A successful interaction with objects in the environment requires integrating information concerning object-location with the shape, dimension and position of body parts in space. The former information is coded in a multisensory representation of the space around the body, i.e. peripersonal space (PPS), whereas the latter is enabled by an online, constantly updated, action-orientated multisensory representation of the body (BR) that is critical for action. One of the critical features of these representations is that both PPS and BR are not fixed, but they dynamically change depending on different types of experience. In a series of experiment, I studied plastic properties of PPS and BR in humans. I have developed a series of methods to measure the boundaries of PPS representation (Chapter 4), to study its neural correlates (Chapter 3) and to assess BRs. These tasks have been used to study changes in PPS and BR following tool-use (Chapter 5), multisensory stimulation (Chapter 6), amputation and prosthesis implantation (Chapter 7) or social interaction (Chapter 8). I found that changes in the function (tool-use) and the structure (amputation and prosthesis implantation) of the physical body elongate or shrink both PPS and BR. Social context and social interaction also shape PPS representation. Such high degree of plasticity suggests that our sense of body in space is not given at once, but it is constantly constructed and adapted through experience. / Allo scopo di interagire con oggetti presenti nell’ambiente esterno è necessario integrare le informazioni sulla posizione degli oggetti nello spazio con informazioni riguardanti la forma, dimensione e posizione delle singole parti del corpo rispetto all’oggetto stesso. Due diverse rappresentazioni supportano la codifica di tali informazioni: da una parte, la rappresentazione dello Spazio Peripersonale, una rappresentazione multisensoriale dello spazio intorno al corpo, e dall’altra una rappresentazione multisensoriale del corpo, costantemente aggiornata e orientata all’azione. Una caratteristica critica di queste rappresentazioni è rappresentata dalle loro proprietà plastiche, cioè dalla possibilità di modificarsi in seguito a diversi tipi di esperienza. In questa tesi mi sono focalizzata sullo studio delle proprietà plastiche delle rappresentazioni del corpo e dello spazio peripersonale. Ho sviluppato una serie di metodi per valutare il confine dello spazio peripersonale (Capitolo 4), per studiare i suoi correlati neurali (Capitolo 3) e per valutare le rappresentazioni multisensoriali del corpo. Questi compiti sono stati usati per studiare modificazioni plastiche del corpo e dello spazio peripersonale in seguito all’utilizzo di uno strumento (Capitolo 5), in seguito a una stimolazione multisensoriale (Capitolo 6), amputazione e impianto di protesi (Capitolo 7) e nell’ambito delle interazioni sociali. I risultati ottenuti hanno mostrato come la modificazione nella funzione (in seguito all’utilizzo di uno strumento) o della struttura fisica (in seguito ad amputazione ed impianto di protesi) del corpo determinano una estensione o una contrazione sia della rappresentazione dello spazio peripersonale che della rappresentazione del corpo. Inoltre, i risultati ottenuti hanno dimostrato che la rappresentazione dello spazio peripersonale viene plasmata anche dalle interazioni sociali. Tale livello di plasticità suggerisce che l’esperienza del nostro corpo viene continuata costruita e aggiornata tramite le diverse esperienze.

Lesions to the primary geniculo-striate visual pathway cause blindness in the contralesional visual field. Nevertheless, previous studies have suggested that patients with visual field defects may still be able to implicitly process the affective valence of unseen emotional stimuli (affective blindsight) through alternative visual pathways bypassing the striate cortex. These alternative pathways may also allow exploitation of multisensory (audio-visual) integration mechanisms, such that auditory stimulation can enhance visual detection of stimuli which would otherwise be undetected when presented alone (crossmodal blindsight). The present dissertation investigated implicit emotional processing and multisensory integration when conscious visual processing is prevented by real or virtual lesions to the geniculo-striate pathway, in order to further clarify both the nature of these residual processes and the functional aspects of the underlying neural pathways. The present experimental evidence demonstrates that alternative subcortical visual pathways allow implicit processing of the emotional content of facial expressions in the absence of cortical processing. However, this residual ability is limited to fearful expressions. This finding suggests the existence of a subcortical system specialised in detecting danger signals based on coarse visual cues, therefore allowing the early recruitment of flight-or-fight behavioural responses even before conscious and detailed recognition of potential threats can take place. Moreover, the present dissertation extends the knowledge about crossmodal blindsight phenomena by showing that, unlike with visual detection, sound cannot crossmodally enhance visual orientation discrimination in the absence of functional striate cortex. This finding demonstrates, on the one hand, that the striate cortex plays a causative role in crossmodally enhancing visual orientation sensitivity and, on the other hand, that subcortical visual pathways bypassing the striate cortex, despite affording audio-visual integration processes leading to the improvement of simple visual abilities such as detection, cannot mediate multisensory enhancement of more complex visual functions, such as orientation discrimination. / Una lesione alla via visiva primaria (genicolo-striata) causa cecità nel campo visivo controlesionale. Ciononostante, studi precedenti suggeriscono che, mediante vie visive alternative che non coinvolgono la corteccia striata, i pazienti con deficit di campo visivo potrebbero ancora riuscire ad elaborare implicitamente la valenza affettiva degli stimoli emotivi non visti (affective blindsight) e di sfruttare meccanismi multisensoriali (audio-visivi), cosicchè la stimolazione uditiva migliori la detezione visiva di stimoli non percepiti quando presentati da soli (crossmodal blindsight). Nella presente tesi si sono indagate l’elaborazione emotiva implicita e l’integrazione multisensoriale osservabili quando l’elaborazione visiva cosciente è impedita da lesioni reali o virtuali della via genicolo-striata, in modo da chiarire sia la natura di tali processi sia gli aspetti funzionali dei circuiti neurali sottostanti. Le evidenze sperimentali qui presentate dimostrano che, in assenza di elaborazione corticale, le vie visive alternative sottocorticali consentono l’elaborazione implicita del contenuto emotivo delle espressioni facciali, ma che tale abilità è limitata alle espressioni di paura. Questo suggerisce l’esistenza di un sistema sottocorticale specializzato nella detezione di segnali di pericolo a partire da segnali visivi grezzi, permettendo dunque il rapido reclutamento di risposte comportamentali di lotta o fuga già prima che possa avvenire un riconoscimento conscio e dettagliato delle potenziali minacce. Inoltre, la presente tesi estende le conoscenze riguardo ai fenomeni di “crossmodal blindsight”, dimostrando che, a differenza della detezione visiva, la discriminazione di orientamento di linee non può essere migliorata dalla presentazione di suoni quando la corteccia striata non è funzionante. Questo dato suggerisce da un lato che la corteccia striata ha un ruolo causativo nel miglioramento “cross-modale” della sensibilità visiva all’orientamento e, dall’altro, che le vie visive sottocorticali che non coinvolgono la corteccia striata, anche se permettono l’integrazione di segnali audio-visivi e il miglioramento della semplice detezione, non possono potenziare abilità visive complesse, come la discriminazione di orientamento

The aim of this thesis was to investigate the respective contribution of prior information and sensorimotor constraints to action understanding, and to estimate their consequences on the evolution of human social learning. Even though a huge amount of literature is dedicated to the study of action understanding and its role in social learning, these issues are still largely debated. Here, I critically describe two main perspectives. The first perspective interprets faithful social learning as an outcome of a fine-grained representation of others’ actions and intentions that requires sophisticated socio-cognitive skills. In contrast, the second perspective highlights the role of simpler decision heuristics, the recruitment of which is determined by individual and ecological constraints. The present thesis aims to show, through four experimental works, that these two contributions are not mutually exclusive. A first study investigates the role of the inferior frontal cortex (IFC), the anterior intraparietal area (AIP) and the primary somatosensory cortex (S1) in the recognition of other people’s actions, using a transcranial magnetic stimulation adaptation paradigm (TMSA). The second work studies whether, and how, higher-order and lower-order prior information (acquired from the probabilistic sampling of past events vs. derived from an estimation of biomechanical constraints of observed actions) interacts during the prediction of other people’s intentions. Using a single-pulse TMS procedure, the third study investigates whether the interaction between these two classes of priors modulates the motor system activity. The fourth study tests the extent to which behavioral and ecological constraints influence the emergence of faithful social learning strategies at a population level. The collected data contribute to elucidate how higher-order and lower-order prior expectations interact during action prediction, and clarify the neural mechanisms underlying such interaction. Finally, these works provide/open promising perspectives for a better understanding of social learning, with possible extensions to animal models. / L’obbiettivo della presente tesi consiste nell’esaminare il contributo dell’informazione a priori e dei vincoli sensorimotori per la comprensione delle azioni altrui, e nello stimare le loro conseguenze sull’evoluzione del apprendimento sociale. Nonostante allo studio della comprensione dell’azione e al suo ruolo nell’ apprendimento sociale sia dedicata un’ampia letteratura, queste problematiche rimangono molto dibattute. Nella tesi illustro due prospettive. La prima interpreta l’apprendimento sociale di alto livello come il prodotto di una rappresentazione a grana fine delle azioni e intenzioni altrui che richiede sofisticate abilità socio-cognitive. La seconda prospettiva sottolinea il ruolo di euristiche decisionali più semplici, il cui reclutamento è determinato da vincoli individuali ed ecologici. Attraverso quattro lavori sperimentali, viene dimostrato che questi due contributi non sono mutuamente esclusivi. Un primo studio esamina il ruolo della corteccia frontale inferiore (IFC), dell’area intraparietale anteriore (AIP) e della corteccia somatosensoriale primaria (S1) nel riconoscimento delle azioni, usando un paradigma di transcranial magnetic stimulation adaptation (TMSA). Il secondo lavoro studia se, e come, informazioni a priori di ordine superiore (acquisite dal campionamento probabilistico di eventi passati) e inferiore (derivate dalla stima degli impedimenti biomecanicci legati alle azione osservate) interagiscono durante la predizione delle intenzioni altrui. Usando una procedura di single-pulse TMS, il terzo lavoro esamina se l’interazione fra queste due classi di informazioni a priori modula l’attività del sistema motorio. Il quarto studio testa l’ampiezza con cui vincoli comportamentali ed ecologici possono influenzare, a livello popolazionale, la comparsa di strategie d’apprendimento sociale di grana fine. I dati raccolti contribuiscono a delucidare come le aspettative a priori di ordine superiore e inferiore interagiscano durante la predizione dell’azione, e chiarificano i meccanismi neurali sottostanti questa interazione. Infine, questi lavori aprono prospettive promettenti per una migliore comprensione dell’apprendimento sociale umano, con possibile estensioni ai modelli animali.

The question addressed by this dissertation is how the human brain builds a coherent representation of the body, and how this representation is used to recognize its own body. Recent approaches by neuroimaging and TMS revealed hints for a distinct brain representation of human body, as compared with other stimulus categories. Neuropsychological studies demonstrated that body-parts and self body-parts recognition are separate processes sub-served by two different, even if possibly overlapping, networks within the brain. Bodily self-recognition is one aspect of our ability to distinguish between self and others and the self/other distinction is a crucial aspect of social behaviour. This is the reason why I have conducted a series of experiment on subjects with everyday difficulties in social and emotional behaviour, such as patients with autism spectrum disorders (ASD) and patients with Parkinson’s disease (PD). More specifically, I studied the implicit self body/face recognition (Chapter 6) and the influence of emotional body postures on bodily self-processing in TD children as well as in ASD children (Chapter 7). I found that the bodily self-recognition is present in TD and in ASD children and that emotional body postures modulate self and others’ body processing. Subsequently, I compared implicit and explicit bodily self-recognition in a neuro-degenerative pathology, such as in PD patients, and I found a selective deficit in implicit but not in explicit self-recognition (Chapter 8). This finding suggests that implicit and explicit bodily self-recognition are separate processes subtended by different mechanisms that can be selectively impaired. If the bodily self is crucial for self/other distinction, the space around the body (personal space) represents the space of interaction and communication with others. When, I studied this space in autism, I found that personal space regulation is impaired in ASD children (Chapter 9).

Made available in DSpace on 2015-02-11T01:01:15Z (GMT). No. of bitstreams: 1 000465110-Texto+Parcial-0.pdf: 1590133 bytes, checksum: dd39e72ae5245a25fe2426fe4524385d (MD5) Previous issue date: 2014 / Introduction: Studies have shown that childhood maltreatment (CM) can be considered one of the most serious and chronic types of psychological stress. Although researches have reported CM as a risk factor for many diseases, studies about CM biomarkers remains underexplored.Objective: Verify the association between CM and biomarkers, specially copeptin, and behavioral changes.Method: This dissertation consists of three studies. The first study is a review of CM neurobiology. The second study presented a systematic review regarding the correlation between childhood maltreatment and inflammatory markers in adulthood. The third study investigated serum copeptin levels in children with and without history of CM.Results: The first study highlights the impact of CM as being a geneenvironment interaction resultant that seems to modulate the neurobiological cascade connected to vulnerabilities and resilience of each individual. Survivors of CM can exhibit alterations in several physiological systems, including the immune, endocrine, cardiovascular, behavioral, and central nervous systems. Childhood trauma is associated with increased autonomic stress responses and reprogramming of glucocorticoid signaling, thus contributing to exaggerated stress and immune responsiveness. There is strong evidence of the association between CM and abnormalities in the immunoendocrine system. In the systematic review study we analyzed 19 articles about the topic. Studies showed that a history of CM was associated with increased levels of C-reactive protein, fibrinogen and proinflammatory cytokines. CM seems to be related with a chronic inflammatory state independent of clinical comorbidities. The third study demonstrated that CM is correlated to increased copeptin serum levels and it is non-related to age, sex and psychopathology symptoms. Furthermore, the copeptin can be considered a promising novel biomarker in CM.Conclusions: The present thesis presents new and promising data regarding biological markers and CM that corroborates with the current literature findings. The data shown here introduces copeptin as a new potential biomarker associated to CM. This thesis also reinforces the presence of neuro-immune-endocrine alterations in individuals presenting CM history. The literature shows CM systematically impacts the physical and mental health, potentializing the development and complications risks of many other diseases. So, it is of extreme importance to investigate these biological mechanisms that seems to be correlated to environmental factors. / Introdução: Estudos têm mostrado que os maus-tratos na infância (MTI) podem ser considerados um dos tipos mais graves e crônicos de estresse. Embora as pesquisas vêm referindo os MTI como um fator de risco para diversas patologias, ainda carecem estudos sobre a psicobiologia e biomarcadores relacionados aos MTI.Objetivo: Investigar biomarcadores, especialmente a copeptina, e características comportamentais associados com história de MTI.Métodos: A presente tese é composta por três estudos. O primeiro estudo aborda uma revisão sobre a neurobiologia dos MTI. O segundo estudo apresentou a revisão sistemática da literatura acerca da associação entre história de MTI e marcadores inflamatórios na vida adulta. O terceiro estudo investigou níveis séricos de copeptina em crianças com e sem história de MTI.Resultados: O primeiro estudo aponta que os MTI estão associados à um aumento na resposta autonômica do estresse e na reprogramação de sinalização dos glicocorticóides, reverberando assim uma capacidade exagerada das respostas imunológicas e de estresse. Destacam-se as evidências das associações existentes entre os MTI e as anormalidades no sistema imunoendocrinológico. Esse estudo também salienta o impacto dos MTI como dependente das interações gene-ambiente que modularão a cascata neurobiológica conectada aos fatores de vulnerabilidade e resiliência de cada indivíduo. No segundo estudo foram sistematicamente analisados artigos sobre o tema, demonstrando que história de MTI está associada com um aumento nos níveis de proteína C-reativa, fibrinogênio e citocinas pró-inflamatórias. Os resultados sugerem que a presença de histórico de MTI está relacionado a um estado crônico inflamatório na vida adulta, independente da presença de comorbidades clínicas psiquiátricas. O terceiro estudo evidenciou que histórico de MTI está associado com a elevação dos níveis séricos de copeptina, independentemente da idade, sexo e sintomas psiquiátricos. Além disso, a copeptina pode ser considerada um novo e promissor biomarcador em crianças com história de MTI.Considerações finais: Considerando estudos prévios acerca de marcadores biológicos e MTI, esta tese vem corroborar sua importância na apresentação de resultados inovadores e promissores para a literatura. Esta tese apresenta um novo e potencial marcador biológico associado a história de MTI: a copeptina; além de reiterar a presença de alterações neuroimunoendocrinológicas em sujeitos com história de MTI. Dentre as pesquisas já realizadas, observa-se sistematicamente que os MTI impactam na saúde física e mental do indivíduo, por vezes potencializando o risco de desenvolvimento e piora no curso de inúmeras doenças. Portanto, é de extrema relevância o avanço da ciência em direção a um entendimento melhor integrado desses mecanismos biológicos que se mostram também respondentes ao ambiente.

Our ability to store knowledge and represent the world within our minds has spanned multiple disciplines (philosophy, psychology, neuroscience). Currently, theories of human conceptual knowledge suggest that human representation of the world is widely distributed across the brain. Regions involved in sensory/motor simulation as well as amodal systems contribute to our flexible ability to manipulate knowledge. A detailed account of how the overall human semantic system works at a network level is still lacking. To begin our investigation into how knowledge is distributed across brain networks, we will first consider a specific kind of knowledge - person related knowledge. Chapter 2 will look at the behavioural indicators of person-knowledge organisation. We will ask participants to judge explicit/subjective similarity between different person-knowledge domains: social, physical, biographical, episodic and nominal knowledge. This will allow us to investigate whether these processes are independent or related to each other. We will then compare these judgements to implicit similarity measures to see whether correlated patterns of responses or reaction are informative about cognitive similarity. Chapter 3 will look at how the brains core/extended system for face perception coordinates across the aforementioned person-knowledge domains. We will investigate the representational similarity of different person-knowledge domains in individual regions, and crucially - across the network as a whole. This will allow us to address whether cognitions are localised in individual regions or distributed across the whole network. Chapter 4 will investigate the stability of network organisation when going across modalities. Extended system for face perception has been shown to be recruited during familiar name reading. We will ask whether network-level patterns of activation during person-knowledge remain stable across input modalities. Chapter 5 will generalize the network-level approach to investigate broader semantic categories. We will interrogate how diverse regions activated during semantic processing, interact during processing of naturally occurring conceptual categories. We will use a corpus derived semantic distance model and compare it to individual region activity to that of the network overall. We will ask whether information about conceptual distance between categories is contained within individual regions or arises as a product of coordinated effort across the network. Combined, evidence presented in this thesis speak to the distributed nature of cognitive representation. Different kinds of person-knowledge and object categories are highly linked and rely on overlapping neural substrates. We demonstrate that instead of being specialised for particular tasks, brain areas involved in meaning extraction tend to be involved in most kinds of conceptual processing. Individually regions have slight cognitive tunings and can be geared towards specific cognitions. Differences in person- knowledge and object categories emerge as a product of the coordinated interplay between multiple brain regions.

Attention is thought to alter appearance by intensifying the sensory impression of the attended stimulus. Current debates are about how this increases might operate and what are the underlying neural mechanisms. Three mechanisms have been proposed to account the effect of attention: contrast gain, response gain and baseline shift. However, psychophysical and neuroimaging studies produced results that are not always consistent. We used the functional magnetic resonance imaging (fMRI) to explore how attention alters the appearance of coherently moving dots. The first experiment assessed coherence response functions for different levels of contrast. This experiment showed which kind of pattern should be expected with attention altering appearance by means of contrast gain mechanism. The results showed that contrast produced a leftward shift of the coherence response function. By our knowledge, this is the first fMRI evidence for the assumption that processing of motion coherence is susceptible to contrast gain. The second experiment assessed the effect of attention on coherence response function. The results showed that attention affects the BOLD response with the same strength for all coherence levels. This pattern of response is compatible with the predictions of the baseline shift model. Finally, in order to explain the discrepancy between psychophysical and neuroimaging results, we suggested a signal detection account for the effect of baseline shift on the perceptual level, proposing that baseline shift may produce a leftward shift of the psychometric function although sensitivity remains unchanged.

In each environment we experience in our daily life, we find ourselves surrounded by complex auditory soundscapes. These auditory scenes are often composed of many concurrent sound sources with both spatially and temporally overlapping spectral details, which humans are consistently able to parse seemingly effortlessly in order to navigate their surroundings. Two main aspects are involved in this capability: directing attention, first outlined by Cherry in 1953 in the form of a seminal paradigm, the so-called “cocktail party problem”, and parsing the sound scene, codified by Bergman in 1990 as “auditory scene analysis”. Attention, in every sensory domain, plays a fundamental role to efficiently select the relevant information and ignore the distracting inputs, with studies showing that it operates in the form of a “biased competition” between neural representation of perceptual objects. Objects were depicted in vision as the central “units”, on which non-spatial selective attention acts in many natural contexts, however in the auditory domain several questions remain to be addressed on that matter. Most notably it is indeed unclear how the attention mechanisms operate at both, the level of the auditory object formation and the level of the auditory object selection. More importantly where and how in the neural pathway an object-based representation of an attended sound emerges, is yet to be fully understood. In the present thesis we designed a novel paradigm to tackle the auditory selective attention at the level of object processing: a repetition target has been embedded in one of the two naturalistic streams in such a way that, after being cued, the participant necessarily had to build up representations of the auditory objects composing the scene across time in order to accomplish the task. This paradigm has been employed in both studies that compose the thesis. The first study was conducted to characterize the auditory selective attention system with a theoretical and empirical focus on high-level attentional modulations on the processing level of auditory objects. In line with studies of object-based attention in the visual domain, we reported a behavioral attentional facilitation effect in the validly cued trials, and an inhibition effect in the invalidly cued trials. In the second study, we focused on the neural activity during the repetition detection period by investigating the temporal dynamic of the cortical activity at the source level. These analyses were accomplished both in time (in form of evoked responses, ERFs) and frequency domain (in form of time-frequency spectrograms) providing not only insights into the time courses of events but also their exact spatial localization in cortex. We reported a significant stronger MEG response, mapped at the source cortical level, when the repetition segment was in the attended stream. The same has been found when the target repetition was detected, suggesting that the time course of the neural activity and its spatial distribution represent one aspect of the neural correlates of the object-based attention. Overall both studies show an attentional modulation effect operating indeed on the object-level in a naturalistic auditory scene supporting the biased competition theory.

What does it mean to be an emotion researcher? First of all, having no idea of what the object of study is. Indeed, there is still no general agreement about the definition of emotion, a vague concept that changes depending on the theoretical approach of each researcher. Given the important role they play in our lives influencing thoughts, behaviors, and social experiences, emotions have increasingly drawn the attention of several researchers in different domains. Specifically, the assumption that we are not slaves of our own emotions, but we can actively change them, has fostered a growing interest in emotion regulation. The field of affective neuroscience highlights the importance of integrating different methodological approaches (e.g., neuroimaging techniques, computational modeling, machine learning) to unveil the psychophysiological mechanisms and neural bases of emotional processes, providing insights about their impairments in mental disorders and the development of more accurate treatments. In light of this, in this thesis I will investigate the neural bases of emotion regulation, considering both its adaptive and detrimental aspects. The goal of the first part is to trace neurophysiological and brain structural representations of emotion regulation. In the second part, this construct will be explored by addressing its less adaptive counterparts, looking for morphometric evidence of emotion dysregulation. In the first study (Study I), I will investigate whether regulating emotions can leave a long-lasting trace in the brain, such as a neurophysiological ‘signature’ in the oscillatory activity, recording EEG signal at rest before and after applying an emotion regulation strategy. After exploring the physiological characterization of emotion regulation, the second study (Study II) will provide a morphometric representation of this process. A supervised machine-learning algorithm, namely Multi-Voxel Pattern Analysis (MVPA), will be applied on MRI images to identify structural networks predicting the use of specific cognitive strategies to regulate emotions. Studying mental disorders characterized by emotional difficulties can give us a direct window into neural mechanisms involved in emotion regulation. To address this issue, I will capitalize on Source-based Morphometry (SBM), a whole-brain multivariate approach to structural images based on Independent Component Analysis, a form of unsupervised machine learning to separate independent sources from a mixed-signal. In the third study (Study III), I will track down the neurostructural markers of emotion dysregulation focusing on Borderline Personality Disorder, whose core feature is dysfunctional emotion regulation, as compared to patients with Bipolar Disorder more characterized by mood disturbances and impulsive behavior. Along with emotions, the ability to control impulses can be dysregulated as well, representing a problematic symptom in many affective disorders. The fourth study (Study IV) will provide evidence of the neural bases of impulses dysregulation, investigating morphometric features of Bipolar Disorder. I will combine both subjective (self-report assessing impulsivity) and objective (MRI) measures, in order to gain a more comprehensive picture of this multifaceted dimension. These studies will be able to shed new light on emotion regulation processes, providing a wider overview of the underlying functional and dysfunctional mechanisms, thanks to the combination of neuroimaging techniques and subjective measures. According to a brain-behavioral approach, this will lead to build a model that can help to increase both scientific knowledge and everyday well-being.

There is a need to increase the efficacy and efficiency of aphasia rehabilitation protocols. In order to do this, we may rely on knowledge about how the language system may be changed by experience, including it’s plasticity to behavioral training and to neuromodulation. In this thesis, I study mechanisms of language facilitation in healthy individuals and mechanisms of language recovery in individuals with aphasia. I use both behavioral modification techniques (repeated naming in healthy individuals, and linguistically motivated aphasia therapy in individuals with aphasia), and neuromodulation (transcranial direct current stimulation, tDCS). The data in this thesis indicate that, in healthy individuals, language facilitation by repetition priming reflects changes in implicit processing of stimuli (at the level of lexical retrieval), and explicit episodic retrieval of the prior occurrence of the stimuli. In patients with aphasia, the data indicates that the observation of item-specific improvement after treatment depend on pre-treatment levels accessibility to the lexeme level via semantics, and also on short term memory skills and/or post-lexical processing skills. Generalization may occur when damage to abstract features is present(semantic and/or grammatical), and when knowledge of abstract features is engaged during treatment. tDCS has been successfully used in prior research to enhance language training and rehabilitation effects. However, our data from healthy individuals did not reveal effects of neuromodulation, and the data with patients was ambigous: it is not possible to discern whether tDCS indeed incrteased the effects of therapy or wether the data are better explained as reflecting a ceiling effect.