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.

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.

(2020). TMS-EEG: a promising tool to study the cathodal tDCS effects on cortical excitability. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2020).

TMS-EEG: a promising tool to study the cathodal tDCS effects on cortical excitability

VAROLI, ERICA
2020

Abstract

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.
ROMERO LAURO, LEONOR JOSEFINA
TMS-EEG; tDCS catodica; PPC destra; attenzione; Posner
TMS-EEG; cathodal tDCS; right PPC; attention; Posner
M-PSI/02 - PSICOBIOLOGIA E PSICOLOGIA FISIOLOGICA
English
30-gen-2020
NEUROSCIENZE
32
2018/2019
open
(2020). TMS-EEG: a promising tool to study the cathodal tDCS effects on cortical excitability. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2020).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/280669
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