Biology subjects

Zubarev, I.

Publications and source records attributed to Zubarev, I..

10 recordsLinked to original sources

bioRxiv2026

Interpretable Decoding of Frequency-Resolved Functional Connectivity

Whole-brain functional connectivity, estimated from magnetoencephalography (MEG) data, provides a compact representation of long-range neuronal communication, making it suitable for predictive biomarker discovery. In this work, we propose a deep learning framework (FC-CNN) for predicting brain states from frequency-resolved functional connectivity estimates derived from resting-state MEG recordings. We systematically compare the performance of FC-CNN to that of conventional regression methods using amplitude and phase-based functional connectivity in the well-studied age-prediction task on the Cam-CAN cohort (n=576). We show that FC-CNN outperforms conventional approaches, and that, compared to phase synchronization, amplitude envelope correlation consistently leads to higher prediction performance. Moreover, we present quantitative evidence that the weights of a trained deep learning model can enable neurophysiological interpretation of the activity patterns that inform successful predictions. Our work demonstrates that the proposed approach successfully decodes brain states from MEG functional connectivity and is promising for discovery of predictive biomarkers for brain disorders.

neuroscience↗

bioRxiv2026

Automated robotic control system for EEG-BCI-guided closed-loop TMS

Brain-state-guided and closed-loop transcranial magnetic stimulation (TMS) protocols have emerged as methods for decreasing the variability and increasing the therapeutic effectiveness of stimulation protocols. However, most existing brain-state-dependent TMS systems only control the timing of stimulation, while the location is fixed and manually adjusted between blocks or sessions. This limits flexible targeting of distributed networks. We developed a system that jointly manages TMS pulse timing and location automatically controlled by an electroencephalography (EEG)-based brain- computer interface (BCI). A machine-learning algorithm infers the brain state in real time to guide the robotic coil placement and target. We present a proof-of-concept study in which a BCI controlled both the target site and the timing of TMS. A pre-trained convolutional neural network discriminated between resting state and movements performed with the right or left hand; the classifier output determined the hemisphere in which primary-motor-cortex hand area was stimulated and when. Preprocessing and decoding of 2-s EEG segments required 150 ms, and the robot took 7.5 s to move from the vertex home position to the predefined motor targets. The EEG-BCI-guided robotic TMS system expands the toolkit for brain-state-dependent and closed-loop neurostimulation by enabling control of stimulus location based on volitional brain activity. Thus, the system can benefit both neuroscience research and clinical neuromodulation applications. A prominent application of the system is automatically controlling spinal cord injury or motor disorder TMS rehabilitation with motor imagery, optimizing stimulation timing to the brain state producing optimal rehabilitation results.

neuroscience↗

bioRxiv2026

TMS timed to interictal epileptiform discharges

Interictal epileptiform discharges (IEDs) are pathological hypersynchronous bursts of electrical brain activity that occur between seizures in patients with epilepsy. IEDs are caused by transient brain states that are difficult to predict, making them a challenging neurophysiological and technological case for brain-state-dependent stimulation. Administering stimulation at IED onset may provide insight into the epileptic network and optimize neurostimulation therapies. Here, we assessed the feasibility of IED-triggered transcranial magnetic stimulation (TMS) in two children with self-limited epilepsy with centrotemporal spikes (SeLECTS), a common pediatric epilepsy in which IEDs emerge from the motor cortex. A convolutional neural network (CNN) was trained on the participants pre-recorded electroencephalography (EEG) data with IEDs annotated by an epileptologist. The CNN was integrated into an EEG-processing pipeline that classified EEG segments as "IED" or "non-IED" in real time. With this pipeline, TMS pulses were administered during IED or non-IED periods in an interleaved, randomized design. We stimulated both the motor cortex generating the IEDs and the contralateral motor cortex and tested the impact of IEDs on TMS-evoked potentials (TEPs). Our study demonstrated that TMS can be timed to IEDs and that there is a site-specific increase in TEP amplitude when stimulating during IEDs. Out of the TMS pulses aimed at an IED, 39% and 19% were successfully delivered during an IED for the two participants, respectively. For future research, we propose ways to address the methodological challenges of IED-timed TMS, enabling brain-state-dependent TMS for epilepsy research and treatment.

neuroscience↗

bioRxiv2025

Magnetically controlled tension of cytoskeletal elements with magnetic nanoparticles affects the expression of signaling pathway genes associated with cytoskeletal elements

Interactions with the extracellular environment and biological responses are based on biochemical pathways. Cytoskeletal reorganization is a dynamic process accompanied by filament polymerization and depolymerization, that allows the cell to effectively perceive and respond to external mechanical stimuli by altering their biomechanical properties. The contribution of mechanical deformations of individual cytoskeletal elements to changes in intracellular signaling has not been covered in the existing literature. In our article, we investigated changes in gene expression after regulated cytoskeletal deformation using a constant magnetic field and magnetic nanoparticles associated with antibodies to cytoskeletal proteins (vimentin, beta-actin and acetylated tubulin). For the first time, we have identified and described the biological pathways involved in the regulation of mechanical deformations of cytoskeletal elements.

bioinformatics↗

bioRxiv2025

MagnEspScope - DIY microscope with integrated magnetic system for magnetogenetic studies

Magnetogenetics is a promising field of biology devoted to the manipulation of biological objects by magnetic fields, where magnetic nanoparticles usually act as actuators. However, studying the response of biological objects is hampered by the fact that microscopes are usually made of ferromagnetic materials, making it difficult to work with them in powerful magnetic fields. This article focuses on building a DIY 3d printed microscope based on the ESPressoscope platform, integrated into a gradient magnetic system of permanent magnets. The article reveals the design, choice of materials and, using the example of cellular spheroids saturated with magnetic nanoparticles, demonstrates the application of MagnEspScope for the observation of magnetophoresis of biological objects.

cell biology↗

bioRxiv2025

MicroSplit: Semantic Unmixing of Fluorescent Microscopy Data

Fluorescence microscopy, a key driver for progress in the life sciences, faces limitations due to the microscopes optics, fluorophore chemistry, and photon exposure limits, necessitating trade-offs in imaging speed, resolution, and depth. Here, we introduce Micro[S]plit, a computational multiplexing technique based on deep learning that allows multiple cellular structures to be imaged in a single fluorescent channel and then unmix them by computational means, allowing faster imaging and reduced photon exposure. We show that Micro[S]plit efficiently separates up to four superimposed noisy structures into distinct denoised fluorescent image channels. Furthermore, using Variational Splitting Encoder-Decoder (VSE) networks, our approach can sample diverse predictions from a trained posterior of solutions. The diversity of these samples scales with the uncertainty in a given input, allowing us to estimate the true prediction errors by computing the variability between posterior samples. We demonstrate the robustness of Micro[S]plit networks, which are trained for each splitting task at hand, across various datasets and noise levels and show its utility to image more, to image faster, and to improve downstream analysis. We provide Micro[S]plit along with all associated training and evaluation datasets as open resources, enabling life scientists to immediately benefit from the potential of computational multiplexing and thus help accelerate the rate of their scientific discovery process.

bioinformatics↗

bioRxiv2024

MSLASpheroidStamp: 3d cell spheroids for everyone

3D cell cultures, such as cell spheroids, are actively used in biology for modeling biological processes, studying intercellular interactions and pharmacological compounds screening and are becoming indispensable objects in cell culture laboratories. There are many methods for producing spheroids, varying in cost and convenience. One of the most handy and affordable is the use of agarose microwells. We have developed approaches to fabricate agarose microwells in standard culture plastic with the assistance of a hobby-grade MSLA 3D printer. The use of 3D printing allows you to customize microwells in a wide range of shapes and sizes and scale the production process from a few spheroids to tens of thousands. We have shown that it is possible to create gel microwells in a dish with a glass bottom, which allows us to easily realize time-lapse confocal microscopy of spheroids, and we have also performed in situ optical clearing in the same dishes to study the spheroid structure. We demonstrated the ability to study the cytotoxicity of various substances and nanoparticles in commonly used 96-well plates. And finally, in this article we describe the difficulties and limitations of our approach and suggest ways for solving them, allowing the reader not only to reproduce it, but also to adapt it to the specific needs of a certain laboratory, using provided 3D models and instructions.

cell biology↗

bioRxiv2024

Effect of a constant magnetic field on morphology and motility of cell with cytoskeleton-associated magnetic nanoparticles

1.Cell motility, shape supporting, and intracellular signaling are followed by changes in cell morphology and cytoskeleton. The cell reaction and the reorganization of the cytoskeleton occurs in a single volume of the cytoplasm and affects all components of the cytoskeleton: intermediate filaments, microtubules and microfilaments. A promising way to manipulate cells is magnetic nanoparticles that control cellular physiology. This approach is called magnetogenetics and has found application in various fields of cell and molecular biology. Using a magnetic field, it is possible to non-invasively regulate biochemical processes, migration and changes in the morphology of cells with magnetic nanoparticles. Our work opens up new possibilities for spatial manipulation of individual cytoskeletal components in vitro and operates biochemical pathways associated with individual cytoskeletal components.

cell biology↗

bioRxiv2020

Magnetocontrolled protein membranes for cell cultures co-cultivation

Investigation of cells and tissues in vitro systems is an attempt to simplify the very complex interactions between the various cell types from multicellular organisms. Monolayer cell cultures with single cell type do not allow to show all the possible paracrine interactions between various types of cells. To analyze intercellular inter-actions, it is possible to use systems that co-cultivate several cell types. This article proposes a new cell co-cultivation system based on levitation in the magnetic field in the culture medium of a magnetic protein membrane with cells. The developed system of co-cultivation of cells can be made in any laboratory of available reagents and have a low manufacturing cost.

bioengineering↗

bioRxiv2020

Heterogeneous somatostatin-expressing neuron population in mouse ventral tegmental area

The cellular architecture of the ventral tegmental area (VTA), the main hub of the brain reward system, remains only partially characterized. To extend the characterization to inhibitory neurons, we have identified three distinct subtypes of somatostatin (Sst)-expressing neurons in the mouse VTA. These neurons differ in their electrophysiological and morphological properties, anatomical localization, as well as mRNA expression profiles. Importantly, similar to cortical Sst-containing interneurons, most VTA Sst neurons express GABAergic inhibitory markers, but some of them also express glutamatergic excitatory markers and a subpopulation even express dopaminergic markers. Furthermore, only some of the proposed marker genes for cortical Sst neurons were expressed in the VTA Sst neurons. Physiologically, one of the VTA Sst neuron subtypes locally inhibited neighboring dopamine neurons. Overall, our results demonstrate the remarkable complexity and heterogeneity of VTA Sst neurons and suggest that these cells are multifunctional players in the midbrain reward circuitry.

neuroscience↗