Biology subjects

Munoz-Moreno, E.

Publications and source records attributed to Munoz-Moreno, E..

9 recordsLinked to original sources

bioRxiv2026

A harmonized phantom MRI quality control framework identifies sources of longitudinal and multi-site variability

The shift towards open science in preclinical research requires high-quality, comparable data adhering to FAIR principles, yet rigorous quality assurance (QA) and quality control (QC) frameworks remain less established in preclinical magnetic resonance imaging (MRI) than in clinical imaging. To address this limitation, a multicenter study was conducted across 21 international laboratories using standardized commercial liquid phantoms for mouse and rat MRI setups and a harmonized acquisition protocol. Data processing was centralized using AIDAqc, an automated pipeline extracting quantitative metrics including signal-to-noise ratio (SNR), temporal SNR (tSNR), ghost-to-signal ratio (GSR), and motion-equivalent temporal instability, combined with five complementary outlier-detection algorithms. The evaluated datasets encompassed magnetic field strengths from 3.0 to 16.4 T and heterogeneous coil and acquisition configurations. In mouse phantom data, SNR and tSNR were significantly lower at 3 T than at 7 and 9.4 T, whereas artifact-related metrics did not differ significantly between field-strength groups. In rat phantom data, differences between field strengths were less pronounced. At 7 T, substantial dataset-specific differences were observed in anatomical and functional quality metrics, also among datasets using the similar coil configuration. Multicenter reference values for frequently represented 7 T configurations were established, including SNR/tSNR of 48 {+/-} 3/48 {+/-} 1 dB for mouse surface-coil datasets and 49 {+/-} 3/44 {+/-} 4 dB for rat array-coil datasets. Longitudinal anatomical SNR showed generally low variability, whereas ghosting was more variable across time. Automated outlier detection additionally identified transient acquisition instabilities that were not always apparent by visual inspection. Together, these findings show that field strength and nominal coil configuration alone do not adequately characterize MRI performance and support standardized, longitudinal phantom-based QC combined with automated analysis as a practical approach for improving the reliability, transparency, and interoperability of multicenter preclinical MRI data.

bioengineering↗

bioRxiv2026

Disrupted Higher-Order Topology in OCD Brain Networks Revealed by Hodge Laplacian - an ENIGMA Study

Brain disorders are increasingly understood as disorders of distributed brain circuits, yet functional connectivity (FC), the dominant framework for mapping them, treats the brain as a collection of pairwise relationships between regions and cannot represent pathology distributed across coordinated sets of connections. We introduce a Hodge-Laplacian topological framework that localizes higher-order "loop" (1-cycle) organization within functional connectome, maps each loop to specific edges and networks, and yields a subject-level measure of loop expression. Applied to resting-state fMRI from the ENIGMA-OCD consortium (1,024 patients and 1,028 controls across 28 sites), the framework identified 93 loop-level abnormalities in obsessive-compulsive disorder (OCD), concentrated in frontoparietal and somatomotor systems. The edges forming these loops largely showed no significant differences between groups, indicating that the abnormalities were invisible to conventional FC analysis. The frontoparietal and somatomotor loop clusters recurred across the clinical subgroups, suggesting convergence on a shared higher-order phenotype. Robustness analyses showed the loop signal reflected higher-order organization rather than an artifact of individual edges, the network backbone, or any single site. These results indicate that coordinated, multi-edge pathology exists and can be localized even when pairwise analyses fail to detect it, positioning higher-order topology as a generalizable axis for mapping circuit pathology across psychiatric and neurological disorders.

neuroscience↗

bioRxiv2025

Pre-amyloid cognitive intervention preserves brain function in aged TgF344-AD rats, maintaining connectivity and enhancing plasticity in a sex-specific manner

BackgroundAlzheimers disease is characterized by progressive cognitive decline and neurodegeneration, with cognitive reserve playing a key role in mitigating disease impact. Cognitive stimulation has been suggested as a non-pharmacological approach to enhance cognitive reserve and delay cognitive deterioration, but its underlying mechanism remains to be fully understood. This study investigates the effects of pre-amyloid cognitive intervention on brain connectivity, memory, synaptic plasticity and neuroinflammation in aged TgF344-AD rats, considering sex-specific differences. MethodsMale and female TgF344-AD and wild-type rats were assigned to trained and untrained groups, with cognitive stimulation administered through repetitive delayed nonmatch-to-sample tasks. Longitudinal magnetic resonance imaging acquisitions assessed training-induced changes in whole-brain functional connectomics and in particular entorhinal cortex connectivity. Memory was evaluated using the novel object recognition test. Cellular analysis of neurons (NeuN+, Parvalbumin+) and microglial cells, as well as molecular (PSD95, TrkB, p-RPS6, and VGLUT) analyses were conducted to determine the role of cognitive stimulation in modulating neuronal density, neuroinflammation and neuroplasticity. ResultsMale TgF344-AD rats undergoing prolonged cognitive stimulation had preserved global functional connectivity and exhibited improved recognition memory, compared to untrained animals, while TgF344-AD females did not follow this pattern. Entorhinal cortex connectivity was significantly loss in 19-month-old rats compared to wild-type rats and this was completely prevented by training. At a cellular level, cognitive stimulation significantly decreased the number of PV+ neurons in the dentate gyrus of trained rats. Moreover, a greater microglial density around A{beta} plaques and a less reactive phenotype was clearly observed at 11 in trained rats. These protective effects diminished by 19 months, coinciding with increased neuroinflammation and microglial dysfunction. At a molecular level, cognitive stimulation preserved PSD95 expression in male TgF344-AD and p-RPS6 in both sexes. ConclusionsPre-amyloid cognitive stimulation enhances synaptic plasticity, sustains brain network integrity, and modulates neuroinflammation, contributing to increased resilience against Alzheimers disease-related cognitive decline. In general, cognitive stimulation exerted a more protective effect in male TgF344-AD rats showing sex-dependent differences in pathology and cognitive reserve mechanisms. These findings highlight the importance of early cognitive engagement as a potential strategy to delay disease onset and underscore sex-specific differences in cognitive resilience mechanisms.

neuroscience↗

bioRxiv2024

Differential contribution of direct and indirect pathways from dorsolateral and dorsomedial striatum to motor symptoms in Huntington's disease mice

The alterations in the basal ganglia circuitry associated with motor symptoms in Huntingtons Disease (HD) have been extensively investigated. Yet, the specific contribution of the direct and indirect striatal output pathways from the dorsolateral (DLS) and dorsomedial striatum (DMS) to the motor dysfunction is still not fully understood. Here, using the symptomatic R6/1 male mouse model of HD, strong functional connectivity alterations between DMS and DLS regions with the rest of brain were observed by fMRI, particularly pronounced in the DLS. Then, we systematically evaluated how the selective optogenetic stimulation of the direct and indirect pathways from DLS and DMS influences locomotion, exploratory behavior, and motor learning. In wild type (WT) mice, optogenetic stimulation of the direct pathway from DLS and the indirect pathway from DMS elicited subtle locomotor enhancements, while exploratory behavior remained unaltered. Additionally, stimulation of the indirect pathway from DLS improved the performance in the accelerated rotarod task. In contrast, in HD mice, optogenetic stimulation of the distinct striatal pathways did not modulate these behaviors. Overall, this study points to deficits in the integration of neuronal activity in HD mice, while it contributes to deeper understanding of the complexity of motor control by the diverse striatal subcircuits.

neuroscience↗

bioRxiv2024

SAMson: an automated brain extraction tool for rodents using SAM

Accurate brain extraction is a critical step in the analysis of rodent head magnetic resonance imaging (MRI) data. However, current methods often encounter difficulties in handling the diverse range of imaging setups, resolutions, and experimental conditions that are commonly found in this field. Based on the Segment Anything Model (SAM), we introduce here SAMson (SAM for Segmentation Of Neuroimages), an automated tool for robust rodent brain extraction. SAMson integrates a bounding box generator and a mask prediction pipeline, offering fully automated and semi-automated modes to address varying experimental complexities. The performance of SAMson was evaluated using three multi-centre rodent MRI datasets annotated at the pixel level, which differed in terms of acquisition parameters, resolution, and animal age groups. SAMson demonstrates superior performance to existing methods, including BET, RBM, and BEN, in terms of segmentation accuracy, with Jaccard indices exceeding 90% across datasets. The semi-automated mode demonstrates particular efficacy in challenging scenarios, including low-resolution images and cases requiring refined mask precision. In contrast to conventional volumetric techniques, SAMson identifies errors at the level of individual slices, thereby enabling rapid and targeted correction when needed. By providing open-source access, SAMson aims to support large-scale research workflows and advance translational neuroscience. The curated data can be downloaded from https://doi.org/10.20350/digitalCSIC/17000, and the code is available at https://github.com/CanalsLab/SAMson.

neuroscience↗

bioRxiv2022

Altered M2 Cortex - Superior Colliculus visual perception circuit in Huntington's Disease

The premotor cortical area -M2 cortex in rodents- connection to the striatum is involved in movement and prominently affected in Huntingtons Disease (HD). M2 cortex also projects to the superior colliculus (SC), implicated in oculomotor functions (i.e. saccades) and visual perception. Here, we investigated the contribution of M2 cortex - SC circuit to HD physiopathology in male mice. Using fMRI, we observed that M2 cortex functional connectivity with the SC was the most prominently affected circuit in the symptomatic R6/1 HD mouse model. Structural alterations were also detected by tractography and viral tracing. HD mice showed decreased defensive behavioral responses towards an unexpected visual stimuli, such as a moving robo-beetle, and decreased locomotion upon unexpected flash of light. Additionally, optogenetic M2 cortex - SC stimulation promoted avoidance responses towards the robo-beetle in WT, but not HD mice. Though, DWI measurements in vivo and ex vivo electrophysiological responses to optogenetic and electrical stimuli in the SC suggested preserved brain structure. Finally, GCamp6f fluorescence recordings with fiber photometry indicated that aberrant M2 cortex engagement might be the underlying mechanism of visual perception alterations in HD. Collectively, our findings point to a key role of M2 cortex - SC circuit alterations in HD pathophysiology.

neuroscience↗

bioRxiv2021

Peripheral CB1 receptor blockade acts as a memory enhancer through an adrenergic-dependent mechanism

Peripheral inputs to the brain continuously shape its function and can influence the formation of non-emotional memory, but the underlying mechanisms have not been fully understood. Cannabinoid type-1 receptors (CB1R), widely distributed in the organism, is a well-recognized player in memory performance, and its systemic modulation significantly influences memory function. By assessing non-emotional memory in mice, we have now found a relevant role of peripheral CB1R in the formation of persistent memory. Indeed, peripherally restricted CB1R antagonism by using AM6545 showed a mnemonic effect that was occluded in adrenalectomized mice, after peripheral adrenergic blockade, or when vagus nerve was chemogenetically inhibited. Genetic CB1R deletion in dopamine {beta}-hydroxylase-expressing cells enhanced the formation of persistent memory, supporting a role of peripheral CB1R modulating the adrenergic tone. Notably, brain connectivity was affected by peripheral CB1R inhibition, and locus coeruleus activity and extracellular hippocampal norepinephrine, were increased. In agreement, intra-hippocampal {beta}-adrenergic blockade prevented AM6545 mnemonic effects. Together, we disclose a novel peripheral mechanism relevant for the modulation of the formation of persistent non-emotional memory.

neuroscience↗

bioRxiv2020

M2 Cortex-Dorsolateral striatum stimulation reverses motor symptoms and synaptic deficits in Huntington's Disease

Huntingtons disease (HD) is a neurological disorder characterized by motor disturbances. HD pathology is most prominent in the striatum, the central hub of basal ganglia. The cortex is the main striatal afference and progressive cortico-striatal disconnection characterizes HD. We mapped cortico-striatal dysfunction in HD mice to ultimately modulate the activity of selected cortico-striatal circuits to ameliorate motor symptoms and recover synaptic plasticity. Multimodal MRI in vivo suggested prominent functional network deficits in fronto-striatal compared to motor-striatal pathways, which were accompanied by reduced glutamate levels in the striatum of HD mice. Moreover, optogenetically-stimulated glutamate release from fronto-striatal terminals was reduced in HD mice and electrophysiological responses in striatal neurons were blunted. Remarkably, repeated M2 Cortex-dorsolateral striatum optogenetic stimulation normalized motor behavior in HD mice and evoked a sustained increase of synaptic plasticity. Overall, these results reveal that the selective stimulation of fronto-striatal pathways can become an effective therapeutic strategy in HD.

neuroscience↗

bioRxiv2019

Brain connectivity during Alzheimer’s disease progression and its cognitive impact in a transgenic rat model

The research of Alzheimers disease (AD) in their early stages and its progression till symptomatic onset is essential to understand the pathology and investigate new treatments. Animal models provide a helpful approach to this research, since they allow for controlled follow-up during the disease evolution. In this work, transgenic TgF344-AD rats were longitudinally evaluated starting at 6 months of age. Every 3 months, cognitive abilities were assessed by a memory-related task and magnetic resonance imaging (MRI) was acquired. Structural and functional brain networks were estimated and characterized by graph metrics to identify differences between the groups in connectivity, its evolution with age, and its influence on cognition. Structural networks of transgenic animals were altered since the earliest stage. Likewise, aging significantly affected network metrics in TgF344-AD, but not in the control group. In addition, while the structural brain network influenced cognitive outcome in transgenic animals, functional network impacted how control subjects performed. TgF344-AD brain network alterations were present from very early stages, difficult to identify in clinical research. Likewise, the characterization of aging in these animals, involving structural network reorganization and its effects on cognition, opens a window to evaluate new treatments for the disease. AUTHOR SUMMARYWe have applied magnetic resonance image based connectomics to characterize TgF344-AD rats, a transgenic model of Alzheimers disease (AD). This represents a highly translational approach, what is essential to investigate potential treatments. TgF344-AD animals were evaluated from early to advanced ages to describe alterations in brain connectivity and how brain networks are affected by age. Results showed that aging had a bigger impact in the structural connectivity of the TgF344-AD than in control animals, and that changes in the structural network, already observed at early ages, significantly influenced cognitive outcome of transgenic animals. Alterations in connectivity were similar to the described in AD human studies, and complement them providing insights into earlier stages and a plot of AD effects throughout the whole life span.

neuroscience↗