Transcranial direct current stimulation (tDCS) is a safe, feasible and affordable non-invasive brain stimulation technique which has gained great scientific and clinical interest in recent years. Low-amplitude direct current (< 4 mA) injected through scalp electrodes generates small electric fields in the brain and induces biological and, ultimately, behavioural changes. Although several computational predictions and in vivo recordings suggest that conventional tDCS can generate significant electric fields in subcortical regions, stimulation in depth is not focal and hardly controllable because fields decay in intensity and focality passing through head and cerebral tissues. Since the distribution of induced electric field depends also upon the number and position of stimulating electrodes, several authors have tried to steer the field by setting these parameters, and proposing a strategy called multi-electrode tDCS. Several computational models suggest this approach could be able to direct the current toward or away from specific brain areas. Also, it was proposed that multi-electrode montages could induce significant stimulation in deep targets and steer the field in such structures avoiding surroundings. These results have raised the interest on optimized tDCS as non-invasive deep brain stimulation (NDBS) technique, i.e., a brain stimulation technique which would allow to affect deep brain regions’ activity without resorting to neurosurgery. In this context, the present PhD dissertation explores the spatial distribution of the electric field induced by monopolar (i.e., with reference placed out of the scalp) multi-electrode tDCS in deep brain structures, using two different modelling approaches (i.e., computational modelling and physical phantom modelling), and studying the physiological effects at deep brain level of such protocols on healthy subjects through pontine and medullary reflexes assessments. Indeed, several studies suggest that the reference outside the scalp induces a concentration of currents and greater electric fields in deeper brain structures compared to cephalic montages. The studies presented in this thesis aim to assess the ability of monopolar multi-electrode montages to focally reach deep brain structures, and more generally, to assess the role of optimized tDCS in the NDBS field. MRI-based computational realistic human models are currently considered the gold-standard tools to estimate spatial-temporal distribution of tDCS-induced electric fields. In this work, several traditional and multi-electrode montages were tested, and electric fields induced in mid-brain and thalamus were assessed. Results suggested that monopolar multi-electrode montages might induce electric field intensities in deep brain structure comparable to those in grey matter. Since computational results are mathematical predictions, their reliability must be validated in real-world condition. Therefore, the monopolar multi-electrode montage was applied to a phantom head model (i.e., physical model reflecting the human brain physical characteristics) and the voltage and electric field distribution inside it was described. Results confirmed that monopolar multi-electrode montage might roughly induce focalized electric field in those layers approximating human brainstem. Lastly, the human application of previously modelled protocols is proposed. Monopolar multi-electrode montages were applied to healthy subjects, and changes in neurophysiological markers (i.e., trigeminal reflexes reflecting activity at pons and mid-brain) were assessed to evaluate the deep effects of stimulation. Results disclosed that trigeminal reflexes were selectively modulated by multi-electrode tDCS only when reference was placed over the right deltoid. In conclusion, this dissertation proposes a tDCS protocol which showed promising results in terms of non-invasive deep stimulation, and which could be used in clinical settings.
La stimolazione transcranica a corrente continua (transcranial direct current stimulation - tDCS) è una tecnica di stimolazione cerebrale non invasiva sicura, fattibile ed economica che ha riscosso grande interesse scientifico e clinico negli ultimi anni. Una corrente continua di bassa ampiezza (< 4 mA) applicata attraverso elettrodi di superficie genera piccoli campi elettrici nel cervello e induce cambiamenti biologici e comportamentali. Sebbene diverse stime computazionali e registrazioni in vivo suggeriscano che la tDCS convenzionale possa generare campi elettrici significativi nelle regioni sottocorticali, la stimolazione in profondità non è focale e difficilmente controllabile perché i campi decadono in intensità e focalità passando attraverso i tessuti cerebrali. Poiché la distribuzione del campo elettrico indotto dipende anche dal numero e dalla posizione degli elettrodi stimolanti, diversi autori hanno cercato di orientare i campi impostando questi parametri, proponendo una strategia chiamata tDCS multi-elettrodo. Diversi modelli computazionali suggeriscono che questo approccio potrebbe essere in grado di modulare il campo elettrico in modo selettivo in specifiche aree cerebrali. Inoltre, è stato suggerito che i montaggi multi-elettrodo possano indurre una stimolazione significativa in target cerebrali profondi, evitando le strutture circostanti. Questi risultati hanno suscitato l'interesse per la tDCS ottimizzata come tecnica di stimolazione cerebrale profonda non invasiva (non-invasive deep brain stimulation - NDBS), ovvero una tecnica di stimolazione cerebrale che consentirebbe di stimolare regioni cerebrali profonde senza ricorrere alla neurochirurgia. In questo contesto, la presente tesi di dottorato esplora la possibilità di utilizzare protocolli di tDCS multi-elettrodo monopolare (ovvero, con la referenza extracefalica) per influenza l’attività di strutture cerebrali profonde, utilizzando un approccio di modellizzazione computazionale validato su un fantoccio e in soggetti sani. Infatti, diversi studi suggeriscono che la referenza al di fuori dello scalpo induce una concentrazione di correnti e campi elettrici di maggiore intensità in strutture cerebrali profonde, rispetto ai montaggi cefalici. Gli studi presentati in questa tesi mirano a valutare la capacità di montaggi monopolari multi-elettrodo di raggiungere focalmente le strutture cerebrali profonde e, più in generale, a valutare il ruolo della tDCS ottimizzata nel campo dell'NDBS. I modelli computazionali umani basati sulla risonanza magnetica sono attualmente considerati gli strumenti gold standard per stimare la distribuzione spazio-temporale dei campi elettrici indotti da tDCS. In questo lavoro, sono stati testati diversi montaggi tradizionali e multi-elettrodo e sono stati valutati i campi elettrici indotti nel mesencefalo e nel talamo. I risultati ottenuti suggeriscono che i montaggi multi-elettrodo monopolari potrebbero indurre intensità di campo elettrico nella struttura cerebrale profonda paragonabili a quelle nella materia grigia. Il montaggio multi-elettrodo monopolare è stato in seguito applicato a un modello fantoccio di testa umana ed è stata confrontata la distribuzione della tensione e del campo elettrico predetta al suo interno con quella effettivamente misurata. I risultati hanno confermato che il montaggio multi-elettrodo monopolare potrebbe indurre approssimativamente un campo elettrico focalizzato in quegli strati che nel modello fantoccio simulano il tronco encefalico umano. Infine, viene proposta l'applicazione umana di protocolli precedentemente modellizzati. I montaggi multi-elettrodo monopolari sono stati applicati a soggetti sani e sono stati valutati i cambiamenti nei marcatori neurofisiologici (cioè riflessi trigeminali che riflettono l'attività del ponte e mesencefalo) per valutare l’efficacia della stimolazione nelle strutture profonde, ovvero ponte ed il mesencefalo. I risultati hanno rivelato che i riflessi del trigemino sono stati selettivamente modulati dalla tDCS multi-elettrodo solo quando il riferimento è stato posto sopra il deltoide destro. In conclusione, questa dissertazione propone un protocollo tDCS che ha mostrato risultati promettenti in termini di stimolazione profonda non invasiva e che si è rivelato promettente per le applicazioni cliniche.
Development of a non-invasive deep brain stimulation protocol through the transcranial electrical stimulation paradigms
Guidetti, Matteo
2022/2023
Abstract
Transcranial direct current stimulation (tDCS) is a safe, feasible and affordable non-invasive brain stimulation technique which has gained great scientific and clinical interest in recent years. Low-amplitude direct current (< 4 mA) injected through scalp electrodes generates small electric fields in the brain and induces biological and, ultimately, behavioural changes. Although several computational predictions and in vivo recordings suggest that conventional tDCS can generate significant electric fields in subcortical regions, stimulation in depth is not focal and hardly controllable because fields decay in intensity and focality passing through head and cerebral tissues. Since the distribution of induced electric field depends also upon the number and position of stimulating electrodes, several authors have tried to steer the field by setting these parameters, and proposing a strategy called multi-electrode tDCS. Several computational models suggest this approach could be able to direct the current toward or away from specific brain areas. Also, it was proposed that multi-electrode montages could induce significant stimulation in deep targets and steer the field in such structures avoiding surroundings. These results have raised the interest on optimized tDCS as non-invasive deep brain stimulation (NDBS) technique, i.e., a brain stimulation technique which would allow to affect deep brain regions’ activity without resorting to neurosurgery. In this context, the present PhD dissertation explores the spatial distribution of the electric field induced by monopolar (i.e., with reference placed out of the scalp) multi-electrode tDCS in deep brain structures, using two different modelling approaches (i.e., computational modelling and physical phantom modelling), and studying the physiological effects at deep brain level of such protocols on healthy subjects through pontine and medullary reflexes assessments. Indeed, several studies suggest that the reference outside the scalp induces a concentration of currents and greater electric fields in deeper brain structures compared to cephalic montages. The studies presented in this thesis aim to assess the ability of monopolar multi-electrode montages to focally reach deep brain structures, and more generally, to assess the role of optimized tDCS in the NDBS field. MRI-based computational realistic human models are currently considered the gold-standard tools to estimate spatial-temporal distribution of tDCS-induced electric fields. In this work, several traditional and multi-electrode montages were tested, and electric fields induced in mid-brain and thalamus were assessed. Results suggested that monopolar multi-electrode montages might induce electric field intensities in deep brain structure comparable to those in grey matter. Since computational results are mathematical predictions, their reliability must be validated in real-world condition. Therefore, the monopolar multi-electrode montage was applied to a phantom head model (i.e., physical model reflecting the human brain physical characteristics) and the voltage and electric field distribution inside it was described. Results confirmed that monopolar multi-electrode montage might roughly induce focalized electric field in those layers approximating human brainstem. Lastly, the human application of previously modelled protocols is proposed. Monopolar multi-electrode montages were applied to healthy subjects, and changes in neurophysiological markers (i.e., trigeminal reflexes reflecting activity at pons and mid-brain) were assessed to evaluate the deep effects of stimulation. Results disclosed that trigeminal reflexes were selectively modulated by multi-electrode tDCS only when reference was placed over the right deltoid. In conclusion, this dissertation proposes a tDCS protocol which showed promising results in terms of non-invasive deep stimulation, and which could be used in clinical settings.| File | Dimensione | Formato | |
|---|---|---|---|
|
PhD thesis_GUIDETTI.pdf
solo utenti autorizzati a partire dal 18/05/2024
Dimensione
8.59 MB
Formato
Adobe PDF
|
8.59 MB | Adobe PDF | Visualizza/Apri |
I documenti in POLITesi sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/10589/204590