Biology subjects

Eippert, F.

Publications and source records attributed to Eippert, F..

15 recordsLinked to original sources

bioRxiv2025

Ultra-high-field fMRI reveals layer-specific responses in the human spinal cord

Developments in functional magnetic resonance imaging (fMRI) at ultra-high field (UHF) now allow for insights into human brain function at mesoscopic scale. However, similar progress has not been achieved for the human spinal cord, despite its importance for reciprocal brain-body communication. Here, we therefore integrate substantial methodological improvements that enable previously unattainable high-resolution UHF spinal fMRI. Using a heat-pain paradigm in healthy volunteers, we investigate fMRI responses in the dorsal horn: we characterize their spatial pattern, establish their robustness and demonstrate that they can be reliably observed even for individual participants. Most importantly, we uncover two physiologically relevant spinal response components - phasic and tonic heat responses - that map differentially onto superficial and deep layers of the dorsal horn. Taken together, our novel UHF fMRI approach allows for differentiating responses across fundamental spinal processing units and will enable insights into human spinal cord function at mesoscopic scale in health and disease.

neuroscience↗

bioRxiv2025

Expectation effects on repetition suppression in nociception

Repetition suppression, the reduced neural response upon repeated presentation of a stimulus, can be explained by models focussing on bottom-up (i.e. adaptation) or top-down (i.e. expectation) mechanisms. Predictive coding models fall into the latter category and propose that repetitions are expected and therefore elicit smaller prediction error responses. While studies in the visual and auditory domain provide some support for such models, in nociception evidence remains inconclusive, despite the substantial influence expectations exert on pain perception. To assess expectation effects on repetition suppression in nociception, we developed a paradigm in which healthy volunteers received brief CO2 laser stimuli, while we acquired electroencephalographic (EEG) and peripheral physiological data. Importantly, laser stimuli could be either repeated after one second or not be repeated, with the probability of repetitions manipulated in a block-wise fashion, such that repetitions were either expected or unexpected. We observed repetition suppression in laser-evoked potentials as well as laser-induced gamma band oscillations, but not in laser-induced desynchronisations in the alpha and beta band. Critically, neither these EEG responses, nor the peripheral physiological data showed significant differences between the expectation conditions, with Bayesian analyses mostly providing evidence for an absence of effects. This indicates that repetition suppression to brief nociceptive laser stimuli is not driven by top-down factors, but rather mediated by other adaptation processes. While this does not preclude an influence of predictive coding models in nociception, it suggests that when the nervous system receives highly precise input, its responses are less susceptible to influence from expectations.

neuroscience↗

bioRxiv2025

Multi-center benchmarking of cervical spinal cord RF coils for 7 T MRI: A traveling spines study

PurposeThe depth within the body, small diameter, long length, and varying tissue surrounding the spinal cord impose specific considerations when designing radiofrequency coils. The optimal coil configuration for 7 T cervical spinal cord MRI is unknown and, currently, there are very few coil options. The purpose of this work was (1) to establish a quality control protocol for evaluating 7 T cervical spinal cord coils and (2) to use that protocol to evaluate the performance of 4 different coil designs. MethodsThree healthy volunteers and a custom anthropomorphic phantom (the traveling spines cohort) were scanned at seven 7 T imaging centers using a common protocol and each centers specific cervical spinal cord coil. Four different coil designs were tested (two in-house, one Rapid Biomedical, and one MRI.TOOLS design). ResultsThe Rapid Biomedical coil was found to have the highest B1+ efficiency, whereas one of the in-house designs (NeuroPoly Lab) had the highest SNR and the largest spinal cord coverage. The MRI.TOOLS coil had the most uniform B1+ profile along the cervical spinal cord; however, it was limited in its ability to provide the requested flip angles (especially for larger individuals). The latter was also the case for the second in-house coil (MSSM). ConclusionThe results of this study serve as a guide for the spinal cord MRI community in selecting the most suitable coil based on specific requirements and offer a standardized protocol for assessing future coils.

bioengineering↗

bioRxiv2025

EPISeg: Automated segmentation of the spinal cord on echo planar images using open-access multi-center data

Functional magnetic resonance imaging (fMRI) of the spinal cord is relevant for studying sensation, movement, and autonomic function. Preprocessing of spinal cord fMRI data involves segmentation of the spinal cord on gradient-echo echo planar imaging (EPI) images. Current automated segmentation methods do not work well on these data, due to the low spatial resolution, susceptibility artifacts causing distortions and signal drop-out, ghosting, and motion-related artifacts. Consequently, this segmentation task demands a considerable amount of manual effort which takes time and is prone to user bias. In this work, we (i) gathered a multi-center dataset of spinal cord gradient-echo EPI with ground-truth segmentations and shared it on OpenNeuro https://openneuro.org/datasets/ds005143/versions/1.3.0, and (ii) developed a deep learning-based model, EPISeg, for the automatic segmentation of the spinal cord on gradient-echo EPI data. We observe a significant improvement in terms of segmentation quality compared to other available spinal cord segmentation models. Our model is resilient to different acquisition protocols as well as commonly observed artifacts in fMRI data. The training code is available at https://github.com/sct-pipeline/fmri-segmentation/, and the model has been integrated into the Spinal Cord Toolbox as a command-line tool.

neuroscience↗

bioRxiv2024

Somatosensory high frequency oscillations across the human central nervous system

Information transmission in the central nervous system (CNS) relies on the propagation of action potentials (neuronal spikes), traditionally thought to be inaccessible with electroencephalography (EEG). Converging evidence from human and animal recordings however demonstrates that high frequency oscillations (HFOs) in EEG recordings represent neuronal population spiking, complementing standard low-frequency EEG recordings in cortex. Here, we developed an approach to simultaneously record HFOs to somatosensory stimulation across the entire human CNS noninvasively: from spinal over subcortical to cortical stages. Our approach provides a detailed temporal and spectral characterization of HFOs at each CNS level, delineating how they evolve across the somatosensory processing hierarchy. Critically, we show that low and high frequency electrophysiological responses represent at least partly independent processing channels across the CNS. We thus demonstrate the feasibility of studying the full spectrum of neuronal information processing across the CNS, offering a multi-level window into human neurophysiology in health and disease.

neuroscience↗

bioRxiv2024

Evaluating noise correction approaches for non-invasive electrophysiology of the human spinal cord

The spinal cord is a vital component of the central nervous system for the processing of sensorimotor information transmitted between the body and the brain. Electrospinography (ESG) is the most accessible non-invasive technique for recording spinal signals in humans, but the vast and detrimental impact of physiological noise (mostly of cardiac nature) has prevented widespread adoption. Here, we aim to address this issue by examining various denoising algorithms for cardiac artefact reduction - including principal component analysis-based techniques (PCA), independent component analysis-based approaches (ICA) and signal space projection (SSP). We observed that in situations where large numbers of spinal electrodes are used, SSP offers the best results in terms of balancing the removal of harmful noise and preserving neural information of interest. In cases where only a small number of electrodes are available, an approach based on PCA is deemed helpful. Approaches based on ICA were found to be unsuitable for cardiac artefact removal in ESG, due to a suboptimal balance of artefact removal and signal preservation. Finally, we also approached this issue from a signal-enhancement perspective and observed that in cases where extensive electrode arrays are used in the context of task-based designs, a spatial filtering technique based on canonical correlation analysis (CCA) reveals clear evoked spinal potentials even with single-trial resolution. Taken together, there are several appropriate algorithms for physiological noise removal in ESG, rendering this an accessible and easy-to-use technique for non-invasive assessments of human spinal cord function.

neuroscience↗

bioRxiv2024

Body size interacts with the structure of the central nervous system: A multi-center in vivo neuroimaging study

Clinical research emphasizes the implementation of rigorous and reproducible study designs that rely on between-group matching or controlling for sources of biological variation such as subjects sex and age. However, corrections for body size (i.e. height and weight) are mostly lacking in clinical neuroimaging designs. This study investigates the importance of body size parameters in their relationship with spinal cord (SC) and brain magnetic resonance imaging (MRI) metrics. Data were derived from a cosmopolitan population of 267 healthy human adults (age 30.1{+/-}6.6 years old, 125 females). We show that body height correlated strongly or moderately with brain gray matter (GM) volume, cortical GM volume, total cerebellar volume, brainstem volume, and cross-sectional area (CSA) of cervical SC white matter (CSA-WM; 0.44[≤]r[≤]0.62). In comparison, age correlated weakly with cortical GM volume, precentral GM volume, and cortical thickness (-0.21[≥]r[≥]-0.27). Body weight correlated weakly with magnetization transfer ratio in the SC WM, dorsal columns, and lateral corticospinal tracts (-0.20[≥]r[≥]-0.23). Body weight further correlated weakly with the mean diffusivity derived from diffusion tensor imaging (DTI) in SC WM (r=-0.20) and dorsal columns (-0.21), but only in males. CSA-WM correlated strongly or moderately with brain volumes (0.39[≤]r[≤]0.64), and weakly with precentral gyrus thickness and DTI-based fractional anisotropy in SC dorsal columns and SC lateral corticospinal tracts (-0.22[≥]r[≥]-0.25). Linear mixture of sex and age explained 26{+/-}10% of data variance in brain volumetry and SC CSA. The amount of explained variance increased at 33{+/-}11% when body height was added into the mixture model. Age itself explained only 2{+/-}2% of such variance. In conclusion, body size is a significant biological variable. Along with sex and age, body size should therefore be included as a mandatory variable in the design of clinical neuroimaging studies examining SC and brain structure.

neuroscience↗

bioRxiv2023

Reliability of task-based fMRI in the dorsal horn of the human spinal cord

The application of functional magnetic resonance imaging (fMRI) to the human spinal cord is still a relatively small field of research and faces many challenges. Here we aimed to probe the limitations of task-based spinal fMRI at 3T by investigating the reliability of spinal cord blood oxygen level dependent (BOLD) responses to repeated nociceptive stimulation across two consecutive days in 40 healthy volunteers. We assessed the test-retest reliability of subjective ratings, autonomic responses, and spinal cord BOLD responses to short heat pain stimuli (1s duration) using the intraclass correlation coefficient (ICC). At the group level, we observed robust autonomic responses as well as spatially specific spinal cord BOLD responses at the expected location, but no spatial overlap in BOLD response patterns across days. While autonomic indicators of pain processing showed good-to-excellent reliability, both {beta}-estimates and z-scores of task-related BOLD responses showed poor reliability across days in the target region (gray matter of the ipsilateral dorsal horn). When taking into account the sensitivity of gradient-echo echo planar imaging (GE-EPI) to draining vein signals by including the venous plexus in the analysis, we observed BOLD responses with fair reliability across days. Taken together, these results demonstrate that heat pain stimuli as short as one second are able to evoke a robust and spatially specific BOLD response, which is however strongly variable within participants across time, resulting in low reliability in the dorsal horn gray matter. Further improvements in data acquisition and analysis techniques are thus necessary before event-related spinal cord fMRI as used here can be reliably employed in longitudinal designs or clinical settings.

neuroscience↗

bioRxiv2023

Assessing adverse effects and unspecific effects of transcutaneous spinal direct current stimulation (tsDCS)

BackgroundTranscutaneous spinal direct current stimulation (tsDCS) is a relatively recent method for non-invasively modulating neuronal activity in the human spinal cord. Despite its growing prominence, comprehensive studies addressing its potential adverse effects (AEs) and unspecific effects (UEs) are lacking. ObjectiveIn this study, we conducted a systematic investigation into the potential AEs and UEs of tsDCS in healthy volunteers. MethodsWe used a randomized double-blind within-participant design, employing anodal, cathodal and sham tsDCS of the thoracolumbar spinal cord. Our approach involved a newly-developed structured questionnaire (to assess subjectively-reported AEs) in combination with tsDCS-concurrent recording of skin conductance, cardiac and respiratory activity (to assess UEs in bodily state). ResultsThe most frequently participant-reported AEs were sensations of burning, tingling, and itching, although they were largely described as mild; skin redness (experimenter-reported) occurred even more frequently. Importantly, when comparing AEs between active and sham tsDCS via frequentist and Bayesian analysis approaches, the results were largely in favour of no difference between conditions (with the exception of skin redness). A similar picture emerged for most UE metrics, suggesting that tsDCS does not induce changes in bodily state, at least as measured by our autonomic nervous system metrics. ConclusionWe believe that the strategy employed here could serve as a starting point for a systematic AE and UE assessment in clinical populations, longitudinal designs and when stimulating different spinal sites. Taken together, our results contribute to assessing the tolerability, safety and specificity of tsDCS, in order to further the investigation of spinal cord function in health and disease.

neuroscience↗

bioRxiv2022

Reliability of resting-state functional connectivity in the human spinal cord: assessing the impact of distinct noise sources

The investigation of spontaneous fluctuations of the blood-oxygen-level-dependent (BOLD) signal has recently been extended from the brain to the spinal cord, where it has stimulated interest from a clinical perspective. A number of resting-state functional magnetic resonance imaging (fMRI) studies have demonstrated robust functional connectivity between the time series of BOLD fluctuations in bilateral dorsal horns and between those in bilateral ventral horns, in line with the functional neuroanatomy of the spinal cord. A necessary step prior to extension to clinical studies is assessing the reliability of such resting-state signals, which we aimed to do here in a group of 45 healthy young adults at the clinically prevalent field strength of 3T. When investigating connectivity in the entire cervical spinal cord, we observed fair to good reliability for dorsal-dorsal and ventral-ventral connectivity, whereas reliability was poor for within- and between-hemicord dorsal-ventral connectivity. Considering how prone spinal cord fMRI is to noise, we extensively investigated the impact of distinct noise sources and made two crucial observations: removal of physiological noise led to a reduction in functional connectivity strength and reliability - due to the removal of stable and participant-specific noise patterns - whereas removal of thermal noise considerably increased the detectability of functional connectivity without a clear influence on reliability. Finally, we also assessed connectivity within spinal cord segments and observed that while the pattern of connectivity was similar to that of whole cervical cord, reliability at the level of single segments was consistently poor. Taken together, our results demonstrate the presence of reliable resting-state functional connectivity in the human spinal cord even after thoroughly accounting for physiological and thermal noise, but at the same time urge caution if focal changes in connectivity (e.g. due to segmental lesions) are to be studied, especially in a longitudinal manner.

neuroscience↗

bioRxiv2022

Non-invasive multi-channel electrophysiology of the human spinal cord - assessing somatosensory processing from periphery to cortex

The spinal cord is of fundamental importance for integrative processing in brain-body communication, yet routine non-invasive recordings in humans are hindered by vast methodological challenges. Here we overcome these challenges by developing an easy-to-use electrophysiological approach based on high-density multi-channel spinal recordings combined with multivariate spatial-filtering analyses. These advances enable a spatiotemporal characterization of spinal cord responses and demonstrate a sensitivity that permits assessing even single-trial responses. To furthermore enable the study of integrative processing along the neural processing hierarchy in somatosensation, we expand this approach by simultaneous peripheral, spinal and cortical recordings and provide direct evidence that bottom-up integrative processing occurs already within the spinal cord and thus after the first synaptic relay in the central nervous system. Finally, we demonstrate the versatility of this approach by providing non-invasive recordings of nociceptive spinal cord responses during heat-pain stimulation. Beyond establishing a new window on human spinal cord function at millisecond timescale, this work provides the foundation to study brain-body communication in its entirety in health and disease.

neuroscience↗

bioRxiv2022

Cortical response variability is driven by local excitability changes with somatotopic organization

Identical sensory stimuli can lead to different neural responses depending on the instantaneous brain state. Specifically, neural excitability in sensory areas may shape the brains response already from earliest cortical processing onwards. However, whether these dynamics affect a given sensory domain globally or occur on a spatially local level is largely unknown. We studied this in the somatosensory domain of 38 human participants with EEG, presenting stimuli to the median and tibial nerves alternatingly, and testing the co-variation of initial cortical responses in hand and foot areas, as well as their relation to pre-stimulus oscillatory states. We found that amplitude fluctuations of initial cortical responses to hand and foot stimulation - the N20 and P40 components of the somatosensory evoked potential (SEP), respectively - were not related, indicating local excitability changes in primary sensory regions. In addition, effects of pre-stimulus alpha (8-13 Hz) and beta (18-23 Hz) band amplitude on hand-related responses showed a robust somatotopic organization, thus further strengthening the notion of local excitability fluctuations. However, for foot-related responses, the spatial specificity of pre-stimulus effects was less consistent across frequency bands, with beta appearing to be more foot-specific than alpha. Connectivity analyses in source space suggested this to be due to a somatosensory alpha rhythm that is primarily driven by activity in hand regions while beta frequencies may operate in a more hand-region-independent manner. Altogether, our findings suggest spatially distinct excitability dynamics within the primary somatosensory cortex, yet with the caveat that frequency-specific processes in one sub-region may not readily generalize to other sub-regions.

neuroscience↗

bioRxiv2021

Automated slice-specific z-shimming for fMRI of the human spinal cord

Functional magnetic resonance imaging (fMRI) of the human spinal cord faces many challenges, such as signal loss due to local magnetic field inhomogeneities. This issue can be addressed with slice-specific z-shimming, which compensates for the dephasing effect of the inhomogeneities using a slice-specific gradient pulse. Here, we aim to address outstanding issues regarding this technique by evaluating its effects on several aspects that are directly relevant for spinal fMRI and by developing two automated procedures in order to improve upon the time-consuming and subjective nature of manual selection of z-shims: one procedure finds the z-shim that maximizes signal intensity in each slice of an EPI reference-scan and the other finds the through-slice field inhomogeneity for each EPI-slice in field map data and calculates the required compensation gradient moment. We demonstrate that the beneficial effects of z-shimming are apparent across different echo times, hold true for both the dorsal and ventral horn, and are also apparent in the temporal signal-to-noise ratio (tSNR) of EPI time-series data. Both of our automated approaches were faster than the manual approach, lead to significant improvements in gray matter tSNR compared to no z-shimming and resulted in beneficial effects that were stable across time. While the field-map-based approach performed slightly worse than the manual approach, the EPI-based approach performed as well as the manual one and was furthermore validated on an external corticospinal data-set (N>100). Together, automated z-shimming may improve the data quality of future spinal fMRI studies and lead to increased reproducibility in longitudinal studies.

neuroscience↗

bioRxiv2021

Temporal-spectral signaling of sensory information and expectations in the cerebral processing of pain

The perception of pain is shaped by somatosensory information about threat. However, pain is also influenced by an individuals expectations. Such expectations can result in clinically relevant modulations and abnormalities of pain. In the brain, sensory information, expectations (predictions), and discrepancies thereof (prediction errors) are signaled by an extended network of brain areas. These brain areas generate evoked potentials and oscillatory responses at different latencies and frequencies. Recent evidence has provided first insights into how oscillatory responses at different frequencies signal predictions and prediction errors. However, a comprehensive picture of how evoked and oscillatory brain responses signal sensory information, predictions, and prediction errors in the processing of pain is lacking so far. We therefore built upon a neuroimaging study which investigated the spatial signalling of sensory information, predictions and predictions errors in the processing of pain (Geuter et al., 2017). To complement and extend this study, we applied brief painful stimuli to 48 healthy human participants and independently modulated sensory information (stimulus intensity) and expectations of pain intensity while measuring brain activity using electroencephalography (EEG). Pain ratings confirmed that pain intensity was shaped by both sensory information and expectations. In contrast, Bayesian analyses revealed that stimulus-induced EEG responses at different latencies (the N1, N2, and P2 components) and frequencies (alpha, beta, and gamma oscillations) were shaped by sensory information but not by expectations. Expectations, however, shaped alpha and beta oscillations before the painful stimuli. These findings indicate that commonly analyzed EEG responses to painful stimuli are more involved in signaling sensory information than in signaling expectations or mismatches of sensory information and expectations. Moreover, they indicate that the effects of expectations on pain are served by brain mechanisms which differ from those conveying effects of sensory information on pain.

neuroscience↗

bioRxiv2018

Cortico-brainstem mechanisms of biased perceptual decision-making in the context of pain

Perceptual decision-making is commonly studied using stimuli with different physical properties but of comparable affective value. Here, we investigate neural processes underlying human perceptual decisions in the affectively rich domain of pain using a drift-diffusion model in combination with a probabilistic cueing paradigm. This allowed us to characterize a novel role for the dorsolateral prefrontal cortex (DLPFC), whose anticipatory responses reflecting a decision bias were dependent on the affective value of the stimulus. During intense noxious stimulation, these model-based anticipatory DLPFC responses were linked to an engagement of the periaqueductal gray (PAG), a midbrain region implicated in defensive responses including analgesia. Complementing these findings on biased decision-making, the model parameter reflecting sensory processing predicted subcortical responses (in amygdala and PAG) when expectations were violated. Our findings highlight the importance of taking a broader perspective on perceptual decisions and link decisions about pain with subcortical circuitry implicated in endogenous pain modulation.

neuroscience↗