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Wenderoth, N.

Publications and source records attributed to Wenderoth, N..

At least 37 records · Page 2Linked to original sources

Through the eye to the brain: Modulating LC-mediated arousal via pupil-based neurofeedback

The brains arousal state is controlled by several neuromodulatory nuclei known to substantially influence cognition and mental well-being. Here, we investigate whether human participants can gain volitional control of their arousal state using a pupil-based biofeedback approach. Our approach inverts a mechanism suggested by previous literature that links activity of the locus coeruleus (LC), one of the key regulators of central arousal, and pupil dynamics. We show that pupil-based biofeedback enables participants to acquire volitional control of pupil size. Applying pupil self-regulation systematically modulates activity of the LC and other brainstem structures involved in arousal control. Further, it modulates cardiovascular measures such as heart rate, and behavioural and psychophysiological responses during an oddball task. We provide evidence that pupil-based biofeedback makes the brains arousal system accessible to volitional control, a finding that has tremendous potential for translation to behavioral and clinical applications across various domains, including stress-related and anxiety disorders.

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Neuromodulation of striatal D1 cells shapes BOLD fluctuations in anatomically connected thalamic and cortical regions

Understanding how the brains macroscale dynamics are shaped by underlying microscale mechanisms is a key problem in neuroscience. In animal models, we can now investigate this relationship in unprecedented detail by directly manipulating cellular-level properties while measuring the whole-brain response using resting-state fMRI. Here we focused on understanding how blood-oxygen-level-dependent (BOLD) dynamics, measured within a structurally well-defined striato-thalamo-cortical circuit, are shaped by chemogenetically exciting or inhibiting D1 medium spiny neurons (MSNs) of the right dorsomedial striatum (CPdm). We characterize changes in both the BOLD dynamics of individual cortical and subcortical brain areas, and patterns of inter-regional coupling (functional connectivity) between pairs of areas. Using a classification approach based on a large and diverse set of time-series properties, we found that CPdm neuromodulation alters BOLD dynamics within thalamic subregions that project back to dorsomedial striatum. In the cortex, the strongest changes in local dynamics were observed in unimodal regions, i.e., regions that process information from a single sensory modality, while changes in the local dynamics weakened along a putative cortical hierarchical gradient towards transmodal regions. In contrast, a decrease in functional connectivity was observed only for cortico-striatal connections after D1 excitation. Our results provide a comprehensive understanding of how targeted cellular-level manipulations affect local BOLD dynamics at the macroscale, including the role of a circuits structural characteristics and hierarchical cortical level in shaping those dynamics. These findings contribute to ongoing attempts to understand the influence of structure-function relationships in shaping inter-regional communication at subcortical and cortical levels.

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Transcranial random noise stimulation of the primary visual cortex but not retina modulates visual contrast sensitivity.

Transcranial random noise stimulation (tRNS) has been shown to significantly improve visual perception. Previous studies demonstrated that tRNS delivered over cortical areas acutely enhances visual contrast detection of stimuli when tRNS intensity is optimized for the individual. However, it is currently unknown whether tRNS-induced signal enhancement could be achieved within different neural substrates along the retino-cortical pathway and whether the beneficial effect of optimal tRNS intensities can be reproduced across sessions. In 3 experimental sessions, we tested whether tRNS applied to the primary visual cortex (V1) and/or to the retina improves visual contrast detection. We first measured visual contrast detection threshold (VCT; N=24, 16 females) during tRNS delivery separately over V1 (no tRNS, 0.75, 1, 1.5mA) and over the retina (no tRNS, 0.1, 0.2, 0.3mA), determined the optimal tRNS intensities for each individual (ind-tRNS), and retested the effects of ind-tRNS within the sessions. We further investigated whether we could reproduce the ind-tRNS-induced modulation on a different session (N=19, 14 females). Finally, we tested whether the simultaneous application of ind-tRNS to the retina and V1 causes additive effects. We found that at the group level tRNS of 0.75mA decreases VCT compared to baseline when delivered to the V1. Beneficial effects of ind-tRNS could be replicated when retested within the same experimental session but not when retested in a separate session. Applying tRNS to the retina did not cause a systematic reduction of VCT, irrespective of whether the individually optimized intensity was considered or not. We also did not observe consistent additive effects of V1 and retina stimulation. Our findings demonstrate that V1 seems to be more sensitive than the retina to tRNS-induced modulation of visual contrast processing. Significance statementOur findings confirm previous evidence showing acute online benefits of tRNS of V1 on visual contrast detection in accordance with the stochastic resonance phenomenon. We further extend it, demonstrating that the optimal tRNS intensity varies among participants, but when individually tailored it can improve visual processing when re-tested within the experimental session. The tRNS-induced enhancement in visual sensitivity seems to be specific for cortical contrast processing as stimulation of the retina did not lead to systematic effects.

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Effects of auditory sleep modulation approaches on brain oscillatory and cardiovascular dynamics

Sleep modulation techniques to elucidate the functional role of sleep brain oscillations in brain and body functions have gained large interest. Slow waves, the hallmark feature of deep non-rapid eye movement sleep, do potentially drive restorative effects on brain and cardiovascular functions. Auditory stimulation to modulate slow waves is a promising tool, however, directly comparing different auditory stimulation approaches within a night and analyzing induced dynamic brain and cardiovascular effects are yet missing. Here, we tested various auditory stimulation approaches in a windowed, 10 s ON (stimulations) followed by 10 s OFF (no stimulations), within-night stimulation design and compared them to a SHAM control condition. We report the results of three studies and a total of 51 included stimulation nights. We found a large and global increase in slow wave activity (SWA) in the stimulation window compared to SHAM. Furthermore, slow wave dynamics were most pronouncedly increased at the start of the stimulation and declined across the stimulation window. Beyond the changes in brain oscillations, we observed, for some conditions, a significant increase in the mean interval between two heartbeats within a stimulation window, indicating a slowing of the heart rate, and increased heart rate variability derived parasympathetic activity. Those cardiovascular changes were positively correlated with the change in SWA and thus, our findings provide mechanistic insight into the potential of auditory slow wave enhancement to modulate cardiovascular restorative conditions during sleep. However, future studies need to investigate whether the potentially increased restorative capacity through slow wave enhancements translates into a more rested cardiovascular system on the subsequent day.

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Finger representations in primary somatosensory cortex are modulated during vibrotactile working memory

It is well-established that several cortical areas represent vibrotactile stimuli in somatotopic maps. However, whether such somatotopic representations remain active during the delay period of working memory (WM) tasks, i.e. in the absence of any tactile stimulation, is unknown. In our experiment, participants had to compare two tactile stimuli with different vibration frequencies that were separated by a delay period (memory condition) or they were exposed to identical stimuli but did not have to solve a WM task (no memory condition). Importantly, both vibrotactile stimuli were either applied to the right index or little finger. Analyzing the delay period, we identified a well-known fronto-parietal network of brain regions involved in WM but we did not find WM specific activity in S1. However, using multi-voxel pattern analysis (MVPA) and representational similarity analysis (RSA), we found that S1 finger representations were more dissimilar during the delay period of the WM condition than during the control condition. These results indicate that WM processes modulate the representational geometry of S1 suggesting that some aspects of the tactile WM content are represented in a somatotopic fashion. HIGHLIGHTSO_LIMultivariate approaches were used to identify finger specific representational changes during vibrotactile frequency discrimination. C_LIO_LIVibrotactile working memory modulates somatotopic finger representations in contralateral S1 during the delay period, i.e. in the absence of any tactile stimuli C_LI

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Hand and face somatotopy shown using MRI-safe vibrotactile stimulation with a novel Soft Pneumatic Actuator (SPA)-Skin interface

The exact somatotopy of the human facial representation in the primary somatosensory cortex (S1) remains debated. One reason that progress has been hampered is due to the methodological challenge of how to apply automated vibrotactile stimuli to face areas in a manner that is: 1) reliable despite differences in the curvatures of face locations; and 2) MR-compatible and free of MR-interference artefacts when applied in the MR head-coil. Here we overcome this challenge by using soft pneumatic actuator (SPA) technology. SPAs are made of a soft silicon material and can be in- or deflated by means of airflow, have a small diameter, and are flexible in structure, enabling good skin contact even on curved body surfaces (as on the face). To validate our approach, we first mapped the well-characterised S1 finger layout using this novel device and confirmed that tactile stimulation of the fingers elicited characteristic somatotopic finger activations in S1. We then used the device to automatically and systematically deliver somatosensory stimulation to different face locations. We found that the forehead representation was least distant from the representation of the hand. Within the face representation, we found that the lip representation is most distant from the forehead representation, with the chin represented in between. Together, our results demonstrate that this novel MR compatible device produces robust and clear somatotopic representational patterns using vibrotactile stimulation through SPA-technology.

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Optogenetic Activation of Striatal D1/D2 Medium Spiny Neurons Differentially Engages Downstream Connected Areas Beyond the Basal Ganglia

The basal ganglia (BG) are a group of subcortical nuclei responsible for motor control, motor learning and executive function. Central to BG function are striatal medium spiny neurons (MSNs) expressing D1 and D2 dopamine receptors. D1 and D2 MSNs are typically considered functional antagonists that facilitate voluntary movements and inhibit competing motor patterns, respectively. While their opposite role is well documented for certain sensorimotor loops of the BG-thalamocortical network, it is unclear whether MSNs maintain a uniform functional role across the striatum and which influence they exert on brain areas outside the BG. Here, we addressed these questions by combining optogenetic activation of D1 and D2 MSNs in the mouse ventrolateral caudoputamen (vl CPu) with whole-brain functional MRI (fMRI) recordings. Neuronal excitation of either cell population in the vl CPu evoked distinct activity patterns in key regions of the BG-thalamocortical network including the pallidum, thalamus and motor cortex. Importantly, we report that striatal D1 and D2 MSN stimulation differentially engaged cerebellar and prefrontal regions. We characterised these long-range interactions by computational modelling of effective connectivity and confirmed that changes in D1 / D2 output drive functional relationships between regions within and beyond the BG. These results suggest a more complex functional organization of MSNs across the striatum than previously anticipated and provide evidence for the existence of an interconnected fronto - BG - cerebellar network modulated by striatal D1 and D2 MSNs. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=129 HEIGHT=200 SRC="FIGDIR/small/436576v1_ufig1.gif" ALT="Figure 1"> View larger version (38K): org.highwire.dtl.DTLVardef@a18349org.highwire.dtl.DTLVardef@1b256faorg.highwire.dtl.DTLVardef@16c454aorg.highwire.dtl.DTLVardef@1392b23_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Mental individuation of imagined finger movements can be achieved using TMS-based neurofeedback

Neurofeedback (NF) in combination with motor imagery (MI) can be used for training individuals to volitionally modulate sensorimotor activity without producing overt movements. However, until now, NF methods were of limited utility for mentally training specific hand and finger actions. Here we employed a novel transcranial magnetic stimulation (TMS) based protocol to probe and detect MI-induced motor activity patterns in the primary motor cortex (M1) with the aim to reinforce selective facilitation of single finger representations. We showed that TMS-NF training but not MI training with uninformative feedback enabled participants to selectively upregulate corticomotor excitability of one finger, while simultaneously downregulating excitability of other finger representations within the same hand. Successful finger individuation during MI was accompanied by strong desynchronisation of sensorimotor brain rhythms, particularly in the beta band, as measured by electroencephalography. Additionally, informative TMS-NF promoted more dissociable EEG activation patterns underlying single finger MI, when compared to MI of the control group where no such feedback was provided. Our findings suggest that selective TMS-NF is a new approach for acquiring the ability of finger individuation even if no overt movements are performed. This might offer new treatment modality for rehabilitation after stroke or spinal cord injury.

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Finger somatotopy is preserved after tetraplegia but deteriorates over time

Following spinal cord injury (SCI), the motor output flow to the limb(s) and sensory input to the brain is largely lost. While attempted movements with the paralysed and sensory deprived body part can still evoke signals in the sensorimotor system, this task-related "net" brain activity of SCI patients differs substantially from healthy controls. Such reorganised and/or altered activity is thought to reflect abnormal processing. It is however possible that this altered net sensorimotor activity in SCI patients conceals preserved somatotopically-specific representations of the paralysed and sensory deprived body parts that could be exploited in a functionally meaningful manner (e.g. via neuroprosthetics). In this cross-sectional study, we investigated whether a functional connection between the periphery and the brain is necessary to maintain somatosensory representations. We used functional MRI and an (attempted) finger movement task to characterise the somatotopic hand layout in the primary somatosensory cortex and structural MRI to assess spared spinal tissue bridges. We tested 14 tetraplegic SCI patients (mean age {+/-} s.e.m.=55 {+/-} 3.6; 1 female) who differed in terms of lesion completeness, retained sensorimotor functioning, and time since injury, as well as 18 healthy control participants (mean age {+/-} s.e.m.=56 {+/-} 3.6 years; 1 female). Our results revealed somatotopically organised representations of patients hands in which neighbouring clusters showed selectivity for neighbouring fingers in contralateral S1, qualitatively similar to those observed in healthy controls. To quantify whether these representations were normal in tetraplegic SCI patients we correlated each participants intricate representational distance pattern across all fingers (revealed using representational similarity analysis) with a canonical inter-finger distance pattern obtained from an independent sample. The resulting hand representation typicality scores were not significantly different between patients and controls. This was even true when considering two individual patients with no sensory hand functioning, no hand motor functioning, and no spared spinal tissue bridges. However, a correlational analysis revealed that over years since SCI the hand representation typicality in primary somatosensory cortex deteriorates. We show that somatosensory representations can be maintained for several years following SCI even in the absence of perhiperhal inputs. Such preserved cortical hand representations could therefore be exploited in a functionally meaningful way by rehabilitation approaches that attempt to establish new functional connections between the hand and the brain after an SCI (e.g. through neuroprosthetics). However, time since injury may critically influence the somatotopic representations of SCI patients and might thereby impact the success of such rehabilitation approaches.

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Brain mapping across 16 autism mouse models reveals a spectrum of functional connectivity subtypes

Autism Spectrum Disorder (ASD) is characterized by substantial, yet highly heterogeneous abnormalities in functional brain connectivity. However, the origin and significance of this phenomenon remain unclear. To unravel ASD connectopathy and relate it to underlying etiological heterogeneity, we carried out a bi-center cross-etiological investigation of fMRI-based connectivity in the mouse, in which specific ASD-relevant mutations can be isolated and modelled minimizing environmental contributions. By performing brain-wide connectivity mapping across 16 mouse mutants, we show that different ASD-associated etiologies cause a broad spectrum of connectional abnormalities in which diverse, often diverging, connectivity signatures are recognizable. Despite this heterogeneity, the identified connectivity alterations could be classified into four subtypes characterized by discrete signatures of network dysfunction. Our findings show that etiological variability is a key determinant of connectivity heterogeneity in ASD, hence reconciling conflicting findings in clinical populations. The identification of etiologically-relevant connectivity subtypes could improve diagnostic label accuracy in the non-syndromic ASD population and paves the way for personalized treatment approaches.

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Transcranial Random Noise Stimulation acutely lowers the response threshold of human motor circuits

AO_SCPLOWBSTRACTC_SCPLOWTranscranial random noise stimulation (tRNS) over cortical areas has been shown to acutely improve performance in sensory detection tasks. One explanation for this behavioural effect is stochastic resonance, a mechanism that explains how signal processing in non-linear systems can benefit from added noise. While acute noise benefits of electrical random noise stimulation have been demonstrated at the behavioural level as well as in in vitro preparations of neural tissue, it is currently largely unknown whether similar effects can be shown at the neural population level using neurophysiological readouts of human cortex. Here we hypothesized that acute tRNS will increase the responsiveness of primary motor cortex (M1) when probed with transcranial magnetic stimulation. Neural responsiveness was operationalized via the well-known concept of the resting motor threshold (RMT). We showed that tRNS acutely decreases RMT. This effect was small, but it was consistently replicated across four experiments including different cohorts (total N=81, 46 females, 35 males), two tRNS electrode montages, and different control conditions. Our experiments provide critical neurophysiological evidence that tRNS can acutely generate noise benefits by enhancing the neural population response of human M1. SO_SCPLOWIGNIFICANCEC_SCPLOWO_SCPCAP C_SCPCAPO_SCPLOWSTATEMENTC_SCPLOWA hallmark feature of stochastic resonance is that signal processing can benefit from added noise. This has mainly been demonstrated at the single-cell level in vitro where the neural response to weak input signals can be enhanced by simultaneously applying random noise. Our finding that tRNS acutely increases the excitability of corticomotor circuits extends the principle of noise benefits to the neural population level in human cortex. Our finding is in line with the notion that tRNS might affect cortical processing via the stochastic resonance phenomenon. It suggests that enhancing the response of cortical populations to an external stimulus might be one neurophysiological mechanism mediating performance improvements when tRNS is applied to sensory cortex during perception tasks.

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No modulatory effect of rhythmic visual alpha/gamma stimulation in a bistable motion illusion

The motion quartet, also called stroboscopic alternative motion (SAM), is a bistable apparent motion paradigm where dots are perceived as moving either horizontally or vertically. These two percepts are known to switch randomly depending on both alpha (8 - 12 Hz) and gamma (30 - 80 Hz) oscillations within and between hemispheres, respectively. However, whether these oscillations play a causal role in triggering perceptual switches remains unknown. Here, we aimed to entrain brain oscillations in the visual system by presenting flickering stimuli. Two LEDs were flickering either at 10 Hz, 40 Hz or corresponding jittered stimulation frequencies on the left and right sides of the visual field during the presentation of a motion quartet. In our control condition (no stimulation), we show that interhemispheric gamma connectivity (spectral coherence) between the visual cortices of both hemispheres is important for sensory feature integration. On the other hand, alpha power did not predict perceptual switches for the motion quartet. Rhythmic visual stimulation with 10 Hz and 40 Hz evoked resonance-like neural responses but did not alter visual perception. Thus, although sensory stimuli seem to entrain ongoing brain rhythms, the effect on human behavior differs from the principles observed for endogenous brain oscillations.

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Integration of action value during action observation

Transcranial magnetic stimulation (TMS) studies demonstrated that observing the actions of other individuals leads to action-specific facilitation of primary motor cortex (M1) (i.e., "motor resonance"). Motor resonance is modulated by contextual information accompanying others actions, however, it is currently unknown whether action value influences behavioural and physiological outcomes during action observation in humans. Here we tested whether response times (RT) and muscle-specific changes of M1 excitability are modulated by the value an observer assigns to the action executed by another agent and whether this effect can be distinguished from attentional engagement. We show that observing highly-valued actions leads to a significant decrease in RT variability and a significant strengthening of action-specific neural representations in M1. This "sharpening" of behavioural and neural responses was observed over and beyond a control task requiring similar attentional engagement but did not include any rewards. Our finding that reward influences action specific representations in human M1 even if no motor response is required is new, suggesting that reward influences the transformation of action stimuli from the perceptual to the motor domain. We suggest that premotor areas are important for mediating the observed effect, most likely by optimizing grasp-specific PMv-M1 interactions which cause muscular facilitation patterns in M1 to be more distinct for rewarded actions.

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Primate homologs of mouse cortico-striatal circuits

With the increasing necessity of animal models in biomedical research, there is a vital need to harmonise findings across species by establishing similarities and differences in rodent and primate neuroanatomy. Using a connectivity fingerprint matching approach, we compared cortico-striatal circuits across humans, non-human primates, and mice using resting state fMRI data in all species. Our results suggest that the connectivity patterns for both the nucleus accumbens and cortico-striatal motor circuits (posterior/lateral putamen) were conserved across species, making them reliable targets for cross-species comparisons. However, a large number of human and macaque striatal voxels were not matched to any mouse cortico-striatal circuit (mouse->human: 85% unassigned; mouse->macaque 69% unassigned; macaque->human; 31% unassigned). These unassigned voxels were largely localised to the caudate nucleus and anterior putamen, overlapping with executive function and social/language regions of the striatum, and connected to prefrontal-projecting cerebellar lobules and anterior prefrontal cortex, forming circuits that seem to be unique for non-human primates and humans. Our results demonstrate the potential of connectivity fingerprint matching to bridge the gap between rodent and primate neuroanatomy.

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Modulation of tactile detection threshold with rhythmic somatosensory entrainment

Ongoing neural activity in human somatosensory cortex has a strong impact on the detectability of weak tactile stimuli. Recent studies suggest that brain oscillations, which determine the state of excitability of a cortical area, play a crucial role in this process. Mainly two frequency bands have been reported to be involved in conscious sensory perception: alpha (8 - 12 Hz) and beta (15 - 30 Hz). In addition to correlative findings, more recent studies investigated causality by measuring the extent to which directly modulating brain oscillations affects sensory perception. While most of these studies use transcranial alternating current stimulation (tACS), rhythmic sensory stimulation has been suggested as a simple and safe alternative to entrain ongoing neural activity. However, convincing findings demonstrating the modulation of neural signals and related behavioral function are scarce.\n\nHere, we investigated whether rhythmically induced brain oscillations by means of vibrotactile stimulation (i.e. sensory entrainment) modulate tactile detection. In line with previous findings, we show in trials without sensory entrainment that preceding alpha power and phase-angles in beta oscillations predict the detection rate of a weak tactile stimulus. Further, we reveal a masking effect induced by sensory entrainment stimulation resulting in higher perception thresholds. Intriguingly, we find that the masking effect is modulated by the strength of neural entrainment resulting from 20 Hz stimulation. Our data provide evidence for the possibility to modulate sensory processing with rhythmic sensory stimulation. However, in light of the induced masking effects, the feasibility of this entrainment method to modulate human behavior remains questionable.

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Steady-state responses in the somatosensory system interact with endogenous beta activity

Brain oscillations have been related to many aspects of human behavior. To understand a potential causal relationship, it is of great importance to develop methods for modulating ongoing neural activity. It has been shown that external rhythmic stimulation leads to an oscillatory brain response that follows the temporal structure of the presented stimulus and is assumed to reflect the synchronization of ongoing neural oscillations with the stimulation rhythm. This interaction between individual brain activity and so called steady-state evoked potentials (SSEPs) is the fundamental requirement of neural entrainment. Here, we investigate whether neural responses to rhythmic vibrotactile stimulation, measured with EEG, are dependent on ongoing individual brain oscillations, and therefore reflect entrained oscillatory activity. For this, we measured phase synchronization in response to rhythmic stimulation across various frequencies in the alpha and beta band. Three different stimulation intensities were applied for each frequency relative to the individual sensory threshold. We found that a higher stimulation intensity, compared to lower intensities, resulted in a more pronounced phase synchronization with the stimulation signal. Moreover, EEG responses to low stimulation frequencies closer to individual beta peak frequencies revealed a higher degree of entrainment, compared to stimulation conditions with frequencies that were more distant to endogenous oscillations. Our findings provide evidence that the efficacy of vibrotactile rhythmic beta stimulation to evoke a SSEPs is dependent on ongoing brain oscillations.

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Motor fatigability as evoked by repetitive movements results from a gradual breakdown of surround inhibition

Motor fatigability emerges when demanding tasks are executed over an extended period of time. Here, we used repetitive low-force movements that cause a gradual reduction in movement speed (or \"motor slowing\") to study the central component of fatigability in healthy adults. We show that motor slowing is associated with a gradual increase of net excitability in the motor network and, specifically, in primary motor cortex (M1), which results from overall disinhibition. Importantly, we link performance decrements to a breakdown of surround inhibition in M1, which is associated with high coactivation of antagonistic muscle groups. This is consistent with the model that a loss of inhibitory control might broaden the tuning of population vectors such that movement patterns become more variable, ill-timed and effortful. We propose that the release of inhibition in M1 is an important mechanism underpinning motor fatigability and, potentially, also pathological fatigue as frequently observed in patients with brain disorders.

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Common functional networks in the mouse brain revealed by multi-centre resting-state fMRI analysis

Preclinical applications of resting-state functional magnetic resonance imaging (rsfMRI) offer the possibility to non-invasively probe whole-brain network dynamics and to investigate the determinants of altered network signatures observed in human studies. Mouse rsfMRI has been increasingly adopted by numerous laboratories world-wide. Here we describe a multi-centre comparison of 17 mouse rsfMRI datasets via a common image processing and analysis pipeline. Despite prominent cross-laboratory differences in equipment and imaging procedures, we report the reproducible identification of several large-scale resting-state networks (RSN), including a murine default-mode network, in the majority of datasets. A combination of factors was associated with enhanced reproducibility in functional connectivity parameter estimation, including animal handling procedures and equipment performance. Our work describes a set of representative RSNs in the mouse brain and highlights key experimental parameters that can critically guide the design and analysis of future rodent rsfMRI investigations.

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