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Huber, L.

Publications and source records attributed to Huber, L..

At least 19 recordsLinked to original sources

Early blindness shifts the feedforward laminar profile of hMT+/V5 from visual to auditory motion

The occipital cortex of people born blind massively enhances its response to sounds, but the brain circuitry supporting such crossmodal plasticity remains elusive. Here we capitalized on ultra-high-field fMRI (7T) coupled with sub-millimetre BOLD and VASO acquisitions to infer whether motion-related information is processed via feedforward or feedback pathways, probing responses to visual motion in sighted participants and auditory motion in both sighted and early blind individuals. By identifying circuitry from layer-dependent activity of the middle temporal cortex (hMT+/V5), we observed that moving, but not static, sounds selectively elicited a feedforward response in the middle layers of hMT+/V5 of blind people, analogous to visual motion processing in sighted individuals. Furthermore, we observed that hMT+/V5 shows enhanced auditory motion-selective connectivity with the Planum Temporale in the sighted and with the cuneus in blind people. These findings reveal that hMT+/V5 implements a feedforward motion selective response profile in sighted and blind individuals, with its sensory input shifting from vision to audition in the absence of visual experience.

neuroscience↗

Peripheral Nerve Stimulation Optimized Pulses for EPI (POPE) allows high-resolution fMRI

PurposeRecent improvements in MRI gradient design and amplifiers, advanced MRI scanners are now routinely utilizing slew rates of several hundred T/m/s. However, full gradient performance cannot be exploited in high-resolution EPI due to peripheral nerve stimulation (PNS) limits. We aim to characterize and mitigate these PNS constraints using a simple sequence modification: PNS-optimized EPI gradient pulse shapes. MethodsPNS-Optimized Pulses for EPI (POPE): we selectively reduce the slew rate of gradient pulses at periods of high predicted PNS spikes, while leaving the rest of the waveform unchanged. PNS sensation was evaluated. ResultsPOPE allows 7%-35% faster imaging of EPI protocols resolutions of 1mm-0.3mm resolutions without exceeding predicted PNS. With such improvements, POPE allows robust 0.3 mm isotropic fMRI protocols that would have exceeded safety limits without it. ConclusionPOPE facilitates locally precise fMRI activation mapping on clinical 7T scanners at spatial resolution that were previously unattainable due to PNS limitations.

neuroscience↗

An annotated bioacoustic dataset of dog vocalizations and related sounds during dog-human social play

Dog (Canis lupus familiaris) vocal communication occurs across a wide range of social contexts, including dog-human social play, a common and dynamic interaction in which diverse vocal signals are expressed, particularly in young dogs. However, most available open datasets of dog vocalizations focus primarily on barks, leaving other sound types underrepresented. Here we present a bioacoustic dataset of dog-human social play sessions recorded under standardized laboratory conditions, comprising 30 play sessions involving 17 young dogs (6-24 months old) of different breeds playing with familiar humans. Raw audio recordings are accompanied by two layers of annotations covering the dog sounds produced during sessions. Video recordings of the sessions are provided for contextual reference, along with metadata describing each dog and the experimental sessions. Additionally, permutation-based classification analysis showed that annotated sound categories exhibit above-chance and generalizable acoustic differences across individuals. The dataset may support research on dog vocal communication and expand the range of sounds documented during positive dog-human social interactions.

animal behavior and cognition↗

ER-Lysosome Cholesterol Exchange Regulates Lysosomal Motility Through mTOR-Dependent LAMTOR1 Phosphorylation

The subcellular distribution of lysosomes, the main degradative organelles of mammalian cells, responds to metabolic cues in a highly dynamic way. While lysosomal positioning due to amino acid levels is well-characterized, cholesterol-dependent regulation of lysosomal motility is incompletely understood. We explored impaired lysosomal cholesterol export using a mass spectrometry-based multi-OMICs approach, identifying widespread reallocation of resources and signaling pathway modulation. We identified increased phosphorylation at LAMTOR1 serine 56 in response to cholesterol level perturbations. We demonstrate that this phosphorylation site is sufficient to disrupt Rag GTPases/SLC38A9 binding to the Ragulator complex, inhibiting canonical mTORC1 and facilitating binding of BORC, therefore promoting lysosomal retrograde movement. LAMTOR1 S56 phosphorylation responds exclusively to depletion of lysosomal limiting membrane cholesterol, is facilitated by mTOR, and presents a negative feedback loop for amino acid independent displacement of Ragulator bound Rag GTPases, limiting canonical mTORC1 activity. Mass spectrometry data are available via ProteomeXchange with identifier PXD073489. HighlightsO_LIPerturbation of lysosomal cholesterol homeostasis results in adaptation of cellular protein and lipid biosynthesis C_LIO_LILAMTOR1 is phosphorylated at serine 56 via mTORC1 C_LIO_LILAMTOR1 S56 phosphorylation is lysosomal membrane cholesterol dependent C_LIO_LILAMTOR1 S56 phosphorylation disrupts binding of Rag GTPases to the Ragulator complex C_LIO_LILAMTOR1 S56 phosphorylation promotes binding of Ragulator to BORC, facilitating lysosomal retrograde transport C_LI

molecular biology↗

Dog brain atlas generated via spatially constrained spectral clustering

Functional parcellations enable reproducible analyses of brain organization, yet the dog fMRI field still lacks a validated, multi-scale functional atlas. We applied spatially constrained spectral clustering to a resting state fMRI dataset (n = 27 dogs) to generate whole-brain parcellations spanning 20-300 parcels. Replicability was evaluated against an independent dataset (n = 20 dogs) using Dice overlap and Adjusted Rand Index (ARI) as measures of spatial overlap and similarity; within-parcel functional coherence was assessed via homogeneity. Functional parcellations were anatomically coherent across scales, with global Dice peaking at 0.625 at N = 140 and 0.623 at N = 100, while decreasing to 0.526 at N = 300. ARI peaked at 0.48 for N = 60 and remained [≥] 0.46 through N = 180. Mean within-parcel homogeneity increased monotonically from 0.08 (N = 20) to 0.19 (N = 300). Concordance with an anatomical atlas (Johnson et al., 2020) increased at the regional level (plateau [~]0.16 for N [≥] 140) while diminishing at gyral and lobar levels as resolution increased, consistent with functionally driven sub-regional differentiation. Together, these results indicate functional segmentations that are replicable across datasets and internally coherent across scales, with intermediate resolutions (100-140 parcels) balancing specificity and reproducibility for common analyses. We introduce a comprehensive, multi-scale functional dog brain atlas derived from data-driven clustering, providing an open resource for comparative studies of brain evolution and canine cognition.

neuroscience↗

Functional imaging of hippocampal layers using VASO and BOLD on the Next Generation (NexGen) 7T Scanner

Spatial accuracy and venous biases are a central concern in mesoscale fMRI, with subcortical brain regions facing additional challenges due to lower sensitivity, high physiological noise, and complicated vasculature. Here, we optimized CBV VASO on the NexGen 7T scanner for layer-specific investigations of the human hippocampus. Both VASO and BOLD (from the same acquisition) detected significant hippocampal activation during an established autobiographical memory task. At the macroscale, activation patterns converged, showing pronounced memory task activation in the anterior hippocampus and consistent engagement across the frontoparietal neocortex. At the laminar scale, however, differences in depth-dependent profiles emerged within the subiculum: BOLD exhibited a pronounced bias toward the inner layers, consistent with the known venous drainage pattern in the subfield. Finally, the optimized effective TR of 3.2 s allowed exploratory study of retrieval stages and neocortical functional connectivity, which both supported hippocampal anterior-posterior dissociation using both VASO and BOLD. Thus, hippocampal fMRI allows mapping layer function with high accuracy and can provide deeper insights into a number of neuropsychological phenomena and disorders. Key pointsO_LIOptimized CBV VASO on NexGen 7T for layer-specific hippocampal imaging C_LIO_LIVASO mitigates structural venous bias in subiculum present in BOLD C_LIO_LILong-axis mapping dissociates retrieval stages and neocortical connectivity patterns C_LI

neuroscience↗

The human brain mechanisms of afterimages: From networks to cortical layers

Afterimages are common visual illusions that have long attracted popular and scientific interest, yet their neural mechanisms remain little understood. We used high-spatial-resolution fMRI to investigate human whole brain and cortical layer activity in primary visual cortex (V1) linked with afterimages and perceptually similar animated images - stimuli designed to imitate the appearance of afterimages. Both afterimages and perceptually similar images engaged overlapping, widespread brain activity, particularly in visual sensory regions that follow the contralateral circuitry of the primary visual pathway. However, afterimages elicited weaker fMRI signals across the brain compared to images, except in salience network regions, where activity was enhanced for afterimages. Salience network activity could reflect conflict or perceptual reality monitoring mechanisms that detect the illusory nature of afterimages. Cortical layer-specific analyses in V1 revealed afterimages selectively engaged middle and deep cortical layers, while perceptually similar images activated middle and superficial layers. In agreement, layer-specific decoding of afterimage and mock afterimage fMRI signals was present only in deep layers. One interpretation of these V1 cortical layer findings is that afterimage perception involves feedback or top-down neural input akin to self-generated or endogenous conscious perception (e.g., visual imagery). In addition, baseline eye behavior (pupil size and blinking) and fMRI signals in arousal, salience, and visual networks differed depending on whether afterimages were perceived or not perceived. These results challenge the prevailing framing on the neurophysiological origins of afterimages as arising from either retinal or central neural processes. As with image perception, typical afterimages emerge by the interaction between retinal and central neural mechanisms. These findings on the neural processing underlying afterimages may be broadly informative of the neural mechanisms of visual consciousness.

neuroscience↗

Blood volume sensitive laminar fMRI with VASO in human hippocampus: Capabilities and biophysical challenges at clinical 7T scanners

Sub-millimeter resolution functional magnetic resonance imaging (fMRI) at ultra-high field ([≥] 7T) has offered an unprecedented opportunity to probe mesoscopic computations at a columnar or laminar level. However, its application has been primarily restricted to the neocortex. Inferior brain regions, particularly the hippocampus (HC), are challenging targets for laminar fMRI. Recent developments in acquisition methods have shown the feasibility of laminar recordings in the HC using gradient-echo blood oxygenation level-dependent (BOLD) contrast. Nonetheless, the spatial specificity of the BOLD signal is compromised by the draining veins bias. Cerebral blood volume (CBV)-sensitive sequences including vascular space occupancy (VASO) have emerged as a promising augmentation tool to capture the vein-free laminar activity. Yet, its feasibility in the HC is unclear and challenged by methodological constraints. Here, we optimized VASO to mitigate the macrovasculature contribution in HC. By evaluating a series of advanced acquisition strategies tailored to HC, we obtained improved VASO signal quality with minimal artifacts. The optimized protocol was further validated with an autobiographical memory task. Our findings show that combining the high detection power of gradient-echo BOLD with the vein-free VASO contrast allows for differentiation between neural activity-related BOLD signals and those biased by draining veins. These results demonstrate the feasibility of submillimeter VASO acquired with conventional 7T scanners in the HC to map the circuit-level mechanisms of memory retrieval across HC subfields, laying a foundation to investigate the microcircuitry of HC-driven complex cognitive functions and their alterations in neurodegeneration.

neuroscience↗

Rapid decoding of neural information representation from ultra-fast functional magnetic resonance imaging signals

High spatio-temporal resolution is crucial for neuroimaging techniques to improve our understanding of human brain function. While the fMRI signal is slow and shows a spread in latencies over space, the precision of hemodynamic response latency for each voxel is preserved and has been shown to be able to detect oscillatory hemodynamic changes approaching 1 Hz, suggesting its potential to reveal rapid neural dynamics. To examine how fast neural information can be derived from fMRI signals, we performed experiments that acquire high-field (7T) fMRI signals at an ultra-fast sampling rate (TR = 125 ms) from the visual cortex while participants observed naturalistic object stimuli. We applied multivariate pattern decoders to extract presented object-category information from the acquired signals at each sampling time after stimulus onset. Results showed that decoding accuracy rose above statistical significance less than 2 s after signal onset, faster than the peak latency of the hemodynamic response. The peak latency of the decoding accuracy was independent of variations in the hemodynamic latency of voxels used for decoding. The application of sparse decoders further revealed that rapid and accurate decoding was possible by pruning vein-rich voxels off from the multivariate voxel input to the decoders. These results suggest that a combination of ultra-fast sampling and multivariate decoding allows fast and temporally precise analysis of neural activity using fMRI signals. Significance statementFunctional magnetic resonance imaging (fMRI) is the most successful method to evaluate human brain function at fine spatial scales but is thought to lack temporal resolution because of slow hemodynamics. We challenge this conventional notion by fast sampling of fMRI signals, combined with multivariate decoding to extract information content represented in the fMRI signals. Results showed that the information content can be extracted faster than the magnitude of hemodynamic response rises, independent of the large spatial variation of hemodynamic latencies across individual voxels, and even after removing venous voxels from decoders. Our method is thus effective at filtering out slow and variable hemodynamic components, leading to the extraction of rapid and temporally precise components reflecting neuronal activity in human fMRI signals.

neuroscience↗

Layer-specific spatiotemporal dynamics of feedforward and feedback in human visual object perception

Visual object perception is mediated by information flow between regions of the ventral visual stream along feedforward and feedback anatomical connections. However, feedforward and feedback signals during naturalistic vision are rapid and overlapping, complicating their identification and precise functional specification. Here we recorded human layer-specific fMRI responses to naturalistic object images in early visual cortex (EVC) and lateral occipital complex (LOC) to isolate feedforward and feedback information signals spatially by their cortical layer-specific termination pattern. We combined these layer-specific fMRI responses with electroencephalography (EEG) responses for the same images to segregate feedforward and feedback signals in both time and space. Feedforward signals emerge early in the middle layers of EVC and LOC, followed by feedback signals in the superficial layer of LOC. Comparing the identified dynamics in LOC to a visual deep neural network (DNN), revealed that early feedforward signals in LOC encode medium-to-high complexity features, whereas later feedback signals increase the representational format to high complexity features. Together this specifies the spatiotemporal dynamics and functional role of feedforward and feedback information flow mediating visual object perception.

neuroscience↗

V1 superficial layers create a saliency map that feeds forward to the parietal cortex for attentional guidance

A salient visual object with a distinct feature from the surrounding environment automatically captures attention. While the saliency signals have been found in many brain regions, their source remains highly controversial. Here, we investigated the neural origin of visual saliency using cortical layer-dependent functional magnetic resonance imaging (fMRI) of cerebral blood volume (CBV) at 7 Tesla. Behaviorally, human observers were better at detecting foreground bars with a larger orientation contrast from uniformly oriented background bars. Saliency-sensitive signals were strongest in the superficial layers of the primary visual cortex (V1), and in the middle layers of the intraparietal sulcus (IPS) of the parietal cortex. Layer-dependent effective connectivity revealed the transmission of saliency signals along the feedforward pathway from V1 to IPS. Furthermore, behavioral sensitivity to the foreground stimulus correlated significantly with the fMRI response in the superficial layers of V1. Our findings provide mesoscale evidence that a visual saliency map is created by iso-feature suppression through lateral inhibition in the superficial layers of V1, and then feeds forward to attentional control brain regions to guide attention and eye movements.

neuroscience↗

T1234: A distortion-matched structural scan solution to misregistration of high resolution fMRI data

PurposeHigh-resolution fMRI at 7T is challenged by suboptimal alignment quality between functional data and structural scans. This study aims to develop a rapid acquisition method that provides distortion-matched, artifact-mitigated structural reference data. MethodsWe introduce an efficient sequence protocol termed T1234, which offers adjustable distortions. This approach involves a T1-weighted 2-inversion 3D-EPI sequence with four spatial encoding directions optimized for high-resolution fMRI. A forward Bloch model was used for T1 quantification and protocol optimization. Twenty participants were scanned at 7T using both structural and functional protocols to evaluate the utility of T1234. ResultsResults from two protocols are presented. A fast distortion-free protocol reliably produced whole-brain segmentations at 0.8mm isotropic resolution within 3:00-3:40 minutes. It demonstrates robustness across sessions, participants, and three different 7T SIEMENS scanners. For a protocol with geometric distortions that matched functional data, T1234 facilitates layer-specific fMRI signal analysis with enhanced laminar precision. ConclusionThis structural mapping approach enables precise registration with fMRI data. T1234 has been successfully implemented, validated, and tested, and is now available to users at our center and at over 50 centers worldwide.

neuroscience↗

In the brain of the beholder: bi-stable motion reveals mesoscopic-scale feedback modulation in V1

Understanding the neural processes underlying conscious perception remains a central goal in neuroscience. Visual illusions, whether static or dynamic, provide an effective ecological paradigm for studying conscious perception, as they induce subjective experiences from constant visual inputs. While previous neuroimaging studies have dissociated perceptual interpretation of visual motion from sensory input within the motion-sensitive area (hMT+) in humans, less is known about the role of V1 and its relationship to hMT+ during a bistable perception. To address this, we conducted a layer-fMRI study at 7 T with human participants exposed to a bistable motion quartet stimulus. Despite a constant sensory input, the bistable motion quartet elicits switching horizontal and vertical apparent motion percepts likely due to lateral and feedback connections across low and high-level brain regions (feedback processing). As control, we used an "unambiguous" version of the motion quartet, hereafter referred to as "physical" motion stimulus, where horizontal and vertical motion is physically presented as visual stimulus in an alternated fashion (feedforward processing). With the advantage of a sub-millimeter resolution gained at ultra-high field (7 Tesla), we aimed to unveil the differential laminar modulation of V1 (low visual area) and hMT+ (high-visual area) during the physical and bistable condition. Our results indicate that: O_LIhMT+ functional activity correlates with conscious perception during both physical and ambiguous stimuli with similar strength. There is no evidence of differential laminar profiles in hMT+ between the two experimental conditions. C_LIO_LIBetween inducer squares, V1 shows a significantly reduced functional response to the ambiguous stimulus compared to the physical stimulus, as it primarily reflects feedback signals with diminished feedforward input. Distinct V1 laminar profiles differentiate the two experimental conditions. C_LIO_LIThe temporal dynamics of V1 and hMT+ become more similar during the ambiguous condition. C_LIO_LIV1 exhibits reduced specificity to horizontal and vertical motion perception during the ambiguous condition at the retinotopic locations corresponding to the perceived motion. C_LI Our findings demonstrate that during the ambiguous condition, there is a stronger temporal coupling between hMT+ and V1 due to feedback signals from hMT+ to V1. Such feedback to V1 might be contributing to the stabilization of the vivid perception of directed motion at the face of constant ambiguous stimulation.

neuroscience↗

Fuzzy ripple artifact in high resolution fMRI: identification, cause, and mitigation

PurposeHigh resolution fMRI is a rapidly growing research field focused on capturing functional signal changes across cortical layers. However, the data acquisition is limited by low spatial frequency EPI artifacts; termed here as Fuzzy Ripples. These artifacts limit the practical applicability of acquisition protocols with higher spatial resolution, faster acquisition speed, and they challenge imaging in lower brain areas. MethodsWe characterize Fuzzy Ripple artifacts across commonly used sequences and distinguish them from conventional EPI Nyquist ghosts, off-resonance effects, and GRAPPA artifacts. To investigate their origin, we employ dual polarity readouts. ResultsOur findings indicate that Fuzzy Ripples are primarily caused by readout-specific imperfections in k-space trajectories, which can be exacerbated by inductive coupling between third-order shims and readout gradients. We also find that these artifacts can be mitigated through complex-valued averaging of dual polarity EPI or by disconnecting the third-order shim coils. ConclusionThe proposed mitigation strategies allow overcoming current limitations in layer-fMRI protocols: O_LIAchieving resolutions beyond 0.8mm is feasible, and even at 3T, we achieved 0.53mm voxel functional connectivity mapping. C_LIO_LISub-millimeter sampling acceleration can be increased to allow sub-second TRs and laminar whole brain protocols with up to GRAPPA 8. C_LIO_LISub-millimeter fMRI is achievable in lower brain areas, including the cerebellum. C_LI

neuroscience↗

Laminar CBV and BOLD response-characteristics over time and space in the human primary somatosensory cortex at 7T

Uncovering the cortical representation of the body has been at the core of human brain mapping for decades, with special attention given to the digits. In the last decade, advances in functional magnetic resonance imaging (fMRI) technologies have opened the possibility of noninvasively unraveling the 3rd dimension of digit representations in humans along cortical layers. In laminar fMRI it is common to combine the use of the highly sensitive blood oxygen level dependent (BOLD) contrast with cerebral blood volume sensitive measurements, like vascular space occupancy (VASO), that are more specific to the underlying neuronal populations. However, the spatial and temporal VASO response characteristics across cortical depth to passive stimulation of the digits are still unknown. Therefore, we characterized haemodynamic responses to vibrotactile stimulation of individual digit-tips across cortical depth at 0.75 mm in-plane spatial resolution using BOLD and VASO fMRI at 7T. We could identify digit-specific regions of interest (ROIs) in putative Brodmann area 3b, following the known anatomical organization. In the ROIs, the BOLD response increased towards the cortical surface due to the draining vein effect, while the VASO response was more shifted towards middle cortical layers, likely reflecting bottom-up input from the thalamus, as expected. Interestingly, we also found slightly negative BOLD and VASO responses for non-preferred digits in the ROIs, potentially indicating neuronal surround inhibition. Finally, we explored the temporal signal dynamics for BOLD and VASO as a function of distance from activation peaks resulting from stimulation of contralateral digits. With this analysis, we showed a triphasic response consisting of an initial peak and a subsequent negative deflection during stimulation, followed by a positive post-stimulus response in BOLD and to some extent in VASO. While similar responses were reported with invasive methods in animal models, here we demonstrate a potential neuronal excitation-inhibition mechanism in a center-surround architecture across layers in the human somatosensory cortex. Given that, unlike in animals, human experiments do not rely on anesthesia and can readily implement extensive behavioral testing, obtaining this effect in humans is an important step towards further uncovering the functional significance of the different aspects of the triphasic response.

neuroscience↗

Holistic Processing Strategy in Cross-Species Face Perception between Dogs and Humans

Extensive studies have shown that humans process faces holistically, considering not only individual features but also the relationships among them. Knowing where humans and dogs fixate first and the longest when they view faces is highly informative, because the locations can be used to evaluate whether they use a holistic face processing strategy or not. However, the conclusions reported by previous eye-tracking studies appear inconclusive. To address this, we conducted an experiment with humans and dogs, employing experimental settings and analysis methods that can enable direct cross-species comparisons. Our findings reveal that humans, unlike dogs, preferentially fixated on the central region, surrounded by the inner facial features, for both human and dog faces. This pattern was consistent for initial and sustained fixations over seven seconds, indicating a clear tendency towards holistic processing. Although dogs did not show an initial preference for what to look at, their later fixations may suggest holistic processing when viewing faces of their own species. We discuss various potential factors influencing species differences in our results, as well as differences compared to the results of previous studies.

animal behavior and cognition↗

Functional mapping of the somatosensory cortex using noninvasive fMRI and touch in awake dogs

Dogs are increasingly used as a model for neuroscience due to their ability to undergo functional MRI fully awake and unrestrained, after extensive behavioral training. Still, we know rather little about dogs basic functional neuroanatomy, including how basic perceptual and motor functions are localized in their brains. This is a major shortcoming in interpreting activations obtained in dog fMRI. The aim of this preregistered study was to localize areas associated with somatosensory processing. To this end, we touched N = 22 dogs undergoing fMRI scanning on their left and right flanks using a wooden rod. We identified activation in anatomically defined primary and secondary somatosensory areas (SI and SII), lateralized to the contralateral hemisphere depending on the side of touch, as well as activations, beyond an anatomical mask of SI and SII, in the cingulate cortex, right cerebellum and vermis, and the Sylvian gyri. These activations may partly relate to motor control (cerebellum, cingulate), but also potentially to higher-order cognitive processing of somatosensory stimuli (rostral Sylvian gyri), and the affective aspects of the stimulation (cingulate). We also found evidence for individual side biases in a vast majority of dogs in our sample, pointing at functional lateralization of somatosensory processing. These findings not only provide further evidence that fMRI is suited to localize neuro-cognitive processing in dogs in vivo, but also expand our understanding of touch processing in mammals, beyond classically defined primary and secondary somatosensory cortices. Significance StatementTo understand brain function and evolution, it is necessary to look beyond the human lineage. This study provides insights into the engagement of brain areas related to somatosensation using whole-brain non-invasive neuroimaging of trained, non-sedated, and unrestrained pet dogs. It showcases again the usefulness of non-invasive methods, in particular fMRI, for investigating brain function and advances the mapping of brain functions in dogs; using this non-invasive approach without sedation, we are able to identify previously unknown potential higher-order processing areas and offer a quantification of touch processing lateralization.

neuroscience↗

Plasma proteome signature of canine acute haemorrhagic diarrhoea syndrome (AHDS)

Acute haemorrhagic diarrhoea is a common complaint in dogs. In addition to causes like intestinal parasites, dietary indiscretion, intestinal foreign bodies, canine parvovirus infection, or hypoadrenocorticism, acute haemorrhagic diarrhoea syndrome (AHDS) is an important and sometimes life-threatening differential diagnosis. There is some evidence supporting the link between Clostridium perfringens toxins and AHDS. These toxins may be partially responsible for the epithelial cell injury, but the pathogenesis of AHDS is still not fully understood. Recent studies have suggested that severe damage to the intestinal mucosa and associated barrier dysfunction can trigger chronic gastrointestinal illnesses. Besides bloodwork and classical markers for AHDS such as protein loss and intestinal bacterial dysbiosis, we focused mainly on the plasma-proteome to identify systemic pathological alterations during this disease and searched for potential biomarkers to improve the diagnosis. To accomplish the goals, we used liquid chromatography-mass spectrometry. We compared the proteomic profiles of 20 dogs with AHDS to 20 age-, breed-, and sex-matched control dogs. All dogs were examined, and several blood work parameters were determined and compared, including plasma biochemistry and cell counts. We identified and quantified 207 plasmatic proteins, from which dozens showed significantly altered levels in AHDS. Serpina3, Lipopolysaccharide-binding protein, several Ig-like domain-containing proteins, Glyceraldehyde-3-phosphate dehydrogenase and Serum amyloid A were more abundant in plasma from AHDS affected dogs. In contrast, other proteins such as Paraoxonase, Selenoprotein, Amine oxidases, and Apolipoprotein C-IV were significantly less abundant. Many of the identified and quantified proteins are known to be associated with inflammation. Other proteins like Serpina3 and RPLP1 have a relevant role in oncogenesis. Some proteins and their roles have not yet been described in dogs with diarrhoea. Our study opens new avenues that could contribute to the understanding of the aetiology and pathophysiology of AHDS.

biochemistry↗