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Severini, G.

Publications and source records attributed to Severini, G..

12 recordsLinked to original sources
bioRxiv2026

Cortical involvement in stroke survivors for balance maintenance

Stroke survivors often experience balance impairments which may result in increased risk of falling. However, it is unclear whether and how a stroke changes cortical involvement for postural control. To clarify this issue, we assessed the effect of stroke on sway-based corticokinematic coherence (CKC), which is a measure of the coupling between cortical electrophysiological signals and postural sways. To that end, we recorded the center-of-pressure fluctuations and electroencephalographic cortical activity of 34 stroke survivors and 34 healthy participants performing balance tasks during which sensory information was manipulated, by either removal or alteration. We found significantly increased CKC derived from medio-lateral sway in stroke participants when standing on foam compared to healthy controls, suggesting an increase in cortical involvement to compensate for the decreased function of the hemiparetic side, even in highly functional stroke survivors. Moreover, a relationship was found between CKC and clinical scores (Berg Balance Scale and Fugl-Meyer). This suggests that CKC could be used as a biomarker to track progress beyond traditional functional recovery as measured by clinical scores.

neuroscience↗
bioRxiv2025

Pre-Human Immunodeficiency Virus (HIV) infection Th17 CD4+ T cells as predictors of early HIV disease progression

Interleukin-17-producing T helper (Th17) CD4+ T cells are highly susceptible to HIV infection and are depleted early in people living with HIV. Here, we investigated whether systemic Th17 cell levels prior to HIV infection are associated with subsequent HIV disease progression. We analyzed archived cryopreserved peripheral blood mononuclear cells (PBMCs) collected within one year prior to HIV acquisition from participants enrolled in a South African cohort (HIV Vaccine Trials Network [HVTN] 503; n = 35) and an East African cohort (Partners Pre-exposure Prophylaxis/Couples Observational Study [PP/COS]; n = 32). Th17 cell frequencies were quantified by flow cytometry. In HVTN 503, higher pre-HIV IL-17+ CD4+ T cell frequencies were inversely correlated with CD4/CD8 ratio measured both within 180 days (Spearman rank R = -0.42, p = 0.012) and beyond 180 days (R = -0.55, p = 0.001) after HIV infection, and were associated with faster CD4+ T cells decline (adjusted hazard ratio [aHR] = 3.5, 95% CI: 1.2-9.9, p = 0.020). In contrast, no significant association with CD4 decline was observed in the PP/COS cohort (HR = 1.2, 95% CI: 0.4-3.4, p = 0.795). Sex-stratified analyses in HVTN 503 indicated a more pronounced association between pre-HIV IL-17+ CD4+ T cells and faster CD4 decline in males than females. In analyses combining all cohorts, higher pre-HIV IL-17+ CD4+ T cell frequencies remained associated with faster CD4 decline, particularly among younger participants (HR = 3.5; 95% CI: 1.35-9.22, p = 0.010). Pre-HIV IL-17+ CD4+ T cell frequencies were not associated with peak or set-point viral load in either cohort. Together, these findings suggest that pre-HIV Th17 cells abundance may influence subsequent HIV disease progression independently of early viral replication. Author SummaryHIV infection leads to progressive damage of the immune system, but the rate at which this damage occurs varies widely between individuals. Understanding the factors that influence HIV disease progression is essential for improving prevention and treatment strategies. Previous studies have suggested that immune characteristics present before infection may shape disease outcomes after HIV acquisition. In this study, we examined whether the abundance of IL-17-producing CD4+ T cells, known as Th17 cells, measured prior to HIV acquisition, were associated with markers of disease progression after infection. We analyzed blood samples from individuals who were HIV-negative at the time of sampling and later acquired HIV during follow-up. We found that individuals with higher pre-infection levels of Th17 cells experienced faster immune decline after HIV infection, including more rapid loss of CD4+ T cells and lower CD4/CD8 ratios. These associations were observed independently of viral load and varied by cohort, age and sex. Our findings indicate that immune conditions present before HIV infection can influence subsequent disease progression and suggest that Th17 cells may serve as biomarkers to identify individuals at higher risk of rapid HIV-related immune damage.

immunology↗
bioRxiv2025

Functional muscle networks reveal the mechanistic effects of post-stroke rehabilitation on motor impairment and therapeutic responsiveness

Standardised assessment of post-stroke motor impairment and treatment responsiveness remains a major clinical challenge. In this study, we tackle this challenge by applying a novel muscle network analysis framework to stroke survivors undergoing intensive upper-limb motor training. Our approach revealed distinct patterns of redundant and synergistic muscle interactions, collectively reflecting the diverse biomechanical roles of flexor- and extensor-driven networks. From these patterns, we derived new biomarkers that stratified patients by gross motor impairment severity and therapeutic responsiveness, each associated with unique physiological signatures. Remarkably, we identified a shift from redundancy to synergy in muscle coordination as a hallmark of effective motor recovery -- a transformation supported by a more precise quantification of impairment over conventional approaches. These findings offer an in-depth characterisation of post-stroke motor recovery and establish a robust, independent tool for evaluating rehabilitation efficacy. Future research should employ this framework to identify biomarkers of activities- and participation-related functional recovery.

neuroscience↗
bioRxiv2024

A physiologically inspired hybrid CPG/Reflex controller for cycling simulations that generalizes to walking

Predictive simulations based on explicit, physiologically inspired, control policies, can be used to test theories on motor control and to evaluate the effect of interventions on the different components of control. Several control architectures have been proposed for simulating locomotor tasks, based on fully feedback, reflex-based, controllers, or on feedforward architectures mimicking the Central Pattern Generators. Recently, hybrid architectures integrating both feedback and feedforward components have been shown to represent a viable alternative to fully feedback or feedforward controllers. Current literature on controller-based simulations, however, almost exclusively presents task-specific controllers that do not generalize across different tasks. The task-specificity of current controllers limits the generalizability of the neurophysiological principles behind such controllers. Here we propose a hybrid controller for predictive simulations of cycling based where the feedforward component is based on a well-known theoretical model, the Unit Burst Generation model, and the feedback component includes a limited set of reflex pathways, expected to be active during submaximal steady cycling. We show that this controller can simulate physiological cycling patterns at different desired speeds. We also show that the controller can generalize to walking behaviors by just adding an additional control component for accounting balance needs. The controller here proposed, although simple in design, represent an instance of physiologically inspired generalizable controller for cyclical lower limb tasks. Author SummaryPredictive simulations allow to synthesize human movements and their associated biomechanical quantities without using experimental data. Such simulations can help understand how humans may perform movement tasks in different scenarios and could provide useful information in fields like rehabilitation. One of the methodologies used for developing predictive simulations is based on creating models of the neural control architectures that generate the activation of the muscles. In this work we propose the first neural control architecture for cycling behaviors. We show that our architecture can be used to develop predictive simulations of cycling at different speeds and that the associated biomechanical quantitites are consistent with experimental data. Moreover, we show that our control architecture can also replicate walking behaviors with minimal modifications.

neuroscience↗
bioRxiv2023

A novel modular architecture for a neural controller architecture for predictive simulations of stand-to-walk motions

Computational models of neural control are a powerful tool for evaluating principles of motor control that cannot be tested directly in conventional experimental settings. Current gait controllers struggle with physiological grounding and can replicate a small set of discrete behaviours. Objectivehere we propose a new neural controller, the Internal Model-based Modular Controller, that can transition between multiple lower-limb motor tasks within a single simulation. The architecture comprises a simplified model of the Mesencephalic Locomotor Region, which activates different internal models. These internal models organise functional muscle synergies into task-specific networks that generate coordinated activity across multiple muscles. Resultsthe controller performs Stand-To-Walk-To-Stand and Stand-To-Backward Walking-To-Stand transitions and modulates gait speed within a simulation by adjusting a few control signals. The observed simulated biomechanics and muscle activation patterns are generally consistent with experimental observations. ConclusionsOur results show that the proposed modular architecture represents a plausible mechanism for producing heterogeneous motor behaviours. IMPACT STATEMENTThis study presents a modular neural controller, which employs internal models and functional muscle synergies to reproduce heterogeneous legged behaviours within a single simulation framework.

neuroscience↗
bioRxiv2022

Subsensory stochastic electrical stimulation targeting muscle afferents alters gait control during locomotor adaptations to haptic perturbations

Subsensory noise stimulation targeting sensory receptors has been shown to improve balance control in healthy and impaired individuals. However, the potential for application of this technique in other contexts is still unknown. Gait control and adaptation rely heavily on the input from proprioceptive organs in the muscles and joints. Here we investigated the use of subsensory noise stimulation as a means to influence motor control by "boosting" proprioception during locomotor adaptations to forces delivered by a robot. The forces increase step length unilaterally and trigger an adaptive response that restores the original symmetry. Healthy participants performed two adaptation experiments, one with stimulation applied to the hamstring muscles and one without. We found that participants adapted faster but to a lesser extent when undergoing subsensory stimulation. We argue that this behaviour is due to the dual effect that the stimulation has on the afferents encoding position and velocity that are present in the muscle spindles.

neuroscience↗
bioRxiv2021

Expansion of tissue-resident CD8+ T cells and CD4+ Th17 cells in the nasal mucosa following mRNA COVID-19 vaccination

Vaccines against SARS-CoV-2 have shown high efficacy in clinical trials, yet a full immunologic characterization of these vaccines, particularly within the upper respiratory tract, remains lacking. We enumerated and phenotyped T cells in nasal mucosa and blood before and after vaccination with the Pfizer-BioNTech COVID-19 vaccine (n =21). Tissue-resident memory (Trm) CD8+ T cells expressing CD69+CD103+ expanded [~]12 days following the first and second doses, by 0.31 and 0.43 log10 cells per swab respectively (p=0.058 and p=0.009 in adjusted linear mixed models). CD69+CD103+CD8+ T cells in the blood decreased post-vaccination. Similar increases in nasal CD8+CD69+CD103-T cells were observed, particularly following the second dose. CD4+ Th17 cells were also increased in abundance following both doses. Following stimulation with SARS-CoV-2 spike peptides, CD8+ T cells increased expression of CD107a and CD154. These data suggest that nasal T cells may be induced and contribute to the protective immunity afforded by this vaccine.

immunology↗
bioRxiv2019

Characterization of the adaptation to visuomotor rotations in the muscle synergies space

The adaptation to visuomotor rotations is one of the most studied paradigms of motor learning. Previous literature has presented evidence of a dependency between the process of adaptation to visuomotor rotations and the constrains dictated by the workspace of the biological actuators, the muscles, and their co-activation strategies, modeled using muscle synergies analysis. To better understand this relationship, we asked a sample of healthy individuals (N =7) to perform two experiments aiming at characterizing the adaptation to visuomotor rotations in terms of rotations of the activation space of the muscle synergies during isometric reaching tasks. In both experiments, subjects were asked to adapt to visual rotations altering the position mapping between the force exerted on a fixed manipulandum and the movement of a cursor on a screen. In the first experiment subjects adapted to three different visuomotor rotation angles (30{degrees}, 40{degrees} and 50{degrees} clockwise) applied to the whole experimental workspace. In the second experiment subjects adapted to a single visuomotor rotation angle (45{degrees} clockwise) applied to eight different sub-spaces of the whole workspace, while also performing movements in the rest of the unperturbed workspace. The results from the first experiment confirmed the observation that visuomotor rotations induce rotations in the synergies activation workspace that are proportional to the visuomotor rotation angle. The results from the second experiment showed that rotations affecting limited sub-spaces of the whole workspace are adapted for by rotating only the synergies involved in the movement, with an angle proportional to the distance between the preferred angle of the synergy and the sub-space covered by the rotation. Moreover, we show that the activation of a synergy is only rotated when the sub-space covered by the visual perturbation is applied at the boundaries of workspace of the synergy. We found these results to be consistent across subjects, synergies and sub-spaces. Moreover, we found a correlation between synergies and muscle rotations further confirming that the adaptation process can be well described, at the neuromuscular level, using the muscle synergies model. These results provide information on how visuomotor rotations can be used to induce a desired neuromuscular response.

bioengineering↗
bioRxiv2019

Analysis of the effectiveness of sub-sensory electrical noise stimulation during visuomotor adaptations in different visual feedback conditions

Sub-sensory electrical noise stimulation has been shown to improve motor performance in tasks that rely principally on proprioceptive feedback. During the generation of movements such as reaching, proprioceptive feedback combines dynamically with visual feedback. It is still unclear whether boosting proprioceptive information in tasks where proprioception mixes with vision can influence motor performance at all, either by improving or worsening it. To better understand this point, we tested the effect of electrical noise stimulation applied superficially to the muscle spindles during four different experiments consisting of isometric reaching tasks under different visual feedback conditions. The first experiment (n=40) consisted of a reach-and-hold task where subjects had to hold a cursor on a target for 30 seconds and had visual feedback removed 10 seconds into the task. Subjects performed 30 repetitions of this task with different stimulation levels, including no stimulation. We observed that trials in which the stimulation was present, displayed smaller movement variability. Moreover, we observed a positive correlation between the level of stimulation and task performance. The other experiments consisted of three versions of an isometric visuomotor adaptation task where subjects were asked to reach to random targets in less than 1.5 seconds (otherwise incurring in negative feedback) while overcoming a 45{degrees} clockwise rotation in the mapping between the force exerted and the movement of the cursor. The three experiments differed in the visual feedback presented to the subjects, with one group (n=20) performing the experiment with full visual feedback, one (n=10) with visual feedback restricted only to the beginning of the trajectory and one (n=10) without visual feedback of the trajectory. All subjects performed their experiment twice, with and without stimulation. We did not observe substantial effects of the stimulation when visual feedback was present (either completely or partially). We observed a limited effect of the stimulation in the absence of visual feedback consisting in a significant smaller number of negative-feedback trials in the first block of the adaptation phase. Our results suggest that sub-sensory stimulation can be beneficial when proprioception is the main feedback modality but mostly ineffective in tasks where visual feedback is actively employed.

neuroscience↗
bioRxiv2018

Effect of temporal and spatial asymmetries to the neuromuscular control of the lower limbs during stationary cycling

Motor adaptations are useful for studying the way in which the lower limbs are controlled by the brain. However, motor adaptation paradigms for the lower limbs are typically based on locomotion tasks, where the necessity of maintaining postural stability is the main driver of adaptation and could possibly mask other underlying processes. In this study we investigated whether small temporal or spatial asymmetries can trigger motor adaptations during stationary cycling, where stability is not directly compromised. Fourteen healthy individuals participated in two experiments: in one of the experiments the angle between the crank arms of the pedals was altered by 10{degrees} to induce a temporal asymmetry; in the other the length of the right pedal was shortened by 2.4 cm to induce a spatial asymmetry. We recorded the acceleration of the crank arms and the EMG signals of 16 muscles (8 per leg). The analysis of the accelerometer data was used to investigate the presence of motor adaptations. Muscle synergy analysis was performed on each side to quantify changes in neuromuscular control. We found that feedforward motor adaptations are present in response to temporal asymmetries and are obtained by progressively shifting the activation patterns of two synergies on the right leg. Spatial asymmetries appear to trigger a feedback-driven response that does not present an aftereffect and is not consistent with a motor adaptation. This response is characterized by a step-like decrease in activity in the right gastrocnemius when the asymmetry is present and likely reflects the altered task demands.\n\nNew and NoteworthyThe processes driving lower limb motor adaptations are not fully clear, and previous research appears to indicate that adaptations are mainly driven by stability. Here we show that lower limb adaptations can be obtained also in the absence of an explicit balance threat. We also show that adaptations are present also when kinematic error cannot be compensated for, suggesting the presence of intrinsic error measures regulating the timing of activation of the two legs.

neuroscience↗
bioRxiv2018

Consistent visuomotor adaptations and generalizations can be achieved through different rotations of robust motor modules

Humans have a remarkable ability to modify their motor commands in response to alterations in the environment. These motor commands are thought to be adaptively tuned by combining different motor primitives, a characteristic that allows for adaptations to be generalized also to relevant untrained scenarios. A complementary theory of motor primitives has shown that natural movements can be described by the combination of relatively invariant sets of muscle synergies. Synergistic structures have been shown to be maintained and tuned during motor adaptations. Here we studied the influence of synergistic organization of movement at the muscular level on the way in which adaptations to a 45{degrees} clockwise visuomotor rotation are achieved and generalized. We confirm that adaptation is achieved by tuning a set of robust muscle synergies and we show that the same biomechanical adaptation can be achieved by differentially tuning the same synergies. We demonstrate that this differential tuning ...

neuroscience↗