Julie Duque

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.

Action-oriented decisions are shaped by a sense of urgency, a state that builds as the need to commit to an action increases. When poorly regulated, this urgency may bias decisions toward impulsive choices. Because this urgency state may be influenced by different factors, we aimed to dissociate context- and reward-based sources of urgency state regulation. We determined how these regulatory modes are implemented in the motor system across healthy individuals whose impulsivity trait was assessed using the UPPS-P Impulsive Behavior Scale, with a focus on the urgency trait dimension. Participants ( n = 20, including 13 women) performed a left-or-right index-finger Tokens decision-making task in which contextual demands and reward prospect were orthogonally manipulated to isolate context- and reward-based urgency regulation, with single-pulse transcranial magnetic stimulation used to probe corticospinal excitability either in leg muscles, indexing broad modulation of motor activity, or in hand muscles, indexing surround inhibition (SI), as candidate mechanisms underlying these regulatory modes. Our results indicate that context-based urgency state regulation is most evident in individuals with a lower urgency trait, whereas reward-based regulation is most prominent in those with a higher urgency trait. Both forms of regulation were associated with broad motor excitability changes, with reward-based regulation additionally associated with SI, suggesting that this signature mainly reflects reward prospect rather than urgency state. Based on our findings, urgency-related trait impulsivity may not simply reflect a persistently “higher state of urgency” but rather a different weighting of influences that shape it during decision-making in the motor system.

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.

Background: Transcutaneous 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. Method: To 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. Results: We 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. Conclusions: This 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.

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 STATEMENT: Why 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.

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.

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 into 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 at rest, on the left primary motor cortex before, at an early-training time point, and after training in the three groups and measured motor-evoked potentials from task-relevant muscle of the right arm. This allowed us to evaluate the amplitude and variability of corticospinal output, GABAergic short-intracortical inhibition, and use-dependent plasticity before training and at two additional time points (early and end 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.

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.