The Sense of Smell (SoS) Atlas: Its Creation and First Application to Investigate COVID-19 Related Anosmia With a Comprehensive Quantitative MRI Protocol Marta Gaviraghi, Eleonora Lupi, Elena Grosso, Andrea Fusari, Mattia Baiguera, et al. Journal of Magnetic Resonance Imaging, 2026 BackgroundThe loss of smell (anosmia) has been noted in numerous diseases, including COVID‐19. Inflammatory and microstructural alterations are possible underlying mechanisms of anosmia in COVID‐19. However, no atlas exists to study olfaction and the associated tissue property changes.PurposeTo develop the sense of smell (SoS) atlas, including gray matter regions and white matter tracts of the olfactory circuit, to investigate the underpinnings of COVID‐19 related anosmia.Study TypeRetrospective.SubjectsFor the SoS atlas, high‐resolution tractograms of 10 healthy controls (HC) of the Human Connectome Project (7 females, 22–35 years) were used. The SoS atlas was applied to 8 subjects with persistent anosmia following COVID‐19 (COVID‐P, 7 females, 52 ± 12 years), 19 subjects that recovered from COVID‐19 anosmia (COVID‐R, 14 females, 38 ± 13 years), and 17 HC (8 females, 39 ± 12 years).Field Strength/Sequence3 T, 3D inversion recovery, 3D fast field echo, and spin‐echo echo‐planar imaging sequences.AssessmentTo create the SoS atlas, regions were identified and tracts were extracted via tractography following biological constraints. MRI metrics sensitive to alterations in neuroinflammation, axonal degeneration, myelin and macromolecular density, and iron were analyzed.Statistical TestsRegion‐based analysis (p‐value < 0.05, false discovery rate (FDR) corrected) and voxel‐based analysis (p‐value < 0.001 uncorrected, FDR‐corrected cluster extent = 5 voxels) were performed on 15 multisequence‐MRI metrics between the three groups.ResultsThe SoS atlas consisted of 35 regions and, after anatomical curation, the initial 506 tracts were refined to 78. Compared to HC, COVID‐P presented alterations in neuroinflammation‐related (mean: 41% of total alterations) and axonal degeneration‐related (31%) MRI metrics, while COVID‐R presented alterations of myelin‐related metrics (68%). COVID‐P alterations mainly affected the hindbrain (56%), while COVID‐R the hindbrain (39%).Data ConclusionA novel tool, the SoS atlas, was developed to study the olfactory system and applied in combination with multisequence‐MRI metrics to investigate the mechanisms of COVID‐19 related anosmia.Evidence Level3.Technical EfficacyStage 1.
A Computational Model of the Respiratory CPG for the Artificial Control of Breathing Lorenzo De Toni, Federica Perricone, Lorenzo Tartarini, Giulia Maria Boiani, Stefano Cattini, et al. Bioengineering, 2025 The human respiratory Central Pattern Generator (CPG) is a complex and tightly regulated network of neurons responsible for the automatic rhythm of breathing. Among the brain nuclei involved in respiratory control, excitatory neurons within the PreBotzinger Complex (PreBötC) are both necessary and sufficient for generating this rhythmic activity. Although several models of the PreBötC circuit have been proposed, a comprehensive analysis of network behavior in response to physiologically relevant external inputs remains limited. In this study, we present a computational model of the PreBötC consisting of 1000 excitatory neurons, divided into two functional subgroups: the rhythm-generating population and the pattern-forming population. To enable real-time closed-loop simulations, we employed parallelized multi-process computing to accelerate network simulation. The network, composed of asynchronous neurons, could produce bursting activity at a eupneic breathing frequency of 0.22 Hz, which could also reproduce the rapid and stable chemoreception of breathing activated in response to hypercapnia. Additionally, it successfully replicated rapid and stable respiratory responses to elevated carbon dioxide levels (hypercapnia), mediated through simulated chemoreception. External inputs from a carbon dioxide sensor were used to modulate the network activity, allowing the implementation of a real-time respiratory control system. These results demonstrate that a network of asynchronous, non-bursting neurons can emulate the behavior of the respiratory CPG and its modulation by external stimuli. The proposed model represents a step toward developing a closed-loop controller for breathing regulation.
Enhanced electrophysiological recordings in acute brain slices, spheroids, and organoids using 3D high-density multielectrode arrays Lisa Mapelli, Danila Di Domenico, Giacomo Sciacca, Francesco Mainardi, Alessandra Ottaviani, et al. Plos One, 2025 Recent advances in three-dimensional (3D) biological brain models in vitro and ex vivo are creating new opportunities to understand the complexity of neural networks but pose the technological challenge of obtaining high-throughput recordings of electrical activity from multiple sites in 3D at high spatiotemporal resolution. This cannot be achieved using planar multi-electrode arrays (MEAs), which contact just one side of the neural structure. Moreover, the specimen adhesion to planar MEAs limits fluid perfusion along with tissue viability and drug application. Here, the efficiency of the tissue-sensor interface provided by advanced 3D high-density (HD)-MEA technology was evaluated in acute brain slices, spheroids, and organoids obtained from different brain regions. The 3D HD-MEA microneedles reached the inner layers of samples without damaging network integrity and the microchannel network between microneedles improved tissue vitality and chemical compound diffusion. In acute cortico-hippocampal and cerebellar slices, signal recording and stimulation efficiency proved higher with the 3D HD-MEA than with a planar MEA improving the characterization of network activity and functional connectivity. The 3D HD-MEA also resolved the challenge of recording from brain spheroids as well as cortical and spinal organoids. Our results show that 3D HD-MEA technology represents a valuable tool to address the complex spatiotemporal organization of activity in brain microcircuits, making it possible to investigate 3D biological models.
Cerebellar control over inter-regional excitatory/inhibitory dynamics discriminates execution from observation of an action Roberta Maria Lorenzi, Gökçe Korkmaz, Adnan A. S. Alahmadi, Anita Monteverdi, Letizia Casiraghi, et al. Cerebellum, 2025 The motor learning theory anticipates that cerebro-cerebellar loops perform sensorimotor prediction, thereby regulating motor control during action execution (AE) and observation (AO), but the causal interaction between the cerebellum and cerebral cortex remains unclear. Therefore, our aim was to understand what triggers neuronal activity between brain areas engaged in a visuo-motor task that involves cortico-cerebellar interactions, organised in loops. We used Dynamic Causal Modelling (DCM) to study functional MRI (fMRI) data obtained in healthy participants during a squeeze-ball task in either execution or observation conditions. In both cases, active regions included bilateral primary visual cortex (V1), left primary motor cortex (M1), supplementary motor and premotor cortex (SMAPMC), cingulate cortex (CC), superior parietal lobule (SPL), and right cerebellum (CRBL). Networks supporting executing or observing an action showed the same effective connectivity, with pathways between regions wired in closed loops. However, the cerebellar communication towards the cerebral cortex switched from excitatory in execution to inhibitory in observation. Moreover, when executing the action signal modulation was non-linear from SMAPMC to CRBL and within the CRBL self-connection, supporting that the CRBL elaborates motor plans received from SMAPMC. Thus, the need for motor planning and the presence of a sensorimotor feedback in action execution discriminate the modality of forward control operated by the CRBL. Interestingly, this study also showed that the CRBL differentially controls the excitatory/inhibitory dynamics of inter-regional effective connectivity, depending on its functional engagement. These findings are fundamental for understanding brain dynamics in health and disease and for designing artificial sensorimotor controllers.
An Equivalent Single Spiking Neuron Model of the Working Memory Navya Ajith, Arathi Rajendran, Giovanni Naldi, Egidio D'Angelo, Shyam Diwakar 2025 International Conference on Cognitive Computing in Engineering Communications Sciences and Biomedical Health Informatics Ic3ecsbhi 2025, 2025
Granule Cells and Parallel Fibers Egidio D’Angelo Essentials of Cerebellum and Cerebellar Disorders A Primer for Graduate Students Second Edition, 2023
Brain-inspired sensorimotor robotic platform learning in cerebellum-driven movement tasks through a cerebellar realistic model Ijcci 2013 Proceedings of the 5th International Joint Conference on Computational Intelligence, 2013
Complex dynamics in the granual layer of the cerebellum: Large-scale computational reconstructions 4th International Conference on Cognitive Systems Cogsys 2010, 2010
Action potential detection by non linear microscopy Leonardo Sacconi, Jacopo Lotti, Rodney P. O’Connor, Jonathan Mapelli, Daniela Gandolfi, et al. Progress in Biomedical Optics and Imaging Proceedings of SPIE, 2009
Calcium-dependent chloride transient currents in the immature oocyte of the frog, Rana esculenta Archives Italiennes De Biologie, 1989
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The Sense of Smell (SoS) Atlas: Its Creation and First Application to Investigate COVID‐19 Related Anosmia With a Comprehensive Quantitative MRI Protocol M Gaviraghi, E Lupi, E Grosso, A Fusari, M Baiguera, A Monteverdi, ... Journal of Magnetic Resonance Imaging 63 (2), 574-593 , 2026 2026 Citations: 2
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MOST CITED SCHOLAR PUBLICATIONS
Beyond parallel fiber LTD: the diversity of synaptic and non-synaptic plasticity in the cerebellum C Hansel, DJ Linden, E D'Angelo Nature neuroscience 4 (5), 467-475 , 2001 2001 Citations: 771
Seeking a unified framework for cerebellar function and dysfunction: from circuit operations to cognition E D'Angelo, S Casali Frontiers in neural circuits 6, 116 , 2013 2013 Citations: 582
Timing and plasticity in the cerebellum: focus on the granular layer E D’Angelo, CI De Zeeuw Trends in neurosciences 32 (1), 30-40 , 2009 2009 Citations: 394
Theta-frequency bursting and resonance in cerebellar granule cells: experimental evidence and modeling of a slow k+-dependent mechanism E D'Angelo, T Nieus, A Maffei, S Armano, P Rossi, V Taglietti, A Fontana, ... Journal of Neuroscience 21 (3), 759-770 , 2001 2001 Citations: 346
Fibroblast growth factor homologous factors control neuronal excitability through modulation of voltage-gated sodium channels M Goldfarb, J Schoorlemmer, A Williams, S Diwakar, Q Wang, X Huang, ... Neuron 55 (3), 449-463 , 2007 2007 Citations: 334
Long-term potentiation of intrinsic excitability at the mossy fiber–granule cell synapse of rat cerebellum S Armano, P Rossi, V Taglietti, E D'Angelo Journal of Neuroscience 20 (14), 5208-5216 , 2000 2000 Citations: 316
Synaptic excitation of individual rat cerebellar granule cells in situ: evidence for the role of NMDA receptors. E D'Angelo, G De Filippi, P Rossi, V Taglietti The Journal of physiology 484 (2), 397-413 , 1995 1995 Citations: 305
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Evidence for NMDA and mGlu receptor-dependent long-term potentiation of mossy fiber–granule cell transmission in rat cerebellum E D'Angelo, P Rossi, S Armano, V Taglietti Journal of neurophysiology 81 (1), 277-287 , 1999 1999 Citations: 242
Tractography dissection variability: What happens when 42 groups dissect 14 white matter bundles on the same dataset? KG Schilling, F Rheault, L Petit, CB Hansen, V Nath, FC Yeh, G Girard, ... NeuroImage 243, 118502 , 2021 2021 Citations: 218
Silencing the majority of cerebellar granule cells uncovers their essential role in motor learning and consolidation E Galliano, Z Gao, M Schonewille, B Todorov, E Simons, AS Pop, ... Cell reports 3 (4), 1239-1251 , 2013 2013 Citations: 200
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The quest for multiscale brain modeling E D’Angelo, V Jirsa Trends in neurosciences 45 (10), 777-790 , 2022 2022 Citations: 192
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Stim and Orai proteins in neuronal Ca 2+ signaling and excitability F Moccia, E Zuccolo, T Soda, F Tanzi, G Guerra, L Mapelli, F Lodola, ... Frontiers in cellular neuroscience 9, 153 , 2015 2015 Citations: 187
Increased neurotransmitter release during long‐term potentiation at mossy fibre–granule cell synapses in rat cerebellum E Sola, F Prestori, P Rossi, V Taglietti, E D'Angelo The Journal of physiology 557 (3), 843-861 , 2004 2004 Citations: 176
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