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Introduction : Despite tDCS is increasingly used in experimental and clinical settings, its precise mechanisms remain largely unknown. At a neuronal level, tDCS modulates the cortical excitability by shifting the resting membrane potential in a polarity-dependent way: anodal stimulation increases the spontaneous firing rate, while cathodal decreases it. So far, the neurophysiological underpinnings of the immediate and delayed effects of tDCS are still unclear, as well as, how the stimulation of a given cerebral region may affect the activity of anatomically connected regions. In a previous study it has been investigated the tDCS anodal’s effect on the cortical excitability, by the means of TMS-EEG, showing a diffuse rise of cortical excitability in a bilateral fronto-parietal networks. Methods : Fifteen healthy, right-handed volunteers participated in the study. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after a 10 minutes long session of cathodal tDCS stimulation over the right PPC, while EEG was recorded from 60 channels. For each TMS session, indexes of global and local cerebral excitability were obtained, computed as global and local mean field power (Global Mean Field Power, GMFP and Local Mean Field Power, LMFP) on the mean TMS-evoked potentials (TEPs) for three temporal windows: 0-50, 50-100 and 100-150 ms. The global index was computed on all the 60 channels. While, the local indexes were computed in four different clusters of electrodes: left and right, in frontal and parietal regions. Results : The preliminary results show no differences in both the TMS sessions during and after cathodal tDCS compared to pre-stimulation one, both at global and local level. A further test using bayesian analysis was performed, providing a moderate indication toward null hypothesis. Discussion : These results are consistent with the literature in which the coupling of anodal-excitatory and cathodal-inhibitory effects are well established in the sensory and motor domains, both at physiological and behavioral levels, while the evidence is more controversial for higher-level mental activity. References : Bindman L. et al. Nature. (1962) 196:584e585. Jacobson L.et al. Exp Brain Res. (2012) 216(1):1-10. Romero Lauro L. J. Et al. Cortex, (2014) 58:99e111

A growing body of research has shown that the psychological experience of power causes people to misperceive their height. As such, people perceive themselves as taller when they felt more powerful. Combining research on embodied cognition with that on neurostimulation, we tested whether feeling powerful affects the vertical boundaries of the own body schema by measuring corticospinal excitability. Participants (N=55) were randomly assigned to feel high power, low power, or positive mood unrelated to power and were asked to view an object positioned either in the peripersonal or in the extrapersonal vertical space. We assessed corticospinal excitability by measuring motor evoked potentials (MEPs) using TMS-EMG co-registration. Results show that in the high power condition MEPs did not differ when the object was in the peripersonal (vs extrapersonal) space. Thus, feeling powerful induces changes in the body representation that is traceable also at the corticospinal level and arises from a remapping of peripersonal space boundaries. Taken together, our findings extend prior work by revealing that the symbolic association between power and height impacts self-perception and the surrounding environment.

Despite transcranial direct current stimulation (tDCS) is increasingly used in experimental and clinical settings, its precise mechanisms of action remain largely unknown. At a neuronal level, tDCS modulates the cortical excitability by shifting the resting membrane potential in a polarity-dependent way: anodal stimulation increases the spontaneous firing rate in the stimulated region, while cathodal decreases it. So far, the neurophysiological underpinnings of the immediate and delayed effects of tDCS are still unclear, as well as, it is not fully understood how the stimulation of a given cerebral region may affect the activity of anatomically connected regions. In a previous study it has been investigated the tDCS anodal’s role in the cortical excitability, by a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG). Results showed a diffuse rise of cortical excitability in a bilateral fronto-parietal networks. In the present study, we used the same technique and methodological setting in order to explore local and global cortical excitability modulation during and after cathodal tDCS. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after 10 minutes of tDCS over the right PPC, while EEG was recorded from 60 channels. For each session, indexes of global and local cerebral excitability were obtained, computed as global and local mean field power (Global Mean Field Power, GMFP and Local Mean Field Power, LMFP) on mean TMS-evoked potentials (TEPs) for four temporal windows: 0-50, 50-100, 100-150 and 150-200 milliseconds. The global index was computed on all 60 channels. The local indexes were computed in four clusters of electrodes: left and right, in frontal and parietal regions. The preliminary results on nine subjects show no differences in both sessions during and after cathodal tDCS compared to pre-stimulation session. These preliminary results suggest the existence of a difference effect due to anodal and cathodal tDCS stimulation, also in other areas, different from the motor cortex.

La stimolazione elettrica transcranica (tDCS) è sempre più impiegata sia in ambito clinico sia sperimentale, nonostante questo i suoi precisi meccanismi di funzionamento rimangono in gran parte sconosciuti. È noto che a livello neuronale, la tDCS modula l’eccitabilità corticale modificando il potenziale di membrana a riposo in modo polarità-dipendente: la stimolazione anodica aumenta il firing rate spontaneo delle regioni direttamente stimolate, al contrario quella catodica lo diminuisce (Bindman et Al, 1964). Tuttavia, le basi neurofisiologiche degli effetti della tDCS, diretti e post-stimolazione, sono ancora poco chiare, così come non si è ancora del tutto compreso come la stimolazione di una data area possa indurre degli effetti anche in regioni anatomicamente connesse a essa (Jacobson et al. 2012). In un precedente lavoro sono stati esplorati gli effetti della stimolazione tDCS anodica sull’eccitabilità corticale tramite l’utilizzo di una tecnica che combina la Stimolazione Magnetica Transcranica (TMS) alla registrazione Elettroencefalografica (EEG). I risultati hanno mostrato un diffuso aumento dell’eccitabilità corticale in un network bilaterale fronto-parietale (Romero Lauro et al., 2014). Nel presente studio è stata utilizzata la stessa tecnica e il medesimo setting sperimentale al fine di esplorare gli effetti di modulazione dell’eccitabilità corticale indotti dalla stimolazione tDCS catodica, sia a livello globale sia a livello locale. Materiali e Metodi È stata applicata la TMS a impulso singolo sulla corteccia parietale posteriore (PPC) sinistra, prima, durante e dieci minuti dopo la stimolazione tDCS in corrispondenza della PPC destra. Durante le tre sessioni di stimolazione sono stati registrati i potenziali evocati dalla TMS (TEPs) mediante una cuffia a sessanta canali. Dei TEPs sono state considerate per l’analisi quattro diverse finestre temporali: 0 (onset TMS) -50, 50-100, 100-150 and 150-200 millisecondi. Per ognuna di esse sono stati ricavati gli indici di eccitabilità corticale, sia globale sia locale, calcolando rispettivamente il Global e Local Mean Field Power (GMFP e LMFP) sulla media dei TEPs. Il GMFP è stato ottenuto analizzando il segnale derivante da tutti i sessanta canali EEG. Il LMFP, invece, è stato calcolato su quattro clusters di elettrodi: parietale destro (CP2, CP4, P2, e P4), parietale sinistro (CP1, CP3, P1, e P3), frontale destro (F2, F6, FC2, e FC6) e frontale sinistro (F1, F5, FC1, e FC3). Risultati e Discussione I risultati preliminari mostrano un’assenza di differenze significative tra le tre condizioni di stimolazione. Un’analisi bayesiana mostra un’indicazione moderata per l’ipotesi nulla. Questi risultati sono in linea con gli studi in letteratura che riportano come gli effetti della tDCS catodica risultino piuttosto controversi quando sono interessate aree che sottendono a funzioni cognitive di ordine superiore (Jacobson et al., 2012). Bibliografia 1. Bindman, L. J., Lippold, O. C., & Redfearn, J. W. (1962). Long-lasting changes in the level of the electrical activity of the cerebral cortex produced by polarizing currents. Nature, 196, 584e585. 2. Jacobson, L., Koslowsky, M., & Lavidor, M. (2012). tDCS polarity effects in motor and cognitive domains: a meta-analytical review. Experimental brain research, 216(1), 1-10. 3. Romero Lauro, L. J., Rosanova, M., Mattavelli, G., Convento, S., Pisoni, A., Opitz, A., et al. (2014). TDCS increases cortical excitability: direct evidence from TMS-EEG. Cortex, 58, 99e111.

The coupling of tDCS polarity-dependent opposite effect is well established in the sensorimotor domain but is still controversial when higher cognitive functions are targeted. Previous studies from our group showed that at resting state anodal tDCS (a-tDCS) over the right parietal cortex (rPPC) elicited a widespread increase of cortical excitability, whereas cathodal stimulation (c-TDCS) failed to modulate cortical excitability, being indistinguishable from sham stimulation. Here we assessed whether the active state of the targeted region might change the picture. We applied c-tDCS over the rPPC while our participants were performing a visuo-attentional task, namely Posner Cueing task (PCT). TDCS neurophysiological aftereffects were tracked performing TMS-EEG recordings pre- and post- either sham or real stimulation. In particular, single pulses TMS were delivered over the left PPC and TMS evoked potentials were recorded with a 64ch cap. Analyses were then performed both at the sensors and at the cortical source level. Behavioral results showed that c-tDCS significantly slowed down PCT performance in comparison to sham condition. Crucially, at a neurophysiological level, c-tDCS but not Sham significantly reduced cortical excitability in the brain areas involved in task execution, namely in a fronto-parietal network. Therefore, c-TDCS neurophysiological effects over rPPC resulted depending on the background activity. These results hold relevant implications for tDCS set up both in cognitive neuroscience experiments and rehabilitation protocols.

La Stimolazione transcranica a Corrente Diretta continua (tDCS) è una tecnica di neurostimolazione non invasiva in grado di generare alterazioni dell’eccitabilità neuronale dipendenti dalla plasticità. Negli ultimi anni si sta assistendo a un crescente interesse nell’utilizzo di questa tecnica, sia in settings clinici che sperimentali. In particolare, la possibilità di indurre effetti a lungo termine rende la tDCS interessante nel trattamento di deficit cognitivi associati a disturbi sia neuropsicologici che psichiatrici. Nonostante la sua crescente diffusione, si sa ancora poco riguardo i meccanismi neurofisiologici alla base del suo funzionamento, soprattutto per quanto riguarda gli effetti su regioni cerebrali che sottostanno a funzioni cognitive di ordine superiore. Una conoscenza più approfondita dei meccanismi alla base della tDCS potrebbe quindi essere cruciale per riuscire a definire e migliorare i protocolli di stimolazione sia clinici che di ricerca. A questo scopo, uno studio sistematico degli effetti corticali della tDCS appare ancora più necessario. In questo progetto abbiamo quindi esplorato gli effetti di plasticità corticale indotti dalla stimolazione catodica in soggetti sani, sia a riposo che durante l’esecuzione di un compito, utilizzando il sistema integrato di Stimolazione Magnetica Transcranica ed Elettroencefalografia (TMS-EEG). Il TMS-EEG è una tecnica molto efficace in quando permette di misurare direttamente la modulazione dell’eccitabilità corticale su tutta la corteccia. In questa tesi sono riportati tre studi. Nel primo, partendo dai risultati sulla tDCS anodica già precedentemente pubblicati, sono stati esplorati gli effetti della tDCS catodica sulla Corteccia Parietale Posteriore (PPC) destra a riposo. Nel secondo studio, abbiamo indagato gli effetti comportamentali indotti dalla tDCS catodica sulla PPC destra, durante l’esecuzione di due compiti: uno di memoria di lavoro visuospaziale e uno di orientamento dell’attenzione visuospaziale. Nel terso studio, infine, abbiamo utilizzato nuovamente il TMS-EEG per tracciare gli effetti neurofisiologici della tDCS catodica sulla PPC di destra mentre i partecipanti erano impegnati nell’esecuzione dei compiti individuati nello studio precedente. I risultati per la tDCS catodica a riposo non hanno mostrato effetti di modulazione dell’eccitabilità corticale, sia a livello dei sensori che a livello delle sorgenti, sia a livello locale che globale. I risultati precedentemente ottenuti con la tDCS anodica, hanno invece mostrato un aumento diffuso dell’eccitabilità corticale lungo un network bilaterale frontoparietale, che rispecchia le connessioni strutturali tra le aree d’interesse. Durante l’esecuzione di un compito, invece, la stimolazione catodica, così come quella anodica, ha mostrato una modulazione nell’eccitabilità corticale solo in quelle aree che sono coinvolte nell’esecuzione del compito. In conclusione, in questo lavoro di tesi emergono diversi interessanti risultati. Innanzitutto, questi dati mostrano un effetto non lineare della tDCS sull’eccitabilità corticale a riposo, che non possono essere completamente spiegati dal semplice dualismo anodico-eccitatorio catodico-inibitorio. Un altro risultato rilevante è dato dal ruolo cruciale giocato dai differenti stati ti attivazione corticale (a riposo Vs attivo). Questi risultati sembrano mostrare che il livello di attivazione corticale di base contribuisca a modulare gli effetti della stimolazione, in accordo con l’ipotesi “attività-selettività”. Lo stato di attivazione di base deve quindi essere preso in considerazione, in particolare se si vogliono osservare degli effetti di neuromodulazione con tDCS catodica. In generale, tutte queste osservazioni contribuiscono a costruire quel corpus di conoscenze necessario soprattutto per la definizione dei parametri tDCS sia per esperimenti di neuroscienze cognitive che per protocolli riabilitativi. Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulatory technique able to induce plasticity-related alterations in neuronal excitability. There is a growing interest in the use of tDCS in both experimental and clinical settings; in particular, the chance to induce long-term effects fostered the used of the technique to treat cognitive impairments associated with different neuropsychological and psychiatric disorders. Although tDCS is increasingly used, presently little is still known about its neurophysiological underpinnings, particularly concerning the activity on the brain regions that underlie high cognitive brain functions. In these cases, optimal tDCS stimulation parameters also have yet to be clearly defined. A deeper understanding of the mechanisms underpinning this technique would be crucial to achieving a better refinement of stimulation protocols for clinical and research purposes. For this reason, a systematic and comprehensive study of its cortical effects acquires a critical relevance. In the last years, there has been indeed a keen interest in understanding the working mechanisms of this technique. To address this issue, in this project we explored the cortical plasticity modulation induced by cathodal stimulation on healthy subjects while resting or during task execution, using an integrated system of Transcranial Magnetic Stimulation and Electroencephalography (TMS-EEG), which allows to directly measure cortical excitability modulation all over the cortex and effective connectivity. In the first study, starting from the previous results with anodal tDCS, the effects of cathodal stimulation over the right Posterior Parietal Cortex (PPC) were explored during resting state. The contralateral homologue brain area, namely the left posterior parietal cortex (PPC), was targeted with TMS before, during, and after cathodal stimulation. In the second study, we explored the behavioural effects induced by the application of cathodal tDCS over right PPC during the execution of two tasks, one of visuospatial working memory and a second tapping visual attention reorienting, which are known to involve this brain area. The aim was to find tasks sensitive to the effect of cathodal tDCS over the right PCC, to be used in the third study. A disruption of the performance was found for the Posner Cueing Task. In the third study, we employed again TMS-EEG to track the neurophysiological effects of cathodal tDCS on right PPC at an active state, i.e. while the participants were performing the task tested on the second study. The results at resting state for cathodal tDCS, both at sensors and cortical sources levels, converge in showing no differences during and after tDCS compared to pre-stimulation sessions, both at a global and local level. The previous results with anodal tDCS, instead, reported a widespread rise of cortical excitability along with a bilateral frontoparietal network, following structural connections. On the other hand, at an active state, cathodal, as well as anodal, tDCS induced modulation of cortical excitability only in the task-relevant brain regions. Several significant findings emerged from this empirical work. First of all, these data highlight a non-linear impact of anodal and cathodal stimulation on cortical excitability at rest that is not depicted by the simplistic view of anodal-excitatory and cathodal-inhibitory effects. Another relevant point is the crucial role played by the different cortical states (resting vs active). These results seem to point out that the level of cortical state can contribute to modulate the tDCS effects, in line with “activity-selectivity” hypothesis. The level of cortical state needs to be taken into account, especially to observe neuromodulatory effects also with cathodal tDCS. All these findings hold relevant implications for tDCS setup in both cognitive neuroscience experiments and rehabilitation protocols.

Transcranial static magnetic stimulation (tSMS) was recently added to the family of non-invasive brain stimulation techniques. It offers promising perspectives being the only neuromodulatory technique that can produce changes in cortical excitability without inducing electric currents. Recent studies demonstrated that the application, for different time intervals, of static magnetic fields on the primary motor cortex (M1) can produce both short and long-lasting effects, consisting in a reduction of motor cortex excitability. Nevertheless, the mechanisms underpinning this new neuromodulatory technique are still mostly unclear. In this study, we use a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG) to explore local and global cortical excitability modulation after a 15 minutes session of tSMS on the supplementary motor area (SMA). Single pulse TMS was delivered over the right SMA, before and after the tSMS sessions, while EEG data were recorded from 60 channels. For each session, indexes of global and local cerebral excitability were obtained, computed as global and local mean field power (Global Mean Field Power, GMFP and Local Mean Field Power, LMFP) on mean TMS-evoked potentials (TEPs), for three temporal windows: 0-50, 50-100 and 100-150 milliseconds. The global index was computed on all 60 channels. The local indexes were computed in different clusters correspondent to the SMA and to the left and right M1 and premotor cortex (PMC). We hypothesize a change in cortical excitability after the tSMS session, not only in the area directly stimulated, but also in the regions functionally and structurally connected to it. These results could prompt the use of this simple, portable and low-cost technique even in clinical and rehabilitation protocols.

Converging evidence suggests that peripersonal space has dynamic properties, that can be influenced by motor and cognitive factors. Here, we investigated whether changes in self-perception may impact upon peripersonal representation. Specifically, employing non-invasive brain stimulation, we tested whether corticospinal excitability elicited by objects placed in the vertical peripersonal vs extrapersonal space can be influenced by changes in self-perception after recalling a personal experience inducing the feeling of high power (vs. positivity vs. low power). In a preliminary study (Study 1, N = 39) participants were presented with an object, whose position was manipulated in the horizontal vs vertical space. We assessed corticospinal excitability by measuring Motor Evoked Potentials (MEPs) using Transcranial Magnetic Stimulation with Electromyography co-registration (TMS-EMG). In the horizontal condition, we replicated the well-known motor facilitation induced by objects falling in the peri vs extrapersonal space, while in the vertical dimension MEPs were higher in the extrapersonal space. In the main experiment (Study 2), participants (N = 55) were randomly assigned to feel high power, low power, or a general positive emotion and were asked to observe the same object positioned either in the peripersonal or in the extrapersonal vertical space. Results showed that in the low power condition MEPs were higher in the extrapersonal vs peripersonal, as in Study 1, while in high power and positive conditions MEPs were not influenced by distance. Taken together, our findings suggest a dissociable pattern of motor facilitation underlying vertical vs horizontal space perception and, crucially, that changes in self-perception can influence such a representation.

In a previous sham-controlled study, we showed the feasibility of increasing language comprehension in healthy participants by applying anodal transcranial direct current stimulation (atDCS) over the left inferior frontal gyrus (LIFG). In the present work, we present a follow-up experiment targeting with atDCS the left inferior parietal cortex (LIPC) while participants performed the same auditory comprehension task used in our previous experiment. Both neural sites (LIFG and LIPC) are crucial hubs of Baddeley’s model of verbal short-term memory (vSTM). AtDCS over LIPC decreased accuracy as compared to sham and LIFG stimulation, suggesting the involvement of this area in sentence comprehension. Crucially, our results highlighted that applying tDCS over different hubs of the same neural network can lead to opposite behavioural results, with relevant implications from a clinical perspective.

We tested the possibility of enhancing natural language comprehension through the application of anodal tDCS (a-tDCS) over the left inferior frontal gyrus, a key region for verbal short-term memory and language comprehension. We designed a between subjects sham- and task-controlled study. During tDCS stimulation, participants performed a sentence to picture matching task in which targets were sentences with different load on short-term memory. Regardless of load on short-term memory, the Anodal group performed significantly better than the Sham group, thus providing evidence that a-tDCS over LIFG enhances natural language comprehension. To our knowledge, we apply for the first time tDCS to boost sentence comprehension. This result is of special interest also from a clinical perspective: applying a-tDCS in patients manifesting problems at the sentence level due to brain damage could enhance the effects of behavioral rehabilitation procedures aimed to improve language comprehension.

Transcranial direct current stimulation (tDCS) is increasingly used in both research and therapeutic settings, but its precise mechanisms remain largely unknown. At a neuronal level, tDCS modulates cortical excitability by shifting the resting membrane potential in a polarity-dependent way: anodal stimulation increases the spontaneous firing rate, while cathodal decreases it. However, the neurophysiological underpinnings of anodal/cathodal tDCS seem to be different, as well as their behavioral effect, in particular when high order areas are involved, compared to when motor or sensory brain areas are targeted. Previously, we investigated the effect of anodal tDCS on cortical excitability, by means of a combination of Transcranial Magnetic Stimulation (TMS) and Electroencephalography (EEG). Results showed a diffuse rise of cortical excitability in a bilateral fronto-parietal network. In the present study, we tested, with the same paradigm, the effect of cathodal tDCS. Single pulse TMS was delivered over the left posterior parietal cortex (PPC), before, during, and after 10 min of cathodal or sham tDCS over the right PPC, while recording HD-EEG. Indexes of global and local cortical excitability were obtained both at sensors and cortical sources level. At sensors, global and local mean field power (GMFP and LMFP) were computed for three temporal windows (0-50, 50-100, and 100-150 ms), on all channels (GMFP), and in four different clusters of electrodes (LMFP, left and right, in frontal and parietal regions). After source reconstruction, Significant Current Density was computed at the global level, and for four Broadmann's areas (left/right BA 6 and 7). Both sensors and cortical sources results converge in showing no differences during and after cathodal tDCS compared to pre-stimulation sessions, both at global and local level. The same holds for sham tDCS. These data highlight an asymmetric impact of anodal and cathodal stimulation on cortical excitability, with a diffuse effect of anodal and no effect of cathodal tDCS over the parietal cortex. These results are consistent with the current literature: while anodal-excitatory and cathodal-inhibitory effects are well-established in the sensory and motor domains, both at physiological and behavioral levels, results for cathodal stimulation are more controversial for modulation of exitability of higher order areas.

When making decisions, people are typically differently sensitive to gains and losses according to the motivational context in which the choice is performed. As hypothesized by Regulatory Focus Theory (RFT), indeed, goals are supposed to change in relation to the set of possible outcomes. In particular, in a promotion context, the goal is achieving the maximal gain, whereas in a prevention context it turns into avoiding the greatest loss. We explored the neurophysiological counterpart of this phenomenon, by applying Transcranial Magnetic Stimulation (TMS) and recording the motor evoked potentials (MEPs) in participants taking part in an economic game, in which they observed actions conveying different goal attainment levels, framed in different motivational contexts. More than the actual value of the economic exchange involved in the game, what affected motor cortex excitability was the goal attainment failure, corresponding to not achieving the maximal payoff in a promotion context and not avoiding the greatest snatch in a prevention context. Therefore, the results provide support for the key predictions of RFT, identifying a neural signature for the goal attainment failure.

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