Biology subjects

Guidali, G.

Publications and source records attributed to Guidali, G..

6 recordsLinked to original sources

bioRxiv2025

Cortical markers of PAS-induced long-term potentiation and depression in the motor system: A TMS-EEG Registered Report

Paired associative stimulation (PAS), a neuromodulation protocol combining transcranial magnetic stimulation (TMS) pulses to the primary motor cortex (M1) with electrical median nerve stimulation, promotes synaptic plasticity (long-term potentiation - LTP, long-term depression - LTD) in the human motor system following Hebbian associative plasticity induction. To date, PAS effects have been mainly investigated at the corticospinal level. In the present Registered Report, we leveraged TMS and electroencephalography (TMS-EEG) co-registration to track the cortical dynamics related to M1-PAS, aiming to characterize the neurophysiological substrates better, grounding the effectiveness of such protocol. In two within-subject sessions, 30 healthy participants underwent the standard M1-PAS protocols inducing LTP (PASLTP) and LTD (PASLTD) while measuring motor-evoked potentials (MEPs) and TMS-evoked potentials (TEPs) from M1 stimulation before, immediately after, and 30 minutes from the end of the PAS, applied both at supra- (i.e., 110%) and sub- (i.e., 90%) resting motor threshold intensities. Besides replicating MEPs enhancement and inhibition after PASLTP and PASLTD, our results showed that the P30 and N100 M1-TEPs components were significantly modulated immediately following PASLTP and PASLTD administration. These effects were detectable only in suprathreshold conditions, suggesting that M1 subthreshold stimulation could not be optimal for tracking cortical effects of PAS. Furthermore, exploratory analyses showed that P60 amplitude at baseline successfully predicted the magnitude of P30 modulations after PASLTP administration. Our findings provide compelling evidence about the specificity of early TEP components in reflecting changes in M1 reactivity underpinning PAS effects and associative plasticity induction within the motor system. From a broader perspective, our study fosters evidence about using TMS-EEG biomarkers to track complex plastic changes induced in the human brain, exploiting neuromodulatory non-invasive brain stimulation protocols based on associative mechanisms, like PAS. Preregistered Stage 1 protocol: https://osf.io/detjc (date of in-principle acceptance: 15/01/2024) Recommended Stage 2 manuscript: https://rr.peercommunityin.org/articles/rec?id=1031

neuroscience↗

bioRxiv2025

Frontal connectivity dynamics encode contextual information during action preparation

The context in which we perform motor acts shapes our behavior, with movement speed and accuracy modulated by contingent factors, such as the occurrence of cues that trigger or inhibit our actions. This flexibility relies on network interactions encompassing premotor and prefrontal regions, including the supplementary motor area (SMA) and the right inferior frontal gyrus (rIFG). However, the dynamic interplay between these regions during action preparation and execution based on contextual demands remains unclear. Here, we demonstrate that contextual information is encoded in SMA and rIFG interareal connectivity before action. Using Transcranial Magnetic Stimulation (TMS) and electroencephalography (EEG) during Go/No- Go tasks with varying target probabilities, we found that, during the preparatory stages of action, -band rIFG connectivity increased in contexts where motor responses were more frequently withheld. In contrast, SMA exhibited a reversed pattern only near the target onset. Finally, {beta}-band connectivity encoded proactive inhibition processes, increasing when action likelihood was low. Accordingly, during response implementation, both areas exhibited greater {beta}-band connectivity when action was withheld compared to when a motor response was required, further supporting its role in inhibitory control. Our results demonstrate that - and {beta}-band oscillatory network dynamics support context-sensitive adaptations, illustrating how premotor and prefrontal regions synergistically modulate their interactions as they transition from preparation to response. These findings advance understanding of how the brain integrates predictive information to dynamically organize motor and cognitive resources before an action unfolds, revealing that connectivity encodes critical information driving behavior. Significance statementAdaptive behavior relies on the brains ability to anticipate and adjust actions based on contextual cues. Using Transcranial Magnetic Stimulation and electroencephalography (TMS-EEG), we show that the supplementary motor area (SMA) and the right inferior frontal gyrus (IFG) dynamically modulate their functional connectivity based on target predictability during action preparation and initiation. We reveal distinct oscillatory mechanisms by which SMA enhances motor readiness and IFG supports inhibitory control before action execution. These findings provide new insights into how frontal networks integrate probabilistic information to optimize action outputs in predictable contexts, with implications for disorders involving deficits in motor planning and control.

neuroscience↗

bioRxiv2025

Tracking changes in corticospinal excitability during visuomotor paired associative stimulation to predict motor resonance rewriting

Mirror properties of the action observation network (AON) can be modulated through Hebbian-like associative plasticity using paired associative stimulation (PAS). We recently introduced a visuomotor protocol (mirror-PAS, m-PAS), which pairs transcranial magnetic stimulation (TMS) over the primary motor cortex (M1) with visual stimuli of ipsilateral (to TMS) movements, leading to atypical corticospinal excitability (CSE) facilitation (i.e., motor resonance) during PAS-conditioned action observation. While m-PAS aftereffects are robust, little is known about markers of associative plasticity during its administration and their predictive value for subsequent motor resonance rewriting. In the present study, we analyzed CSE dynamics in 81 healthy participants undergoing the m-PAS before and after passively observing left- or right-hand index finger movements. Here, typical and PAS-conditioned motor resonance was assessed with TMS over the right M1. We examined CSE changes during the m-PAS and used linear regression models to explore their relationship with motor resonance modulations. Results showed that the m-PAS transiently reshaped both typical and PAS-conditioned motor resonance. Importantly, we found a gradual increase of CSE during m-PAS, which predicted the loss of typical motor resonance but not the emergence of atypical responses after the protocols administration. Our findings suggest that the motor resonance reshaping induced by the m-PAS is not fully predictable by CSE online modulations. Likely, this rewriting is the product of a large-scale reorganization of the AON rather than a phenomenon restricted to the PAS-stimulated motor cortex. This study underlines that monitoring CSE during non-invasive brain stimulation protocols could provide valuable insight into some, but not all, their plastic outcomes.

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bioRxiv2024

Stimulation parameters shape effective connectivity pathways: insights from microstate analysis on TMS-evoked potentials

Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs) represent an innovative measure for examining brain connectivity and developing biomarkers of psychiatric conditions. Minimising TEP variability across studies and participants, which may stem from methodological choices, is therefore vital. By combining classic peak analysis and microstate investigation, we tested how TMS pulse waveform and current direction may affect effective connectivity when targeting the primary motor cortex (M1). We aim to disentangle whether changing these parameters affects the degree of activation of the same neural circuitry or may lead to changes in the pathways through which the induced activation spreads. Thirty-two healthy participants underwent a TMS-EEG experiment in which the pulse waveform (monophasic, biphasic) and current direction (posterior-anterior, anterior-posterior, latero-medial) were manipulated. We assessed the latency and amplitude of M1-TEP components and employed microstate analyses to test differences in topographies. Results revealed that TMS parameters strongly influenced M1-TEP components amplitude but had a weaker role over their latencies. Importantly, microstate analysis showed that the current direction in monophasic stimulations changed the pattern of evoked microstates at the early TEP latencies, as well as their duration and the overall amount of activated brain resources associated. This study shows that the current direction of monophasic pulses may modulate cortical sources contributing to TEP signals, activating neural populations and cortico-cortical paths more selectively. Biphasic stimulation reduces the variability associated with current direction and may be better suited when TMS targeting is blind to anatomical information.

neuroscience↗

bioRxiv2024

M1 Large-scale Network Dynamics Support Human Motor Resonance and Its Plastic Reshaping

Motor resonance - the activation of the observers motor system when viewing others actions - grounds the intertwined nature of action perception and execution, with profound implications for social cognition and action understanding. Despite extensive research, the neural underpinnings supporting motor resonance emergence and rewriting remain unexplored. In this study, we investigated the role of sensorimotor associative learning in motor resonance neural mechanisms. To this aim, we applied cross-systems paired associative stimulation (PAS) to induce novel visuomotor associations in the human brain. This protocol, which repeatedly pairs transcranial magnetic stimulation (TMS) pulses over the primary motor cortex (M1) with visual stimuli of actions, drives the emergence of an atypical, PAS-conditioned motor resonance response. Using TMS and electroencephalography (EEG) co-registration during action observation, we tracked the M1 functional connectivity profile during this process to map the inter-areal connectivity profiles associated with typical and PAS-induced motor resonance phenomena. Besides confirming, at the corticospinal level, the emergence of newly acquired motor resonance responses at the cost of typical ones after PAS administration, our results reveal dissociable aspects of motor resonance in M1 interregional communication. On the one side, typical motor resonance effects acquired through the lifespan are associated with prominent M1 alpha-band and reduced beta-band connectivity, which might facilitate the corticospinal output while integrating visuomotor information. Conversely, the atypical PAS-induced motor resonance is linked to M1 beta-band cortical connectivity modulations, only partially overlapping with interregional communication patterns related to the typical mirroring responses. This evidence suggests that beta-phase synchronization may be the critical mechanism supporting the formation of motor resonance by coordinating the activity of motor regions during action observation, which also involves alpha-band top-down control of frontal areas. These findings provide new insights into the neural dynamics underlying (typical and newly acquired) motor resonance, highlighting the role of large-scale interregional communication in sensorimotor associative learning within the action observation network.

neuroscience↗

bioRxiv2024

Investigating visuo-tactile mirror properties in Borderline Personality Disorder: a TMS-EEG study

Patients with Borderline Personality Disorder (pw-BPD) are characterized by lower levels of cognitive empathy compared to healthy controls (HCs), indicating difficulties in understanding others perspective. A candidate neural mechanism subtending empathic abilities is represented by the Tactile Mirror System (TaMS), which refers to mirror-like mechanisms in the somatosensory cortices. However, little is known about TaMS alterations in BPD, specifically in terms of brain connectivity within this network. Here, we aimed at providing novel insights on TaMS as neurophysiological candidate for BPD empathic deficits, with a special focus on TaMS connectivity by means of the combined use of transcranial magnetic stimulation and electroencephalography (TMS-EEG). Twenty pw-BPD and 20 HCs underwent a thorough investigation: we collected measures of empathic abilities obtained from self-report questionnaires, behavioral performance in a visuo-tactile spatial congruency task, and TMS-evoked potentials (TEPs) as effective connectivity indexes. In the TMS-EEG session, TMS was delivered over the right primary somatosensory cortex (S1) following the presentation of real touches and visual touches, while 74-channel EEG was continuously recorded. In the visuo-tactile spatial congruency task and the TMS-EEG recording, control conditions with visual touches on objects instead of body parts enabled to disentangle the involvement of TaMS from non-specific effects. The study is the first one employing TMS-EEG in pw-BPD and it has been preregistered before data collection. Consistent with previous findings, results show that pw-BPD reported significantly lower levels of cognitive empathy. Moreover, pw-BPD made significantly more errors than controls in the visuo-tactile spatial congruency task during visual touches on human body parts and not on objects. Finally, pw-BPD displayed a different connectivity pattern from S1-TEPs that was not specific for TaMS: they showed a lower P60 component during touch observation, as well as reduced amplitude of later TEPs responses (after [~]100 ms) during real touches. Overall, the present study shows behavioral evidence of TaMS impairment and a more general alteration in the connectivity pattern of the somatosensory network in pw-BPD.

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