Biology subjects

Finsterbusch, J.

Publications and source records attributed to Finsterbusch, J..

12 recordsLinked to original sources

bioRxiv2026

Conditioned pain modulation recruits the descending pain modulatory system to inhibit spinal activity

Conditioned pain modulation (CPM) is a phenomenon where the perception of pain is reduced in the presence of a second painful stimulus. In rodents, a similar phenomenon involves descending control pathways that rely on the brainstem to modulate spinal cord activity while in humans, descending mechanisms including the spinal cord remain elusive. In this study, we applied functional MRI to simultaneously record brain and spinal cord responses during CPM in healthy participants. CPM developed over time and was associated with reduced activity in key pain-related brain regions and the spinal cord dorsal horn. Conversely, regions involved in descending pain modulation showed increased activity during CPM. Functional connectivity analyses revealed reduced coupling during CPM between spinal and descending control regions. Our findings demonstrate that CPM involves both the descending pain control system to inhibit spinal activity and bottom-up pain signalling of attenuated spinal responses.

neuroscience↗

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

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

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.

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bioRxiv2024

Altered visual cortex excitatory/inhibitory ratio following transient congenital visual deprivation in humans

Non-human animal models have indicated that the ratio of excitation to inhibition (E/I) in neural circuits is experience dependent and changes across development. Here, we assessed 3T Magnetic Resonance Spectroscopy (MRS) and electroencephalography (EEG) markers of cortical E/I ratio in ten individuals who had been treated for dense bilateral congenital cataracts, after an average of 12 years of blindness, to test for dependence of the E/I ratio in humans on early visual experience. First, participants underwent MRS scanning at rest with their eyes opened and eyes closed, to obtain visual cortex Gamma-Aminobutyric Acid (GABA+) concentration, Glutamate/Glutamine (Glx) concentration and the concentration ratio of Glx/GABA+, as measures of inhibition, excitation, and E/I ratio respectively. Subsequently, EEG was recorded to assess aperiodic activity (1-20 Hz) as a neurophysiological measure of the cortical E/I ratio, during rest with eyes open and eyes closed, and during flickering stimulation. Across conditions, congenital cataract-reversal individuals demonstrated a significantly lower visual cortex Glx/GABA+ ratio, and a higher intercept and steeper aperiodic slope at occipital electrodes, compared to age-matched sighted controls. In the congenital cataract-reversal group, a lower Glx/GABA+ ratio was associated with better visual acuity, and Glx concentration correlated positively with the aperiodic intercept in the conditions with visual input. We speculate that these findings result from an increased E/I ratio of the visual cortex as a consequence of congenital blindness, which might require commensurately increased inhibition in order to balance the additional excitation from restored visual input. The lower E/I ratio in congenital cataract-reversal individuals would thus be a consequence of homeostatic plasticity.

neuroscience↗

bioRxiv2024

Functional magnetic resonance imaging of the lumbosacral cord during a lower extremity motor task

Blood-oxygen-level dependent (BOLD) functional magnetic resonance imaging (fMRI) can be used to map neuronal function in the cervical cord, yet conclusive evidence supporting its applicability in the lumbosacral cord is still lacking. This study aimed to (i) demonstrate the feasibility of BOLD fMRI in mapping neuronal activation in the lumbosacral cord during a unilateral lower extremity motor task and (ii) investigate the impact of echo time (TE) on the BOLD effect size. Twelve healthy volunteers underwent BOLD fMRI using four reduced-field-of-view single-shot gradient-echo echo planar imaging sequences, all with the same geometry but different TE values ranging from 20 to 42 ms. Each sequence was employed to acquire a single 6-minute rest run and two 10-minute task runs, which included alternating 15-second blocks of rest and unilateral ankle dorsi- and plantar flexion. We detected lateralized task-related neuronal activation at neurological levels S4 to L1, centered at the ipsilateral (right) ventral spinal cord but also extending into the ipsilateral dorsal spinal cord. This pattern of activation is consistent with our current understanding of spinal cord organization, wherein lower motor neurons are located in the ventral gray matter horn, while sensory neurons of the proprioceptive pathway, activated during the movement, are located in the dorsal horns. At the subject level, BOLD activation showed considerable variability but was lateralized in all participants. The highest BOLD effect size within the ipsilateral ventral spinal cord was observed at TE=42 ms. Sequences with a shorter TE (20 and 28 ms) also detected activation in the medioventral part of the spinal cord, likely representing a large vein effect. In summary, our results demonstrate the feasibility of detecting neuronal activation in the lumbosacral cord induced by voluntary lower limb movements. BOLD fMRI in the lumbosacral cord has significant implications for assessing motor function and its alterations in disease or after spinal cord injury.

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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.

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bioRxiv2023

Brainstem arousal systems adaptively shape large-scale cortical interactions for flexible decision-making

Most perceptual decisions entail a flexible mapping from sensory input to motor output. Flexible input-output mapping is reflected in correlated variability within the cortical network involved in perceptual decisions. Here, we tested the idea that brainstem arousal systems are involved in flexible input-output mapping and changes in cortical correlated variability. We combined brainstem fMRI, pupillometry, and time-resolved assessment of the intrinsic correlations between cortical population codes for stimulus and action. Human participants reported the orientation of visual stimuli by button presses, while the required stimulus-response mapping rule could undergo hidden and unpredictable changes. Rule switches evoked brainstem and pupil responses as well as changes in computational model-inferred, latent variables. These variables governed participants rule-switching behavior and pupil responses. Brainstem activity and pupil dilation preceded increases in the strength of correlations between cortical stimulus and action codes. Brainstem arousal systems may promote the reorganization of sensorimotor cortical pathways for flexible decisions.

neuroscience↗

bioRxiv2023

Conditioned pain modulation of pressure pain is associated with reduced activation in the parietal operculum and posterior insula

Conditioned pain modulation (CPM) is the phenomenon of pain inhibiting further pain. CPM is impaired in patients suffering from various chronic pain conditions and may resemble a pro-nociceptive profile. A possible neural mechanism for CPM is descending control from cortical regions via brainstem that modulates neural activity at the level of the dorsal horn of the spinal cord where noxious input first arrives. We studied the involvement of the descending pain modulatory pathway by simultaneous functional imaging of the brain, brainstem, rostral medulla, and cervical spinal cord during CPM with pressure cuff algometry in 42 healthy human participants. Subjective CPM as measured by decreased pain ratings developed over the experiment with application of repeated short test stimuli for long conditioning pain compared with non-painful conditioning. Test stimuli paired with painful conditioning were associated with decreased BOLD fMRI activity in the parietal operculum (secondary somatosensory cortex) and posterior insula, as well as increased responses in bilateral primary somatosensory cortices. Subjective CPM reflected in pain ratings was associated with decreased test stimulus responses in somatosensory and pain-responsive brain regions such as the anterior and posterior insula and the parietal operculum. Conditioning pain and test pain were associated with increased neural activity in stimulus-ipsilateral spinal cord dorsal horn at segment C6 and C4, respectively. No evidence for neural correlates of CPM or associations with subjective CPM was observed in the spinal cord. Functional connectivity between the brain and spinal cord was altered during both conditioning and test pain but did not depend on conditioning intensity. Taken together, we observed neural activity associated with both negative (CPM) and positive modulation of pain in different somatosensory and pain-associated brain regions, and an association of these and other neural responses with subjective CPM. While we found that painful stimuli altered the connectivity along the descending pain modulatory pathway, we did not find evidence for a modulation by conditioning intensity nor neural correlates of CPM in the spinal cord.

neuroscience↗

bioRxiv2023

Ventral premotor cortex influences spinal cord activation during force generation

Force generation is a crucial element of dexterity and a highly relevant skill of the human motor system. How cerebral and spinal components interact and how spinal activation is influenced by cerebral primary motor and premotor areas is poorly understood. Here we conducted combined cortico-spinal functional MRI during a simple visually guided isometric force generation task in a group of 20 healthy young subjects. Activation was localized in the ipsilateral cervical spinal cord and contralateral primary motor and premotor areas. The main finding is that spinal activation was influenced by ventral premotor cortex activation. Spinal activation was furthermore significantly correlated with primary motor cortex activation while increasing target forces led to an increase in the amount of activation. These data indicate that human premotor areas such as the ventral premotor cortex might be functionally connected to the lower cervical spinal cord contributing to distal upper limb functions, a finding which extends our understanding about human motor function beyond the animal literature.

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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.

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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↗