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BackgroundAlthough they form a unitary phenomenon, the relationship between extracranial M/EEG and transmembrane ion flows is understood only as a general principle rather than as a well-articulated and quantified causal chain.MethodWe present an integrated multiscale model, consisting of a neural simulation of thalamus and cortex during stage N2 sleep and a biophysical model projecting cortical current densities to M/EEG fields. Sleep spindles were generated through the interactions of local and distant network connections and intrinsic currents within thalamocortical circuits. 32,652 cortical neurons were mapped onto the cortical surface reconstructed from subjects' MRI, interconnected based on geodesic distances, and scaled-up to current dipole densities based on laminar recordings in humans. MRIs were used to generate a quasi-static electromagnetic model enabling simulated cortical activity to be projected to the M/EEG sensors.ResultsThe simulated M/EEG spindles were similar in amplitude and topography to empirical examples in the same subjects. Simulated spindles with more core-dominant activity were more MEG weighted.Comparison with existing methodsPrevious models lacked either spindle-generating thalamic neural dynamics or whole head biophysical modeling; the framework presented here is the first to simultaneously capture these disparate scales.ConclusionsThis multiscale model provides a platform for the principled quantitative integration of existing information relevant to the generation of sleep spindles, and allows the implications of future findings to be explored. It provides a proof of principle for a methodological framework allowing large-scale integrative brain oscillations to be understood in terms of their underlying channels and synapses.

This article contains information about strengthening the under-ground parts of buildings and restoration of their bearing capacity, along with solutions of urea-formaldehyde resin and solutions based on sodium silicate (which have a number of significant drawbacks, such as short-lived strengthening, low strength of reinforced soil (0.1-0.5 MPa), brittle destruction under dynamic loads, environmental pollution), using impregnation compositions based on fine mineral binders. This compositions, with the name «Mikrodur», are obtained on the basis of air separation of Portland cement CEM I 52.5 (PC D0 M600) and fine-divided blast furnace slag. The method of preparation of suspension on the basis of finely dispersed binder is considered. The main characteristics determining the finely dispersed binder suspension, such as viscosity and stability of the injectable suspension (sedimentation), are established. It is proved that the indexes of viscosity and stability of solutions depend on the method of their preparation, water/binding ratio and chemical admixtures. A variety of finely dispersed binders grades on mineral composition allows providing ground, stone and concrete structures of underground constructions stabilization taking into account various requirements: strength enhancement and anti-filtration properties of the strengthened masses, their resistance to various aggressive influences, the possibility of hardening in conditions of negative temperature, acceleration of a strength enhancement.

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., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 the authors.)

Understanding the function of sleep and its associated neural rhythms is an important goal in neuroscience. While many theoretical models of neural dynamics during sleep exist, few include the effects of neuromodulators on sleep oscillations and describe transitions between sleep and wake states or different sleep stages. Here, we started with a C++-based thalamocortical network model that describes characteristic thalamic and cortical oscillations specific to sleep. This model, which includes a biophysically realistic description of intrinsic and synaptic channels, allows for testing the effects of different neuromodulators, intrinsic cell properties, and synaptic connectivity on neural dynamics during sleep. We present a complete reimplementation of this previously-published sleep model in the standardized NEURON/Python framework, making it more accessible to the wider scientific community.

Distinguishing between nectar and non-nectar odors is challenging for animals due to shared compounds and changing ratios in complex mixtures. Changes in nectar production throughout the day and potentially many times within a forager's lifetime add to the complexity. The honeybee olfactory system, containing less than 1000 principal neurons in the early olfactory relay, the antennal lobe (AL), must learn to associate diverse volatile blends with rewards. Previous studies identified plasticity between AL neurons but its role in odor learning remains poorly understood. We used a computational network model and live imaging of the honeybee's AL to explore the neural mechanisms and functions of plasticity in the early olfactory system. Our findings revealed that when trained with a set of rewarded and unrewarded odors, the AL inhibitory network suppresses shared chemical compounds while enhancing responses to distinct compounds. This results in improved pattern separation and a more concise neural code. Our Calcium imaging data support these predictions. Analysis of a Graph Convolutional Network in machine learning performing an odor categorization task revealed a similar mechanism of contrast enhancement. Our model provides insights into how inhibitory plasticity in the early olfactory network reshapes coding for efficient learning of complex odors., Significance Statement: By combining computational modeling, machine learning, and analysis of calcium imaging data, we demonstrate that associative and non-associative plasticity in the honeybee antennal lobe (AL) - first relay of the insect olfactory system - work together to enhance the contrast between rewarded and unrewarded odors. Training the AL's inhibitory network within specific odor environments enables the suppression of neural responses to common odor components, while amplifying responses to distinctive ones. This study sheds light on the olfactory system's ability to adapt and efficiently learn new odor-reward associations across varying environments, and it proposes innovative, energy-efficient principles applicable to artificial intelligence.

Slow-wave sleep (SWS), characterized by slow oscillations (SOs, <1Hz) of alternating active and silent states in the thalamocortical network, is a primary brain state during Non-Rapid Eye Movement (NREM) sleep. In the last two decades, the traditional view of SWS as a global and uniform whole-brain state has been challenged by a growing body of evidence indicating that SO can be local and can coexist with wake-like activity. However, the mechanisms by which global and local SOs arise from micro-scale neuronal dynamics and network connectivity remain poorly understood. We developed a multi-scale, biophysically realistic human whole-brain thalamocortical network model capable of transitioning between the awake state and SWS, and we investigated the role of connectivity in the spatio-temporal dynamics of sleep SO. We found that the overall strength and a relative balance between long and short-range synaptic connections determined the network state. Importantly, for a range of synaptic strengths, the model demonstrated complex mixed SO states, where periods of synchronized global slow-wave activity were intermittent with the periods of asynchronous local slow-waves. An increase in the overall synaptic strength led to synchronized global SO, while a decrease in synaptic connectivity produced only local slow-waves that would not propagate beyond local areas. These results were compared to human data to validate probable models of biophysically realistic SO. The model producing mixed states provided the best match to the spatial coherence profile and the functional connectivity estimated from human subjects. These findings shed light on how the spatio-temporal properties of SO emerge from local and global cortical connectivity and provide a framework for further exploring the mechanisms and functions of SWS in health and disease., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Marsh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Brain activity during the resting state is widely used to examine brain organization, cognition and alterations in disease states. While it is known that neuromodulation and the state of alertness impact resting-state activity, neural mechanisms behind such modulation of resting-state activity are unknown. In this work, we used a computational model to demonstrate that change in excitability and recurrent connections, due to cholinergic modulation, impacts resting-state activity. The results of such modulation in the model match closely with experimental work on direct cholinergic modulation of Default Mode Network (DMN) in rodents. We further extended our study to the human connectome derived from diffusion-weighted MRI. In human resting-state simulations, an increase in cholinergic input resulted in a brain-wide reduction of functional connectivity. Furthermore, selective cholinergic modulation of DMN closely captured experimentally observed transitions between the baseline resting state and states with suppressed DMN fluctuations associated with attention to external tasks. Our study thus provides insight into potential neural mechanisms for the effects of cholinergic neuromodulation on resting-state activity and its dynamics., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Sanda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Slow-wave sleep (SWS), characterized by slow oscillations (SO, <1Hz) of alternating active and silent states in the thalamocortical network, is a primary brain state during Non-Rapid Eye Movement (NREM) sleep. In the last two decades, the traditional view of SWS as a global and uniform whole-brain state has been challenged by a growing body of evidence indicating that SO can be local and can coexist with wake-like activity. However, the understanding of how global and local SO emerges from micro-scale neuron dynamics and network connectivity remains unclear. We developed a multi-scale, biophysically realistic human whole-brain thalamocortical network model capable of transitioning between the awake state and slow-wave sleep, and we investigated the role of connectivity in the spatio-temporal dynamics of sleep SO. We found that the overall strength and a relative balance between long and short-range synaptic connections determined the network state. Importantly, for a range of synaptic strengths, the model demonstrated complex mixed SO states, where periods of synchronized global slow-wave activity were intermittent with the periods of asynchronous local slow-waves. Increase of the overall synaptic strength led to synchronized global SO, while decrease of synaptic connectivity produced only local slow-waves that would not propagate beyond local area. These results were compared to human data to validate probable models of biophysically realistic SO. The model producing mixed states provided the best match to the spatial coherence profile and the functional connectivity estimated from human subjects. These findings shed light on how the spatio-temporal properties of SO emerge from local and global cortical connectivity and provide a framework for further exploring the mechanisms and functions of SWS in health and disease.

Cortical stimulation with single pulses is a common technique in clinical practice and research. However, we still do not understand the extent to which it engages subcortical circuits which contribute to the associated evoked potentials (EPs). Here we find that cortical stimulation generates remarkably similar EPs in humans and mice, with a late component similarly modulated by the subject's behavioral state. We optogenetically dissect the underlying circuit in mice, demonstrating that the late component of these EPs is caused by a thalamic hyperpolarization and rebound. The magnitude of this late component correlates with the bursting frequency and synchronicity of thalamic neurons, modulated by the subject's behavioral state. A simulation of the thalamo-cortical circuit highlights that both intrinsic thalamic currents as well as cortical and thalamic GABAergic neurons contribute to this response profile. We conclude that the cortical stimulation engages cortico-thalamo-cortical circuits highly preserved across different species and stimulation modalities., Competing Interests: Competing Interests CK holds an executive position, and CK and MM have a financial interest, in Intrinsic Powers, Inc., a company whose purpose is to develop a device that can be used in the clinic to assess the presence of consciousness in patients. MR and SS are advisors of Intrinsic Powers, Inc. SR is the Chief Medical Officer of Manava Plus.

Key Message: The first-time generation of hexaploid triticale plants harbouring variable panels of novel mutations in gene families involved in starch biosynthesis has been achieved by the subgenome-independent multiplexed CRISPR/Cas9-mediated editing., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Brain rhythms of sleep reflect neuronal activity underlying sleep-associated memory consolidation. The modulation of brain rhythms, such as the sleep slow oscillation (SO), is used both to investigate neurophysiological mechanisms as well as to measure the impact of sleep on presumed functional correlates. Previously, closed-loop acoustic stimulation in humans targeted to the SO Up-state successfully enhanced the slow oscillation rhythm and phase-dependent spindle activity, although effects on memory retention have varied. Here, we aim to disclose relations between stimulation-induced hippocampo-thalamo-cortical activity and retention performance on a hippocampus-dependent object-place recognition task in mice by applying acoustic stimulation at four estimated SO phases compared to sham condition. Across the 3-h retention interval at the beginning of the light phase closed-loop stimulation failed to improve retention significantly over sham. However, retention during SO Up-state stimulation was significantly higher than for another SO phase. At all SO phases, acoustic stimulation was accompanied by a sharp increase in ripple activity followed by about a second-long suppression of hippocampal sharp wave ripple and longer maintained suppression of thalamo-cortical spindle activity. Importantly, dynamics of SO-coupled hippocampal ripple activity distinguished SOUp-state stimulation. Non-rapid eye movement (NREM) sleep was not impacted by stimulation, yet preREM sleep duration was effected. Results reveal the complex effect of stimulation on the brain dynamics and support the use of closed-loop acoustic stimulation in mice to investigate the inter-regional mechanisms underlying memory consolidation., (© 2023 The Authors. European Journal of Neuroscience published by Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)

Magnetoencephalography (MEG) is a non-invasive functional imaging technique for pre-surgical mapping. However, movement-related MEG functional mapping of primary motor cortex (M1) has been challenging in presurgical patients with brain lesions and sensorimotor dysfunction due to the large numbers of trials needed to obtain adequate signal to noise. Moreover, it is not fully understood how effective the brain communication is with the muscles at frequencies above the movement frequency and its harmonics. We developed a novel Electromyography (EMG)-projected MEG source imaging technique for localizing early-stage (-100 to 0 ms) M1 activity during ~l min recordings of left and right self-paced finger movements (~1 Hz). High-resolution MEG source images were obtained by projecting M1 activity towards the skin EMG signal without trial averaging. We studied delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), gamma (30-90 Hz), and upper-gamma (60-90 Hz) bands in 13 healthy participants (26 datasets) and three presurgical patients with sensorimotor dysfunction. In healthy participants, EMG-projected MEG accurately localized M1 with high accuracy in delta (100.0%), theta (100.0%), and beta (76.9%) bands, but not alpha (34.6%) or gamma/upper-gamma (0.0%) bands. Except for delta, all other frequency bands were above the movement frequency and its harmonics. In three presurgical patients, M1 activity in the affected hemisphere was also accurately localized, despite highly irregular EMG movement patterns in one patient. Altogether, our EMG-projected MEG imaging approach is highly accurate and feasible for M1 mapping in presurgical patients. The results also provide insight into movement-related brain-muscle coupling above the movement frequency and its harmonics., Competing Interests: All authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Massachusetts Institute of Technology. Published under a Creative Commons Attribution 4.0 International (CC BY 4.0) license.)

Background: Phosphorus nutrition is important for obtaining high yields of crop plants. However, wheat plants are known to be almost incapable of taking up phosphorus from insoluble phosphate sources, and reduced height genes are supposed to decrease this ability further., Methods: We performed a pot experiment using Triticum durum Desf. tall spring variety LD222, its near-isogenic semidwarf line carrying Rht17 ( Reduced height 17 ) gene, and winter rye ( Secale cereale L.) variety Chulpan. The individual plants were grown in quartz sand. The phosphorus was provided either as phosphate rock powder mixed with sand, or as monopotassium phosphate solution (normal nutrition control) or was not supplemented at all (no-phosphorus control). Other nutrients were provided in soluble form. During experiment the plants were assessed using the TraitFinder (Phenospex Ltd., Heerlen, Netherlands) digital phenotyping system for a standard set of parameters. Double scan with 90 degrees turns of pots around vertical axis vs . single scan were compared for accuracy of phenotyping., Results: The phenotyping showed that at least 20 days of growth after seedling emergence were necessary to get stable differences between genotypes. After this initial period, phenotyping confirmed poor ability of wheat to grow on substrate with phosphate rock as the only source of phosphorus compared to rye; however, Rht17 did not cause an additional reduction in growth parameters other than plant height under this variant of substrate. The agreement between digital phenotyping and conventionally measured traits was at previously reported level for grasses (R 2 = 0.85 and 0.88 for digital biomass and 3D leaf area vs . conventionally measured biomass and leaf area, single scan). Among vegetation indices, only the normalized differential vegetation index (NDVI) and the green leaf index (GLI) showed significant correlations with manually measured traits, including the percentage of dead leaves area. The double scan improved phenotyping accuracy, but not substantially., Competing Interests: The authors declare that they have no competing interests., (© 2023 Bazhenov et al.)

The slow oscillation (SO) observed during deep sleep is known to facilitate memory consolidation. However, the impact of age-related changes in sleep electroencephalography (EEG) oscillations and memory remains unknown. In this study, we aimed to investigate the contribution of age-related changes in sleep SO and its role in memory decline by combining EEG recordings and computational modeling. Based on the detected SO events, we found that older adults exhibit lower SO density, lower SO frequency, and longer Up and Down state durations during N3 sleep compared to young and middle-aged groups. Using a biophysically detailed thalamocortical network model, we simulated the "aged" brain as a partial loss of synaptic connections between neurons in the cortex. Our simulations showed that the changes in sleep SO properties in the "aged" brain, similar to those observed in older adults, resulting in impaired memory consolidation. Overall, this study provides mechanistic insights into how age-related changes modulate sleep SOs and memory decline.Clinical Relevance- This study contributes towards finding feasible biomarkers and target mechanism for designing therapy in older adults with memory deficits, such as Alzheimer's disease patients.

Magnetoencephalography (MEG) is a non-invasive functional imaging technique for pre-surgical mapping. However, movement-related MEG functional mapping of primary motor cortex (M1) has been challenging in presurgical patients with brain lesions and sensorimotor dysfunction due to the large numbers of trails needed to obtain adequate signal to noise. Moreover, it is not fully understood how effective the brain communication is with the muscles at frequencies above the movement frequency and its harmonics. We developed a novel Electromyography (EMG)-projected MEG source imaging technique for localizing M1 during ~1 minute recordings of left and right self-paced finger movements (~1 Hz). High-resolution MEG source images were obtained by projecting M1 activity towards the skin EMG signal without trial averaging. We studied delta (1-4 Hz), theta (4-7 Hz), alpha (8-12 Hz), beta (15-30 Hz), and gamma (30-90 Hz) bands in 13 healthy participants (26 datasets) and two presurgical patients with sensorimotor dysfunction. In healthy participants, EMG-projected MEG accurately localized M1 with high accuracy in delta (100.0%), theta (100.0%), and beta (76.9%) bands, but not alpha (34.6%) and gamma (0.0%) bands. Except for delta, all other frequency bands were above the movement frequency and its harmonics. In both presurgical patients, M1 activity in the affected hemisphere was also accurately localized, despite highly irregular EMG movement patterns in one patient. Altogether, our EMG-projected MEG imaging approach is highly accurate and feasible for M1 mapping in presurgical patients. The results also provide insight into movement related brain-muscle coupling above the movement frequency and its harmonics.

Cortical stimulation is emerging as an experimental tool in basic research and a promising therapy for a range of neuropsychiatric conditions. As multielectrode arrays enter clinical practice, the possibility of using spatiotemporal patterns of electrical stimulation to induce desired physiological patterns has become theoretically possible, but in practice can only be implemented by trial-and-error because of a lack of predictive models. Experimental evidence increasingly establishes traveling waves as fundamental to cortical information-processing, but we lack an understanding of how to control wave properties despite rapidly improving technologies. This study uses a hybrid biophysical-anatomical and neural-computational model to predict and understand how a simple pattern of cortical surface stimulation could induce directional traveling waves via asymmetric activation of inhibitory interneurons. We found that pyramidal cells and basket cells are highly activated by the anodal electrode and minimally activated by the cathodal electrodes, while Martinotti cells are moderately activated by both electrodes but exhibit a slight preference for cathodal stimulation. Network model simulations found that this asymmetrical activation results in a traveling wave in superficial excitatory cells that propagates unidirectionally away from the electrode array. Our study reveals how asymmetric electrical stimulation can easily facilitate traveling waves by relying on two distinct types of inhibitory interneuron activity to shape and sustain the spatiotemporal dynamics of endogenous local circuit mechanisms. SIGNIFICANCE STATEMENT Electrical brain stimulation is becoming increasingly useful to probe the workings of brain and to treat a variety of neuropsychiatric disorders. However, stimulation is currently performed in a trial-and-error fashion as there are no methods to predict how different electrode arrangements and stimulation paradigms will affect brain functioning. In this study, we demonstrate a hybrid modeling approach, which makes experimentally testable predictions that bridge the gap between the microscale effects of multielectrode stimulation and the resultant circuit dynamics at the mesoscale. Our results show how custom stimulation paradigms can induce predictable, persistent changes in brain activity, which has the potential to restore normal brain function and become a powerful therapy for neurological and psychiatric conditions., (Copyright © 2023 the authors.)

Odorants binding to olfactory receptor neurons (ORNs) trigger bursts of action potentials, providing the brain with its only experience of the olfactory environment. Our recordings made in vivo from locust ORNs showed that odor-elicited firing patterns comprise four distinct response motifs, each defined by a reliable temporal profile. Different odorants could elicit different response motifs from a given ORN, a property we term motif switching. Further, each motif undergoes its own form of sensory adaptation when activated by repeated plume-like odor pulses. A computational model constrained by our recordings revealed that organizing responses into multiple motifs provides substantial benefits for classifying odors and processing complex odor plumes: each motif contributes uniquely to encode the plume's composition and structure. Multiple motifs and motif switching further improve odor classification by expanding coding dimensionality. Our model demonstrated that these response features could provide benefits for olfactory navigation, including determining the distance to an odor source., Competing Interests: BK, SH, AM, SJ, ZA, NR, AK, MB, MS No competing interests declared

Artificial neural networks are known to suffer from catastrophic forgetting: when learning multiple tasks sequentially, they perform well on the most recent task at the expense of previously learned tasks. In the brain, sleep is known to play an important role in incremental learning by replaying recent and old conflicting memory traces. Here we tested the hypothesis that implementing a sleep-like phase in artificial neural networks can protect old memories during new training and alleviate catastrophic forgetting. Sleep was implemented as off-line training with local unsupervised Hebbian plasticity rules and noisy input. In an incremental learning framework, sleep was able to recover old tasks that were otherwise forgotten. Previously learned memories were replayed spontaneously during sleep, forming unique representations for each class of inputs. Representational sparseness and neuronal activity corresponding to the old tasks increased while new task related activity decreased. The study suggests that spontaneous replay simulating sleep-like dynamics can alleviate catastrophic forgetting in artificial neural networks., (© 2022. The Author(s).)

Cortical slow oscillations (SOs) and thalamocortical sleep spindles are two prominent EEG rhythms of slow wave sleep. These EEG rhythms play an essential role in memory consolidation. In humans, sleep spindles are categorized into slow spindles (8-12 Hz) and fast spindles (12-16 Hz), with different properties. Slow spindles that couple with the up-to-down phase of the SO require more experimental and computational investigation to disclose their origin, functional relevance and most importantly their relation with SOs regarding memory consolidation. To examine slow spindles, we propose a biophysical thalamocortical model with two independent thalamic networks (one for slow and the other for fast spindles). Our modeling results show that fast spindles lead to faster cortical cell firing, and subsequently increase the amplitude of the cortical local field potential (LFP) during the SO down-to-up phase. Slow spindles also facilitate cortical cell firing, but the response is slower, thereby increasing the cortical LFP amplitude later, at the SO up-to-down phase of the SO cycle. Neither the SO rhythm nor the duration of the SO down state is affected by slow spindle activity. Furthermore, at a more hyperpolarized membrane potential level of fast thalamic subnetwork cells, the activity of fast spindles decreases, while the slow spindles activity increases. Together, our model results suggest that slow spindles may facilitate the initiation of the following SO cycle, without however affecting expression of the SO Up and Down states., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Mushtaq et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)