Biology subjects

Duque, J.

Publications and source records attributed to Duque, J..

At least 19 recordsLinked to original sources

bioRxiv2026

Phasic arousal sharpens, rather than amplifies, goal-dependent feedback control

Voluntary movements tolerate variability that does not threaten the goal: when reaching toward a wide target the hand can drift sideways, whereas a narrow target demands tighter control. The nervous system enforces this through corrective feedback responses that scale with task demands, yet how this scaling is set remains unclear. Arousal is a candidate, but how it would act is contested: the classical view casts it as a global amplifier that raises neural gain uniformly, whereas a more recent account holds that it is selective, strengthening task-relevant signals while suppressing others. These accounts make opposite predictions for goal-dependent feedback control, which we tested causally. In 27 human participants (24 {+/-} 2.7 years old) reaching toward narrow or wide targets on a KINARM robot, a 4-second pulsed train of transcutaneous auricular vagus nerve stimulation (taVNS) evoked a phasic boost of arousal before each movement, confirmed by pupil dilation. On a subset of trials the robot applied a mechanical perturbation during the reach, and we measured the corrective muscle activity it evoked in the short- and long-latency reflex windows. The results favored the selective account. Phasic arousal sharpened corrections to the goal: it amplified the difference between narrow and wide responses in the long-latency window, the established readout of goal-dependent control, and suppressed the short-latency response, normally insensitive to the goal, specifically for the wide target, where deviations are harmless. Phasic arousal therefore does not energize the motor system indiscriminately but allocates corrective control to where it serves the task, extending the principle of selective gain, established in perception and memory, to the online control of movement.

neuroscience↗

bioRxiv2026

Motor implementation of control and reward-based urgency regulation across impulsivity

Everyday decisions unfold dynamically, with commitment shaped by a growing sense of urgency that can, when excessive, contribute to impulsive choices. Here we aimed at dissociating two modes of urgency regulation, control-driven (accuracy-oriented) and reward-driven (motivation-based), and asked whether their relative influence varies across individuals differing in impulsivity. We further investigated how these regulatory modes are implemented in the motor system, focusing on two modulatory effects: surround inhibition and broad modulation. Healthy participants, whose impulsivity was assessed with the UPPS urgency dimension, performed a modified Tokens task crossing control demands (low vs high control blocks) with motivational context (low vs high reward trials). In two separate sessions, single-pulse TMS was applied either over the hand motor representation to probe corticospinal excitability indexing surround inhibition, or over the leg representation to index broad modulations of motor activity. This design successfully dissociated the two regulatory modes: control-driven adjustments (across blocks) were most evident in less impulsive participants, whereas reward-driven adjustments (across trials) were most evident in more impulsive participants. Consistent with this dissociation, control-driven urgency regulation was associated with broad modulation of motor activity, whereas reward-driven urgency adjustments were associated with changes in surround inhibition. These motor signatures may serve as probes of the respective contributions of control- and reward-driven regulation even when they are not explicitly dissociated. Our findings suggest that impulsivity may not simply reflect "more urgency" but a different weighting of the influences that shape it during decision making, a hypothesis that can now be tested in clinical conditions.

neuroscience↗

bioRxiv2025

Short trains of transcutaneous vagus nerve stimulation increase online corticospinal excitability and pupil size in humans

BackgroundTranscutaneous vagus nerve stimulation (tVNS) has emerged as a method for interrogating the role of the locus coeruleus (LC) norepinephrine system in human behavior. Tuning of excitability in the corticospinal tract is central to many cognitive and motor processes, but little is known about how the LC contributes to this tuning. In particular, no existing studies have examined the effect of tVNS on corticospinal excitability "online" during active stimulation, where the largest effects on pupil size are observed. MethodTo address this question, we delivered repeated 4-second trains of tVNS and sham stimulation and elicited MEPs during stimulation trains (online) and shortly after train offset (offline). Pupil size was concurrently recorded throughout each train. ResultsWe discovered that tVNS significantly increases corticospinal excitability compared to sham stimulation, but only when measured online and not offline. The excitatory effects on corticospinal excitability were greater in the latter half of tVNS trains. Pupil size was also significantly increased by tVNS compared to sham; however, the effect on pupil size peaked earlier during the tVNS trains compared to corticospinal excitability. In line with these distinct temporal profiles, changes in corticospinal excitability and pupil size were not significantly correlated, likely reflecting differences in the anatomical circuits underpinning each effect. ConclusionsThis work demonstrates for the first time that tVNS increases corticospinal excitability at rest, but the effect only emerges when corticospinal excitability is measured online during active tVNS. Implications for basic and clinical neuroscientific research are discussed.

neuroscience↗

bioRxiv2025

White matter microstructure predicts effort and reward sensitivity

From rodents to humans, animals constantly face a central question: is the reward worth the effort? Effort and reward sensitivity in such situations vary substantially across individuals and ultimately shape goal-directed behavior. Yet, the brain mechanisms underlying this variability across individuals remain unclear. Here, we combined computational modeling of effort and reward sensitivity during decision-making with whole-brain diffusion MRI in 45 healthy participants to identify white matter substrates of individual sensitivity. A data-driven, cluster-based analysis of fractional anisotropy and mean diffusivity revealed 12 clusters: five linked to effort sensitivity, all within tracts connected to major frontal valuation nodes (e.g., supplementary motor area [SMA], dorsal anterior cingulate cortex [dACC], orbitofrontal cortex [OFC]), and seven linked to reward sensitivity, spanning frontal valuation, fronto-parietal, and sensorimotor networks. The strongest associations involved two SMA-connected clusters, one shared across effort and reward sensitivity and another consistent across both microstructural metrics. Critically, microstructural features from the five effort-related and seven reward-related clusters reliably predicted individual effort and reward sensitivity in out-of-sample machine learning analyses, respectively, whereas randomly sampled clusters did not. SMA-connected tracts were the dominant predictors in these decoding analyses, with additional contributions from fronto-parietal and sensorimotor pathways for reward sensitivity. These findings reveal a distributed white matter architecture underlying inter-individual differences in effort and reward sensitivity, with SMA pathways emerging as central hubs. They demonstrate that localized white matter microstructure can robustly predict these individual differences, offering a framework to forecast the impact of lesions or interventions on goal-directed behavior, including apathy and impulsivity. SIGNIFICANCE STATEMENTWhy do some people give up easily when faced with high effort demands, while others persist even when rewards are small? Such differences in effort and reward sensitivity shape goal-directed behavior, yet their neural basis is unclear. Using diffusion MRI and computational modeling, we show that white matter microstructure in specific pathways reliably predicts individual differences in these sensitivities. Tracts connected to the supplementary motor area emerged as central hubs, with additional contributions from fronto-parietal and sensorimotor networks. These results demonstrate that variability in effort and reward sensitivity is rooted not only in brain activity but also in structural connectivity, providing a framework to anticipate how white matter lesions or interventions may alter goal-directed behavior, including apathy and impulsivity.

neuroscience↗

bioRxiv2025

Non-invasive Stimulation of Contralateral Primary Motor Cortex Reduces the Amount of Skill Generalization to the Untrained Arm

Successfully learned motor skills can generalize or transfer to the untrained arm. The neural substrate underlying such intermanual/interlimb generalization of newly acquired skill memory is unclear. Here, we focused on contralateral primary motor cortex (cM1) which is considered a key brain area for skill learning and memory consolidation. We probed the causal role of cM1 in intermanual skill generalization in a two-day study involving right-handed young individuals (n=31) who learned a novel motor skill reaching task. Immediately following (right-arm) learning, we delivered low-frequency (1Hz, 1800 pulses) repetitive transcranial magnetic stimulation (rTMS) to target left cM1 in one group of individuals (n=15), while another group (n=16) served as an active control in which ipsilateral M1 (iM1) was targeted. On the same day we measured corticospinal excitability (CSE) to assess learning-induced and rTMS-induced neuroplastic changes occurring in the targeted M1s. Next day after 24-hours, both groups were tested for intermanual skill generalization (left-arm), followed by a brief test of intralimb retention (right-arm). Our results show that stimulating cM1, versus iM1, reduced the amount of generalization to the untrained arm on the next day, without affecting its (re)learning ability or the follow-up retention performance of the trained arm. Further, rTMS stimulation induced a net facilitation in CSE- with higher facilitation tending to correlate to lower generalization in a subset of high learners in cM1 group. Taken together, this study highlights the role of cM1 in skill generalization such that it seems to mediate the early transfer of learning to the untrained arm. NEW AND NOTEWORTHYIntermanual skill generalization from trained to the untrained arm is causally mediated by the contralateral (trained) primary motor cortex (cM1) as opposed to the ipsilateral (untrained) motor cortex. Low-frequency stimulation of M1 in our study led to a facilitation of corticospinal excitability, while impairing the amount of skill generalization in the cM1 group. This highlights a rather paradoxical and opposite effect of non-invasive brain stimulation, such as rTMS, on motor behavior and associated motor excitability. Our data also suggest involvement of additional brain areas for such motor skill behavior that were rendered unperturbed by rTMS in this case and, thus, contributed to an overall positive skill performance achieved by both arms the next day.

neuroscience↗

bioRxiv2025

Transcutaneous Vagus Nerve Stimulation boosts evidence accumulation during perceptual decision-making

The locus coeruleus-norepinephrine (LC-NE) system has been implicated in perceptual decision-making, but its causal contribution and underlying mechanisms in humans remain unclear. Here, we used transcutaneous vagus nerve stimulation (tVNS) to modulate LC-NE activity during a random dot motion task, with stimulation delivered at three distinct time points across groups, each targeting different stages of LC-NE engagement during the task. tVNS reliably increased pupil-linked LC-NE activity across all groups. Notably, early stimulation, at a time when LC-NE activity was still at baseline, elicited a more sustained pupil dilation that extended into the decision phase, resulting in comparable pupil responses during decision-making across groups. For behavior, tVNS selectively improved decision accuracy in contexts characterized by initially low performance, without affecting response times. Drift diffusion modeling revealed that this improvement was specifically associated with increased drift rate, consistent with more efficient evidence accumulation with tVNS. These effects were consistent across groups but most pronounced when tVNS was applied at the early time point. Our results provide causal evidence that tVNS enhances decision-making in a state-dependent manner, likely by stabilizing attentional engagement and facilitating evidence accumulation when endogenous control is suboptimal.

neuroscience↗

bioRxiv2025

CRISPR RiPCA for Investigating eIF4E-m7GpppX Capped mRNA Interactions

Post-transcriptional modifications expand the information encoded by an mRNA. These dynamic and reversible modifications are specifically recognized by reader RNA-binding proteins (RBPs), which mediate the regulation of gene expression, RNA processing, localization, stability, and translation. Given their crucial functions, any disruptions in the normal activity of these readers can have significant implications for cellular health. Consequently, the dysregulation of these RBPs has been associated with neurodegenerative disorders, cancers, and viral infections. Therefore, there has been growing interest in targeting reader RBPs as a potential therapeutic strategy since developing molecules that restore proper RNA processing and function may offer a promising avenue for treating diseases. In this work, we coupled our previously established live-cell RNA-protein interaction (RPI) assay, RNA interaction with Protein-mediated Complementation Assay (RiPCA), with CRISPR technology to build a new platform, CRISPR RiPCA. As a model for development, we utilized the interaction of eukaryotic translation initiation factor 4E (eIF4E), a reader RBP that binds to the m7GpppX cap present at the 5' terminus of coding mRNAs, with an m7G capped RNA substrate. Using eIF4E CRISPR RiPCA, we demonstrate our technologys potential for measuring on-target activity of inhibitors of the eIF4E RPI of relevance to cancer drug discovery.

cell biology↗

bioRxiv2025

Dual targeting of transferrin receptor and CD98hc enhances brain exposure of large molecules

Targeting proteins highly expressed at the blood-brain barrier, including transferrin receptor (TfR) and CD98hc, is a transformative approach enabling more effective brain delivery of biotherapeutics for treatment of neurological diseases. TfR-mediated delivery promotes rapid, high brain uptake, while CD98hc-mediated delivery is slower with more prolonged exposure. Here, we engineer a huIgG Fc domain to bind both TfR and CD98hc to create a dual transport vehicle (TV) platform that drives distinct brain delivery properties. Dual TVs achieve significantly higher brain concentrations than TVs targeting either TfR or CD98hc alone. Modulation of TfR and CD98hc affinities shifts dual TV brain exposure kinetics and biodistribution. Stronger TfR affinity drives faster brain uptake and clearance, while stronger CD98hc affinity yields higher, more sustained concentrations, likely due to CD98hc affinity-dependent reduction in TfR-mediated neuronal internalization. This dual targeting strategy leverages the complementary properties of TfR and CD98hc-mediated brain exposure to increase optionality for brain delivery of biotherapeutics.

neuroscience↗

bioRxiv2024

Transcallosal generation of phase aligned beta-bursts underlies TMS-induced interhemispheric inhibition

The excitability of the sensorimotor (SM1) cortices is reflected in the bilateral [~]20 Hz beta oscillations. The extent to which these oscillations subtend the interhemispheric inhibition (IHI) captured by the Transcranial Magnetic Stimulation (TMS) ipsilateral Silent Period (iSP) protocol remains unclear. Therefore, we investigated the relationship between movement-related beta suppression and the iSP, along with their role for manual dexterity. Forty adults underwent an Electroencephalography assessment of beta suppression during volitional left hand movement and a TMS assessment of iSP recorded from the right hand. In both cases, left SM1 beta oscillations (contralateral to the activated right SM1), were monitored through a proxy signal - the Electromyography of the contracted right hand. Bimanual dexterity was assessed with the Purdue Pegboard. Volitional movement caused significant bilateral SM1 beta suppression in nearly all participants ([≥] 85 %). ISPs were observed in every participant. In the proxy signal for the left SM1, the iSP coincided with TMS-evoked high-amplitude beta bursts. These bursts showed significant phase alignment across participants 10-70 ms after the TMS pulse. There was no significant association between the left-/right-hemisphere beta suppression, iSP, and bimanual dexterity. Our results highlight the distinct nature of beta oscillation changes during volitional movement compared to TMS-iSP and show that TMS induces IHI via transcallosal generation of phase aligned beta bursts. Furthermore, our data suggests that only the initial phase of a beta burst carries an inhibitory effect. It also highlights the possibility of evoking a beta burst with the iSP protocol, opening perspectives for future neuroimaging and modeling studies.

neuroscience↗

bioRxiv2024

Transcutaneous Vagus Nerve Stimulation Boosts Post-Error Accuracy During Perceptual Decision-Making

The locus coeruleus-norepinephrine (LC-NE) system is a well-established regulator of behavior, yet its precise role remains unclear. Animal studies predominantly support a "gain" hypothesis, suggesting that the LC-NE system enhances sensory processing, while human studies have proposed an alternative "urgency" hypothesis, postulating that LC-NE primarily accelerates responses. To address this discrepancy, we administered transcutaneous vagus nerve stimulation (tVNS) in two experiments involving 43 participants. In the first experiment, we showed that 4-second tVNS trains reliably induced greater pupil dilation compared to SHAM condition, indicating increased LC-NE activity. In the second experiment, we applied tVNS during a random dot motion task to assess its impact on perceptual decision-making. Notably, tVNS improved accuracy without affecting reaction times, which appears inconsistent with the "urgency" hypothesis. Drift-diffusion model analyses further supported the "gain" hypothesis, revealing that tVNS increased the drift rate, indicative of enhanced evidence accumulation. Accuracy and drift-rate improvements were especially pronounced following errors and in less proficient participants, who otherwise exhibited post-error declines in these measures under SHAM condition. Our findings suggest that the influence of the LC-NE system adapts to task demands, becoming especially beneficial in challenging contexts. Overall, this study underscores the potential of tVNS as a non-invasive tool to investigate the causal role of the LC-NE system in human behavior.

neuroscience↗

bioRxiv2024

Fronto-motor circuits linked to subclinical apathy

Apathy is a syndrome characterized by a disruption in effort-reward decision-making, accompanied by structural and functional changes in a related fronto-basal ganglia (BG) network. While activity changes in the primary motor cortex (M1) during effort and reward valuation have been repeatedly observed, previous work on apathy has largely overlooked the connections between the fronto-BG network and M1, potentially missing key circuits in the apathy network. This study addresses this gap by investigating structural and effective connectivity in fronto-M1, fronto-BG-M1, and intra-M1 circuits in relation to apathy in 45 healthy subjects. Behavior was assessed using a battery of apathy-related questionnaires and computational modeling of effort and reward valuation in a decision-making task. Fronto-motor circuits were examined through a combination of MRI-derived tractography and paired-pulse transcranial magnetic stimulation, which probed structural and effective connectivity, respectively. The data reveal that apathy scores are associated with both structural and effective connectivity in fronto-M1 and fronto-BG-M1 circuits. Circuits originating from the supplementary motor area primarily index effort valuation, while connectivity in intra-M1 GABAergic circuits correlates exclusively with reward valuation. These findings suggest that distinct fronto-motor circuits are linked to different dimensions of motivated behavior and may constitute specific neuromodulation targets for patients suffering from apathy.

neuroscience↗

bioRxiv2024

Effects Of Extrinsic Reward Based Skill Learning On Motor Plasticity

Human motor skill acquisition is improved by performance feedback and coupling such feedback with extrinsic reward (such as money) can enhance skill learning. However, the neurophysiology underlying such behavioral effect is unclear. To bridge this gap, we assessed the effects of reward on multiple forms of motor plasticity during skill learning. Sixty-five healthy participants divided in three groups performed a pinch-grip skill task with sensory feedback only, sensory and reinforcement feedback or both feedback coupled with an extrinsic monetary reward during skill training. To probe motor plasticity, we applied transcranial magnetic stimulation on the left primary motor cortex at rest before, during and after training in the three groups. We evaluated the amplitude and variability of corticospinal output, GABA-ergic short-intracortical inhibition and use-dependent plasticity before training and at two time points during and after training. At the behavioral level, monetary reward accelerated skill learning. In parallel, corticospinal output became less variable early on during training in the presence of extrinsic reward. Interestingly, this effect was particularly pronounced for participants who were more sensitive to reward, as evaluated in an independent questionnaire. Other measures of motor excitability remained comparable across groups. These findings highlight that a mechanism underlying the benefit of reward on motor skill learning is the fine tuning of early-training resting-state corticospinal variability. SIGNIFICANCE STATEMENTSkill acquisition is enhanced in the presence of reward. Despite its potential clinical relevance for motor rehabilitation, the underlying neurophysiological mechanisms remain largely unexplored. Specifically, whether reward affects the plasticity of motor cortex in the context of skill learning is unclear. We show that reward reduces the variability of corticospinal output at an early stage during training and that this effect correlates with individual sensitivity to reward. Our results suggest that a key mechanism underlying the beneficial effect of reward on motor skill learning may be an increase in the stability of motor output in response to training during early stages of skill learning.

neuroscience↗

bioRxiv2024

Engineering anti-amyloid antibodies with transferrin receptor targeting improves safety and brain biodistribution

Although the first generation of immunotherapies for Alzheimers disease (AD) are now clinically approved, amyloid-related imaging abnormalities (ARIA) remain a major safety problem for this class of drugs. Here, we report an antibody transport vehicle (ATV) targeting the transferrin receptor (TfR) for brain delivery of amyloid beta (A{beta}) antibodies that significantly reduced ARIA-like lesions and improved plaque target engagement in a mouse model of amyloid deposition. Asymmetrical Fc mutations (ATVcisLALA) allowed the molecule to selectively retain effector function only when bound to A{beta} while mitigating TfR-related hematology liabilities. Mice treated with ATVcisLALA:A{beta} exhibited broad brain parenchymal antibody distribution; in contrast, anti-A{beta} IgG was highly enriched at arterial perivascular spaces where vascular A{beta} localizes and likely plays a role in induction of ARIA. Importantly, ATVcisLALA: A{beta} almost completely eliminated ARIA-like lesions and vascular inflammation associated with anti-A{beta} treatment. Taken together, ATVcisLALA has the potential to significantly improve both safety and efficacy of A{beta} immunotherapy through enhanced biodistribution mediated by transport across the blood-brain barrier.

neuroscience↗

bioRxiv2024

Fc-engineered large molecules targeting blood-brain barrier transferrin receptor and CD98hc have distinct central nervous system and peripheral biodistribution compared to standard antibodies

The blood-brain barrier (BBB) poses a significant challenge drug delivery to the brain. BBB-crossing molecules are emerging as a new class of therapeutics with significant potential for central nervous system (CNS) indications. In particular, transferrin receptor (TfR)- and CD98 heavy chain (CD98hc)-targeting molecules have been demonstrated to cross the BBB for enhanced brain delivery. Previously, we reported TfR and CD98hc antibody transport vehicles (ATVTfR and ATVCD98hc) that utilize these BBB receptors to improve CNS drug delivery1,2. Here, we provide a comprehensive and unbiased biodistribution characterization of ATVTfR and ATVCD98hc compared to a standard IgG at a multiscale level, ranging from whole-body to brain region- and cell type-targeting specificity. Mouse whole-body tissue clearing revealed distinct organ localization for each molecule. In the CNS, ATVTfR and ATVCD98hc not only achieves enhanced brain delivery but importantly, much broader parenchymal distribution in contrast to the severely limited distribution observed with a standard antibody that was not able to be improved even at very high dose levels. Using cell sorting and single-cell RNA sequencing of mouse brain, we revealed that standard IgG predominantly localizes to perivascular and leptomeningeal cells and reaches the CNS by entering the CSF, rather than crossing the BBB. In contrast, ATVTfR and ATVCD98hc enables broad parenchymal cell-specific distribution via transcytosis through brain endothelial cells (BECs) along the neurovasculature. Finally, we extended the translational relevance of our findings by revealing enhanced and broad brain and spinal cord biodistribution of ATVTfR compared to standard IgG in cynomolgus monkey. Taken together, this multiscale analysis reveals in-depth biodistribution differences between ATVTfR, ATVCD98hc, and standard IgG. These results may better inform platform selection for specific therapeutic targets of interest, optimally matching platforms to desired CNS target engagement, peripheral organ exposures, and predict or potentially reduce off-target effects.

neuroscience↗

bioRxiv2023

Task goals shape the relationship between decision and movement speed

The speed at which we move is linked to the speed at which we decide to make these movements. Yet, the principles guiding such relationship remain unclear: while some studies point towards a shared invigoration process boosting decision and movement speed jointly, others rather indicate a tradeoff between both levels of control, with slower movements accompanying faster decisions. Here, we aimed (1) at further investigating the existence of a shared invigoration process linking decision and movement and (2) at testing the hypothesis that such a link is masked when detrimental to the reward rate. To this aim, we tested 62 subjects who performed the tokens task in two experiments (separate sessions): Experiment 1 evaluated how changing decision speed affects movement speed while Experiment 2 assessed how changing movement speed affects decision speed. In the latter experiment, subjects were either encouraged to favor decision speed (fast decision group) or decision accuracy (slow decision group). Various mixed model analyses revealed a coregulation of decision (urgency) and movement speed in Experiment 1 and in the fast decision group of Experiment 2, but not in the slow decision group despite the fact that these same subjects displayed a coregulation effect in Experiment 1. Altogether, our findings support the idea that coregulation occurs as a default mode but that this form of control is diminished or supplanted by a tradeoff relationship, contingent on reward rate maximization. Drawing from these behavioral observations, we propose that multiple processes contribute to shaping the speed of decisions and movements. New & NoteWorhtyThe principles guiding the relationship between decision and movement speed are unclear. In the present behavioral study involving two experiments conducted on 62 human subjects, we report findings indicating a relationship that varies as a function of the task goals. Coregulation emerges as a default mode of control that fades when detrimental to the reward rate, possibly due to the influence of other processes that can selectively shape the speed of our decisions and movements.

neuroscience↗

bioRxiv2023

Fracture in Living Cell Monolayers

The ability of tissues to sustain mechanical stress and avoid rupture is a fundamental pillar of their function. Rupture in response to physiological levels of stress can be undesired, for example resulting from disease or genetic mutations, or be an integral part of developmental processes, such as during blastocoel formation in mouse or leg eversion in flies. Despite its importance, we know very little about rupture in cellularised tissues because it is a multi-scale phenomenon that necessitates comprehension of the interplay between mechanical forces and processes at the molecular and cellular scales. Using a combination of mechanical measurements, live imaging and computational modelling, we characterise rupture in epithelial monolayers. We show that, despite consisting of only a single layer of cells, monolayers can withstand surprisingly large deformations, often accommodating several-fold increases in their length before rupture. At large deformation, epithelia increase their stiffness multiple-fold in a process controlled by a supracellular network of keratin filaments. Perturbing keratin organisation fragilised monolayers and prevented strain stiffening. Using computational approaches, we show that, although the kinetics of adhesive bond rupture ultimately control tissue strength, tissue rheology and the history of deformation prior to failure set the strain and stress that the tissue reaches at the onset of fracture. Our data paint a picture of epithelia as versatile materials that combine resistance to shocks with deformability when subjected to low strain rates.

biophysics↗

bioRxiv2022

Non-invasive stimulation of the human striatum disrupts reinforcement learning of motor skills

Reinforcement feedback can improve motor learning, but the underlying brain mechanisms remain underexplored. Especially, the causal contribution of specific patterns of oscillatory activity within the human striatum is unknown. To address this question, we exploited an innovative, non-invasive deep brain stimulation technique called transcranial Temporal Interference Stimulation (tTIS) during reinforcement motor learning with concurrent neuroimaging, in a randomised, sham-controlled, double-blind study. Striatal tTIS applied at 80Hz, but not at 20Hz, abolished the benefits of reinforcement on motor learning. This effect was related to a selective modulation of neural activity within the striatum. Moreover, 80Hz, but not 20Hz tTIS increased the neuromodulatory influence of the striatum on frontal areas involved in reinforcement motor learning. These results show for the first time that tTIS can non-invasively and selectively modulate a striatal mechanism involved in reinforcement learning, opening new horizons for the study of causal relationships between deep brain structures and human behaviour.

neuroscience↗

bioRxiv2022

Movement characteristics impact decision-making and vice versa

Previous studies suggest that humans are capable of coregulating the speed of decisions and movements if promoted by task incentives. It is unclear however whether such behavior is inherent to the process of translating decisional information into movements, beyond posing a valid strategy in some task contexts. Therefore, in a behavioral online study we imposed time constraints to either decision or movement -phases of a sensorimotor task, ensuring that coregulating decisions and movements was not promoted by task incentives. We found that participants indeed moved faster when fast decisions were promoted and decided faster when subsequent movements had to be executed swiftly. Furthermore, inflicting faster movements seems to alter decision-making in a similar fashion as conditions promoting faster decisions: In both fast-decision and fast-movement blocks, decisions relied more strongly on information presented shortly rather than long before movement onset. Taken together, these findings suggest that decisions not only impact movement characteristics, but that properties of movement impact the time and manner with which decisions are made. We interpret these behavioral results in the context of embodied decision-making, whereby shared neural mechanisms may not only enable faster movements but also assist in making decisions in less time.

neuroscience↗