Materiali biomimetici per l'ingegneria dei tessuti neurali

I danni al sistema nervoso centrale affliggono circa 2 milioni di persone all’anno, con conseguenze spesso devastanti. In questo lavoro di tesi sono presentate le enormi possibilità che sembrano poter essere offerte dall’ingegneria dei tessuti per la riparazione di midollo spinale lesionato. Sono descritte le caratteristiche richieste allo scaffold, i materiali che meglio rispondono a tali necessità e le principali tecniche di produzione. L’attenzione viene poi rivolta all’approccio biomimetico, che combina l’utilizzo di scaffolds con molecole biologicamente attive per ottenere materiali biomimetici capaci di indurre specifiche risposte cellulari e dirigere la formazione di nuovo tessuto mediante meccanismi di riconoscimento molecolare. Il lavoro si conclude citando alcuni studi sperimentali con lo scopo di mostrare come il comportamento cellulare in vitro possa essere influenzato da molteplici aspetti, sia fisici che biochimiciope

Electrophysiological evidence for domain-general processes in task-switching

open5noopenCapizzi, Mariagrazia; Ambrosini, Ettore; Arbula, Sandra; Mazzonetto, Ilaria; Vallesi, AntoninoCapizzi, Mariagrazia; Ambrosini, Ettore; Arbula, Sandra; Mazzonetto, Ilaria; Vallesi, Antonin

The neural bases of event monitoring across domains: a simultaneous ERP-fMRI study.

The ability to check and evaluate the environment over time with the aim to detect the occurrence of target stimuli is supported by sustained/tonic as well as transient/phasic control processes, which overall might be referred to as event monitoring. The neural underpinning of sustained control processes involves a fronto-parietal network. However, it has not been well-defined yet whether this cortical circuit acts irrespective of the specific material to be monitored and whether this mediates sustained as well as transient monitoring processes. In the current study, the functional activity of brain during an event monitoring task was investigated and compared between two cognitive domains, whose processing is mediated by differently lateralized areas. Namely, participants were asked to monitor sequences of either faces (supported by right-hemisphere regions) or tools (left-hemisphere). In order to disentangle sustained from transient components of monitoring, a simultaneous EEG-fMRI technique was adopted within a block design. When contrasting monitoring versus control blocks, the conventional fMRI analysis revealed the sustained involvement of bilateral fronto-parietal regions, in both task domains. Event-related potentials (ERPs) showed a more positive amplitude over frontal sites in monitoring compared to control blocks, providing evidence of a transient monitoring component. The joint ERP-fMRI analysis showed that, in the case of face monitoring, these transient processes rely on right-lateralized areas, including the inferior parietal lobule and the middle frontal gyrus. In the case of tools, no fronto-parietal areas correlated with the transient ERP activity, suggesting that in this domain phasic monitoring processes were masked by tonic ones. Overall, the present findings highlight the role of bilateral fronto-parietal regions in sustained monitoring, independently of the specific task requirements, and suggest that right-lateralized areas subtend transient monitoring processes, at least in some task contexts

Testing the domain-general nature of monitoring in the spatial and verbal cognitive domains

While it is well-established that monitoring the environment for the occurrence of relevant events represents a key executive function, it is still unclear whether such a function is mediated by domain-general or domain-specific mechanisms. We investigated this issue by combining event-related potentials (ERPs) with a behavioral paradigm in which monitoring processes (non-monitoring vs. monitoring) and cognitive domains (spatial vs. verbal) were orthogonally manipulated in the same group of participants. They had to categorize 3-dimensional visually presented words on the basis of either spatial or verbal rules. In monitoring blocks, they additionally had to check whether the word displayed a specific spatial configuration or whether it contained a certain consonant. The behavioral results showed slower responses for both spatial and verbal monitoring trials compared to non-monitoring trials. The ERP results revealed that monitoring did not interact with domain, thus suggesting the involvement of common underlying mechanisms. Specifically, monitoring acted on lower-level perceptual processes (as expressed by an enhanced visual N1 wave and a sustained posterior negativity for monitoring trials) and on higher-level cognitive processes (involving larger positive modulations by monitoring trials over frontal and parietal scalp regions). The source reconstruction analysis of the ERP data confirmed that monitoring was associated with increased activity in visual areas and in right prefrontal and parietal regions (i.e., superior and inferior frontal gyri and posterior parietal cortex), which previous studies have linked to spatial and temporal monitoring. Our findings extend this research by supporting the domain-general nature of monitoring in the spatial and verbal domains

Bayesian modeling of temporal expectations in the human brain

The brain predicts the timing of forthcoming events to optimize processes in response to them. Temporal predictions are driven by both our prior expectations on the likely timing of stimulus occurrence and the information conveyed by the passage of time. Specifically, such predictions can be described in terms of the hazard function, that is, the conditional probability that an event will occur, given it has not yet occurred. Events violating expectations cause surprise and often induce updating of prior expectations. While it is well-known that the brain is able to track the temporal hazard of event occurrence, the question of how prior temporal expectations are updated is still unsettled. Here we combined a Bayesian computational approach with brain imaging to map updating of temporal expectations in the human brain. Moreover, since updating is usually highly correlated with surprise, participants performed a task that allowed partially differentiating between the two processes. Results showed that updating and surprise differently modulated activity in areas belonging to two critical networks for cognitive control, the fronto-parietal (FPN) and the cingulo-opercular network (CON). Overall, these data provide a first computational characterization of the neural correlates associated with updating and surprise related to temporal expectation

EEG source reconstruction accuracy and integration of simultaneous EEG-fMRI resting state data

The resting state functional magnetic resonance imaging (fMRI) approach has allowed to investigate the large scale organization of processing systems in the human brain, revealing that it can be viewed as an integrative network of functionally interacting regions. However, to date the neuronal basis of the fluctuations of the fMRI signal at rest are not fully understood, preventing the possibility to elucidate their functional role. In this scenario, the integration with information derived from electroencephalography (EEG) is very useful, since conversely from fMRI, EEG represents a direct measure of neuronal activity. EEG-fMRI resting state studies investigating the correlation between fMRI signals and corresponding global EEG spectral characteristics in single spectral bands have provided a certain degree of inconsistency in the results. This may be due to the fact that the distinct functional networks involve more than a single frequency band and therefore analysis of simultaneous EEG/fMRI data should consider the whole frequency spectrum. A couple of studies have been performed in this directions but they either did not investigate how the scalp distribution of the EEG spectral metrics affects the patterns of correlations between EEG spectral dynamics and fMRI-derived resting state network or did not identify the specific scalp regions that specifically determined the pattern of observed results. To overcome this gap, with the aim to identify specific spatio-spectral fingerprints of distinct networks, a first study was conducted using an analytical approach that allows to take into account the interplay between the different EEG frequency bands and the corresponding topographic distribution within each network. Specifically, this approach was applied to four sub-components of the Default Mode Network (DMN). Results revealed for the first time the presence of distinctive subcomponent-specific spatial-frequency patterns of correlation between the fMRI signal and EEG rhythm. It should however be noted that spatial resolution of the EEG signal is too low to reliably infer about the location of the involved EEG sources. Therefore, a further step forward could be to try extending the findings of the first study in this direction by performing a source estimation study. Since it is not clear whether the 64 channels EEG system employed in the first study can provide adequate localization performance as regard our regions of interest, an investigation of the source reconstruction accuracy throughout the brain was performed in a second study. Specifically, the 64-channel montage was compared to 32-channel montage, the standard in the clinical practice, as well as to 128-channel montage and to 256- channel montage, considered as the upper reference point. Unlike previous studies, source performances were evaluated all over the cortical grey matter. Results indicate that the localization of the cortical sources of the spatio-spectral fingerprints revealed by the previous study can be adequately inferred by using 64 channels, but a confirmation study with a 128, or even better 256, channels montage is needed. Moreover, particular attention should be paid to investigate deep regions, where localization performance is worse regardless the number of electrodes used.Gli studi di risonanza magnetica funzionale (fMRI) in resting state hanno permesso di studiare l'organizzazione del cervello umano su ampia scala, rivelando che esso può essere visto come una rete di regioni funzionalmente connesse (networks). Ad oggi, però, le basi neurali delle fluttuazioni del segnale fMRI nelle varie regioni nella condizione di resting non sono pienamente comprese e ciò impedisce di chiarire il loro ruolo funzionale. In questo scenario, l'integrazione con l'informazione derivata dall'elettroencefalografia (EEG) è molto utile poiché questa,contrariamente alla risonanza magnetica funzionale, fornisce una misura diretta dell'attività neuronale. Finora, gli studi EEG-fMRI in condizioni di riposo che valutano le correlazioni fra il segnale fMRI e le caratteristiche spettrali del segnale EEG in una singola banda di interesse hanno portato a risultati tra loro incosistenti. Questo può essere dovuto al fatto che network funzionalmente distinti possono coinvolgere più di una singola banda, e quindi andrebbe analizzato l'intero spettro delle frequenze. Alcuni studi sono stati condotti in questa direzione ma o non hanno studiato come la distribuzione delle frequenze sullo scalpo influenza i pattern di correlazioni, o non hanno individuato quali regioni dello scalpo determinano in maniera specifica il pattern dei risultati osservati. Per superare questo limite, con lo scopo di identificare gli specifici correlati spazio-spettrali dei vari networks, un primo studio è stato condotto usando un approccio analitico che permette di considerare la relazione tre le differenti bande di frequenza EEG e la corrispondente distribuzione topografica all'interno di ciascun network. Specificatamente, questo approccio è stato applicato a quattro sottocomponenti del Default Mode Network. I risultati hanno rilevato per la prima volta la presenza di specifici pattern spazio-spettrali di correlazioni tra il segnale fMRI di un network e i diversi ritmi EEG. Dato che la risoluzione spaziale dell'EEG non permette di fare precise inferenze sulla localizzazione spaziale delle sorgenti neurali corrispondenti, un ulteriore passo in avanti potrebbe essere quello di estendere questi risultati con uno studio di ricostruzione delle sorgenti corticali. Inoltre, visto che non è chiaro se il sistema EEG a 64 canali utilizzato nel primo studio possa fornire performance accettabili, è stato fatto un secondo studio volto a valutare l’adeguatezza di questo sistema allo scopo. Nello specifico, l'accuratezza nel localizzare le sorgenti EEG ottenuta con il montaggio a 64 canali è stata confrontata con quelle ottenute con montaggi a 32 canali, lo standard in clinica, a 128 e a 256 canali. Diversamente da studi precedenti, le performance sono state valutate su tutto lo scalpo. I risultati indicano che le sorgenti corticali dei correlati spazio-spettrali dei network individuati nello studio precedente possono essere localizzate con una risoluzione spaziale adeguata usando 64 canali, sebbene sia necessario uno studio confermativo con 128 o 256 canali. Inoltre, andrebbe prestata particolare attenzione nel caso vengano investigate regioni cerebrali più profonde, nelle queli le performance sono basse a prescindere dal numero di canali utilizzato

Metodi e modelli per lo studio della connettività effettiva del default mode network estratto da immagini di risonanza magnetica funzionale in resting state

L’obiettivo di questa tesi è l’individuazione di un modello di connettività effettiva rappresentante le influenze causali che si esercitano tra i principali nodi del Default Mode Network a partire da dati fMRI in resting-state di nove volontari sani. Per ogni soggetto, mediante l’Independent Component Analysis, è stato individuato il default mode network, ciò ha consentito di localizzare i quattro principali nodi della rete di cui s

Materiali biomimetici per l'ingegneria dei tessuti neurali

I danni al sistema nervoso centrale affliggono circa 2 milioni di persone all’anno, con conseguenze spesso devastanti. In questo lavoro di tesi sono presentate le enormi possibilità che sembrano poter essere offerte dall’ingegneria dei tessuti per la riparazione di midollo spinale lesionato. Sono descritte le caratteristiche richieste allo scaffold, i materiali che meglio rispondono a tali necessità e le principali tecniche di produzione. L’attenzione viene poi rivolta all’approccio biomimetico, che combina l’utilizzo di scaffolds con molecole biologicamente attive per ottenere materiali biomimetici capaci di indurre specifiche risposte cellulari e dirigere la formazione di nuovo tessuto mediante meccanismi di riconoscimento molecolare. Il lavoro si conclude citando alcuni studi sperimentali con lo scopo di mostrare come il comportamento cellulare in vitro possa essere influenzato da molteplici aspetti, sia fisici che biochimic

The Neural Bases of Event Monitoring across Domains: a Simultaneous ERP-fMRI Study

The ability to check and evaluate the environment over time with the aim to detect the occurrence of target stimuli is supported by sustained/tonic as well as transient/phasic control processes, which overall might be referred to as event monitoring. The neural underpinning of sustained attentional control processes involves a fronto-parietal network. However, it has not been well-defined yet whether this cortical circuit acts irrespective of the specific material to be monitored and whether this mediates sustained as well as transient monitoring processes. In the current study, the functional activity of brain during an event monitoring task was investigated and compared between two cognitive domains, whose processing is mediated by differently lateralized areas. Namely, participants were asked to monitor sequences of either faces (supported by right-hemisphere regions) or tools (left-hemisphere). In order to disentangle sustained from transient components of monitoring, a simultaneous EEG-fMRI technique was adopted within a block design. When contrasting monitoring versus control blocks, the conventional fMRI analysis revealed the sustained involvement of bilateral fronto-parietal regions, in both task domains. Event-related potentials (ERPs) showed a more positive amplitude over frontal sites in monitoring compared to control blocks, providing evidence of a transient monitoring component. The joint ERP-fMRI analysis showed that, in the case of face monitoring, this transient component relies on right-lateralized areas, including the inferior parietal lobule and the middle frontal gyrus. In the case of tools, no fronto-parietal areas correlated with the transient ERP activity, suggesting that in this domain phasic monitoring processes were masked by tonic ones. Overall, the present findings highlight the role of bilateral fronto-parietal regions in sustained monitoring, independently of the specific task requirements, and suggest that right-lateralized areas subtend transient monitoring processes, at least in some task contexts