Biology subjects

Wenderoth, N.

Publications and source records attributed to Wenderoth, N..

At least 19 recordsLinked to original sources

bioRxiv2026

Centrally generated movement-related signals engage ipsilateral S1 finger representations after tetraplegia

Ipsilateral primary somatosensory cortex (S1) exhibits somatotopically organized activity during unilateral hand movements, but whether this activity depends on peripheral input remains debated. We addressed this question using functional magnetic resonance imaging (fMRI) in 14 individuals with tetraplegia and 18 able-bodied controls. Participants performed or attempted individual finger movements during 3T fMRI. We quantified movement-related univariate activity and multivariate representational structure within ipsilateral S1. Univariate activity within the anatomically defined ipsilateral S1 hand area did not differ significantly between groups, whereas a continuous spatial analysis identified greater movement-related activity in individuals with tetraplegia in S1 bands lateral to the hand representation. Multivariate analyses revealed reliable separation of finger-specific activity patterns in both groups, with no significant group difference in mean inter-finger distance. The typicality of the overall representational geometry also did not differ significantly between groups. Finally, a person with complete hand paralysis and no measurable feeling or movement still showed clear, finger-specific brain activity patterns and a typical representation of the affected hand. Together, these findings indicate that centrally generated movement-related signals can engage finger-specific representations in ipsilateral S1 without overt movement or measurable hand-related peripheral input. Ipsilateral somatotopic activity therefore cannot be explained solely by sensory reafference from the moving hand.

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bioRxiv2026

Video-based eye movements are linked to cortical and pupil-based arousal in human sleep

Study ObjectivesTo quantify high-resolution video-based eye kinematics across sleep macro- and microstructure and determine their coupling with pupil-based and cortical arousal markers. MethodsWe recorded polysomnography and utilized infrared video-based eye-tracking in 17 healthy adults. Computer vision was employed to extract eye position and speed, which were related to pupil size (subcortical arousal marker) and EEG spectral slope (cortical arousal marker) across sleep stages, rapid eye movement (REM) substates, and K-complexes. ResultsEye kinematics varied significantly across sleep stages (p<0.001), except for horizontal pupil position (p=0.192). Video-based eye position and speed are sufficient to classify stages with above chance level accuracy (47%). Eye movement speed positively correlated with pupil size during non-REM sleep (R[≥]0.21, p<0.001) and with spectral slope during wakefulness and REM sleep (R[≥]0.11, p<0.018). These strengths of the correlations differ depending on the direction of the eye movement. Phasic REM exhibited faster eye movements, larger pupil size (p<0.001), and a flatter spectral slope (p=0.014) compared to tonic REM, indicating elevated subcortical and cortical arousal. K-complexes were accompanied by increased eye movement speed (p<0.05) and a steeper spectral slope (p[≤]0.010), suggesting a transient shift toward a sleep-protective cortical state despite concurrent oculomotor activation. ConclusionsVideo-based eye-tracking reveals that eye movements are quantitatively coupled to brain-wide arousal fluctuations in a state-dependent manner. This methodology provides a ground-truth framework for resolving fine-grained eye dynamics during sleep, offering a high-fidelity tool for sleep phenotyping and clinical assessment. Statement of significanceTraditional sleep monitoring relies on low-resolution electrical signals that often confound true eye movements with brain or muscle activity. This study uses high-resolution video tracking to establish a physical ground truth for eye kinematics across human sleep. We demonstrate that eye movements are coupled with both cortical and subcortical arousal levels in a state-dependent manner, providing a clearer neurophysiological distinction between, for example, sleep substates like tonic and phasic REM. This framework reveals how the eyes serve as a non-invasive window into the brains internal arousal state. Such insights address critical gaps in understanding sleep microarchitecture and offer a novel pathway for developing high-fidelity biomarkers for neurological disorders, such as Parkinsons disease, characterized by disrupted sleep-related arousal.

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bioRxiv2026

Top-down processing alone activates the early somatosensory nuclei

The early somatosensory brainstem and thalamic nuclei are classically viewed as relays of peripheral input, yet research in animal models indicates they also receive top-down cortical signals. Whether such processing exists in humans remains unknown. Using cervical spinal cord injury (SCI), in which peripheral somatosensory input is reduced or absent while cortical processing is preserved, we tested whether top-down processing can elicit activation across the somatosensory nuclei. We combined 3 Tesla functional and quantitative MRI data to assess activity and structural properties along the somatosensory hand pathway in a cross-sectional study of 16 individuals with chronic cervical SCI (mean age {+/-} s.e.m.=52.4 {+/-} 3.5 years) and 20 age-, sex-, and handedness-matched able-bodied control subjects (mean age=50.8 {+/-} 3.5 years). Participants were visually cued to make overt or, in cases of hand paralysis, attempted right- and left-hand movements. Activation was quantified across the cuneate nucleus, ventroposterior lateral thalamus, and primary somatosensory hand cortex, while structural properties were assessed using quantitative MRI measures sensitive to myelin and tissue integrity, including magnetisation transfer saturation (MTsat) and effective transverse relaxation rate (R2*), alongside morphometric measures. Despite reduced or absent peripheral input, SCI participants exhibited robust and lateralised activation across all levels of the somatosensory pathway. This pattern persisted even in a participant with complete hand paralysis who lacked bottom-up afferent input during the fMRI task, indicating that top-down processing alone is sufficient to drive activity in early somatosensory relays. We simultaneously observed structural degeneration in the cuneate nucleus of SCI participants, marked by reduced volume and myelin-sensitive metrics (MTsat and R2*), consistent with secondary degeneration. The extent of atrophy was related to time since injury and reduced sensorimotor hand function, but showed no significant relationship with functional activation, suggesting that preserved corticocuneate signalling is not dependent on the degree of structural degeneration. This provides the first evidence that the cuneate nuclei in humans are subject to both bottom- up and top-down somatosensory processing. Although these nuclei are vulnerable to structural atrophy following dorsal column injury, our results suggest that top-down processing remains intact decades after SCI. This may have implications for the development of rehabilitation treatments targeting preserved somatosensory processing after injury.

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bioRxiv2026

Reward Reduces Motor Fatigability by Increasing Movement Vigour

Reward can enhance motor performance. However, its potential to counteract motor fatigability, a reduction in motor performance during sustained movements, remains underinvestigated. This could be particularly relevant in neurological conditions such as multiple sclerosis, where increased motor fatigability is a prominent symptom. One form of motor fatigability is motor slowing, a decline in movement speed over time evoked by fast, repetitive movements. In this study, we investigated whether the possibility to earn reward attenuates motor slowing, and examined associated changes in muscle activity and pupil size, a putative marker of physical effort. Participants performed a wrist tapping task at maximal voluntary speed with or without the possibility of earning a reward. We found that wrist tapping induced motor slowing and that slowing was significantly reduced by reward. Over time, tapping became more costly as indicated by higher muscle activity and coactivation per tap. This was accompanied by a sustained pupil dilation, which could not solely be explained by tapping speed. These findings suggest that, rather than restoring efficient motor control, reward attenuates motor slowing by allowing participants to access a performance reserve and invest more resources into the task, reflected by increased muscle activation per tap and sustained pupil dilation.

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bioRxiv2025

Transcutaneous auricular vagus nerve stimulation during movement modulates motor neural circuitry without widespread cortical or autonomic activation

Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising neuromodulatory approach for treating neurological disorders, with growing interest in its potential to support motor rehabilitation. Yet, its mechanisms of action, potentially influenced by behavioral context, remain elusive. This sham-controlled study investigated transient taVNS interactions with movement in healthy adults, focusing on autonomic, neuromodulatory, and motor circuits. During a finger-tapping paradigm, heart rate (HR), galvanic skin response (GSR), pupil diameter, and electroencephalography (EEG) were recorded to probe movement-dependent stimulation effects. This study first identified a novel physiological dissociation: all measures responded to movement, but taVNS did not significantly alter HR, GSR, or general EEG spectral slope; taVNS increased pupil diameter in both conditions, but enhanced sensorimotor EEG spectral slope solely during movement. This context-specific effect on motor systems was further supported by a transcranial magnetic stimulation (TMS) experiment demonstrating increased corticospinal excitability during taVNS. These findings provide mechanistic insights into how taVNS may selectively enhance motor system responsiveness during active states, supporting future exploration of behaviorally paired stimulation protocols for neurorehabilitation.

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bioRxiv2025

Revisiting face-to-hand area remapping in the human primary somatosensory cortex after a cervical spinal cord injury

Spinal cord injury (SCI) leads to profound disruptions in sensorimotor processing. Seminal research in non-human primates suggests this sensory deprivation causes functional remapping in the primary somatosensory cortex (S1), where somatotopic representations of deprived body parts, such as the hand in cervical SCI, become responsive to touch on intact body parts, such as the face. However, evidence for such remapping in humans remains inconclusive. We investigated face-to-hand remapping in 16 chronic cervical SCI patients and 21 able-bodied controls using two fMRI experiments. Experiment 1 employed a lip movement task, while Experiment 2 investigated the full architecture of S1 face reorganisation through vibrotactile stimulation of the forehead, lips and chin. We assessed (1) the level of face activity in the anatomical S1 hand area, (2) cortical shifts in peak face activity, (3) face-part separability in the S1 hand area and (4) correlations with clinical characteristics that may drive face-to-hand area remapping. Our results revealed no significant evidence in favour of face-to-hand area remapping in tetraplegic patients across markers of face-to-hand remapping during either lip movement or vibrotactile stimulation of face parts. Furthermore, our markers of remapping did not correlate with clinical characteristics. These findings suggest that cortical face-to-hand remapping is not apparent in human cervical SCI patients. Beyond providing insight into the limitations of cortical reorganisation in humans, this highlights the need to reassess rehabilitation strategies based on the assumption of large-scale face-to-hand reorganisation after an SCI.

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bioRxiv2025

Biological subtyping of autism via cross-species fMRI

It is frequently assumed that the phenotypic heterogeneity in autism spectrum disorder reflects underlying pathobiological variation. However, direct evidence in support of this hypothesis is lacking. Here, we leverage cross-species functional neuroimaging to examine whether variability in brain functional connectivity reflects distinct biological mechanisms. We find that fMRI connectivity alterations in 20 distinct mouse models of autism (n=549 individual mice) can be clustered into two prominent hypo- and hyperconnectivity subtypes. We show that these connectivity profiles are linked to distinct signaling pathways, with hypoconnectivity being associated with synaptic dysfunction, and hyperconnectivity reflecting transcriptional and immune-related alterations. Extending these findings to humans, we identify analogous hypo- and hyperconnectivity subtypes in a large, multicenter resting state fMRI dataset of n=940 autistic and n=1036 neurotypical individuals. Remarkably, hypo- and hyperconnectivity autism subtypes are replicable across independent cohorts (accounting for 25.1% of all autism data), exhibit distinct functional network architecture, are behaviorally dissociable, and recapitulate synaptic and immune mechanisms identified in corresponding mouse subtypes. Our cross-species investigation, thus, decodes the heterogeneity of fMRI connectivity in autism into distinct pathway-specific etiologies, offering a new empirical framework for targeted subtyping of autism.

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bioRxiv2024

Motor imagery and execution activate similar finger representations that are spatially consistent over time

Finger representations in the sensorimotor cortex can be activated even in the absence of somatosensory input or motor output through mere top-down processes, such as motor imagery. While executed finger movements activate finger representations in the primary sensorimotor cortex that are spatially consistent over time within participants, the stability of top-down activated finger representations remains largely unexplored. Given the increasing use of top-down activated sensorimotor representations to both plan implantation of and control brain-computer interfaces, it is crucial to understand the stability of these representations. Here, we investigated the spatial consistency, and thereby reliability, of finger representations activated through motor imagery in the primary somatosensory and primary motor cortex over time. To assess this, participants performed imagined and executed individual finger movements in two 3T fMRI sessions that were [~]2 weeks apart. We observed highly consistent univariate finger-selective activity clusters and multivariate vertex-wise activity patterns within participants over time in both the motor imagery and motor execution task. Using a multivariate across-task decoding approach, we further found that motor execution and motor imagery activate similar finger representations in both the primary somatosensory and primary motor cortex. This demonstrates that motor imagery can be used to identify finger representations related to movement execution. Our findings not only validate the use of top-down processes for brain-computer interface planning and control, but also open up new opportunities for the development of sensorimotor training interventions that do not rely on overt movements.

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bioRxiv2024

Distinguishing the activity of adjacent somatosensory nuclei within the brainstem using 3T fMRI

Experimental evidence in animal models indicates that the brainstem plays a major role in sensory modulation. However, mapping functional activity within the human brainstem presents many methodological challenges. These constraints have deterred essential research into human sensory brainstem processing. Here, using a 3T fMRI sequence optimised for the brainstem, combined with uni- and multivariate analysis approaches, we investigated the extent to which functional activity of neighbouring somatosensory nuclei can be delineated in the brainstem, thalamus and primary somatosensory cortex (S1). Whilst traditional univariate approaches offered limited differentiation between adjacent hand and face activation in the brainstem, multivariate classification enabled above-chance decoding of these activity patterns across S1, the thalamus, and the brainstem. Our findings establish a robust methodological approach to explore signal processing within the brainstem and across the entire somatosensory stream. This is a fundamental step towards broadening our understanding of somatosensory processing within humans and determining what changes in sensory integration may occur in clinical populations following sensory deprivation.

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bioRxiv2024

Pupil self-regulation modulates markers of cortical excitability and cortical arousal

The brains arousal state (i.e., central arousal) is regulated by multiple neuromodulatory nuclei in the brainstem and significantly influences high-level cognitive processes. By exploiting the mechanistic connection between the locus coeruleus (LC), a key regulator of central arousal, and pupil dynamics, we recently demonstrated that participants can gain volitional control over arousal-regulating centers including the LC using a pupil-based biofeedback approach. Here, we test whether pupil-based biofeedback modulates electrophysiological markers of cortical excitability, cortical arousal, and phasic LC activity. Combining pupil-based biofeedback with single-pulse TMS, EEG recordings, and an auditory oddball task revealed three main results: pupil self-regulation significantly modulates (i) cortical excitability, (ii) the EEG spectral slope, a marker of cortical arousal, and (iii) the P300 response to target tones, an event-related potential suggested to be tightly linked to phasic LC activity. Interestingly, pupil self-regulation strength was linearly linked to the modulation of the spectral slope, suggesting a common physiological mechanism. Here, we have shown that pupil-based biofeedback modulates fundamental aspects of brain function. Whether this method could further be used to modulate these aspects in case of disturbances associated with neurological and psychiatric disorders needs to be investigated in future studies.

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bioRxiv2024

TMS-based neurofeedback training of mental finger individuation induces neuroplastic changes in the sensorimotor cortex

Neurofeedback (NF) training based on motor imagery is increasingly used in neurorehabilitation with the aim to improve motor functions. However, the neuroplastic changes underpinning these improvements are poorly understood. Here, we used mental finger individuation, i.e., the selective facilitation of single finger representations without producing overt movements, as a model to study neuroplasticity induced by NF. To enhance mental finger individuation, we used transcranial magnetic stimulation (TMS)-based NF training. During motor imagery of individual finger movements, healthy participants were provided visual feedback on the size of motor evoked potentials, reflecting their finger-specific corticospinal excitability. We found that TMS-NF improved the top-down activation of finger-specific representations. First, intracortical inhibitory circuits in the primary motor cortex were tuned after training such that inhibition was selectively reduced for the finger that was mentally activated. Second, motor imagery finger representations in sensorimotor areas assessed with functional MRI became more distinct after training. Together, our results indicate that the neural underpinnings of finger individuation, a well-known model system for neuroplasticity, can be modified using TMS-NF guided motor imagery training. These findings demonstrate that TMS-NF induces neuroplasticity in the sensorimotor system, highlighting the promise of TMS-NF on the recovery of fine motor function.

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bioRxiv2024

Cardiovascular responses to natural and auditory evoked slow waves predict post-sleep cardiac function

The interplay between slow-wave sleep and cardiovascular health is increasingly recognized. Our prior research showed that auditory-enhanced slow waves can boost cardiac function, yet the mechanisms behind this remain unclear. Advancing these findings, our current analysis dissected the effects of two slow wave types on cardiovascular function, using data from 18 middle-aged men across three nights. We found that the strength of heart rate and blood pressure responses concurrent with slow waves predicts cardiac function post-sleep. Notably, we identified that highly synchronized type I slow waves, as opposed to lower-amplitude type II slow waves, primarily co-occur with these cardiovascular pulsations. While auditory stimulation enhances both types of slow waves, they exhibit distinct temporal dynamics, pointing to different underlying biological mechanisms. This study crucially addresses how distinct slow wave types can affect cardiovascular function, implying that targeted slow wave stimulation could be a strategic approach to improve heart health.

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bioRxiv2024

Functional-based parcellation of the mouse prefrontal cortex for network perturbation analysis

The prefrontal cortex (PFC) is a region of the brain involved in higher-order cognitive processes such as attention, emotional regulation, and social behavior, making it a hotspot for an ongoing clinical and fundamental research. Importantly, its functionality is intricately interconnected within a wide array of functional networks encompassing multiple other brain areas. However, the delineation of distinct subdivisions within the mouse PFC and their contributions to the broader brain network function remain topics of ongoing debate. In the current study, we used resting-state functional magnetic resonance imaging (rsfMRI) from a large cohort of wildtype animals to derive the functional-connectivity (FC) based parcellation of the mouse PFC with voxel resolution. Our findings indicate the presence of FC-based clusters that deviate from the established anatomical subdivisions within the cingulate and prelimbic areas, while they align in infralimbic and orbital cortices. To further underscore the association of these FC-based clusters with distinct functional networks, we performed network-specific perturbations using chemogenetics in the identified clusters in dorsal PFC and monitor the elicited effects with fMRI (chemo-fMRI). Our recordings revealed that FC perturbations were observed only within the functional networks linked to the targeted clusters and did not spread to neighbouring anatomical areas or functional clusters. We propose that FC-based parcellation is a valuable approach for tracking the impact of external activations and confirming the precise site of activation. O_FIG O_LINKSMALLFIG WIDTH=127 HEIGHT=200 SRC="FIGDIR/small/586664v1_ufig1.gif" ALT="Figure 1"> View larger version (19K): org.highwire.dtl.DTLVardef@11d4042org.highwire.dtl.DTLVardef@165cb5forg.highwire.dtl.DTLVardef@b0a4aorg.highwire.dtl.DTLVardef@d093c9_HPS_FORMAT_FIGEXP M_FIG C_FIG

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bioRxiv2023

Dynamic Causal Modelling Highlights the Importance of Decreased Self-Inhibition of the Sensorimotor Cortex in Motor Fatigability

Motor fatigability emerges when challenging motor tasks must be maintained over an extended period of time. It is a frequently observed phenomenon in everyday life which affects patients as well as healthy individuals. Motor fatigability can be measured using simple tasks like finger tapping at maximum speed for 30s. This typically results in a rapid decrease of tapping frequency, a phenomenon called motor slowing. In a previous study (Bachinger et al. 2019), we showed that motor slowing goes hand in hand with a gradual increase of activation in the primary sensorimotor cortex (SM1), supplementary motor area (SMA), and dorsal premotor cortex (PMd). Previous electrophysiological measurements further suggested that the increase in SM1 activity might reflect a breakdown of inhibition and, particularly, a breakdown of surround inhibition which might have led to heightened coactivation of antagonistic muscles. It is unclear what drives the activity increase in SM1 caused by motor slowing and whether motor fatigability affects the dynamic interactions between SM1 and upstream motor areas like SMA and PMd. Here, we performed dynamic causal modelling to answer this question. Our main findings revealed that motor slowing was associated with a significant reduction in SM1 self-inhibition which is in line with previous electrophysiological results. Additionally, the model revealed a significant decrease in the driving input to premotor areas suggesting that structures other than cortical motor areas might cause motor fatigability.

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bioRxiv2023

Pupil size reveals arousal level dynamics in human sleep

Recent animal research has revealed the intricate dynamics of arousal levels that are potentially crucial for maintaining proper sleep resilience and memory consolidation. Also in humans, changes in arousal level are believed to be a determining characteristic of healthy and pathological sleep but tracking arousal fluctuations has been methodologically challenging. Here we measured pupil size, an established indicator of arousal levels, during overnight sleep and tested whether the arousal level affects cortical response to auditory stimulation. We show that pupil size dynamics change as a function of sleep macrostructure and microstructural events. In particular, pupil size is inversely related to the occurrence of sleep spindle clusters, a marker of sleep resilience. Additionally, pupil size prior to auditory stimulation influences the evoked response, most notably in delta power, a marker of several restorative and regenerative functions of sleep. Recording pupil size dynamics provides novel insights into the interplay between arousal levels and sleep oscillations, opening new avenues for future research and clinical applications in diagnosing and treating pathological sleep associated with abnormal arousal levels.

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bioRxiv2022

Contrast detection is enhanced by non-stochastic, high-frequency transcranial alternating current stimulation with triangle and sine waveform.

Stochastic Resonance (SR) describes a phenomenon where an additive noise (stochastic carrier-wave) enhances the signal transmission in a nonlinear system. In the nervous system, nonlinear properties are present from the level of single ion channels all the way to perception and appear to support the emergence of SR. For example, SR has been repeatedly demonstrated for visual detection tasks, also by adding noise directly to cortical areas via transcranial random noise stimulation (tRNS). We mathematically show that high-frequency, non-stochastic, periodic signals can yield resonance-like effects with linear transfer and infinite signal-to-noise ratio at the output. Here we tested this prediction empirically and investigated whether non-random, high-frequency, transcranial alternating current stimulation (hf-tACS) applied to visual cortex could induce resonance-like effects and enhance performance on a visual detection task. We demonstrated in 28 participants that applying 80 Hz triangular-waves or sine-waves with hf-tACS reduced visual contrast detection threshold for optimal brain stimulation intensities. The influence of hf-tACS on contrast sensitivity was equally effective to tRNS-induced modulation, demonstrating that both hf-tACS and tRNS can reduce contrast detection thresholds. Our findings suggest that a resonance-like mechanism can also emerge when non-stochastic electrical waveforms are applied via hf-tACS. New & NoteworthyOur findings extend our understanding of neuromodulation induced by noninvasive electrical stimulation. We provide first evidence showing acute online benefits of hf-tACStriangle and hf-tACSsine targeting the primary visual cortex (V1) on visual contrast detection in accordance with the resonance-like phenomenon. The non-stochastic hf-tACS and stochastic hf-tRNS are equally effective in enhancing visual contrast detection.

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bioRxiv2022

Prior information improves tactile representation in primary somatosensory cortex

Perception and adaptive decision making rely on the integration of incoming sensory input with prior knowledge or expectations. While tactile stimuli play a significant role in shaping our perception and decision making, if and how prior information modulates the representation of tactile stimuli in early somatosensory cortices is largely unknown. Here, we employed functional magnetic resonance imaging (fMRI) and a vibrotactile detection paradigm to study the effect of prior information on tactile perception and tactile stimulus representation in early somatosensory areas. The supra-voxel somatotopic organization of early somatosensory areas allowed us to assess the effect of prior information on finger-specific representations. We found that vibrotactile stimuli congruent with expectations are associated with improved vibrotactile detection performance and a decrease of the mean blood-oxygen-level-dependent (BOLD) signal in the contralateral primary somatosensory cortex (S1). Concurrently, finger-specific activity associated with anticipated vibrotactile stimulation revealed higher multivariate decoding accuracies and better alignment with S1s somatotopic organization. In addition, we observed that prior information induced somatotopically organized activity in contralateral S1 even before tactile stimulation onset. The accuracy of the multivariate decoding of stimulus-specific expectations was therefore strongly associated with upcoming behavioral detection performance. Thus, our results reveal a role for S1 in the integration of upcoming tactile stimuli with prior information based on its somatotopic organization as well as the presence of behaviorally relevant activity in S1 before stimulation onset.

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bioRxiv2022

Locus Coeruleus firing patterns selectively modulate brain activity and dynamics

Noradrenaline (NA) release from the brainstem nucleus locus coeruleus (LC) changes activity and connectivity in neuronal networks across the brain, thus modulating multiple behavioural states. NA release is mediated by both tonic and burst-like neuronal LC activity. However, it remains unknown whether the functional changes in downstream projection areas depend on these firing patterns. Using optogenetics, pupillometry, photometry, and functional MRI in mice, we show that tonic and burst LC firing patterns elicit brain responses that are specific to the activation frequency and temporal pattern. Tonic activation of the LC evokes nonlinear responses in prefrontal, limbic, and cerebellar regions, in line with the proposed inverted-U relationship between LC activity and behaviour. We further demonstrate that LC activity enhances network integration and acts as a facilitator of brain state transitions, hence increasing brain flexibility. Together, these findings reveal how the LC-NA system achieves a nuanced regulation of global circuit operations.

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