Biology subjects

Vassiliadis, P.

Publications and source records attributed to Vassiliadis, P..

12 recordsLinked to original sources

bioRxiv2026

Reward and punishment differentially shape basketball free-throw learning

Motor learning is shaped by motivational context: punishment can accelerate initial learning, whereas reward enhances memory retention. Yet it remains unclear whether the dissociable effects of reward and punishment observed in laboratory tasks generalize to complex real-world skills. Here, we tested this idea using a naturalistic motor task--basketball free-throw shooting. Sixty-eight participants trained under four motivational contexts that differed only in how points were awarded for each pair of consecutive shots: control (standard scoring), reward (bonus points for two consecutive successful shots), punishment (penalty for two consecutive missed shots), or mixed (both bonus and penalty). Performance was assessed before training, immediately after, and 1 and 3 days later. Punishment and mixed schedules significantly improved early acquisition, resulting in higher accuracy immediately after training compared to the control and reward conditions. This advantage emerged during the first training block, indicating a rapid motivational influence on performance. In contrast, reward selectively enhanced offline consolidation: three days after training, the reward group showed the largest gains in accuracy, outperforming both the control and punishment groups. The mixed schedule produced quick early gains similar to punishment, but achieved smaller long-term improvements than reward. Consistent with these findings, individual punishment sensitivity was associated with gains in acquisition, while reward sensitivity correlated with offline improvements. Together, these findings demonstrate dissociable effects of motivational valence on the acquisition and consolidation of a complex real-world motor skill. More generally, they position motivational interventions as simple and cost-effective strategies to enhance rehabilitation and sports training.

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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.

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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.

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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.

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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.

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bioRxiv2023

Effects of hippocampal noninvasive theta-burst stimulation on consolidation of associative memory in healthy older adults

Stimulation of deep brain areas can offer benefits against cognitive impairments associated with aging. So far, this was only possible via invasive methods accompanied by risks. Grossman et al. proposed a new noninvasive stimulation technique, transcranial temporal interference electric stimulation (tTIS), which can be steered to target and modulate activity of deep brain structures. Memory capacity depends on subcortical structures such as the hippocampus, hence, modulation of hippocampal activity could benefit declining cognitive functions. The current study investigates whether theta-burst patterned tTIS targeting the hippocampus influences performance of associative memory in older adults. We found that theta-burst patterned tTIS, but not the control stimulation, improved recollection time in a follow-up 24h after the stimulation, suggesting that theta-burst patterned tTIS can influence the efficiency of longer-term encoding. This outcome indicates that tTIS may provide a new noninvasive deep brain stimulation method to modulate senescent memory processes.

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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.

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bioRxiv2022

LTP-like noninvasive striatal brain stimulation enhances striatal activity and motor skill learning in humans

The stimulation of deep brain structures has thus far only been possible with invasive methods. Transcranial electrical temporal interference stimulation (tTIS) is a novel, noninvasive technology that might overcome this limitation. The initial proof-of-concept was obtained through modeling, physics experiments and rodent models. Here, we show for the first time successful noninvasive neuromodulation of the striatum via tTIS in humans using computational modeling, fMRI studies and behavioral evaluations. Theta-burst patterned striatal tTIS increased activity in the striatum and associated motor network. Furthermore, striatal tTIS enhanced motor performance, especially in healthy older participants as they have lower natural learning skills than younger subjects. These findings place tTIS as exciting new method to target deep brain structures in humans noninvasively, thus enhancing our understanding of their functional roles. Moreover, our results lay the groundwork for innovative, noninvasive treatment strategies for brain disorders in which deep striatal structures play key pathophysiological roles.

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bioRxiv2022

Probing the influence of SMA and vmPFC on the motor system with dual-site transcranial magnetic stimulation

Dual-site transcranial magnetic stimulation (TMS) has been widely employed to investigate the influence of cortical structures on the primary motor cortex (M1). Here, we leveraged this technique to probe the causal influence of two key areas of the medial frontal cortex, namely the supplementary motor area (SMA) and the medial orbitofrontal cortex (mOFC), on M1. We show that SMA stimulation facilitates M1 activity across short (6 and 8 ms) and long (12 ms) inter-stimulation intervals, putatively recruiting cortico-cortical and cortico-subcortico-cortical circuits, respectively. Crucially, magnetic resonance imaging revealed that this facilitatory effect depended on a key morphometric feature of SMA: individuals with larger SMA volumes exhibited more facilitation from SMA to M1. Notably, we also provide evidence that the facilitatory effect of SMA stimulation at short intervals did not arise from spinal interactions of volleys descending simultaneously from SMA and M1. On the other hand, mOFC stimulation moderately suppressed M1 activity at both short and long intervals, irrespective of mOFC volume. These results suggest that dual-site TMS is an interesting tool to study the differential influence of SMA and mOFC on M1 activity, paving the way for the multi-modal assessment of these fronto-motor circuits in health and disease. Key pointsO_LIDual-site TMS has been widely employed to investigate effective connectivity between cortical structures and the primary motor cortex (M1). C_LIO_LIHere, we probed the causal influence of the supplementary motor area (SMA) and the medial orbitofrontal cortex (mOFC) on M1 activity. C_LIO_LISMA stimulation facilitates M1 activity at both short and long inter-stimulation intervals; this facilitatory effect is related to SMA volume. C_LIO_LImOFC stimulation moderately suppresses M1 activity, independent of mOFC volume. C_LIO_LIThe findings pave the way for multi-modal assessment of fronto-motor circuits in health and disease. C_LI

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bioRxiv2021

Reward timing matters in motor learning

Reward can improve motor learning and the consolidation of motor memories. Identifying the features of reward feedback that are critical for motor learning is a necessary step for successful integration into rehabilitation programs. One central feature of reward feedback that may affect motor learning is its timing - that is, the delay after which reward is delivered following movement execution. In fact, research on associative learning has shown that short and long reward delays (e.g., 1 and 6 s following action execution) activate preferentially the striatum and the hippocampus, respectively, which both contribute with varying degrees to motor learning. Given the distinct functional role of these two areas, we hypothesized that reward timing could modulate how people learn and consolidate a new motor skill. In sixty healthy participants, we found that delaying reward delivery by a few seconds influenced motor learning dynamics. Indeed, training with a short reward delay (i.e., 1 s) induced slow, yet continuous gains in performance, while a long reward delay (i.e., 6 s) led to initially high learning rates that were followed by an early plateau in the learning curve and a lower endpoint performance. Moreover, participants who successfully learned the skill with a short reward delay displayed overnight consolidation, while those who trained with a long reward delay exhibited an impairment in the consolidation of the motor memory. Overall, our data show that reward timing affects motor learning, potentially by modulating the engagement of different learning processes, a finding that could be exploited in future rehabilitation programs.

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bioRxiv2021

Reward boosts reinforcement-based motor learning

Besides relying heavily on sensory and reinforcement feedback, motor skill learning may also depend on the level of motivation experienced during training. Yet, how motivation by reward modulates motor learning remains unclear. In 90 healthy subjects, we investigated the net effect of motivation by reward on motor learning while controlling for the sensory and reinforcement feedback received by the participants. Reward improved motor skill learning beyond performance-based reinforcement feedback. Importantly, the beneficial effect of reward involved a specific potentiation of reinforcement-related adjustments in motor commands, which concerned primarily the most relevant motor component for task success and persisted on the following day in the absence of reward. We propose that the long-lasting effects of motivation on motor learning may entail a form of associative learning resulting from the repetitive pairing of the reinforcement feedback and reward during training, a mechanism that may be exploited in future rehabilitation protocols.

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bioRxiv2020

Motor training strengthens corticospinal suppression during movement preparation

Training can improve motor skills and modify neural activity at rest and during movement execution. Learning-related modulations may also concern motor preparation but the neural correlates and the potential behavioral relevance of such adjustments remain unclear. In humans, preparatory processes have been largely investigated using transcranial magnetic stimulation (TMS) with several studies reporting decreased corticospinal excitability (CSE) relative to a baseline measure; a phenomenon called preparatory suppression. Here, we investigated the effect of motor training on preparatory suppression of CSE in humans, as compared to modulatory changes at rest. We trained participants to initiate quick movements in an instructed-delay reaction time (RT) task and used TMS to investigate changes in CSE over the practice blocks. Training on the task speeded up RTs, with no repercussion on error rates. Training also increased baseline CSE at rest. Most interestingly, we found that motor activity during action preparation did not mirror the training-related rise in resting CSE. Rather, the degree of preparatory suppression from the rising baseline strengthened with practice. This training-related change in preparatory suppression predicted RT gains (but not the changes in baseline CSE): subjects showing a stronger expansion of preparatory suppression were also those exhibiting larger gains in RTs. Finally, such relationship between RTs and preparatory suppression was also evident at the single-trial level: RTs were generally faster in trials where preparatory suppression was deeper. These findings suggest that training induces changes in motor preparatory processes that are linked to an enhanced ability to initiate fast movements. New and NoteworthyAny movement is preceded by a period of preparation, which involves a broad suppression of the corticospinal pathway, a phenomenon called preparatory suppression. Here, we show that motor training strengthens preparatory suppression and that this strengthening is associated with an acceleration of movement initiation. Our findings yield an extension of former work, highlighting a key role of preparatory suppression in training-driven behavioral improvements.

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