dynamic modelling system. We account for the heterogeneity of disease by fitting the model at the individual level, allowing the epicenters and rate of progression to vary among subjects. We construct a Bayesian model selection framework to account for feature importance and parameter uncertainty. This provides a combination of mechanisms that best explains the observations for each individual from the ADNI dataset. With the obtained distribution of mechanism importance for each subject, we are able to identify subgroups of patients sharing similar combinations of apparent mechanisms.
Arsenii Onuchin, Alina Chernizova, Mikhail Lebedev
et al.
The fundamental relationship between the mesoscopic structure of neuronal circuits and organismic functions they subserve is one of the major challenges in contemporary neuroscience. Formation of structurally connected modules of neurons enacts the conversion from single-cell firing to large-scale behaviour of an organism, highlighting the importance of their accurate profiling in the data. While connectomes are typically characterized by significant sparsity of neuronal connections, recent advances in network theory and machine learning have revealed fundamental limitations of traditionally used community detection approaches in cases where the network is sparse. Here we studied the optimal community structure in the structural connectome of C.elegans, for which we exploited a non-conventional approach that is based on non-backtracking random walks, virtually eliminating the sparsity issue. In full agreement with the previous asymptotic results, we demonstrated that non-backtracking walks resolve the ground truth annotation into clusters on stochastic block models (SBM) with the size and density of the connectome better than the spectral methods related to simple random walks. Based on the cluster detectability threshold, we determined that the optimal number of modules in a recently mapped connectome of C.elegans is 10, which precisely corresponds to the number of isolated eigenvalues in the spectrum of the non-backtracking flow matrix. Broadly, our work provides a robust network-based framework to reveal mesoscopic structures in sparse connectomic datasets, paving way to further investigation of connectome mechanisms for different functions.
We have used Bayesian Optimisation (BO) to find hyper-parameters in an existing biologically plausible population neural network. The 8-dimensional optimal hyper-parameter combination should be such that the network dynamics simulate the resting state alpha rhythm (8 - 13 Hz rhythms in brain signals). Each combination of these eight hyper-parameters constitutes a 'datapoint' in the parameter space. The best combination of these parameters leads to the neural network's output power spectral peak being constraint within the alpha band. Further, constraints were introduced to the BO algorithm based on qualitative observation of the network output time series, so that high amplitude pseudo-periodic oscillations are removed. Upon successful implementation for alpha band, we further optimised the network to oscillate within the theta (4 - 8 Hz) and beta (13 - 30 Hz) bands. The changing rhythms in the model can now be studied using the identified optimal hyper-parameters for the respective frequency bands. We have previously tuned parameters in the existing neural network by the trial-and-error approach; however, due to time and computational constraints, we could not vary more than three parameters at once. The approach detailed here, allows an automatic hyper-parameter search, producing reliable parameter sets for the network.
In our recent article (Tu et al., Warnings and caveats in brain controllability, arXiv:1705.08261) we provided quantitative evidence to show that there are warnings and caveats in the way Gu and collaborators (Gu et al. Controllability of structural brain networks. Nature communications 6 (2015): 8414) define brain controllability. The comment by Pasqualetti et al. (Pasqualetti et al. RE: Warnings and Caveats in Brain Controllability. NeuroImage 297 (2019), 586-588) confirms the need to go beyond the methodology and approach presented in Gu et al. original work. In fact, they recognize that the source of confusion is due to the fact that assessing controllability via numerical analysis typically leads to ill-conditioned problems, and thus often generates results that are difficult to interpret. This is indeed the first warning we discussed: our work was not meant to prove that brain networks are not controllable from one node, rather we wished to highlight that the one node controllability framework and all consequent results were not properly justified based on the methodology presented in Gu et al. We used in our work the same method of Gu et al. not because we believe it is the best methodology, but because we extensively investigated it with the aim of replicating, testing and extending their results. And the warning and caveats we have proposed are the results of this investigation.
In neurons, neuropeptides are synthesized in the soma and are then transported along the axon in dense core vesicles (DCVs). DCVs are captured in varicosities located along the axon terminal called en passant boutons, which are active terminal sites that accumulate and release neurotransmitters. Recently developed experimental techniques allow for the estimation of the age of DCVs in various locations in the axon terminal. Accurate simulation of the mean age of DCVs in boutons requires the development of a model that would account for resident, transiting-anterograde, and transiting-retrograde DCV populations. In this paper, such a model is developed. The model is applied to simulating DCV transport in Drosophila type II motoneurons. The model simulates DCV transport and capture in the axon terminals and makes it possible to predict the age density distribution of DCVs in en passant boutons as well as DCV's mean age in boutons. The predicted prevalence of older organelles in distal boutons may explain the "dying back" pattern of axonal degeneration observed in dopaminergic neurons in Parkinson's disease. The predicted difference of two hours between the age of older DCVs residing in distal boutons and the age of younger DCVs residing in proximal boutons is consistent with an approximate estimate of age difference deduced from experimental observations. The age density of resident DCVs is found to be bimodal, which is because DCVs are captured from two transiting states: the anterograde transiting state that contains younger DCVs and the retrograde transiting state that contains older DCVs.
Both action potentials and mechanosensitive signalling are an important communication mechanisms in plants. Considering an information theoretic framework, this paper explores the effective range of multiple action potentials for a long chain of cells (i.e., up to 100) in different configurations, and introduces the study of multiple mechanosensitive activation signals (generated due to a mechanical stimulus) in plants. For both these signals, we find that the mutual information per cell and information propagation speed tends to increase up to a certain number of receiver cells. However, as the number of cells increase beyond 10 to 12, the mutual information per cell starts to decrease. To validate our model and results, we include an experimental verification of the theoretical model, using a PhytlSigns biosignal amplifier, allowing us to measure the magnitude of the voltage associated with the multiple AP and mechanosensitive activation signals induced by different stimulus in plants. Experimental data is used to calculate the mutual information and information propagation speed, which is compared with corresponding numerical results. Since these signals are used for a variety of important tasks within the plant, understanding them may lead to new bioengineering methods for plants.
Background : depression and anxiety are common in patients with cancer, classical antidepressant has no proven efficacy on this type of distress compared to placebo. A Psilocybin (serotoninergic hallucinogen) based therapy appear to give promising results among recent studies. Aims : to examine if a Psilocybin based therapy could be considered for patients with cancer related depression and anxiety and to assume it's safety. To sum up Heffter institute work, as the main institute working on this topic. Method : following PRISMA (Preferred Reporting Items for Systematic reviews and Meta Analyses) guidelines, a systematic review was conducted, for quantitative and qualitative studies about psilocybin for treating cancer related depression and anxiety. Pubmed and the Heffter institute databases have been reached for this purpose, separating studies in types : qualitative or quantitative. We studied the effects on cancer related depression and anxiety separately and investigated the psychological and neurobiological mechanisms. Results : the four studies included a total of 105 randomized patients, meta analysis on depression and anxiety with pooled Peto odds ratio showed a significant superiority of Psilocybin over placebo. The substance appeared to be safe for this type of patients. Surprising psychological mechanisms hypothesis have been found out. Conclusion : psilocybin appear to be potentially useful as a treatment for cancer related depression and anxiety. Future research should verify these findings on wider population and eventually seek a way to apply therapy to non hospitalized (ambulatory) patients. Keywords : psilocybin, depression, anxiety, review, meta-analysis
Víctor J. López-Madrona, Fernanda Matias, Claudio Mirasso
et al.
The specific connectivity of a neuronal network is reflected in the dynamics of the signals recorded on its nodes. The analysis of how the activity in one node predicts the behaviour of another gives the directionality in their relationship. However, each node is composed of many different elements which define the properties of the links. For instance, excitatory and inhibitory neuronal subtypes determine the functionality of the connection. Classic indexes such as the Granger causality (GC) quantifies these interactions, but they do not infer into the mechanism behind them. Here, we introduce an extension of the well-known GC that analyses the correlation associated to the specific influence that a transmitter node has over the receiver. This way, the G-causal link has a positive or negative effect if the predicted activity follows directly or inversely, respectively, the dynamics of the sender. The method is validated in a neuronal population model, testing the paradigm that excitatory and inhibitory neurons have a differential effect in the connectivity. Our approach correctly infers the positive or negative coupling produced by different types of neurons. Our results suggest that the proposed approach provides additional information on the characterization of G-causal connections, which is potentially relevant when it comes to understanding interactions in the brain circuits.
Ann E. Sizemore, Jennifer Phillips-Cremins, Robert Ghrist
et al.
The application of network techniques to the analysis of neural data has greatly improved our ability to quantify and describe these rich interacting systems. Among many important contributions, networks have proven useful in identifying sets of node pairs that are densely connected and that collectively support brain function. Yet the restriction to pairwise interactions prevents us from realizing intrinsic topological features such as cavities within the interconnection structure that may be just as crucial for proper function. To detect and quantify these topological features we must turn to methods from algebraic topology that encode data as a simplicial complex built of sets of interacting nodes called simplices. On this substrate, we can then use the relations between simplices and higher-order connectivity to expose cavities within the complex, thereby summarizing its topological nature. Here we provide an introduction to persistent homology, a fundamental method from applied topology that builds a global descriptor of system structure by chronicling the evolution of cavities as we move through a combinatorial object such as a weighted network. We detail the underlying mathematics and perform demonstrative calculations on the mouse structural connectome, electrical and chemical synapses in \textit{C. elegans}, and genomic interaction data. Finally we suggest avenues for future work and highlight new advances in mathematics that appear ready for use in revealing the architecture and function of neural systems.
Brain decoding algorithms form an important part of the arsenal of analysis tools available to neuroscientists, allowing for a more detailed study of the kind of information represented in patterns of cortical activity. While most current decoding algorithms focus on estimating a single, most likely stimulus from the pattern of noisy fMRI responses, the presence of noise causes this estimate to be uncertain. This uncertainty in stimulus estimates is a potentially highly relevant aspect of cortical stimulus processing, and features prominently in Bayesian or probabilistic models of neural coding. Here, we focus on sensory uncertainty and how best to extract this information with fMRI. We first demonstrate in simulations that decoding algorithms that take into account correlated noise between fMRI voxels better recover the amount of uncertainty (quantified as the width of a probability distribution over possible stimuli) associated with the decoded estimate. Furthermore, we show that not all correlated variability should be treated equally, as modeling tuning-dependent correlations has the greatest impact on decoding performance. Next, we examine actual noise correlations in human visual cortex, and find that shared variability in areas V1-V3 depends on the tuning properties of fMRI voxels. In line with our simulations, accounting for this shared noise between similarly tuned voxels produces important benefits in decoding. Our findings underscore the importance of accurate noise models in fMRI decoding approaches, and suggest a statistically feasible method to incorporate the most relevant forms of shared noise.
Olga Vasieva, Sultan Cetiner, Abigail Savage
et al.
The hominid-specific non-LTR retrotransposon termed SINE VNTR Alu (SVA) is the youngest of the transposable elements in the human genome. The propagation of the most ancient SVA type A took place about thirteen millions years ago ago, and the youngest SVA types appeared in the human genome after the chimpanzee divergence. Functional enrichment analysis of genes associated with SVA insertions demonstrated their strong link to multiple ontological categories attributed to brain function and the disorders. SVA types that expanded their presence in the human genome at different stages of hominoid life history were also associated with progressively evolving behavioural features that indicated a potential impact of SVA propagation on a cognitive ability of a modern human. The SVA-associated genes were highly cross-linked in functional networks suggesting an accumulative impact of functional alterations potentially caused by SVA insertions. Our analysis uncovered a potential role of SVAs in evolution of human CNS and especially emergence of functional trends relevant to social and parental behaviour. It also supports models which explain in part how brain function can be modulated by both the immune and reproductive systems based on the gene expression patterns and gene pathways potentially altered by SVA insertions.
Investigation of neural circuit functioning often requires statistical interpretation of events in subthreshold electrophysiological recordings. This problem is non-trivial because recordings may have moderate levels of structured noise and events may have distinct kinetics. In addition, novel experimental designs that combine optical and electrophysiological methods will depend upon statistical tools that combine multimodal data. We present a Bayesian approach for inferring the timing, strength, and kinetics of postsynaptic currents (PSCs) from voltage-clamp recordings on a per event basis. The simple generative model for a single voltage-clamp recording flexibly extends to include network-level structure to enable experiments designed to probe synaptic connectivity. We validate the approach on simulated and real data. We also demonstrate that extensions of the basic PSC detection algorithm can handle recordings contaminated with optically evoked currents, and we simulate a scenario in which calcium imaging observations, available for a subset of neurons, can be fused with electrophysiological data to achieve higher temporal resolution. We apply this approach to simulated and real ground truth data to demonstrate its higher sensitivity in detecting small signal-to-noise events and its increased robustness to noise compared to standard methods for detecting PSCs. The new Bayesian event analysis approach for electrophysiological recordings should allow for better estimation of physiological parameters under more variable conditions and help support new experimental designs for circuit mapping.
Joaquin Rapela, Marissa Westerfield, Jeanne Townsend
et al.
Expecting events in time leads to more efficient behavior. A remarkable early finding in the study of temporal expectancy is the foreperiod effect on reaction times; i.e., the influence or reaction time of the time period between a warning signal and an imperative stimulus to which subjects are instructed to respond as quickly as possible. Recently it has been shown that the phase of oscillatory activity preceding stimulus presentation is related to behavior. Here we connect both of these findings by reporting a novel foreperiod effect on the inter-trial phase coherence of the electroencephalogram (EEG) triggered by stimuli to which subjects are instructed not to respond. Inter-trial phase coherence has been used to describe regularities in phases of groups of trials time locked to an event of interest. We propose a single-trial measure of inter-trial phase coherence and prove its soundness. Equipped with this measure, and using a multivariate decoding method, we demonstrate that the foreperiod duration in and audiovisual attention-shifting task modulates single-trial phase coherence. In principle, this modulation could be an artifact of the decoding method used to detect it. We show that this is not the case, since the modulation can also be observed using a simple averaging method. We show that the strength of this modulation correlates with subject behavior (both error rates and mean-reaction times). We anticipate that the new foreperiod effect on inter-trial phase coherence, and the decoding method used here to detect it, will be important tools to understand cognition at the single-trial level. In Part II of this manuscript, we support this claim, by showing that changes in attention modulate the strength of the new foreperiod effect on a trial-by-trial basis.