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Multisensory integration is quintessential to adaptive behavior, with clinical populations showing significant impairments in this domain, most notably hallucinatory reports. Interestingly, altered cross-modal interactions have also been reported in healthy individuals when engaged in tasks such as the Sound-Induced Flash-Illusion (SIFI). The temporal dynamics of the SIFI have been recently tied to the speed of occipital alpha rhythms (IAF), with faster oscillations entailing reduced temporal windows within which the illusion is experienced. In this regard, entrainment-based protocols have not yet implemented rhythmic transcranial magnetic stimulation (rhTMS) to causally test for this relationship. It thus remains to be evaluated whether rhTMS-induced acoustic and somatosensory sensations may not specifically interfere with the illusion. Here, we addressed this issue by asking 27 volunteers to perform a SIFI paradigm under different Sham and active rhTMS protocols, delivered over the occipital pole at the IAF. Although TMS has been proven to act upon brain tissues excitability, results show that the SIFI occurred for both Sham and active rhTMS, with the illusory rate not being significantly different between baseline and stimulation conditions. This aligns with the discrete sampling hypothesis, for which alpha amplitude modulation, known to reflect changes in cortical excitability, should not account for changes in the illusory rate. Moreover, these findings highlight the viability of rhTMS-based interventions as a means to probe the neuroelectric signatures of illusory and hallucinatory audiovisual experiences, in healthy and neuropsychiatric populations.

Paired associative stimulation (PAS) protocols can be used to induce Hebbian plasticity in the human brain. A modified, cross-modal version, of the PAS (cross-modal PAS, cm-PAS) has been recently developed. The cm-PAS consists in the repetitive pairings of a transcranial magnetic stimulation (TMS) pulse over the primary somatosensory cortex (S1) and a visual stimulus depicting a hand being touched; a 20 ms of inter-stimulus interval (ISI) is required to affect S1 plasticity, in turn modulating tactile acuity and somatosensory evoked potentials. The present study explores the role of anticipatory simulation in the cm-PAS efficacy, which could be responsible for such a short ISI. To this aim, we compared the effect of the original, fixed-frequency, cm-PAS to that of a jittered version, in which the time interval between trials was not steady but jittered, hence avoiding the anticipation of the upcoming visual-touch stimulus. Moreover, in the jittered PAS, the ISI between the paired stimulations was varied: it could match the early, somatosensory-driven, activation of S1 (20 ms), or the mirror recruitment of S1 by touch observation (150 ms). Results showed that tactile acuity is enhanced by the fixed-frequency cm-PAS, with an ISI of 20 ms between paired stimulation (visual-touch stimulus and TMS pulse over S1), and also by the jittered cm-PAS but only if the ISI is of 150 ms. These findings suggest that the cm-PAS with a jittered frequency, by preventing an anticipatory pre-activation of S1, delays the timing of the interaction between the visual-touch stimulus and the cortical pulse. On a broader perspective, our study highlights the possible involvement of sensory anticipation, likely through mirror-like simulation mechanisms, in tactile mirroring, as well as its influence of the optimal interval between the afferent and the magnetic pulse during PAS protocols.

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Transcranial magnetic stimulation (TMS)-electroencephalography coregistration (TMS-EEG) is a promising technique to measure effective connectivity, i.e., the directed transmission of physiological signals along cortico-cortical tracts. Indeed, the activation induced by the TMS pulse in the target region travels to distant connected areas along white matter tracts, generating TMS-evoked potentials (TEPs). A crucial point to be addressed for developing connectivity biomarkers from TEPs is how they are affected by changes in stimulation parameters, such as pulse waveform and the direction of the induced current. Different stimulation parameters across studies may impact latency or amplitude of responses, contributing to the general variability in TMS-EEG findings. To date, the impact of TMS parameters on responses generated in cerebral cortico-cortical pathways has been poorly investigated. To deepen this investigation, we will use as an operative model the M1-P15, an early TEP component reflecting the interhemispheric inhibition of motor areas contralateral to TMS via the corpus callosum. Assuming that the M1-P15 can be recorded regardless of TMS parameters, namely, the direction of the induced current in the brain – anterior-posterior, posterior-anterior, latero-medial – and the TMS pulse waveform – monophasic, biphasic, we will investigate whether these modulations influence M1-P15 latency and amplitude. We will also test M1-P15 reproducibility across our experimental conditions using the concordance and intraclass correlation coefficients. Finally, resting motor threshold and motor-evoked potentials will be collected in every experimental condition as control variables, allowing us to deepen the possible relationship between cortico-spinal and cortico-cortical pathways that different stimulator parameters may activate within the motor system.

Objective Communication-through-coherence proposes that the phase synchronization (PS) of neural oscillations between cortical areas supports neural communication. In this study, we exploited transcranial magnetic stimulation (TMS)-evoked potentials (TEPs) to test this hypothesis at the macroscale level, i.e., whether PS between cortical areas supports interarea communication. TEPs are electroencephalographic (EEG) responses time-locked to TMS pulses reflecting interarea communication, as they are generated by the transmission of neural activity from the stimulated area to connected regions. If interarea PS is important for communication, it should be associated with the TEP amplitude in the connected areas. Methods TMS was delivered over the left primary motor cortex (M1) of fourteen healthy volunteers, and 70-channel EEG was recorded. Early TEP components were source-localized to identify their generators, i.e., distant brain regions activated by M1 through effective connections. Next, linear regressions were used to test the relationship between the TEP amplitude and the pre-stimulus PS between the M1 and the connected regions in four frequency bands (range 4–45 Hz). Results Pre-stimulus interarea PS in the alpha-band was positively associated with the amplitude of early TEP components, namely, the N15 (ipsilateral supplementary motor area), P25 (contralateral M1) and P60 (ipsilateral parietal cortex). Conclusions Alpha-band PS predicts the response amplitude of the distant brain regions effectively connected to M1. Significance Our study supports the role of EEG-PS in interarea communication, as theorized by communication-through-coherence.

The present work aims at investigating the TaMS in BPD and its relationship with empathic abilities. The study will involve BPD patients and healthy controls (HCs). In both groups we will collect measures of empathic abilities, evaluated by means of self-report questionnaires, performance in a behavioral task involving TaMS activity, and connectivity indexes, obtained by TMS-EEG recording.

The Motor-TCD project aims at replicating and extending our previous finding that the M1-P15 component of transcranial magnetic stimulation (TMS)-evoked potentials (TEPs) represents an index of transcallosal inhibition and its latency predicts bimanual coordination.

Ongoing oscillatory neural activity before stimulus onset influences subsequent visual perception. Specifically, both the power and the phase of oscillations in the alpha-frequency band (9-13 Hz) have been reported to predict the detection of visual stimuli. Up to now, the functional mechanisms underlying pre-stimulus power and phase effects on upcoming visual percepts are debated. Here, we used magnetoencephalography recordings together with a near-threshold visual detection task to investigate the neural generators of pre-stimulus power and phase and their impact on subsequent visual-evoked responses. Pre-stimulus alpha-band power and phase opposition effects were found consistent with previous reports. Source localization suggested clearly distinct neural generators for these pre-stimulus effects: Power effects were mainly found in occipital-temporal regions, whereas phase effects also involved prefrontal areas. In order to be functionally relevant, the pre-stimulus correlates should influence post-stimulus processing. Using a trial-sorting approach, we observed that only pre-stimulus power modulated the Hits versus Misses difference in the evoked response, a well-established post-stimulus neural correlate of near-threshold perception, such that trials with stronger pre-stimulus power effect showed greater post-stimulus difference. By contrast, no influence of pre-stimulus phase effects were found. In sum, our study shows distinct generators for two pre-stimulus neural patterns predicting visual perception, and that only alpha power impacts the post-stimulus correlate of conscious access. This underlines the functional relevance of prestimulus alpha power on perceptual awareness, while questioning the role of alpha phase.

BackgroundIn a recently published study combining transcranial magnetic stimulation and electroencephalography (TMS-EEG), we provided first evidence of M1-P15, an early component of TMS-evoked potentials, as a measure of transcallosal inhibition between motor cortices. However, considering the technical challenges of TMS-EEG recordings, further evidence is needed before M1-P15 can be considered a reliable index.ObjectiveHere, we aimed at validating M1-P15 as a cortical index of transcallosal inhibition, by replicating previous findings on its relationship with the ipsilateral silent period (iSP) and with performance in bimanual coordination. Moreover, we aimed at inducing a task-dependent modulation of transcallosal inhibition.MethodsA new sample of 32 healthy right-handed participants underwent behavioral motor tasks and TMS-EEG recording, in which left and right M1 were stimulated during bimanual tasks and during an iSP paradigm. Hypotheses and methods were preregistered before data collection.ResultsWe successfully replicated our previous findings on the positive relationship between M1-P15 amplitude and the iSP normalized area. However, we did not confirm the relationship between M1-P15 latency and bimanual coordination. Finally, we show a task-dependent modulation of M1-P15 amplitude, which was affected by the characteristics of the bimanual task the participants were performing, but not by the contralateral hand activity during the iSP paradigm.ConclusionsThe present results corroborate our previous findings in validating the M1-P15 as a reliable cortical marker of transcallosal inhibition, and provide novel evidence of its task-dependent modulation. Importantly, we demonstrate the feasibility of a preregistration approach in the TMS-EEG field to increase methodological rigor and transparency.

Substantial evidence has shown that ongoing neural activity significantly contributes to how the brain responds to upcoming stimuli. In visual perception, a considerable portion of trial-to-trial variability can be accounted for by prestimulus magneto/electroencephalographic (M/EEG) alpha oscillations, which play an inhibitory function by means of cross-frequency interactions with gamma-band oscillations. Despite the fundamental theories on the role of oscillations in perception and cognition, a clear theorization of the neural mechanisms underlying prestimulus activity effects that includes electrophysiological phenomena at different scales (e.g., local field potentials and macro-scale M/EEG) is still missing. Here, we present a model called the oscillation-based probability of response (OPR), which directly assesses the link between meso-scale neural mechanisms, macro-scale M/EEG, and behavioural outcome. The OPR model includes distinct meso-scale mechanisms through which alpha oscillations modulate M/EEG gamma activity, namely, by decreasing a) the amplitude and/or b) the degree of neural synchronization of gamma oscillations. Crucially, the OPR model makes specific predictions on the effects of these mechanisms on visual perception, as assessed through the psychometric function.SIGNIFICANCE STATEMENTThe oscillation-based probability of response (OPR) is grounded on a psychophysical approach focusing on the psychometric function estimation and may be highly informative in the study of ongoing brain activity because it provides a tool for distinguishing different neural mechanisms of alpha-driven modulation of sensory processing.

Transcranial magnetic stimulation (TMS)-electroencephalography coregistration (TMS-EEG) is a promising technique to measure effective connectivity, i.e., the directed transmission of physiological signals along cortico-cortical tracts. Indeed, the activation induced by the TMS pulse in the target region travels to distant connected areas along white matter tracts, generating TMS-evoked potentials (TEPs). A crucial point to be addressed for developing connectivity biomarkers from TEPs is how they are affected by changes in stimulation parameters, such as pulse waveform and the direction of the induced current. Different stimulation parameters across studies may impact latency or amplitude of responses, contributing to the general variability in TMS-EEG findings. To date, the impact of TMS parameters on responses generated in cerebral cortico-cortical pathways has been poorly investigated. To deepen this investigation, we will use as an operative model the M1-P15, an early TEP component reflecting the interhemispheric inhibition of motor areas contralateral to TMS via the corpus callosum. Assuming that the M1-P15 can be recorded regardless of TMS parameters, namely, the direction of the induced current in the brain – anterior-posterior, posterior-anterior, latero-medial – and the TMS pulse waveform – monophasic, biphasic, we will investigate whether these modulations influence M1-P15 latency and amplitude. We will also test M1-P15 reproducibility across our experimental conditions using the concordance and intraclass correlation coefficients. Finally, resting motor threshold and motor-evoked potentials will be collected in every experimental condition as control variables, allowing us to deepen the possible relationship between cortico-spinal and cortico-cortical pathways that different stimulator parameters may activate within the motor system.

When acting together, we may represent not only our own individual goals but also a collective goal. Although behavioural evidence suggests that agents' motor plans might be related to collective goals, direct neurophysiological evidence of whether collective goals are motorically represented is still scarce. The aim of the present transcranial magnetic stimulation (TMS) study is to begin to fill this gap. A participant and a confederate were asked to sequentially perform a two-choice reaction time task by acting on pressure sensors. In their own turn, they saw a cue indicating whether to lift their fingers from (or to press them on) a pressure sensor to shoot a ball across the screen as fast as possible. The confederate responded with the right hand, the participant with the left hand. While the confederate acted on the sensor, the participant's motor evoked potentials (MEPs) were collected from the right Extensor Carpi Ulnaris. If participants represent their own and the confederate's actions as being directed to a collective goal, MEPs amplitude should be modulated according to the action the confederate should perform. To test this conjecture, we contrasted three conditions: a Joint condition, in which both players worked together with their collective goal being to shoot the ball to get it to a common target, a Parallel condition, in which the players performed exactly the same task but received independent outcomes for their performance, and a Competitive condition, in which the outcome of the game still depended on the other player performance, but without the collective goal feature. Results showed no MEPs modulation according to the confederate's action in the Joint condition. Post-hoc exploratory analyses both provide some hints about this negative finding and also suggest possible improvements (i.e., adopting a different dependent variable, avoiding task-switching between conditions) for testing our hypothesis that collective goal can be represented motorically.

Introduction : In the last years, the evidence that the primary somatosensory cortex (S1) is activated not only during the perception of tactile stimuli but also during their observation, has been widely investigated. A highly influential hypothesis suggests that the cross-modal, mirror-like, activity of S1 may arise from Hebbian associative plasticity: the contingency of seeing a touch and the feeling of a tactile sensation on one’s own body may reinforce synapses between visual and somatosensory neurons. However, to date, a causal demonstration is still lacking. To test this hypothesis, we developed a novel cross-modal Paired Associative Stimulation protocol (cm-PAS) where a visual stimulus depicting the palm of a left hand being touched is repeatedly presented (i.e. visual-touch stimulus), time-locked with a Transcranial Magnetic Stimulation (TMS) pulse over right S1. Methods : In 4 within-subjects experiments, we tested temporal (Experiment 1), cortical (Experiment 2) and visual (Experiment 3) specificity of cm-PAS by assessing its effects on tactile acuity. Experiment 3 explored neurophysiological changes in S1 by recording Somatosensory Evoked Potentials (SEPs). The last study (Experiment 4) investigated the role of predictive coding mechanisms through a jittered, unpredictable, cm-PAS version where the frequency between trials was not fixed (at variance with the fixed frequency of 0.1 Hz employed in previous experiments). Temporal constraints were explored by varying the inter-(paired) stimulus interval (ISI), according to different chronometry of S1 activation by touch processing and touch observation (i.e., 20 and 150 ms). Results : Results show that cm-PAS is effective in inducing Hebbian Long-Term Potentiation-like plasticity, increasing tactile acuity at the observer’s hand. Importantly, this effect is present only when (a) the ISI between the two stimuli (i.e., the visual-touch stimulus and the TMS pulse) is of 20 ms (Experiment 1), (b) the TMS pulse is delivered over S1 (Experiment 2) and (c) the visual stimulus depicts an hand being touched, not a mere hand action (Experiment 3). The cm-PAS also increases SEPs (i.e., the P40 component peak). Finally, Experiment 4 showed that the unpredictability of temporal occurrence of the paired stimuli changes the temporal window required for integrating the visual-touch stimulus with the cortical activation of S1, now requiring an ISI of 150 ms. Discussion : Our study provides novel insight into the cross-modal, mirroring, activity of S1, and the chance of inducing changes in this area by activating spike-timing-dependent plasticity and, in a broader perspective, Hebbian associative plasticity. Our original protocol, the cm-PAS, effectively modulates S1 functioning, improving tactile acuity and increasing SEPs. Interestingly, the cm-PAS recruits predictive coding mechanisms that act by pre-activating S1, anticipating the upcoming touch. Taken together, our results show how the cm-PAS can be a very useful non-invasive stimulation protocol to cross-modally induce neuroplasticity in the human brain, as well as uncovering the underpinning of mirroring mechanisms and the shaping role of predictive coding.

It has been theorized that hemispheric dominance and more segregated information processing have evolved to overcome long conduction delays through the corpus callosum (transcallosal conduction delay - TCD) but that this may still impact behavioral performance, mostly in tasks requiring high timing accuracy. Nevertheless, a thorough understanding of the temporal features of interhemispheric communication is lacking. Here, we aimed to assess the relationship between TCD and behavioral performance with a noninvasive directional cortical measure of TCD obtained from transcranial magnetic stimulation (TMS)-evoked potentials (TEPs) in the motor system. Twenty-one healthy right-handed subjects were tested. TEPs were recorded during an ipsilateral silent period (iSP) paradigm and integrated with diffusion tensor imaging (DTI) and an in-phase bimanual thumb-opposition task. Linear mixed models were applied to test relationships between measures. We found TEP indexes of transcallosal communication at ∼15 ms both after primary motor cortex stimulation (M1-P15) and after dorsal premotor cortex stimulation (dPMC-P15). Both M1-and dPMC-P15 were predicted by mean diffusivity in the callosal body. Moreover, M1-P15 was positively related to iSP. Importantly, M1-P15 latency was linked to bimanual coordination with direction-dependent effects, so that asymmetric TCD was the best predictor of bimanual coordination. Our findings support the idea that transcallosal timing in signal transmission is essential for interhemispheric communication and can impact the final behavioral outcome. However, they challenge the view that a short conduction delay is always beneficial. Rather, they suggest that the effect of the conduction delay may depend on the direction of information flow.