Biology subjects

Gallo, E.

Publications and source records attributed to Gallo, E..

9 recordsLinked to original sources

bioRxiv2026

Structural topology shapes regional roles in neuronal avalanche initiation and termination

Whole-brain dynamics unfold as fast, discrete, transient events known as, neuronal avalanches, whose propagation is constrained by the connectome, that is, the large-scale scaffolding of structural connections wiring the brain. However, the role of the connectome in determining the topographies of the start and end of these transient cascades remains unclear. Leveraging resting-state Magnetoencephalography (MEG) recordings and diffusion magnetic resonance imaging (dMRI) tractography across 42 healthy individuals, we examined whether the structural architecture of white matter tracts dictates the spatial origins and the end of cortical avalanches. We found that the probability of triggering and finishing an avalanche is strongly related to the structural nodal strength, showing a positive correlation that is highly robust to non-parametric spatial permutation testing and bootstrapping. This structure-function coupling is highly stable and robust across different activation thresholds, demonstrating that the choice of avalanche extraction threshold does not drive or alter our main findings. Collectively, our results suggest that structural properties determine a region's propensity to initiate and terminate neuronal avalanches.

neuroscience↗

bioRxiv2026

Departure from OFF-State Microstate Dynamics Tracks Levodopa Response in Parkinson's Disease

Although dopaminergic therapies in Parkinsons disease primarily restore dopamine within nigrostriatal circuits, symptoms are better indexed by whole-brain dynamics than by local activity. In this manuscript, we hypothesize that L-Dopa therapy affects whole-brain dynamics alike, which in turn relate to clinical improvement. To test this hypothesis, we conducted a repeated-measures, source-reconstructed MEG study in 13 bradykinetic-dominant PD patients, recording resting-state cortical activity OFF medication and [~]1 hour after levodopa administration (ON). We characterize brain dynamics using a microstate framework, in which transition probabilities between microstates are used to contrast pathological OFF-state dynamics with those in the ON-state. Microstate dynamics were stable within medication states but reconfigured by L-Dopa, with greater departures from the OFF-state pattern associated, at the individual level, with larger clinical improvements. Our results suggest that individualized changes in microstate dynamics may serve as a neurophysiological marker of dopaminergic responsiveness.

neuroscience↗

bioRxiv2026

Data-driven gait cycle decomposition based on whole-body coordination dynamics

The study of human locomotion has long relied on descriptive frameworks of the gait cycle, which have provided essential insights into the functional phases of walking and their underlying biomechanical demands. While these models remain highly informative, they are largely based on observational analyses and may not fully capture the continuous, global coordination that characterizes human movement. The present study proposes an integrated framework to study whole-body coordination. This framework combines network theory with non-negative matrix factorization (NNMF) to treat gait as a dynamic system of coordinated joint interactions. Using three-dimensional kinematic data from 60 healthy subjects, we constructed a representation of whole-body coordination across time, named "dynamic kinectome". It was then decomposed using NNMF to extract spatial patterns of joint coordination and their corresponding temporal activations, allowing for an interpretable characterization of locomotor organization while preserving physiological meaning. Our analysis extracted six robust, highly consistent, and symmetrical coordination patterns across participants, effectively capturing the primary functional subtasks of locomotion. Rather than challenging classical phase descriptions, these findings enrich them by showing how coordination emerges as a continuous, often proactive process that can extend across conventional phase boundaries and systematically integrates the upper limbs for dynamic stability. Overall, this study provides a holistic, data-driven perspective on human locomotion, offering a promising basis for future investigations in motor control and may contribute to the development of sensitive biomarkers for clinical and rehabilitative applications.

bioengineering↗

bioRxiv2026

Hormone-Dependent Microstates and the Reconfiguration of Resting-State Dynamics across the Menstrual Cycle

While behavioral fluctuations across the menstrual cycle (MC) are well-documented, the neural underpinnings of these changes remain elusive. This study investigated the hypothesis that cyclic variations in sex hormones modulate large-scale brain activation patterns. To test this, longitudinal magnetoencephalographic (MEG) recordings were acquired and source reconstructed from 24 naturally cycling women across three distinct MC phases: early follicular, peri-ovulatory, and mid-luteal. Microstate analysis was employed to characterize large-scale cortical dynamics as "visits" to specific global configurations (i.e., maps) of brain activity. Our results revealed significant variations in the occurrence of specific microstate maps, particularly between the early follicular and mid-luteal phases. Furthermore, the occurrence of these specific configurations was significantly associated with fluctuations in hormone levels. Critically, both the hormonal levels and microstate dynamics were predictive of individual longitudinal changes in psychological well-being. These findings propose a neurophysiological substrate for the behavioral effects of hormonal cycling, identifying specific topographic maps whose dynamics are sensitive to the hormonal profile and carry predictive power for psychological health. Collectively, these results underscore the necessity of accounting for the MC in neuroimaging research and introduce a novel framework for defining microstates (Hormone-Dependent Microstates - HDMs) with respect to slowly changing dynamical properties across a month-long timescale.

neuroscience↗

bioRxiv2025

The role of structural heterogeneity in shaping whole-brain dynamics across scales

The brain must rapidly and dynamically recruit the appropriate brain regions to respond to environmental changes and sustain flexible cognition. An extensive body of literature views the ability to spontaneously explore a rich repertoire of activity patterns, even during rest, as a correlate of the capacity to respond rapidly to internal fluctuations and external stimuli. Moreover, brain flexibility at rest successfully indexes pathological conditions such as Parkinsons disease, multiple sclerosis, and amyotrophic lateral sclerosis. However, previous work provides no information about the contribution of each region to the flexibility of brain dynamics. Given the functional and structural heterogeneity of brain regions, we hypothesized their roles in sustaining flexibility to be heterogeneous and related to regional structural properties. To systematically investigate these hypotheses, we define the flexibility gradient (FG), a new measure, which quantifies regional contributions to flexibility. We employed three datasets spanning different recording techniques and a range of spatial and temporal scales: 47 MEG recordings, 11 EEG recordings, and 77 fMRI recordings along with the corresponding tractographies. We found that FG is not homogeneously distributed, with associative and occipital regions contributing the most. This gradient is symmetric across left and right hemispheres, and the structural properties of brain regions correlate with their contribution to flexibility. Our findings are stable across modalities and temporal scales, highlighting that brain flexibility is not only a global dynamical property but also a spatially structured feature shaped by the anatomical organization of the brain.

neuroscience↗

bioRxiv2025

Nuclear rerouting of paracrine Fgf3 in source cells represses target genes to pattern morphogen responses

Morphogen gradients direct tissue patterning by inducing dose-dependent transcriptional responses, yet ligand-producing cells often respond differently from their neighbors. Using the zebrafish lateral line organogenesis model, we uncover a cell-autonomous role for the paracrine ligand Fgf3. Transcriptomic profiling and quantitative single-molecule imaging identify target genes, including the chemokine scavenger cxcr7b, whose expression decreases both when FGF receptor signaling is inhibited and when Fgf3 is overexpressed. High-resolution live imaging reveals nuclear accumulation of Fgf3 in producing cells, whereas neighbors receive only extracellular ligand, a feature also observed in other embryonic tissues. Mosaic gain- of-function and nanobody-mediated degradation demonstrate that the nuclear pool of Fgf3 autonomously represses specific targets without impairing canonical receptor signaling. Structure-guided comparative assays indicate nuclear targeting as a latent property of several paracrine FGFs. Dual secreted-nuclear functionality of FGF ligands may represent an intrinsic symmetry-breaking mechanism during organogenesis.

developmental biology↗

bioRxiv2022

A role for the centrosome in regulating the rate of neuronal efferocytosis by microglia in vivo

During brain development, many newborn neurons undergo apoptosis and are engulfed by microglia, the tissue-resident phagocytes of the brain, in a process known as efferocytosis. A hallmark of microglia is their highly branched morphology characterised by the presence of numerous dynamic extensions that these cells use for scanning the brain parenchyma and engulfing unwanted material. The mechanisms driving branch formation and apoptotic cell engulfment in microglia are unclear. By taking a live imaging approach in zebrafish, we show that while microglia generate multiple microtubule-based branches, they only successfully engulf one apoptotic neuron at a time. Further investigation into the mechanism underlying this sequential engulfment revealed that targeted migration of the centrosome into one branch is predictive of phagosome formation and polarised vesicular trafficking. Moreover, experimentally doubling centrosomal numbers in microglia increases the rate of engulfment and even allows microglia to remove two neurons simultaneously, providing direct supporting evidence for a model where centrosomal migration is a rate-limiting step in branch-mediated efferocytosis. Conversely, light-mediated depolymerization of microtubules causes microglia to lose their typical branched morphology and switch to an alternative mode of engulfment, characterised by directed migration towards target neurons, revealing unexpected plasticity in their phagocytic ability. Finally, building on work focusing on the establishment of the immunological synapse, we identified a conserved signalling pathway underlying centrosomal movement in engulfing microglia.

cell biology↗

bioRxiv2022

AA-amyloidosis in cats (Felis catus) housed in shelters

Systemic AA-amyloidosis is a protein-misfolding disease that is characterized by fibril deposition of serum amyloid-A protein (SAA) in several organs in humans and many animal species. Fibril deposits originate from abnormally high serum levels of SAA during chronic inflammation. In domestic short-hair cats, AA-amyloidosis has only been anecdotally reported and is considered a rare disease. Here we report that an astonishing 57-73% of early deceased short-hair cats kept in three independent shelters suffer from amyloid deposition in the liver, spleen, or kidney. Histopathology and mass spectrometry of post-mortem extracted deposits identified SAA as the major protein source. The duration of stay in the shelters was positively associated with a histological score of AA-amyloidosis (B=0.026, CI95%=0.007-0.046; p=0.010). Presence of SAA fragments in bile secretions raises the possibility of fecal-oral transmission of the disease.

pathology↗

bioRxiv2020

An Image-Based Data-Driven Analysis of Cellular Architecture in a Developing Tissue

Quantitative microscopy is becoming increasingly crucial in efforts to disentangle the complexity of organogenesis, yet adoption of the potent and ever-growing toolbox provided by modern data science has been slow, primarily because data-driven tools focus on "big data" whereas microscopy produces "rich data". We tackle this issue using a newly developed algorithm for point cloud-based morphometry to unpack the rich information encoded in high-resolution 3D image data into a straightforward numerical representation. This allowed us to employ machine learning for multi-modal data integration of cell morphology, intracellular organization, gene expression and annotated contextual knowledge that facilitates data exploration. We apply these techniques to construct and explore a quantitative atlas of cellular architecture for the zebrafish posterior lateral line primordium, an experimentally tractable model of complex self-organized organogenesis. In doing so, we are able to retrieve both previously established and novel biologically relevant patterns, demonstrating the potential of our data-driven approach.

developmental biology↗