Effects of transcranial magnetic stimulation (TMS) current direction and pulse waveform on cortico-cortical connectivity: A registered report TMS-EEG study.

Transcranial magnetic stimulation (TMS)-evoked potentials (TEPs) are a promising proxy for measuring effective connectivity, that is, the directed transmission of physiological signals along cortico-cortical tracts, and for developing connectivity-based biomarkers. A crucial point is how stimulation parameters may affect TEPs, as they may contribute to the general variability of findings across studies. Here, we manipulated two TMS parameters (i.e. current direction and pulse waveform) while measuring (a) an early TEP component reflecting contralateral inhibition of motor areas, namely, M1-P15, as an operative model of interhemispheric cortico-cortical connectivity, and (b) motor-evoked potentials (MEP) for the corticospinal pathway. Our results showed that these two TMS parameters are crucial to evoke the M1-P15, influencing its amplitude, latency, and replicability. Specifically, (a) M1-P15 amplitude was strongly affected by current direction in monophasic stimulation; (b) M1-P15 latency was significantly modulated by current direction for monophasic and biphasic pulses. The replicability of M1-P15 was substantial for the same stimulation condition. At the same time, it was poor when stimulation parameters were changed, suggesting that these factors must be controlled to obtain stable single-subject measures. Finally, MEP latency was modulated by current direction, whereas non-statistically significant changes were evident for amplitude. Overall, our study highlights the importance of TMS parameters for early TEP responses recording and suggests controlling their impact in developing connectivity biomarkers from TEPs. Moreover, these results point out that the excitability of the corticospinal tract, which is commonly used as a reference to set TMS intensity, may not correspond to the excitability of cortico-cortical pathways.

M1-P15 as a cortical marker for transcallosal inhibition: A preregistered TMS-EEG study.

In a recently published study combining transcranial magnetic stimulation and electroencephalography (TMS-EEG), an early component of TMS-evoked potentials (TEPs), i.e., M1-P15, was proposed as a measure of transcallosal inhibition between motor cortices. Given that early TEPs are known to be highly variable, further evidence is needed before M1-P15 can be considered a reliable index of effective connectivity. Here, we conceived a new preregistered TMS-EEG study with two aims. The first aim was validating the 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. The second aim was inducing a task-dependent modulation of transcallosal inhibition. A new sample of 32 healthy right-handed participants underwent behavioral motor tasks and TMS-EEG recording, in which left and right M1 were stimulated both during bimanual tasks and during an iSP paradigm. Hypotheses and methods were preregistered before data collection. Results show a replication of our previous findings on the positive relationship between M1-P15 amplitude and the iSP normalized area. Differently, the relationship between M1-P15 latency and bimanual coordination was not confirmed. Finally, M1-P15 amplitude was modulated by the characteristics of the bimanual task the participants were performing, and not by the contralateral hand activity during the iSP paradigm. In sum, the present results corroborate our previous findings in validating the M1-P15 as a cortical marker of transcallosal inhibition and provide novel evidence of its task-dependent modulation. Importantly, we demonstrate the feasibility of preregistration in the TMS-EEG field to increase methodological rigor and transparency.

A TMS/EEG protocol for the causal assessment of the functions of the oscillatory brain rhythms in perceptual and cognitive processes.

The combined use of transcranial magnetic stimulation (TMS), electroencephalogram (EEG), and behavioral performance allows investigation of causal relationships between neural markers and their functional relevance across a number of perceptual and cognitive processes. Here, we present a protocol for combining and applying these techniques on human subjects. We describe correlation approach and causal approach to disentangle the role of different oscillatory parameters, namely alpha frequency and amplitude that control for accuracy and metacognitive abilities, respectively, in a visual detection task. For complete details on the use and execution of this protocol, please refer to Di Gregorio et al. (2022).

Sharing motor plans while acting jointly: A TMS study.

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.

Tuning alpha rhythms to shape conscious visual perception.

It is commonly held that what we see and what we believe we see are overlapping phenomena. However, dissociations between sensory events and their subjective interpretation occur in the general population and in clinical disorders, raising the question as to whether perceptual accuracy and its subjective interpretation represent mechanistically dissociable events. Here, we uncover the role that alpha oscillations play in shaping these two indices of human conscious experience. We used electroencephalography (EEG) to measure occipital alpha oscillations during a visual detection task, which were then entrained using rhythmic-TMS. We found that controlling prestimulus alpha frequency by rhythmic-TMS modulated perceptual accuracy, but not subjective confidence in it, whereas controlling poststimulus (but not prestimulus) alpha amplitude modulated how well subjective confidence judgments can distinguish between correct and incorrect decision, but not accuracy. These findings provide the first causal evidence of a double dissociation between alpha speed and alpha amplitude, linking alpha frequency to spatiotemporal sampling resources and alpha amplitude to the internal, subjective representation and interpretation of sensory events.