Biology subjects

Gallea, C.

Publications and source records attributed to Gallea, C..

8 recordsLinked to original sources

bioRxiv2026

Saccadic network dysfunction underlies eye-movement variability in early Parkinson's disease

Parkinsons disease is a neurodegenerative disorder characterized by altered subcortical-cortical connectivity, leading to motor and cognitive deficits. Saccadic eye movement abnormalities are among the earliest and most persistent markers of the disease, serving as sensitive indicators of disrupted oculomotor and cognitive control. While changes in average saccadic behavioral measures are widely reported in Parkinson's disease, intra-individual variability in saccadic performance and the underlying network dysfunction remain poorly understood. Here, we quantified intra-individual saccadic variability in early-stage Parkinsons disease and identified its functional correlates within the resting-state saccadic network. We analyzed data from 91 patients with early-stage Parkinsons disease and 46 healthy controls who underwent oculomotor testing and resting-state functional magnetic resonance imaging. First, at the behavioral level, we assessed intra-individual variability in saccadic performance within each group using the coefficient of variation of reaction time and normalized peak velocity across trials. Second, at the brain level, we assessed group differences in static and dynamic functional connectivity across 39 regions comprising the saccadic network. We examined the relationship between network connectivity and saccadic variability using partial least squares analysis. We also quantified network organization using graph-theory measures of global efficiency and clustering coefficient. Finally, we tested the relevance of intra-individual saccadic variability and network features in distinguishing patients from healthy controls using a multivariate Mahalanobis classifier. Our results showed that, compared to HC, patients had higher intra-individual variability in saccadic behavioral measures of reaction time (pHolm = 0.012) and normalized peak velocity (pHolm = 0.012). Interestingly, patients had (i) reduced static and dynamic connectivity within the saccadic network and (ii) weaker associations between network connectivity and intra-individual saccadic variability of specifically normalized peak velocity. These results were particularly driven by regions within the cognitive saccade network. The classifier that integrated intra-individual saccadic variability and network connectivity achieved 95.62% accuracy in distinguishing patients from healthy controls, with dynamic connectivity contributing more strongly to classification performance than static connectivity. We demonstrate that elevated intra-individual variability of saccades, underpinned by altered functional connectivity within cognitive-oculomotor networks, is a prominent feature of early-stage Parkinsons disease. Emerging as a promising physiological marker of disease pathophysiology, intra-individual variability offers a powerful new framework to refine early diagnosis and improve the tracking of neurodegeneration before severe clinical milestones are reached.

neuroscience↗

bioRxiv2026

Functional cerebellar connectomes interfacing motor adaptation and reinforcement feedback

Motor adaptation is driven by sensory prediction errors, yet reinforcement feedback can alter the speed and retention of adaptive behaviors. The cerebellum is central in motor adaptation, but posterior lobules, especially Lobule VI (CB6) and Crus I (CBcrus1), also participate in reinforcement-related signaling. Serotoninergic and dopaminergic systems, key modulators of motivational processes, directly influence cerebellar activity. However, how these neuromodulatory systems contribute to cerebellar network organization and to reinforcement-based adaptation in humans remains unclear. We employed a multimodal framework (Receptor-Enriched Analysis of functional Connectivity by Targets; REACT) using PET-derived Serotonin/Dopamine Transporter (SERT/DAT) templates to enrich resting-state functional Magnetic Resonance Imaging (rs-fMRI). We estimated SERT- and DAT-enriched functional connectivity from CB6 and CBcrus1 within motor-adaptation and reinforcement-learning networks, and tested their correlations with performance in a visuomotor adaptation task completed under reward and punishment. Our findings show lobule-specific neuromodulatory organization within the cerebellum. CB6 exhibited predominantly DAT- and SERT-enriched connectivity with motor adaptation networks, while CBcrus1 showed stronger SERT-enriched communication extending to both motor and reinforcement networks. Crucially, distinct cerebello-cortical neuromodulatory networks predicted individual differences in adaptation rate. DAT-enriched CBcrus1 connectivity was linked to punishment-driven adaptation, whereas SERT-enriched cerebello-orbitofrontal connectivity predicted faster adaptation across both reward and punishment contingencies. Furthermore, we observed overlaps between SERT- and DAT-enriched networks in the medial orbitofrontal area for Crus I, which predicted retention following punishment, underscoring the role of convergent neuromodulation in stabilizing adapted movements. We conclude that partially segregated yet convergent cerebello-cortical networks support interactions between motor and motivational behaviors, with combined and opposing effects of serotonergic and dopaminergic neuromodulation accounting for the speed and retention of adaptive behaviors.

neuroscience↗

bioRxiv2025

EPICURUS: E-field-based spatial filtering procedure for an accurate estimation of local EEG activity evoked by Transcranial Magnetic Stimulation

BackgroundThe concurrent use of Transcranial magnetic stimulation and electroencephalography (TMS-EEG) is increasingly integrated into research and clinical protocols. However, a reliable isolation of EEG responses that are locally evoked by TMS at the targeted cortical sites independent from contaminating sources, remains challenging. MethodsHere we introduce EPICURUS, a novel spatial filtering approach for TMS-EEG that uses individualized MRI-based simulations of the TMS-induced electric field (E-field) to define the spatial extent of locally evoked activity. This method guides the reconstruction of EEG signals originating from the direct stimulation site while minimizing crosstalk from distant, non-targeted sources. ResultsIn synthetic simulations and a human TMS-EEG dataset, EPICURUS preserved early-latency TMS-evoked local activity while substantially attenuating later components, consistent with suppression of non-local activity. ConclusionBy leveraging the spatial precision of individualized E-field modeling, EPICURUS may enhance the specificity of EEG signal reconstruction, offering a promising tool for improving the spatiotemporal resolution of local early and late cortical local responses directly elicited by TMS.

neuroscience↗

bioRxiv2024

Emergence of Pre-movement Beta Activity with Stable Sensorimotor Predictions to Facilitate Motor Adjustments

Adaptive behavior enables flexible responses to environmental changes. This process is particularly crucial when transitioning between environments with different features, relying on the progressive formation of expectations based on prior experience. In humans, beta oscillations are central to adaptive behavior. Yet, the brain mechanisms underlying the detection of environmental changes, and the iterative update needed to progressively improve behavioral performance remain elusive. Here, we reveal that beta activity emerges in a cerebello-cortical network two seconds before action initiation, as the features of a new environment become known and behavioral outcomes become more predictable. Within this period, the cerebellum and parietal cortex drive prefrontal activity to form expectations. Using a single-trial approach, we establish that beta bursts before action initiation predict performance in the upcoming trial based on previous outcomes. These findings uncover a novel anticipatory mechanism that reflects predictive processes critical for stabilizing performance and adapting to environmental changes.

neuroscience↗

bioRxiv2024

The role of dopaminergic, cholinergic and noradrenergic networks in hyposmia in Parkinson's disease

BackgroundOlfactory impairment is frequently observed in Parkinsons disease (PD) before motor symptom onset. Patients with isolated rapid eye movement sleep behaviour disorder (iRBD) are at risk to develop PD and present olfactory dysfunction. Subcortical neuromodulatory nuclei including the substantia nigra, the nucleus basalis of Meynert, and the locus coeruleus, may all contribute to olfactory dysfunction. ObjectiveThe objective of this study was to understand the network alterations underlying olfactory dysfunction in PD and in the early prodromal iRBD patients using multimodal MRI. MethodsPD (n = 107), iRBD patients (n = 35) and healthy controls (HC, n = 39) were recruited from the ICEBERG cohort for a cross-sectional study. We separated subjects in Healthy Controls, iRBD patients, and PD patients with or without RBD and with or without anosmia. Olfactory, motor, and cognitive scores were assessed and combined with multimodal imaging. ResultsWe found that olfaction positively correlated with (i) striatal DaT signal in PD patients; (ii) neuromelanin contrast in the locus coeruleus and (iii) Nucleus Basalis of Meynert grey matter (GM) volume in all patients. These signals were uncorrelated with motor and cognitive scores. Functional connectivity was reduced in regions of the cholinergic olfactory network in anosmic patients. Functional connectivity was also reduced in the noradrenergic network of patients with RBD. DiscussionOur results indicate the implication of the cholinergic network in PD patients with anosmia and a contribution of the noradrenergic network to olfactory dysfunction, only in patients with RBD.

neuroscience↗

bioRxiv2024

Age-trajectories of higher-order diffusion properties of major brain metabolites in cerebral and cerebellar grey matter using in vivo diffusion-weighted MR spectroscopy at 3T

Healthy brain aging involves changes in both brain structure and function, including alterations in cellular composition and microstructure across brain regions. Unlike diffusion-weighted MRI (dMRI), diffusion-weighted MR spectroscopy (dMRS) can assess cell-type specific microstructural changes, providing indirect information on both cell composition and microstructure through the quantification and interpretation of metabolites diffusion properties. This work investigates age-related changes in the higher-order diffusion properties of three major intracellular metabolites (N-Acetyl-aspartate, Creatine and Choline) beyond the classical apparent diffusion coefficient in cerebral and cerebellar grey matter of healthy human brain. Twenty-five subjects were recruited and scanned using a diffusion-weighted semi-LASER sequence in two brain regions-of-interest (ROI) at 3T: posterior-cingulate (PCC) and cerebellar cortices. Metabolites diffusion was characterized by quantifying metrics from both Gaussian and non-Gaussian signal representations and biophysical models. All studied metabolites exhibited lower apparent diffusivities and higher apparent kurtosis values in the cerebellum compared to the PCC, likely stemming from the higher microstructural complexity of cellular composition in the cerebellum. Multivariate regression analysis (accounting for ROI tissue composition as a covariate) showed slight decrease (or no change) of all metabolites diffusivities and slight increase of all metabolites kurtosis with age, none of which statistically significant (p>0.05). The proposed age-trajectories provide benchmarks for identifying anomalies in the diffusion properties of major brain metabolites which could be related to pathological mechanisms altering both the brain microstructure and cellular composition.

biophysics↗

bioRxiv2020

Loss of floor plate Netrin-1 impairs midline crossing of corticospinal axons and leads to mirror movements

In human, execution of unimanual movements requires lateralized activation of the primary motor cortex, which then transmits the motor command to the contralateral hand through the crossed corticospinal tract (CST). Mutations in NETRIN-1 alter motor control lateralization, leading to congenital mirror movements. To address the role of midline Netrin-1 on CST development and subsequent motor control, we analyzed the morphological and functional consequences of floor-plate Netrin-1 depletion in conditional knock-out mice (Shh::cre;Ntn1lox/lox mice). Here, we show that depletion of floor plate Netrin-1 critically disrupts midline crossing of the CST, whereas the other commissural systems are mostly preserved. The CST defect results in abnormal but functional ipsilateral projections, and is associated with abnormal symmetric movements. Therefore, our study reveals a new role for Netrin-1 in CST development. It also describes a unique mouse model recapitulating characteristics of human congenital mirror movements, through abnormal CST decussation.

neuroscience↗

bioRxiv2018

Offline impact of transcranial focused ultrasound on cortical activation in primates

To understand brain circuits it is necessary both to record and manipulate their activity. Despite increased availability of techniques for manipulating neural activity in rodents, manipulating neural activity in primates remains difficult. Here we show that a minimally invasive technique, transcranial focused ultrasound stimulation (TUS), induced offline changes to activity of circumscribed brain regions in the macaque. Applying TUS to the supplementary motor area or frontal polar cortex resulted in spatially specific patterns of activity change measurable with functional magnetic resonance imaging. In each case changes reflected each areas known network of interactions with the rest of the brain. Independent of these specific neural effects, TUS over these regions also induced widespread signal changes that might have a non-neuronal origin possibly mediated by the cerebral spinal fluid compartment. Although sustained for more than one hour beyond the 40s stimulation period, TUS effects were reversible and not associated with histological changes.\n\nHighlights O_LIMany studies of ultrasound neuromodulation focus on online effects in rodents.\nC_LIO_LIWe use fMRI connectivity to investigate its offline impact in the primate brain.\nC_LIO_LI40 s of ultrasound leads to a sustained, specific, reversible neural modulation.\nC_LIO_LIUltrasound caused a sharpening of the stimulated regions connectivity profile.\nC_LI\n\nIn BriefA new application of focused ultrasound safely modulates brain activation in primates for up to 2 hours after 40 seconds of stimulation. Ultrasound caused the stimulated area to interact more selectively with the rest of the brain.

neuroscience↗