Biology subjects

Cardinale, F.

Publications and source records attributed to Cardinale, F..

11 recordsLinked to original sources

bioRxiv2026

Different spatial profiles of aberrant N-glycans in pediatric and adult MOGHE brain tissue

Mild malformation of cortical development with oligodendroglial hyperplasia in epilepsy (MOGHE) is a recently recognized epilepsy-associated lesion frequently linked to brain-restricted somatic variants in SLC35A2, a gene encoding the Golgi UDP-galactose transporter. Although previous studies demonstrated altered glycosylation in SLC35A2-mutated MOGHE tissue, the spatial relationship between glycosylation defects and histopathological abnormalities remains poorly understood. We applied matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) using formalin-fixed paraffin-embedded brain tissue from six histologically confirmed MOGHE cases (three pediatric and three adult) and three temporal lobe epilepsy with hippocampal sclerosis (TLE-HS). We spatially evaluated N-glycan profiles across diagnostic tissue groups, with particular attention to molecular differences between lesional and perilesional regions and to recurrent abundance trends. All MOGHE cases harboured somatic SLC35A2 variants. Histologically, oligodendroglial hyperplasia and heterotopic neurons were present in all cases, while patchy hypomyelination was restricted to pediatric cases. Unsupervised spatial segmentation, integrated with neuropathological evaluation, revealed marked molecular heterogeneity in pediatric MOGHE. In these cases, lesional and perilesional regions were clearly distinguishable in both white matter (WM) and overlying grey matter (GM) boundaries patterns, whereas adult MOGHE and TLE-HS mainly showed a clearcut separation between WM and GM. Spatial analysis confirmed enrichment of the previously reported aberrant N-glycan species m/z 2094 and, to a lesser extent, m/z 2297 within MOGHE tissue, particularly in pediatric lesional WM. Notably, the distribution of m/z 2094 closely overlapped with areas of hypomyelination. Quantitative trajectory analysis of 151 detected N-glycan ions identified recurrent abundance profiles. Three representative spatial patterns emerged: pediatric lesion-enriched, pediatric perilesion-enriched, and TLE-HS-enriched profiles. Pediatric lesions were characterized by increased abundance of multiantennary glycans lacking terminal galactose residues and reduced abundance of galactosylated biantennary and multiantennary structures, consistent with defective UDP-galactose transport. In contrast, adult lesional and perilesional tissues exhibited largely overlapping glycomic profiles. These findings provide the first spatially resolved evidence that glycosylation abnormalities in SLC35A2-mutated MOGHE are closely associated with lesional pathology, particularly hypomyelination, and are substantially more pronounced in pediatric than adult cases. Spatial glycomics may therefore offer new insights into MOGHE pathophysiology and support the development of targeted therapeutic approaches aimed at correcting galactosylation defects.

neuroscience↗

bioRxiv2026

Frequency modulations of cortical synchronization in human cortex during wakefulness and sleep

Vigilance states are associated with reproducible reconfigurations of large-scale brain dynamics, reflected in changes in inter-areal phase synchronization and cross-frequency phase-amplitude coupling. Here, we characterized how these two forms of phase-based coordination jointly organize across sleep and wakefulness in the human brain at local and regional levels. We analysed phase-locking value (PLV) and phase-amplitude coupling (PAC) from intracranial stereo-electroencephalography (SEEG) recordings in 46 individuals with drug-resistant focal epilepsy, focusing on contacts outside the epileptogenic zone (non-epileptogenic zone, nEZ) to define physiological coupling profiles and comparing them with contacts within the EZ. For each subject, representative epochs of wakefulness, NREM sleep stages N2 and N3, and REM sleep were examined. Across vigilance states, large-scale phase synchronization exhibited distinct spectral fingerprints. Theta and sigma synchronization predominated during NREM sleep, beta synchronization increased during REM sleep, and theta interactions characterized wakefulness. PAC showed complementary state-dependent reorganizations: N3 was characterized by delta-driven modulation of broadband high-frequency activity; N2 additionally exhibited theta- and spindle-phase modulation of beta-gamma amplitudes; REM sleep showed reduced coupling; and wakefulness was marked by theta-to-beta interactions. Within vigilance states, epileptogenic regions displayed increased delta and gamma synchronization and enhanced delta-to-beta/gamma PAC, most prominently during N2 sleep and wakefulness, whereas differences between EZ and nEZ tissue were attenuated during REM sleep. Using partial least squares analysis, we further identified system-specific patterns of PLV-PAC covariation, with prominent involvement of temporal networks during NREM sleep and visual and limbic systems during REM sleep. Together, these findings delineate a frequency-specific, state-dependent architecture linking phase synchronization and phase-amplitude coupling in the human brain and describe how epileptogenic networks deviate from physiological coupling profiles across vigilance states.

neuroscience↗

bioRxiv2026

REM sleep reconfigures large-scale network dynamics: a link to its suppressive role in epilepsy

Converging evidence suggests that human brain activity operates near a critical-like regime in which balanced excitation and inhibition support efficient large-scale communication. The brains proximity to criticality may be dynamically reset across the sleep-wake cycle and altered by epilepsy, leading to aberrant oscillatory dynamics. Building on recent work demonstrating a tripartite interaction between networks synchronization, oscillatory amplitude bistability, and cross-frequency coupling in the human brain that seems to favour epileptic activity, we examined how this interaction, and its underlying large-scale dynamics are modulated across vigilance states. We analyzed overnight recordings from 20 patients with drug-resistant epilepsy undergoing presurgical evaluation and selected overall 20 minutes of continuous, artifact free stereo-electroencephalography (SEEG) spanning REM sleep, NREM stages N2 and N3, and eyes-closed resting wakefulness. Across states, we quantified phase synchronization, phase-amplitude coupling, bistability and their correlation. REM sleep was consistently associated with a reduction of these dynamics relative to NREM sleep and wakefulness. Importantly, the canonical correlation between these measures -- reflecting the strength of the tripartite interaction -- was significantly weaker during REM sleep. These findings indicate that vigilance states modulate this previously identified multiscale interaction in human brain networks and suggest that the reduced epileptogenicity of REM sleep can be associated with a disruption of coordinated synchronization, coupling, and bistable dynamics at the large-scale network level.

neuroscience↗

bioRxiv2025

Scalp EEG predicts intracranial brain activity in humans

Inferring deep brain activity from noninvasive scalp recordings remains a fundamental challenge in neuroscience. Here, we analyzed concurrent scalp and intracranial recordings from 1918 electrode contacts across 20 patients affected by drug-resistant epilepsy undergoing intracranial depth electrode monitoring for pre-surgical evaluation to establish predictive relationships between surface and deep brain signals. Using regularized and cross-validated linear regression within subjects, we demonstrate that scalp recordings can predict spontaneous intracranial activity, with accuracy varying by region, depth, and frequency. Low-frequency signals (<12 Hz) were most predictable, with our models explaining approximately 10% of intracranial signal variance across contacts. Prediction accuracy decreased with contact depth, particularly for high-frequency signals. Using Bayesian modeling with leave-one-patient-out cross-validation, we observed generalizable prediction of activity in mesial temporal, prefrontal, and orbitofrontal cortices, explaining 10-12% of low-frequency signal variance. This scalp-to-intracranial mapping derived from spontaneous activity was further validated by its correlation with scalp responses evoked by direct electrical stimulation. These findings support the development of improved inverse models of brain activity and potentially more accurate scalp-based markers of disease and treatment response.

neuroscience↗

bioRxiv2025

Sleep-Modulated Cross-Frequency Coupling Between δ Phase and β-γ Bistability: A System-Level Modulation of Epileptic Activity

ObjectiveWhile slow waves in {delta} (0.5-4 Hz) characterize NREM sleep, in patients with sleep-related epilepsy, seizures most frequently emerge during NREM stage 2, known to be promoted by {delta}-band instability. Meanwhile, the epileptogenic zone (EZ) shows localized bistability in {beta}-{gamma} band (15-200 Hz) neuronal oscillations--indicating a catastrophic shift toward seizure. We aim to clarify the mechanistic link between {delta}-band synchrony and {beta}-{gamma} band bistability in epilepsy. MethodsWe studied a cohort of fourteen patients with Sleep Hypermotor Epilepsy (22.3 {+/-} 10.8 years old; 7 males). 7-9-hour stereo-EEG sleep recordings were segmented into 10-minute of uninterrupted, interictal N2 and N3 epochs, and phase synchrony, phase-amplitude coupling (PAC), and bistability were assessed. Canonical correlation was examined to answer whether PAC links {delta}-phase to {beta}-{gamma} bistability. ResultsCompared to non-EZ, the EZ exhibited larger 15-200 Hz bistability along with stronger 2-8 Hz and 15-100 Hz synchrony throughout N2 and N3. Compared to N3, N2 showed stronger PAC between 2-30 Hz phases in the non-EZ and 5-150 Hz amplitudes in the EZ. Canonical correlations between {delta}-phase modulated PAC and both bistability and synchrony were identified during N2 (r = 0.86 and 0.82) and N3 (r = 0.84 and 0.80), with the strongest contributors being 2-4 Hz synchrony and bistability in 2-4 Hz and 15-200 Hz bands. Correlations between interictal spikes and canonical covariates of bistability and PAC (r2 = 0.62 for N2 and 0.56 for N3) validated their relevance to epileptogenicity. Significance{delta}-band synchrony and {beta}-{gamma} band bistability are not isolated epileptogenic mechanisms but likely act synergistically, playing a pivotal role in seizure generation through the coupling of {delta} phases and {beta}-{gamma} amplitudes across large networks, with significant contributions from non-epileptogenic tissues. Key pointsO_LIStrong {beta}-{gamma} bistability in neuronal oscillations localizes the EZ throughout N2 and N3 sleep. C_LIO_LIElevated {delta}-band phase synchrony characterizes the EZ and its functional neighbors throughout N2 and N3 sleep. C_LIO_LIa-band synchrony modulates local {beta}-{gamma} bistability through PAC, with significant contributions from non-EZ tissues. C_LI

neuroscience↗

bioRxiv2024

Novel Mechanisms of Strigolactone-Induced DWARF14 Degradation in Arabidopsis thaliana

Strigolactones (SLs) are carotenoid-derived compounds that regulate various aspects of plant development, physiological responses and plant interactions with microorganisms. In angiosperms, the SL receptor is the /{beta} hydrolase D14 that, upon SL binding, undergoes conformational changes, triggers SL-dependent responses and hydrolyses SLs. Arabidopsis SL signalling involves the formation of a complex between SL-bound D14, the E3-ubiquitin ligase SCFMAX2 and the transcriptional corepressors SMXL6/7/8 (SMXLs), which become ubiquitinated and degraded by the proteasome. However, the sequence of events that result in SL signalling and the requirement of SL hydrolysis for this process remain unclear. In addition, SL destabilises the D14 receptor. The biological significance of SL-induced D14 degradation is unclear, although it has been proposed to create a negative feedback loop in SL signalling. The current model proposes that D14 degradation occurs after SMXLs ubiquitination and proteolysis, via the same E3-ubiquitin ligase that targets the repressors. In this work we quantitatively studied the degradation dynamics of Arabidopsis D14 in response to SLs in planta. For this, we conducted fluorescence and luminescence assays to monitor D14 stability dynamics upon SL treatments, in transgenic lines expressing D14 fused to GREEN FLUORESCENT PROTEIN (GFP) or LUCIFERASE (LUC), in wild-type and SL-signalling mutant backgrounds. Mutant D14 proteins predicted to be non-functional for SL signalling were also examined, and their capability to bind SLs in vitro was studied using Differential Scanning Fluorimetry (DSF). Finally, we used a non-hydrolysable SL to test the requirements of SL hydrolysis for D14 and SMXL7 degradation. Our research revealed that SL-induced D14 degradation may occur in the absence of SCFMAX2 and/or SMXLs by a proteasome-independent mechanism. Additionally, we observed conditions in which the efficiency of SL-induced degradation of D14 is not aligned with that of SMXL7 degradation. Finally, our results indicate that the hydrolysis of SLs is not a prerequisite to trigger either D14 or SMXL7 degradation. These findings suggest the existence of a regulatory mechanism governing D14 degradation more complex than anticipated, and provide novel insights into the dynamics of SL signalling in Arabidopsis.

plant biology↗

bioRxiv2021

An in-vivo validation of ESI methods with focal sources

Electrical source imaging (ESI) aims at reconstructing the electrical brain activity from measurements of the electric field on the scalp. Even though the localization of single focal sources should be relatively straightforward, different methods provide diverse solutions due to the different underlying assumptions. Furthermore, their input parameter(s) further affects the solution provided by each method, making localization even more challenging. In addition, validations and comparisons are typically performed either on synthetic data or through post-operative outcomes, in both cases with considerable limitations. We use an in-vivo high-density EEG dataset recorded during intracranial single pulse electrical stimulation, in which the true sources are substantially dipolar and their locations are known. We compare ten different ESI methods under multiple choices of input parameters, to assess the accuracy of the best reconstruction, as well as the impact of the parameters on the localization performance. Best reconstructions often fall within 1 cm from the true source, with more accurate methods outperforming less accurate ones by 1 cm, on average. Expectedly, dipolar methods tend to outperform distributed methods. Sensitivity to input parameters varies widely between methods. Depth weighting played no role for three out of six methods implementing it. In terms of regularization parameters, for several distributed methods SNR=1 unexpectedly turned out to be the best choice among the tested ones. Our data show similar levels of accuracy of ESI techniques when applied to "conventional" (32 channels) and dense (64, 128, 256 channels) EEG recordings. Overall findings reinforce the importance that ESI may have in the clinical context, especially when applied to identify the surgical target in potential candidates for epilepsy surgery.

neuroscience↗

bioRxiv2021

A comparative study between state-of-the-art MRI deidentification and AnonyMI, a new method combining re-identification risk reduction and geometrical preservation

Deidentifying MRIs constitutes an imperative challenge, as it aims at precluding the possibility of re-identification of a research subject or patient, but at the same time it should preserve as much geometrical information as possible, in order to maximize data reusability and to facilitate interoperability. Although several deidentification methods exist, no comprehensive and comparative evaluation of deidentification performance has been carried out across them. Moreover, the possible ways these methods can compromise subsequent analysis has not been exhaustively tested. To tackle these issues, we developed AnonyMI, a novel MRI deidentification method, implemented as a user-friendly 3D Slicer plugin-in, which aims at providing a balance between identity protection and geometrical preservation. To test these features, we performed two series of analyses on which we compared AnonyMI to other two state-of-the-art methods, to evaluate, at the same time, how efficient they are at deidentifying MRIs and how much they affect subsequent analyses, with particular emphasis on source localization procedures. Our results show that all three methods significantly reduce the re-identification risk but AnonyMI provides the best geometrical conservation. Notably, it also offers several technical advantages such as a user-friendly interface, multiple input-output capabilities, the possibility of being tailored to specific needs, batch processing and efficient visualization for quality assurance.

neuroscience↗

bioRxiv2020

Simultaneous human intracerebral stimulation and HD-EEG: ground-truth for source localization methods

Precisely localizing the sources of brain activity as recorded by EEG is a fundamental procedure and a major challenge for both research and clinical practice. Even though many methods and algorithms have been proposed, their relative advantages and limitations are still not well established. Moreover, these methods involve tuning multiple parameters, for which no principled way of selection exists yet. These uncertainties are emphasized due to the lack of ground-truth for their validation and testing. Here we provide the first open dataset that comprises EEG recorded electrical activity originating from precisely known locations inside the brain of living humans. High-density EEG was recorded as single-pulse biphasic currents were delivered at intensities ranging from 0.1 to 5 mA through stereotactically implanted electrodes in diverse brain regions during pre-surgical evaluation of patients with drug-resistant epilepsy. The uses of this dataset range from the estimation of in vivo tissue conductivity to the development, validation and testing of forward and inverse solution methods.

neuroscience↗

bioRxiv2019

Stereotactic electroencephalography in humans reveals multisensory signal in early visual and auditory cortices

Unequivocally demonstrating the presence of multisensory signals at the earliest stages of cortical processing remains challenging in humans. In our study, we relied on the unique spatio-temporal resolution provided by intracranial stereotactic electroencephalographic (SEEG) recordings in patients with drug-resistant epilepsy to characterize the signal extracted from early visual (calcarine and pericalcarine) and auditory (Heschls gyrus and planum temporale) regions during a simple audio-visual oddball task. We provide evidences that both cross-modal responses (visual responses in auditory cortex or the reverse) and multisensory processing (alteration of the unimodal responses during bimodal stimulation) can be observed in intracranial event-related potentials (iERPs) and in power modulations of oscillatory activity at different temporal scales within the first 150 ms after stimulus onset. The temporal profiles of the iERPs are compatible with the hypothesis that MSI occurs by means of direct pathways linking early visual and auditory regions. Our data indicate, moreover, that MSI mainly relies on modulations of the low-frequency bands (foremost the theta band in the auditory cortex and the alpha band in the visual cortex), suggesting the involvement of feedback pathways between the two sensory regions. Remarkably, we also observed high-gamma power modulations by sounds in the early visual cortex, thus suggesting the presence of neuronal populations involved in auditory processing in the calcarine and pericalcarine region in humans.

neuroscience↗

bioRxiv2018

Long-range phase synchronization of high-gamma activity in human cortex

Inter-areal synchronization of neuronal oscillations below 100 Hz is ubiquitous in cortical circuitry and thought to regulate neuronal communication. In contrast, faster activities are generally considered to be exclusively local-circuit phenomena. We show with human intracerebral recordings that 100-300 Hz high-gamma activity (HGA) may be synchronized between widely distributed regions. HGA synchronization was not attributable to artefacts or to epileptic pathophysiology. Instead, HGA synchronization exhibited a reliable cortical connectivity and community structures, and a laminar profile opposite to that of lower frequencies. Importantly, HGA synchronization among functional brain systems during non-REM sleep was distinct from that in resting state. Moreover, HGA synchronization was transiently enhanced for correctly inhibited responses in a Go/NoGo task. These findings show that HGA synchronization constitutes a new, functionally significant form of neuronal spike-timing relationships in brain activity. We suggest that HGA synchronization reflects the temporal microstructure of spiking-based neuronal communication per se in cortical circuits.

neuroscience↗