Dissertations / Theses on the topic 'Event related potentials (ERPs)'

This Thesis aimed at investigating, by using the event-related potentials (ERPs) technique, some relevant aspects involved in human ability to read others’ emotions and in empathizing with others’ affective states. Social and affective neuroscience has largely studied faces and facial expressions since they represent relevant “pieces of information” in guiding individuals during interaction. Their importance is strictly related to the fact that they provide unique information about identity, gender, age, trustworthiness, and attractiveness, but they also convey emotions. In Chapter 1, I have introduced the reader to the contents of this Thesis, in particular the ability to “read” others’ facial expressions and to empathize with others’ affective states. In Chapter 2, I have offered an overview of knowledge available today on how humans process faces in general and facial expressions in particular. I have proposed a theoretical excursus starting from Bruce and Young’s cognitive model (1986) to a recent simulative model of recognition of emotional facial expressions by Wood and colleagues (2016), which considers facial mimicry helpful in discriminating between subtle emotions. In Chapter 3 and 4, I have presented two different studies (Experiments 1 and 2, respectively) strongly related to each other, since they aimed both at testing a functional link between the visual system and facial mimicry/sensorimotor simulation during the processing of facial expressions of emotions. I have described two different studies in which ERPs, by virtue of its high temporal resolution, allowed to track the time-course of the hypothesized influence of mimicry/simulation on the stages of visual analysis of facial expressions. The aim of Experiment 1 was to explore the potential connection between facial mimicry and the early stage of the construction of visual percepts of facial expressions; while the Experiment 2 investigated whether and how facial mimicry could interact with later stages of visual processing focusing on the construction of visual working memory representations of facial expressions of emotions, by also monitoring whether this process could depend on the degree of the observers’ empathy. For both studies, the results strongly suggest that mimicry may influence early and later stages of visual processing of faces and facial expressions. In the second part of my Thesis, I introduced the reader to the construct of empathy, dealing with its multifaceted nature and the role of different factors in the modulation of an empathic response, especially to others’ pain (Chapter 5). In Chapter 6 and 7, I have discussed two ERP studies (Experiments 3 and 4a) with one behavioral study included as a control study (Experiment 4b) to investigate the empathic reaction to others’ pain as a function of different variables that could play a role in daily life. Experiment 3 investigated the role of prosodic information in neural empathic responses to others’ pain. Results from this study demonstrated that prosodic information can enhance human ability to share others’ pain by acting transversely on the two main empathy components, the experience sharing and the mentalizing. The aim of Experiment 4a was to study whether the physical distance between an observer and an individual in a particular affective state, induced by a painful stimulation, is a critical factor in modulating the magnitude of an empathic neural reaction in the observer. Thus, by manipulating the perceived physical distance of face stimuli, I observed a moderating effect on empathic ERP reactions as a function of the perceived physical distance of faces. Results of Experiment 4b clarified that the critical factor triggering differential empathic reactions in the two groups in Experiment 4a was not related to the likelihood of identifying the faces of the two sizes but to the perceived physical distance. Finally, in Chapter 8, a general discussion highlights the main findings presented in this Thesis, by also providing future suggestions to extend the research on this topics debated in the previous Chapters.
Questo elaborato ha l’obiettivo di indagare, tramite l’utilizzo della tecnica dei potenziali evento-relati (ERPs, Event-Related Potentials), alcuni aspetti che caratterizzano e guidano l’interazione sociale umana, come l’abilità di leggere e comprendere le emozioni altrui. Le neuroscienze sociali hanno studiato nel dettaglio volti ed espressioni facciali, in quanto stimoli che, oltre a fornire informazioni uniche circa l’identità, il genere, l’età, l’affidabilità, l’attrattività e la direzione dello sguardo, tramettono indicazioni circa gli stati emotivi dell’altro. Il Capitolo 1 fornisce una panoramica teorica, primum, rispetto al processamento dei volti e delle espressioni facciali, deinde, sull’empatia, in particolare al dolore, intesa come capacità umana di comprendere l’altrui stato affettivo. Nel Capitolo 2 è proposto un excursus teorico sul processamento dei volti e delle emozioni da essi veicolate, partendo dal modello cognitivo di Bruce e Young (1986) ai recenti modelli simulativi, fino a quello più attuale di Wood e colleghi (2016), che considera il ruolo della mimica facciale nella discriminazione di emozioni sottili. Nei Capitoli 3 e 4, sono presentati due studi strettamente interconnessi (rispettivamente, Esperimento 1 e 2). Entrambi hanno come obiettivo lo studio di un collegamento funzionale tra il sistema visivo e la mimica facciale/simulazione senso-motoria, nel processamento di emozioni tramite l’osservazione di espressioni facciali. Nei due studi è stata utilizzata la tecnica degli ERPs che, data la sua alta risoluzione temporale, ha permesso di tracciare una dinamica temporale chiarendo il ruolo della mimica/simulazione sugli stadi di analisi visiva coinvolti nell’elaborazione di espressioni facciali. L’obiettivo dell’Esperimento 1 era di indagare una possibile connessione tra la mimica facciale e uno dei primi stadi di costruzione del percetto visivo del volto; mentre l’Esperimento 2, indagava se e come la mimica facciale interagisse con uno stadio più tardivo legato alla costruzione di una rappresentazione in memoria di lavoro visiva e se questo processo dipendesse dal grado di empatia dell’osservatore. I risultati dei due Esperimenti suggeriscono come la mimica facciale influenzi sia gli stadi precoci che tardivi del processamento di emozioni tramite l’osservazione di espressioni facciali. Nella seconda parte della Tesi, viene affrontato il tema dell’empatia, con particolare riferimento alla sua natura sfaccettata e al come variabili diverse possano modulare la risposta empatica stessa, specialmente al dolore altrui (Capitolo 5). All’interno dei Capitoli 6 e 7 sono presentati due studi ERPs (Esperimento 3 e 4a) e un’indagine comportamentale (Esperimento 4b) con l’obiettivo di indagare la risposta empatica, elicitata nell’osservatore, quando si trova di fronte a qualcuno che sta provando dolore. L’esperimento 3 vuole studiare il ruolo della prosodia nel modulare la risposta neurale empatica nell’osservatore. I risultati dimostrano che l’informazione prosodica può aumentare la risposta empatica, agendo trasversalmente sulle due grandi componenti dell’empatia, experience sharing e mentalizing. Nell’Esperimento 4a, l’obiettivo era di comprendere se la distanza fisica tra l’osservatore e un individuo in una situazione dolorosa, potesse rappresentare un fattore importante nel modulare la grandezza della risposta empatica. Questo studio, attraverso la manipolazione della distanza fisica percepita di volti, ha mostrato una riduzione della risposta empatica rilevata nell’osservatore, in funzione della distanza fisica percepita. Il risultato dell’Esperimento 4b, invece, ha chiarito che il fattore critico nella generazione della risposta empatica (studio 4a) fosse la distanza fisica percepita e non quanto fossero discriminabili i volti tra loro. In conclusione, nel Capitolo 8, è fornita una discussione generale che integri i risultati più importanti ottenuti negli studi descritti, cercando di delineare risvolti e prospettive future.

The aim of the current series of experiments was to further explore the boundary conditions of the recognition memory old/new effect in the context of the recognition/associative recall task (Rugg, Schloerscheidt, Doyle, Cox, & Patching, 1996). The study by Rugg et al. was replicated and extended by manipulating both the semantic relatedness between study items and the timing of recall. Eventrelated potentials (ERPs) were recorded from 17 scalp electrode sites during performance of a recognition/associative recall task. Forty participants were visually presented with four blocks of 50 word pairs which were either unrelated (Experiments 1 and 2) or weakly semantically related (Experiments 3 and 4). Participants were instructed to form an association between the members of each word pair. At test, the first members of each pair were visually presented intermixed with a similar number of unstudied items. Participants were required to discriminate (i.e., recognise) previously studied items (old) from new items. Participants were also required to recall the study associate for words judged old, and to provide confidence levels for each recognition decision on a 3-point scale. Recall was either immediate (Experiments 1 and 3) or delayed (Experiments 2 and 4). Relative to ERPs to new items, the ERPs elicited by words correctly recognised and for which the associate was correctly recalled exhibited a positive-going shift between 500-800 ms poststimulus onset. The effect was maximal at posterior temporal-parietal electrode sites (the parietal old/new effect). Although the effect was not lateralised to the left hemisphere, this result may be due to the variability in encoding strategies employed by the participants. Behavioural data consistently indicated that response confidence is confounded with response category. The ERP results also revealed that the old/new effect is not evident following the experimental control of response confidence, and that immediate recall is associated with a negative-going shift at posterior electrode sites between 800-1100 ms poststimulus onset. Manipulating the semantic relatedness between the word pairs did not influence the distribution of the old/new effect. The results are discussed in terms of the view that the parietal old/new effect reflects neural activity associated with the recollection of specific previous experiences, and may reflect retrieval processes supported by the medial temporal lobe memory system (Moscovitch, 1992, 1994; Squire, 1992; Squire, Knowlton, & Musen, 1993). It is suggested that future research extend the current findings by examining the influence of response confidence in alternative recognition memory paradigms.

What are the effects of non-balanced bilingualism on cognitive performance? And how do proficient, non-native speakers acquire and use lexical, syntactic and semantic information during sentence processing? Whilst there is growing research on these topics, there is no firm consensus on how to answer these questions. In the literature on cognitive effects of bilingualism, this lack of consensus has even resulted in radically opposing views and a heated debate. In this thesis, I seek to provide a balanced treatment of the literature and to address the above-mentioned questions by employing behavioral and neurophysiological paradigms. First, using a structural priming paradigm, I examine how proficient, non-native speakers of different native language backgrounds (Romance and Germanic) acquire lexically-specific syntactic restrictions of non-alternating verbs in English. Results from these experiments suggest that, although non-native speakers partially acquire lexically-specific syntactic restrictions, their knowledge is not native-like. Moreover, transfer from the first language does not seem to play a role in the acquisition of the relevant restrictions. Second, using Event-Related Potentials (ERPs) I examine whether proficient non-native Spanish-English speakers draw on different forms of semantic information such as relatedness and animacy incrementally during sentence comprehension. Results of these experiments suggest that, while relatedness facilitates processing (indexed by N400s) in both native and non-native speakers, effects of animacy are smaller in non-native speakers, relative to native speakers. Third, I employ a series of auditory attentional tasks and measures of lexical access and verbal fluency to assess cognitive functions in non-balanced bilinguals with different levels of language proficiency. Results show a bilingual advantage in inhibitory control and a non-significant trend towards bilingual better performance in attentional switching, and the groups exhibit similar performance on verbal fluency. Results of all the studies are discussed in the context of the existing literature on cognitive performance in bilinguals and accounts of language processing in native and non-native speakers and suggestions for future research are provided.

Event-related potentials have been found to be a useful indicator of brain states and brain abnormality. The contingent negative variation, P300 and bereitschafts potential are well researched event-related potentials of particular interest. Many factors have to be considered in the design of measurement systems to record multiple channels of these signals accurately. The correlation between channels must be high and channel noise and distortion must be minimal, whilst the system as a whole must meet the requirements of the medical safety standards. For further research there was found to be a requirement for a dedicated thirty-two channel ERP measurement system that met these criteria. This has been achieved in a PC based system that utilises simultaneous sampling of all channels, and filters that extend to very low frequencies. Software control of the system enables user adjustment of recording parameters and paradigm implementation. Data processing using high level software enables digital signal processing techniques to be applied for further noise removal and signal analysis. The system has been tested using synthetically generated signals and by limited recording of the three ERPs. The results prove that the system is a suitable tool for high accuracy, multi-channel recording of ERPs.

Background: The event related potential (ERP) is an important electrophysiological response to an internal or external stimulus on human body. In some studies, the ERP-based brain computer interface (BCI) systems were created in visual or auditory modality. However, in these type of BCIs, either the eyes or ears of the users are occupied when they are making a choice. It is not convenient to communicate with others. Thus, a somatosensory ERP based BCI can be developed to overcome this issue. According to this, the analysis of somatosensory ERP features is necessary to evaluate if somatosensory ERP is eligible for BCIs as an input. Objective: 1. To study ERP features and design of P300 experiment. 2. To compare three types of P300 features elicited by three modalities. 3. To produce ERP response by electrical stimuli delivered to different position, and analyze ERP features. Methods: Two experiments were conducted. In experiment 1, three modalities, including visual, auditory and electrical modality, were used to produce P300 response. Experiment 2 only presented electrical stimuli. In experiment 1 two electrical stimuli were presented with different intensities at one location, whereas four electrical stimuli were showed at different location with the same intensity. The amplitude and latency were compared among three modalities, and the ERP topography of experiment 2 was also analyzed. Result and conclusion: Fourteen subjects’ data were analyzed in our study. The amplitude and latency of electrical P300 were similar to auditory ERP. But the ERP of visual modality had the largest amplitude and shortest latency. This result shows that electrical P300 can work as well as auditory P300 in BCIs, but not as good as visual P300. In experiment 2, the latency of electrical ERP occurred around 280 ms, and the amplitude and the topography showed that the largest amplitude was located around Cz electrode. This type of ERP in experiment 2 was considered as P3a, which also can be used in BCI systems.
published_or_final_version
Orthopaedics and Traumatology
Master
Master of Medical Sciences

The electroencephalogram (EEG) reflects summated, slow post-synaptic potentials of cortical neurons. Sensory, motor or cognitive events (such as a fast-rising sensory stimulus, a brisk self-paced movement or a stimulus-triggered cognitive task) can elicit transient changes in the ongoing human EEG, called event-related potentials (ERPs). ERPs are widely used in clinical practice, and believed to reflect the activity of the sensory system activated by the stimulus (for example, laser-evoked potentials are used to substantiate the neuropathic nature of clinical pain conditions). When ERPs are elicited by pairs or trains of stimuli delivered at short inter-stimulus intervals (ISIs), the magnitude of the ERP elicited by the repeated stimuli is markedly reduced, a phenomenon known as response decrement. While the interval between two consecutive stimuli becomes longer, the reduced response is recovered. Thus, this phenomenon has been traditionally interpreted in terms of neural refractoriness of generators of ERPs ("neural refractoriness hypothesis"). This thesis, however, challenges this neural refractoriness hypothesis by describing the results of manipulating the preceding events of the eliciting stimulus. The first study examined the effect of variable and short ISIs on sensory ERPs, delivering trains of auditory and electrical stimuli with random ISIs ranging from 100 to 1000ms. In the second study, pairs of laser stimuli were presented in two comparable conditions. In the constant condition, the ISI was identical across trials in each block, while in the variable condition, the ISI was variable across trials. By directly comparing ERPs elicited by laser stimulation, this study aimed to explore whether lack of saliency in the eliciting stimulus could explain the response decrement during stimulus repetition. Finally, the third study tested the hypothesis that the reduced eliciting ERPs would recover if saliency were introduced by changing the modality of the preceding event. Thus, trains of three stimuli (S1-S2-S3) with 1s ISI were presented; S2 was either same or different in modality as S1 and S3 in each block. Results from these three experiments demonstrate that this "refractoriness hypothesis" does not hold, and suggest that the magnitude of ERPs is only partly related to the magnitude of the incoming sensory input, and instead largely reflects neural activities triggered by salient events in the sensory environment. These results are important for the correct interpretation of ERPs in both physiological and clinical studies.

Semantic richness is a multidimensional and dynamic construct that can be defined as the amount of semantic information a word possesses. In this thesis, the semantic richness dimensions of number of associates, number of semantic neighbours, and body-object interaction were investigated. Forty-eight young adults were randomly assigned to perform either lexical decision (LDT) or semantic categorization tasks (SCT). The goal of this thesis was to investigate behavioural and electrophysiological differences (using the Event-Related Potential technique) between semantically rich words and semantically impoverished words. Results revealed that the amplitude of the N400 ERP component was smaller for words with high number of associates and high number of semantic neighbours compared to words with low number of associates or low number of semantic neighbours, respectively, but only during LDT. Behavioural results, however, only showed an accuracy and reaction time advantage (during item analyses) for words with many associates. In contrast, N400 amplitudes did not differ for words with high body-object interaction rating when compared to words with low body-object interaction rating in any of the tasks, although a behavioural reaction time advantage was observed in item analyses of the LDT. These results suggest that words with many associates or semantic neighbours may be processed more efficiently and be easier to integrate within the neural semantic network than words with few associates or semantic neighbours. In addition, the N400 effect was seen in the LDT but not in the SCT, suggesting that semantic richness information may be used in a top-down manner in order to fulfill the task requirements using available neural resources in a more efficient manner.

La reconnaissance experte de l'expression faciale est cruciale pour l'interaction et la communication sociale. Le comportement, les potentiels évoqués (ERP), et les techniques d’oculométrie peuvent être utilisés pour étudier les mécanismes cérébraux qui participent au traitement visuel automatique. La reconnaissance d'expressions faciales implique non seulement l'extraction d'informations à partir de caractéristiques faciales diagnostiques, stratégie qualifiée de traitement local, mais aussi l'intégration d'informations globales impliquant des traitements configuraux. Des nombreuses recherches concernant le traitement des informations faciales émotionnelles il apparaît que l’interaction des traitements locaux et configuraux pour la reconnaissance des émotions est mal comprise. La complexité inhérente à l'intégration de l'information faciale est mise en lumière lorsque l'on compare la performance de sujets sains et d’individus atteints de schizophrénie, car ces derniers ont tendance à s’attarder sur quelques éléments locaux, parfois peu informatifs. Les différentes façons d'examiner les visages peuvent avoir un impact sur la capacité socio-cognitive de reconnaître les émotions. Pour ces raisons, cette thèse étudie le rôle des caractéristiques diagnostiques et configurales dans la reconnaissance de l'expression faciale. En plus des aspects comportementaux, nous avons donc examiné la dynamique spatiale et temporelle des fixations à l’aide de mesures oculométriques, ainsi que l’activité électrophysiologique précoce considérant plus particulièrement les composantes P100 et N170. Nous avons créé de nouveaux stimuli des esquisses par une transformation numérique de portraits photos en esquisses, pour des visages exprimant colère, tristesse, peur, joie ou neutralité, issus de la base Radboud Faces Database, en supprimant les informations de texture du visage et ne conservant que les caractéristiques diagnostiques (yeux et sourcils, nez, bouche). Ces esquisses altèrent le traitement configural en comparaison avec les visages photographiques, ce qui augmente le traitement des caractéristiques diagnostiques par traitement élémentaire, en contrepartie. La comparaison directe des mesures neurocognitives entre les esquisses et les visages photographiques exprimant des émotions de base n'a jamais été testée, à notre connaissance. Dans cette thèse, nous avons examiné (i) les fixations oculaires en fonction du type de stimulus, (ii) la réponse électrique aux manipulations expérimentales telles que l'inversion et la déconfiguration du visage. Concernant, les résultats comportementaux montrent que les esquisses de visage transmettent suffisamment d'information expressive (compte tenu de la présence des caractéristiques diagnostiques) pour la reconnaissance des émotions en comparaison des visages photographiques. Notons que, comme attendu, il y avait un net avantage de la reconnaissance des émotions pour les expressions heureuses par rapport aux autres émotions. En revanche, reconnaître des visages tristes et en colère était plus difficile. Ayant analysé séparément les fixations successives, les résultats indiquent que les participants ont adopté un traitement plus local des visages croqués et photographiés lors de la deuxième fixation. Néanmoins, l'extraction de l'information des yeux est nécessaire lorsque l'expression transmet des informations émotionnelles plus complexes et lorsque les stimuli sont simplifiés comme dans les esquisses. Les résultats de l’électroencéphalographie suggèrent également que les esquisses ont engendré plus de traitement basé sur les parties. Les éléments transmis par les traits diagnostiques pourraient avoir fait l'objet d'un traitement précoce, probablement dû à des informations de bas niveau durant la fenêtre temporelle de la P100, suivi d'un décodage ultérieur de la structure faciale dans la fenêtre temporelle de la N170
Proficient recognition of facial expression is crucial for social interaction. Behaviour, event-related potentials (ERPs), and eye-tracking techniques can be used to investigate the underlying brain mechanisms supporting this seemingly effortless processing of facial expression. Facial expression recognition involves not only the extraction of expressive information from diagnostic facial features, known as part-based processing, but also the integration of featural information, known as configural processing. Despite the critical role of diagnostic features in emotion recognition and extensive research in this area, it is still not known how the brain decodes configural information in terms of emotion recognition. The complexity of facial information integration becomes evident when comparing performance between healthy subjects and individuals with schizophrenia because those patients tend to process featural information on emotional faces. The different ways in examining faces possibly impact on social-cognitive ability in recognizing emotions. Therefore, this thesis investigates the role of diagnostic features and face configuration in the recognition of facial expression. In addition to behavior, we examined both the spatiotemporal dynamics of fixations using eye-tracking, and early neurocognitive sensitivity to face as indexed by the P100 and N170 ERP components. In order to address the questions, we built a new set of sketch face stimuli by transforming photographed faces from the Radboud Faces Database through the removal of facial texture and retaining only the diagnostic features (e.g., eyes, nose, mouth) with neutral and four facial expressions - anger, sadness, fear, happiness. Sketch faces supposedly impair configural processing in comparison with photographed faces, resulting in increased sensitivity to diagnostic features through part-based processing. The direct comparison of neurocognitive measures between sketch and photographed faces expressing basic emotions has never been tested. In this thesis, we examined (i) eye fixations as a function of stimulus type, and (ii) neuroelectric response to experimental manipulations such face inversion and deconfiguration. The use of these methods aimed to reveal which face processing drives emotion recognition and to establish neurocognitive markers of emotional sketch and photographed faces processing. Overall, the behavioral results showed that sketch faces convey sufficient expressive information (content of diagnostic features) as in photographed faces for emotion recognition. There was a clear emotion recognition advantage for happy expressions as compared to other emotions. In contrast, recognizing sad and angry faces was more difficult. Concomitantly, results of eye-tracking showed that participants employed more part-based processing on sketch and photographed faces during second fixation. The extracting information from the eyes is needed when the expression conveys more complex emotional information and when stimuli are impoverished (e.g., sketch). Using electroencephalographic (EEG), the P100 and N170 components are used to study the effect of stimulus type (sketch, photographed), orientation (inverted, upright), and deconfiguration, and possible interactions. Results also suggest that sketch faces evoked more part-based processing. The cues conveyed by diagnostic features might have been subjected to early processing, likely driven by low-level information during P100 time window, followed by a later decoding of facial structure and its emotional content in the N170 time window. In sum, this thesis helped elucidate elements of the debate about configural and part-based face processing for emotion recognition, and extend our current understanding of the role of diagnostic features and configural information during neurocognitive processing of facial expressions of emotion

This study examined the ability of reaction time (RT) and Event-Related Potentials (ERP) to detect malingered neurocognitive deficit (MNCD)in two new tasks compared to the TOMM (N = 47). Honest (HON), malingering (MAL), and traumatic brain injury (TBI) groups were compared on accuracy, RT and ERP measures. Overall, the Test of Memory Malingering (TOMM) accuracy was the most effective at classifying groups (hit rate = 100%). Several non-TOMM accuracy variables and RT variables reached hit rates in the range of 71%-88%. The TOMM RT variable had an unlimited time for participants to respond and was the most successful RT variable compared to the Old/New and Repetition Priming tasks that had a short time limit for participants to respond (approximately 1.5 seconds). The classic old/new effect RT pattern was evident for both the HON and TBI groups with significantly faster RTs for old items compared to new items. A logistic regression was employed to see if a RT and/or ERP variable added any unique prediction power in detecting malingering. The frontal-posterior ERP difference score had unique prediction power to detect malingering when classifying MAL vs. TBI (hit rate = 86%). In the Old/New task, ERP responses of HON produced greater activity in the frontal region compared to the posterior region. The opposite trend was found in TBI (posterior activity andgt; frontal) and MAL showed no significant difference.

This dissertation consists of a review of the N2 component of the ERP and five experiments investigating the role of complex visual object categorization in modulating the N2 and two other ERP components: the P300, and a late prefrontal positivity. In the review, we focus on paradigms that elicit N2 components with an anterior scalp distribution, namely cognitive control, novelty, and sequential matching, arguing that the anterior N2 should be divided into separate control- and mismatch-related subcomponents. The experiments manipulated categorical typicality and the presence of conflicting information as participants categorized multi-featured artificial animals. In Experiments 1 and 2, rule-irrelevant features were correlated with particular categories during training. During transfer, participants applied a one- dimensional rule to stimuli with category-congruent, category-incongruent, or novel rule-irrelevant features. Category-incongruent and novel features delayed RT and P300 latency, but had no effect on the N2. Experiment 3 used a two-dimensional rule to create conflict between rule-relevant features. Conflict resulted in prolonged RTs, P300 latency, and larger amplitudes of a prefrontal positive component, but had no impact on the N2. Novel features did enhance the N2 relative to frequent features. In Experiments 4 and 5, participants categorized stimuli using a more complex three dimensional rule. Conflicting stimuli shared two features with one prototype and one feature with a second prototype while prototypes contained no conflicting information. A third category contained stimuli with either common or novel features. Again, perceptual novelty, but not conflict, increased the amplitude of the N2. Compared to prototypes, stimuli with conflicting information slowed reaction times but had no effect on P300 latency, instead enhancing a late prefrontal positive component. These results suggest limitations on the generality of the N2's sensitivity to conflicting information, while confirming its sensitivity to attended visual novelty. We suggest that, while P300 latency tracks stimulus evaluation time, application of a complex categorization rule requires a later stage of evaluation involving prefrontal cortex. In very complex rules, computations indexed by the P3 may be terminated early in favor of computations in PFC.

Over the last 30 or more years evidence has accumulated in favour of the view that memory is not a unitary faculty; rather, it can be subdivided into a num- ber of functionally independent subsystems. Whilst dividing memory phenomena into these distinct subsystems has undoubtedly advanced our understanding of memory as a whole, the approach of studying subsystems in isolation fails to address potential interactions between them. Over the last few decades there has been a gradual increase in the number of studies attempting to move be- yond dissociation by characterising functional interactions between subsystems of memory. The main aim of this thesis was to contribute to this endeavour, by examining interactions between two specific subsystems that are positioned on opposite sides of the declarative and non-declarative divide in long-term mem- ory: priming and episodic recognition. Event-Related Potentials (ERPs) were employed to monitor neural markers of repetition priming and episodic memory during recognition tests with masked priming of test cues. In the standard pro- cedure, half of the studied and unstudied test trials began with a brief (48ms) masked repetition of the to-be-recognized word prior to the onset of test items; the remaining unprimed trials were preceded by the word “blank”. The pattern of priming effects across experiments was reasonably consistent, with differences between experiments directly related to the intended manipulations. In contrast to priming effects, the pattern of memory effects was variable across experiments, demonstrating that the engagement of explicit recognition signals is influenced by the outcome of implicit processing, and suggesting that interactions between priming and explicit retrieval processes do occur. Taken together, results from experiments reported in this thesis indicate (1) that under certain circumstances, priming is sufficient to support accurate recognition and does not necessitate changes in memory performance, (2) that mid-frontal old/new effects indexing familiarity are not merely driven by repeated access to semantic information, and (3) that priming influences neural correlates of recollection by speeding their onset. Overall, the data clearly demonstrate that there are multiple potentially interacting routes to recognition.

Many questions remain unanswered regarding the intricacies of the human brain, especially with regard to the complexities of language processing. One essential component of human sentence processing is the ability to detect, decipher, and recover from errors in the interpretation of both verbal and written language. This process of repair of ungrammatical sentences and revision or reinterpretation of ambiguous sentences has been studied extensively in recent years. A variety of tools have been developed, including the use of event-related potentials (ERPs) in order to assess how language is processed and developed, and to help better identify the nature of these processes. The purpose of this study was to compare event-related potential effects of speech processing of spoken and written sentences containing both incorrect and correct semantic and syntactic information. Specifically, sentences containing correct and incorrect gapping structures, each with a "missing" verb, were presented along with other grammatical and ungrammatical sentences in order to elicit and measure the P300, N400, and P600 amplitudes and latencies. The aim was to determine some of the commonalities and differences in these electrophysiological responses via the auditory and visual modalities. Two experiments were conducted with each participant, one in the auditory modality, and one within the visual using two sets of stimuli. Amplitude and topography differences were noted within and between modalities for each of the components (P300, N400, and P600), as well as between stimulus types. Significant findings suggest that in the adolescent population, incorrect gapping structures are generally processed as semantic errors, as evidenced by the N400 response, followed by the P600 response in both the auditory and visual modalities. The exact nature of the P600 component within gapping structures remains unclear. Of particular interest was the involvement of the occipital area of the brain for the processing of gapping structures. Minimal differences were noted overall between adolescents and the adult populations.

This thesis investigated the relationship between prediction and attention in visual perception by recording electrophysiological brain responses. Visual paradigms were implemented using various manipulations of stimuli (shapes, neutral faces, and emotional faces), types of attention (spatial, featural, and emotion-guided), and prior precision of spatial location (low and high). This thesis found that during the early stages of visual processing prediction error signalling consistently occurs, with information then diverging into the associated brain regions for further processing for information updating. This thesis demonstrates that prediction and attention both interact and dissociate in the brain in distinct stages during visual perception.

The phonological structure differs between languages. Human brain structure subserving speech perception is shaped through early exposure to and long-term experience with one’s native language, so that the sensitivity to specific acoustic cues that are relevant in that language develops. Such adaptive process of brain plasticity facilitates to recognize phonemes and capture prosodic signals correctly in the native language, whereas it augments difficulty to perceive some linguistic cues in foreign languages. Speech phonology consists of segmental and suprasegmental components. Segmental components are expressed by formants defining phonemes, and suprasegmental components are defined by pitch (fundamental frequency: F0), intensity and temporal parameters (duration of phonemes and of pauses). The present studies are aimed at investigating cortical auditory processing of segmental and suprasegmental components of speech using the techniques of event-related brain potentials (ERPs). In Study I, two experiments were conducted to explore the auditory perception of vowels that belong or not to the phonemic inventory of listeners’ native language. The mismatch negativity (MMN) is an ERP component reflecting pre-attentive detection of auditory deviance compared with the integrated representation of standard features in the sensory memory (Näätänen et al., 2007; Kujala et al., 2007 for reviews). In the present study, this component was used to tap language-specific long-term memory traces for vowels (Näätänen et al., 1997; Cheour et al., 1998; Winkler et al., 1999a). An auditory sequence including four vowels (one standard and three deviants), each pronounced by three speakers, was presented in passive and active listening conditions. When all the vowels were distinctive in the native inventory (Experiment 1), the MMN was elicited by each deviant vowel category independently of speaker variability, demonstrating pre-attentive categorization based on long-term memory traces. By contrast, when a part of vowels did not belong to the native phonemic inventory (Experiment 2), deviant vowels did not elicit MMNs, indicating the lack of automatic categorization. Moreover, speaker’s variability interacted with vowel category only in the active listening condition, as reflected by behavioral data and cognitive ERP components, suggesting that listeners depended more on conscious acoustic analysis of each stimulus than on pre-attentive categorization, when the deviant to discriminate is physically similar to the standard or is not supported by the inventory in the native language. In Study II, another experiment (Experiment 3) was conducted to investigate the perception of small and large pitch changes embedded in sentences spoken in listeners’ native language, jabberwocky or a foreign language. Behavioral performance in a pitch change detection task and the ERP components elicited by pitch changes (an early centro-temporal negativity and a later positivity) were analyzed. Results showed that subjects processed phrasal pitch better in their native language than in the foreign language, while the results for jabberwocky sentences were intermediate, suggesting that both familiar prosodic patterns and natural and meaningful context in the native language help listeners to detect subtle changes in phrasal pitch contour. Overall results confirmed that long-term experience with one’s native language has effects from early stages of cortical auditory processing involved in speech perception, modulating conscious perception of speech stimuli in different languages.
La struttura fonologica varia tra le lingue. I sistemi neurali nel cervello umano che sottostanno la percezione del linguaggio parlato vengono strutturati mediante l’esposizione precoce e la lunga esperienza con la lingua nativa, in modo che la sensibilità a specifici segnali acustici che sono pertinenti in quella lingua si sviluppi in modo ottimale ed estremamente efficiente. Tale processo adattivo di plasticità cerebrale facilita il riconoscimento dei fonemi e l’acquisizione degli indizi prosodici nella lingua nativa. D’altro canto, lo stesso processo aumenta la difficoltà di percepire alcuni segnali linguistici in lingue straniere. La presente tesi presenta degli studi effettuati per indagare l’elaborazione corticale delle componenti segmentali e soprasegmentali del linguaggio parlato utilizzando le tecniche di potenziali evento-relati (ERP). Nello Studio I, sono stati condotti due esperimenti sulla percezione uditiva delle vocali che appartengono o non appartengono all'inventario fonemico della lingua nativa dei soggetti. La Mismatch Negativity (MMN) è una componente di ERP che riflette la rilevazione pre-attentiva della devianza acustica dello stimolo attuale rispetto alla rappresentazione integrata dello stimolo standard nella memoria sensoriale (Näätänen, 2007; Kujala et al., 2007) ed è stata utilizzata anche per sondare le rappresentazioni lingua-specifiche nella memoria a lungo termine (Näätänen, 1997; Cheour et al., 1998; Winkler et al., 1999a). Una sequenza uditiva è stata costruita con quattro vocali (una standard e tre devianti), ciascuna pronunciata da tre parlanti diverse, ed è stata presentata ai soggetti nelle condizioni di ascolto attivo e passivo. Quando tutte le vocali erano distintive nell'inventario della lingua nativa, la MMN è stata generata da ciascuna vocale deviante indipendentemente dalla variabilità delle parlanti, dimostrando la categorizzazione pre-attentiva basata sulle rappresentazioni nella memoria a lungo termine (Esperimento 1). Al contrario, quando una parte delle vocali non apparteneva all'inventario fonemico nativo, la MMN è stata generata da nessuna delle vocali devianti, che indica la mancanza di categorizzazione automatica (Esperimento 2). Inoltre, la variabilità dovuta alle parlanti ha interagito con la categoria vocale nella condizione di ascolto attivo, come risulta dai dati comportamentali e dalle componenti cognitive di ERP, quando il deviante per discriminare è fisicamente simile allo standard (Esperimento 1) oppure non è supportato dall'inventario nella lingua nativa (Esperimento 2), suggerendo che l’analisi acustica consapevole ed altre strategie cognitive sono impiegate per categorizzare i devianti acusticamente difficili o ambigui. Nello Studio II (Esperimento 3), è stata indagata la percezione dei cambiamenti piccoli e grandi di altezza tonale (pitch) immessi nelle frasi parlate nella lingua nativa degli ascoltatori, jabberwocky o in una lingua straniera. Sono state analizzate le prestazioni in un compito di rilevazione delle incongruenze prosodiche e gli ERP generati dai cambiamenti di altezza tonale (una componente negativa precoce e una positività più tardiva). I risultati hanno dimostrato che i soggetti sono più efficienti ad elaborare l’altezza tonale nel contesto frasale della loro lingua nativa che della lingua straniera, mentre i risultati per le frasi in jabberwocky erano intermedi, suggerendo che sia la prosodia familiare che il contesto naturale e semanticamente interpretabile della lingua nativa aiutano gli ascoltatori a rilevare i cambiamenti sottili di altezza tonale. I risultati globali di questi studi hanno confermato che la lunga esperienza con la lingua nativa ha un impatto sull’elaborazione uditiva nella corteccia fin dagli stadi precoci della percezione del linguaggio parlato, di conseguenza modulando la percezione cosciente degli stimoli parlati in lingue diverse.

This study recorded Event Related Potentials (ERPs) during completion of a Continuous Performance Task (CPT) in order to identify the contribution of response inhibition, working memory, and response monitoring to the pattern of hyperactive and impulsive and inattentive behaviour observed in patients with Attention Deficit Hyperactive Disorder (ADHD). Four ERP components, Nogo N2, Nogo P3, Go P3, and the ERN were examined and compared using a symptomatic and asymptomatic ADHD sample, and a healthy control group. The Nogo N2 had the expected frontal scalp distribution and was affected by changes to inhibitory demands. It was also suggested that this component was not wholly determined by inhibitory processing and may have been influenced by differing presentation rates of the Go stimulus, a template matching process or an in-depth response strategy. Source localisation analysis suggested a right frontal generator for this component. The Nogo P3 had the expected central distribution and had equal amplitude for those participants that were more efficient at inhibiting behaviours compared to those participants that were less efficient inhibitors. Contrary to expectations, the Nogo P3 was not affected by increasing the inhibitory demands of the task and was suggested as being a less reliable indicator of response inhibition in the present study. The Go P3 had the expected centro-parietal distribution, and appeared to provide a reliable index of working memory. Response inhibition and working memory were not impaired in the sample of symptomatic and asymptomatic ADHD adults used in this study. The symptomatic group elicited a slightly enhanced ERN compared to the asymptomatic and control groups, indicating that deficits in response monitoring may contribute to the pattern of problematic behaviour observed in people with ADHD.

The present thesis faces the ongoing debate on the linguistic nature of Developmental Dyslexia (DD), based on evidence of grammatical deficits in dyslexic individuals (e.g., Robertson & Joanisse, 2010), and on the frequently reported overlap with Specific Language Impairment (e.g., Bishop & Snowling, 2004). In particular, the morphosyntactic processing deficit in DD has been explored by means of particularly sensitive measures, namely event-related potentials (ERPs). The dissertation collects the results from three studies performed on different samples of individuals with DD (Italian adults, Italian children, and German adults), reporting consistent data in support of a general morphosyntactic processing weakness. Specifically, the ERP results reveal different language processing modalities in the dyslexic samples, characterised by the need of an additional process related to rules retrieval and/or lexical access. Further behavioural data collected on the same participants support the ERP data. In the third study, advantage has been taken of the morphological features characterising German to additionally investigate the specificity of the reported morphosyntactic deficits, and their relationship with phonological and acoustical processing difficulties. The results are discussed within a developmental and psycholinguistic framework.

The ability to recognise an individual's affective state from their facial expression is crucial to human social interaction. However, understanding of facial expression recognition processes is limited because mounting evidence has revealed important differences between posed and genuine facial expressions of emotion. Most previous studies of facial expression recognition have used only posed or simulated facial expressions as stimuli, but posed expressions do not reflect underlying affective state unlike genuine expressions. The current study compared behavioural responses and Evoked Response Potentials (ERPs) to neutral expressions, posed smiles and genuine smiles, during three different tasks. In the first task, no behavioural judgment was required, whereas participants were required to judge whether the person was showing happiness in the second task or feeling happiness in the third task. Behavioural results indicated that participants exhibited a high degree of sensitivity in detecting the emotional state of expressions. Genuine smiles were usually labelled as both showing and feeling happiness, but posed smiles were far less likely to be labelled as feeling happiness than as showing happiness. Analysis of P1 and N170 components, and later orbitofrontal activity, revealed differential activity levels in response to neutral expressions as compared to posed and genuine smiles. This differential activity occurred as early as 135ms at occipital locations and from 450ms at orbitofrontal locations. There were significant interactions between participant behavioural sensitivity to emotional state and P1 and N170 amplitudes. However, no significant difference in ERP activity between posed smiles and genuine smiles was observed until 850ms at orbitofrontal locations. An additional finding was greater right temporal and left orbitofrontal activation suggesting hemispheric asymmetry of facial expression processing systems.

Two decades of event-related potential (ERP) research have established that the most consistent correlates of the onset of visual consciousness are the early visual awareness negativity (VAN), a negative component in the N2 time range over posterior electrode sites, and the late positivity (LP), a positive component in the P3 time range over fronto-parietal electrode sites. A review by Koivisto & Revonsuo (2010) had looked at 39 studies and concluded that the VAN is the earliest and most reliable correlate of visual phenomenal consciousness, whereas the LP probably reflects later processes associated with reflective/access consciousness. However, an “early” vs. “late” debate still persists. This thesis provides an update to that earlier review. All ERP and MEG studies that have appeared since 2010 and directly compared ERPs of aware and unaware conditions are considered. The result corroborates the view that VAN is the earliest and most consistent signature of visual phenomenal consciousness, and casts further doubt on the LP as an ERP correlate of consciousness. Important new methodological, empirical, and theoretical developments in the field are described, and the empirical results are related to the theoretical background debates.

The studies investigated the impact of predictive visual information about the pitch and location of a forthcoming sound on the sound processing. In Symbol-to-Sound matching paradigms, symbols induced predictions of particular sounds. The brain’s error signals (IR and N2b components of the event-related potential) were measured in response to occasional violations of the prediction, i.e. when a sound was incongruent to the corresponding symbol. IR and N2b index the detection of prediction violations at different levels, IR at a sensory and N2b at a cognitive level. Participants evaluated the congruency between prediction and actual sound by button press. When the prediction referred to only the pitch or only the location feature (Exp. 1), the violation of each feature elicited IR and N2b. The IRs to pitch and location violations revealed differences in the in time course and topography, suggesting that they were generated in feature-specific sensory areas. When the prediction referred to both features concurrently (Exp. 2), that is, the symbol predicted the sound´s pitch and location, either one or both predictions were violated. Unexpectedly, no significant effects in the IR range were obtained. However, N2b was elicited in response to all violations. N2b in response to concurrent violations of pitch and location had a shorter latency. We conclude that associative predictions can be established by arbitrary rule-based symbols and for different sound features, and that concurrent violations are processed in parallel. In complex situations as in Exp. 2, capacity limitations appear to affect processing in a hierarchical manner. While predictions were presumably not reliably established at sensory levels (absence of IR), they were established at more cognitive levels, where sounds are represented categorially (presence of N2b).

The brain generates internal models of the world to interpret incoming information and predict future sensation. These models need to be constantly updated so as to maintain accurate predictions. Fundamental to this is the signalling of violated expectations when new evidence contradicts predictions. Recent evidence has identified a candidate brain signal of violated expectation in visual perception. Here I investigate the operating characteristics of this signal and the extent to which it is consistent with indexing visual surprise. Over four experiments I robustly demonstrate response characteristics supporting current theoretical frameworks of predictive coding in the brain.

In this doctoral dissertation I present some of the studies conducted during my PhD aimed to investigate how face processing abilities develop across the lifespan and how the face representation system adapts to reflect each individual's social experience. As adults we are expert at processing faces; nevertheless our ability is greater for some categories of faces than for others, giving rise to recognition biases based on social dimensions such as species, race and age. These biases have been interpreted as a result of the interaction between individual motivation and perceptual experience provided by social environment, which work together in affecting the way we encode, process and mentally represent faces. The studies presented in this dissertation focused on the age bias that is the variability in face recognition abilities determined by the relation between the age of the observer and the age of the perceived face. Specifically I will discuss recent evidence suggesting the presence of a processing advantage for adult versus non-adult faces in the lifespan (from infancy to old age) and I will provide novel evidence on how the time of acquisition modulates the effects of individual experience with non –adult faces on this perceptual advantage for adult faces across the life-span. In Chapter 1 I will investigate the short- and long-term effects of early-acquired experience with a child or an infant face provided by the presence of a younger or older sibling in our participants’ family household. Study 1 and Study 2 investigated the behavioral and the neural correlates of the perceptual tuning towards adult faces and its modulation as a consequence of sibling experience, within the first year of life. These two studies show that early-acquired experience has a critical role in the emergence of neurocognitive specialization for adult faces. Study 3 provides evidence on the long-lasting effects of this early acquired experience in interaction with later-acquired experience during adulthood: recognition ability for adult and infant faces was tested in first-time mothers who were or were not exposed to sibling experience in their first years of life. Results show that experience acquired early in life has a greater impact than the one acquired later in life, as only mothers with a younger sibling were able to bootstrap perceptual learning of infant faces from exposure to their own child. These findings suggest that early-acquired experience has continuous effects into adulthood, as it preserves the system from the loss of plasticity that would otherwise take place. In Chapter 2 I will investigate the extent to which face representation system remains plastic during adulthood and old age. Results show that professional experience with older adult individuals in adulthood and social experience with peers in old age reduce the magnitude of the recognition advantage for adult faces suggesting that experience with multiple individuals is capable to modulate face processing abilities even in adulthood and old age. Lastly Study 6 investigated how face age affects the deployment of selective visual attention and whether this effect is modulated by professional experience with non-adult faces acquired later in development. Findings provided by this last work extend the few existing evidence on the impact of face dimensions, such as age and race, on visual attention and yielded novel insights into the differential mechanisms underlying the age and the race bias. Overall these studies confirmed the plasticity of the face representational system which constantly adapts to reflect the individual’s current social and perceptual experience across the whole lifespan from infancy up to old age.

SUMMARY Introduction: There has recently been a great deal of interest in the role of synchronous high-frequency gamma oscillations in brain function. This interest has been motivated by an increasing body of evidence, that oscillations which are synchronous in phase across separated neuronal populations, may represent an important mechanism by which the brain binds or integrates spatially distributed processing activity which is related to the same object. Many models of schizophrenia suggest an impairment in the integration of brain processing, such as a loosening of associations, disconnection, defective multiple constraint organization, or cognitive dysmetria. This has led to recent speculation that abnormalities of high-frequency gamma synchronization may reflect a core dimension of the disturbance underlying this disorder. However, examination of the phase synchronization of gamma oscillations in patients with schizophrenia has never been previously undertaken. Method: In this thesis a new method of analysis of gamma synchrony was introduced, which enables the phase relationships of oscillations in a specific frequency band to be examined across multiple scalp sites as a function of time. This enabled, for the first time, the phase synchronization of gamma oscillations across widespread regions, to be studied in electrical brain activity measured at the scalp in humans. Gamma synchrony responses were studied in electroencephalographic (EEG) data acquired during a commonly employed conventional auditory oddball paradigm. The research consisted of two sets of experiments. In the first set of experiments, data from 100 normal subjects, consisting of 10 males and 10 females in each age decade from 20 to 70, was examined. These experiments were designed to characterize the gamma synchonizations that occurred in response to target and background stimuli and their functional significance in normal brain activity, and to exclude the possibility of these findings being due to electromyogram (EMG) or volume conduction artifact. The examination of functional significance involved the development of an additional new analysis technique. In the second set of experiments, data acquired from 35 patients with schizophrenia and 35 matched normal controls was analyzed. The purpose of these experiments was to determine whether patients showed disturbances of gamma synchrony compared to controls, and to establish the relationship of any such disturbances to medication levels, symptom profiles, duration of illness, and a range of psychophysiological variables. Results: In the 100 normals, responses to target stimuli were characterized by two bursts of synchronous gamma oscillations, an early (evoked) and a late (induced) synchronization, with different topographic distributions. Only the early gamma synchronization was seen in response to background stimuli. The main variable modulating the magnitude of these gamma synchronizations from epoch to epoch was pre-stimulus EEG theta (3-7 Hz) and delta (1-3 Hz) power. Early and late gamma synchrony were also associated with N1 and P3 ERP component amplitude across epochs. Across subjects, the early gamma synchronization was associated with shorter latency of the ERP components P2, N2 and P3, smaller amplitude of N1 and P2, and smaller pre-stimulus beta power. The control analyses showed that these gamma responses were specific to a narrow frequency range (37 to 41 Hz), and were not present in adjacent frequency bands. The responses were not generated by EMG contamination or volume conduction. In the 35 patients with schizophrenia, significant abnormalities of both the early and late synchronizations were observed compared to the 35 normal controls, with distinctive topographic characteristics. In general, early gamma synchrony was increased in patients compared to controls, and late gamma synchrony was decreased. These gamma synchrony disturbances were not related to medication level or the four summed symptom profile scores (positive, negative, general and total). They were, however, associated with duration of illness, becoming less severe the longer the patient had suffered from the disorder. The disordered gamma synchrony in patients was not secondary to abnormalities in other psychophysiological variables, but appeared to represent a primary disturbance. Discussion: The early synchronization may relate to the binding of object representations in early sensory processing, or, given that a constant inter-stimulus interval was employed, may be anticipatory and related to active memory. The late response is probably involved in binding in relation to activation of the internal contextual model involved in late expectancy/contextual processing (context updating or context closure) for target stimuli. The across epochs effects may relate to whether the focus of attention immediately prior to stimulus presentation is internal or is directed at the task. The across subjects effects suggest that a larger magnitude of the early gamma synchronization might indicate that the subject maintains a more stable and less ambiguous internal representation of the environment, that reduces the complexity of input and facilitates target/background discrimination and subsequent processing. The early gamma synchronization findings in patients with schizophrenia suggest that anticipatory processing involving active memory and forward-prediction of the environment is subject to over-binding or the formation of inappropriate associations. The late synchronization disturbances may reflect a fragmentation of contextual processing, and an inability to maintain contextual models of the environment intact over time. Conclusion: This research demonstrates the potential importance of integrative network activity as indexed by gamma phase synchrony in relation to normal cognition, and the possible broad relevance of such activity in psychiatric disorders. In particular, the application in this study to patients with schizophrenia showed that an impairment of brain integrative activity (missing links) might be a key feature of this illness.

Certain electrophysiological markers hold promise in distinguishing individuals with major depressive disorder (MDD) and in predicting antidepressant response, thereby assisting with assessment and optimizing treatment, respectively. This thesis examined resting brain activity via electroencephalographic (EEG) recordings, as well as EEG-derived event-related potentials (ERPs) to auditory stimuli and facial expression presentations in individuals with MDD and controls. Additionally, the utility of resting EEG as well as auditory ERPs (AEPs), and the associated loudness-dependence of AEPs (LDAEP) slope, were assessed in predicating outcome to chronic treatment with one of three antidepressant regimens [escitalopram (ESC); bupropion (BUP); ESC+BUP]. Relative to controls, depressed adults had lower pretreatment cortical activity in regions implicated in approach motives/positive processing. Increased anterior cingulate cortex (ACC)-localized theta was observed, possibly reflecting emotion/cognitive regulation disturbances in the disorder. AEPs and LDAEPs, putative indices of serotonin activity (implicated in MDD etiology), were largely unaltered in MDD. Assessment of ERPs to facial expression processing indicated slightly blunted late preconscious perceptual processing of expressions, and prolonged processing of intensely sad faces in MDD. Faces were rated as sadder overall in MDD, indicating a negative processing bias. Treatment responders (vs. non-responders) exhibited baseline cortical hypoactivity; after a week of treatment, cortical arousal emerged in responders. Increased baseline left fronto-cortical activity and early shifts towards this profile were noted in responders (vs. non-responders). Responders exhibited a steep, and non-responders shallow, baseline N1 LDAEP derived from primary auditory cortex activity. P2 LDAEP slopes (primary auditory cortex-derived) increased after a week of treatment in responders and decreased in non-responders. Consistent with overall findings, ESC responders displayed baseline cortical hypoactivity and steep LDAEP-sLORETA slopes (vs. non-responders). BUP responders also exhibited steep baseline slopes and high ACC theta. These results indicate that specific resting brain activity profiles appear to distinguish depressed from non-depressed individuals. Subtle ERP modulations to simple auditory and emotive processing also existed in MDD. Resting alpha power, ACC theta activity and LDAEP slopes predicted antidepressant response in general, but were limited in predicting outcome to a particular treatment, which may be associated with limited sample sizes.

The present thesis is composed of two main parts. In the first part, the effect of aging was investigated on performance and on event-related potentials (ERPs) associated with several goal-directed cognitive tasks. In the second part, cognitive and ERP changes were explored in patients with minimal hepatic encephalopathy, a syndrome characterized by cognitive and neurophysiological abnormalities in patients with liver cirrhosis. 1° PART: COGNITIVE AND ELECTROPHYSIOLOGICAL ALTERATIONS ASSOCIATED WITH HEALTHY AGING. It is a truism that as people grow older, performance on a large number of cognitive tasks declines. These age-sensitive tasks include simple and choice reaction times (RTs) tasks, tests of episodic memory, working-memory tasks, tasks involving executive functions, spatial and reasoning abilities, mental rotation (e.g., Kausler, 1991; Salthouse, 1991). Given that deficits are so widespread across the cognitive domains, it is reasonable to assume that a limited number of mechanisms might be responsible. Different theories tried to address this issue. Some of them suggested that cognitive deficits in aging are due to a reduction in the amount of attentional resources (Craik, 1986; Craik & Byrd, 1982), or a slowing down of processing speed (Salthouse, 1996), or a decline in the inhibitory control of working-memory contents (Hasher & Zacks, 1988). One explanation that has recently gained some prominence is the increasing impairment of executive control with age, likely related to age-specific changes in prefrontal cortex (“theory of Cognitive Control”, also called “goal maintenance account”; Braver & West, 2008; Raz, 2000; West, 1996). Executive control is intended as the ability to represent, maintain and update goal information in order to exert control over behaviour and thoughts (Cohen et al., 1996). According to Miyake and collaborators (2000), executive control is not a single function, but is composed of several cognitive sub-processes, namely shifting, updating and inhibition. To explore the role of executive control in explaining the age-related cognitive decline, the effect of cognitive aging was measured on those tasks involving high recruitment of such ability. Specifically, the first study of the present thesis (Experiment 1) investigated the age-related changes on a time-based prospective memory (PM) task, and focused on exploring the effect of aging on ERPs. Time-based PM refers to the ability of remembering to perform an action at a specific point in the future, (for example, remembering to attend an appointment at 3 pm; Brandimonte et al., 1996; Einstein & McDaniel, 2000; Kliegel et al., 2009). A fundamental process required for successfully accomplishing PM tasks is the ability to maintain and update the PM intentions (i.e., goal information) active in memory. Such ability, being impaired based on the “theory of cognitive control”, might be the factor determining the age-related alterations observed in time-based PM tasks. The analysis of ERPs elicited in time-based PM tasks is useful to test this hypothesis, and to better clarify the mechanisms responsible for age-related alterations in these kinds of tasks. The second study focused on the relationship between executive control and cognitive aging by comparing performance of older and younger adults on a task in which the executive control load was manipulated. The task, called Inhibitory Control task (ICT; Bajaj et al., 2008a), is indeed composed of three different conditions, which varies for the executive resources needed. I expected that, if the executive control is the key factor responsible for cognitive impairment in aging, thus the deleterious effect of age on performance would be greater as the executive load increases. Moreover, ICT provides an investigation of the age-related alterations on ERPs associated with the different processes composing executive control, such as updating, shifting, and response inhibition (Miyake et al., 2000). The two studies will be described in details below. Experiment 1: ERP mechanisms underlying age-related alterations in Time-Based Prospective Memory. There is a general agreement, across studies on PM, towards a deleterious effect of age on time-based PM performance (Bastin & Meulemans, 2002; McDaniel & Einstein, 1992; Park et al., 1997; see Henry, MacLeod, Phillips, & Crawford, 2004, for a review). According to Craik’s theory (Craik, 1986), since in PM tasks there are no explicit prompts from the environment that instigate the retrieval of intention, individuals need to engage self-initiated and attentional demanding processes to retrieve the PM intentions. Given that aging is associated with a reduction in the availability of these attentional resources, thus PM performance would be altered in older people. On the other hand, according to the “theory of cognitive control” (or “goal maintenance account”; Braver & West, 2008), older adults have difficulties in the maintenance of goal representations over an extended period. In the case of time-based PM, failure to maintain active the goal (i.e., the intention) would lead to failure to correctly execute the intended action. Although a large number of studies investigated the impairment of time-based PM with aging, nevertheless none study has ever focused on neural activity underpinning such alterations. Therefore, in order to shed light on such poorly investigated issue, the present study explored the age-related alterations in the electrophysiological correlates of time-based PM tasks. To this end, ERPs associated with ongoing task (i.e., a task executed concurrently with the PM task) were examined in 18 older and 15 younger adults and compared between a baseline block, in which individuals were required to perform merely the ongoing task; and a PM block, in which individuals were required to perform simultaneously the ongoing and the PM tasks. The ongoing task consisted in evaluating in five-letter strings whether the letters in second and fourth positions (target positions) were equal or different by pressing one of two possible keys. In the PM task, participants were required to remember to press the “PM key” every five minutes from the beginning of the block. To help them to estimating the passing of time, they had the opportunity to check the digital clock in any moment of the task by pressing another key. The ERPs were locked to ongoing trials (i.e., the strings of letter). Reaction times, accuracy and ERPs relative to ongoing trials were compared between the baseline and the PM block, for both younger and older adults. Moreover, the percentage of accuracy in PM task and the number of clock checks were recorded. Concerning the behavioural results, older adults showed a lower percentage of accuracy in PM task respect to younger adults. Moreover, the older adults displayed a slowing down of RTs in the ongoing task, both in the baseline and in PM block, as compared to younger adults. Concerning the ERPs of younger adults, the addition of a time-based PM task to an ongoing activity led to a sustained positive modulation of the ERPs elicited by the ongoing trials, mainly expressed over prefrontal and frontal regions. This frontal activity seems to reflect the load of maintaining the intention active in memory, as recently suggested (Cona et al., in press; West et al., 2011). On the other hand, in older adults these ERP modulations were more expressed over posterior regions. Interesting, a difference in the ERP amplitude between baseline and PM block was observed over prefrontal sites in younger adults (with the ERPs being more positive in PM block), but not in older adults. At first glance, the absence of the prefrontal mofulation in older adults seems to reflect their difficulties in keeping the PM intention in mind, as suggested by the “theory of cognitive control” (Braver & West, 2008). Nevertheless, the exploration of the ERP differences as observed between the two groups in the baseline block allowed to better clarify the mechanisms responsible of these age-related changes in PM. Indeed in baseline block, compared to younger adults, older adults showed a lower P300 over parietal regions, and a higher P300 over prefrontal regions. The anteriorisation of the P300 shown by older adults has been well documented in literature (Daffner et al., 2006; 2011), and it is supposed to reflect the greater recruitment of attentional resources to compensate for olders’ difficulties in the ongoing task. Taken together, these results suggest that older adults had difficulties already in the baseline block, and cope with such difficulties by recruiting additional frontal resources (as reflected by the anteriorisation of P300). If too many resources were allocated to perform the ongoing task, then fewer resources would be available to adequately maintain the intentions in memory, leading to an impaired PM performance. Therefore, it seems more reasonable that the decline in executive control, required for intention maintenance, is not the primary cause of the age-related changes in PM tasks, but rather is itself the consequence of a reduced amount of available resources, as postulated by Craik’s theory (1986). Experiment 2: Influence of aging on ERP correlates of executive control processes. According to the “theory of cognitive control” (Braver & West, 2008), an age-related impairment in executive control is hypothesized to determine specific decrements in those cognitive tasks that are more demanding for that function. In order to test this prediction, we adopted the Inhibitory Control task (ICT; Bajaj et al., 2008a). During the ICT, a continuous stream of letters is presented, very quickly, one after the other. In the first part of the task, it is required to respond by pressing a key only to the target letters (i.e., “X” and “Y,”). Trials containing a target letter are labelled as Detect trials. In the second part, it is required to respond whenever the target letters are alternated (Go trials), as when an “X” is preceded by a “Y”, or vice versa, regardless of the irrelevant letters presented between them. In contrast, it must withhold response if target letters are repeated (Nogo trials), as when an “X” precedes another “X”, or a “Y” precedes another “Y”. In light of this, ICT includes trials requiring different demands of executive control. Detect trials requires to merely pay selective attention and to respond to specific stimuli. These trials are relatively low demanding in terms of executive control. Go trials are more demanding, implying the process of working memory updating. Finally, Nogo trials are the highest demanding trials since imply not only an updating process but also inhibitory control of response. According to the theory of control, differences on ICT performance between younger and older adults should be lowest in detect trials, intermediate in go trials and greatest in nogo trials. Furthermore, this study was aimed at investigating the effect of age on the different processes composing the executive control (Miyake et al., 2000). Therefore it was explored the influence of aging on peak latency and amplitude of P3b, nogo-P3 and RON (i.e., reorienting negativity) components, which reflect updating, inhibition, and shifting processes, respectively. In order to better dissociate the ERP components related to these different processes, a partial least square (PLS) analysis was run. Seventeen younger and sixteen older adults performed the ICT. Against the formulated predictions, older adults exhibited a worse performance in all kinds of trial, as from detect trials to nogo trials. More importantly, the age effect did not interact with the type of trials, hence was independent from the degree of executive control required to perform them. This means that executive control, when formulated as a unitary construct responsible for the age-related deficits in cognition, does not seem to be the elective factor for explaining the deficits shown in ICT task. In line with behavioural results, older adults showed a delay in all the ERP components studied (P3b, N2, RON, nogo-P3), regardless of the type of trial. These age-related alterations in the latency of the ERPs seem to reflect a slowing of speed of cognitive processing in the elderly individuals. Such an idea gives support to Sathouse's theory (Salthouse, 1996), which assumed that age-related cognitive decline might be due to a general reduction in the speed of processing. Another relevant finding consists in the fact that the RON components were found particularly sensitive to aging. Specifically, these components, reflecting attentional shifting (Berti et al., 2008), were shown delayed and reduced in older adults. To my knowledge, only one study has investigated the age-related alterations in the RON components before, but utilizing an auditory distraction-paradigm (Horváth et al., 2009). Thus, the present study extended the results obtained in the work by Horváth, suggesting that the age-related impairment of attentional shifting occurred not only after distracter stimuli (as found by Horváth), but also after task-relevant ones. It suggests that in older adults shifting mechanism of attention take longer and is more effortful, probably because they are still engaged in processing the previous stimulus. Summarizing, electrophysiological and behavioural data converged in revealing that age-related cognitive impairment might be, at least partially, attributable to a general slowing of information processes. Indeed, coherently with the review by Verhaegen (2011), reduction on processing speed seems to explain cognitive deficits in elderly better than deterioration in executive control, when this is conceptualized as a unitary construct. On the other hand, a subprocess of executive control, attentional shifting, resulted particularly affected by age, and it could be another candidate to explain multiple age-related cognitive alterations. 1° Part: Conclusions Although the present studies utilized different paradigms and tasks, they converged in revealing that executive control does not play a crucial role in determining the age-related deficits seen in these tasks. Rather, a decline in more basic, or lower-level, mechanisms seems to be the key factor to explain the multitude of age-related cognitive deficits. Specifically, the analysis of the ERPs allowed to highlight that age-related alterations were more likely due to a reduction: 1) in the amount of available resources and 2) in processing speed. The age-related alterations concerned mainly ERPs over prefrontal regions and were they were mainly expressed as delay in the ERP latencies. Interestingly, compensatory mechanisms in older adults were also observed, and were reflected in the increase of amplitude of several components (respect to the younger adults). This led to the suggestion that aging does not simply mean cognitive and neural decline, but may also involve adaptive cognitive and neural responses. 2° PART: COGNITIVE AND ELECTROPHYSIOLOGICAL ALTERATIONS ASSOCIATED WITH MINIMAL HEPATIC ENCEPHALOPATHY. Hepatic encephalopathy (HE) is a neuropsychiatric syndrome occurring in acute or chronic liver failure. The detection of the first, sometimes apparently negligible, signs of hepatic encephalopathy is greatly important since this condition, called minimal hepatic encephalopathy (MHE; Ferenci et al., 1998), impinges on the health-related quality of life (Groeneweg et al., 1998; Zhou et al. 2009) and it is likely to affect driving ability (Wein et al., 2004). Furthermore, it has a negative prognostic value in relation to the occurrence of both bouts of overt hepatic encephalopathy and death (Amodio et al., 1999; Romero-Gomez et al., 2007). The profile of MHE is characterized by cognitive alterations that involve selective attention and executive functions, visuomotor ability, psychomotor speed, response inhibition, and response selection (Amodio et al., 2005). MHE also causes brain dysfunction detectable by slowing of the electroencephalogram (EEG) and prolonged ERPs, such as P300 (Amodio et al., 2005; Weissenborn et al., 2005). Therefore, where possible, the diagnosis of MHE is preferably based on a combination of psychometric and neurophysiological/psychophysiological tools. The inhibitory control task (ICT) has been recently proposed as a simple diagnostic tool for MHE (Bajaj et al., 2007; 2008a). However, its applicability to different populations of patients with cirrhosis and its relation to other measures of MHE need to be confirmed. Therefore, Experiment 3 was designed to address this issue and was aimed at assessing the specificity and sensitivity of ICT for the diagnosis of MHE. The Experiment 4 focused on the effect of MHE on the ERPs elicited by ICT, in order to highlight cognitive and electrophysiological alterations characterizing MHE. In order to further investigate the electrophysiological alterations of MHE, another study (Experiment 5) explored the intra-individual variability (IIV) of P300 parameters (i.e., latency and amplitude) in cirrhotic patients with MHE. There is an increasing interest in IIV of cognitive performance (e.g., of RTs) within the field of cognitive neuroscience (MacDonald et al., 2006), since IIV has been widely considered to be a behavioral indicator of compromised neural mechanisms (e.g., Hultsch, et al., 2000). Nevertheless, studies establishing links between intra-individual variability in behavioral and brain responses are sparse, with most evidence being indirect. MHE seems to be a suitable model of pathology for studying this relation, given that patients with MHE showed increased IIV of RTs (Elssas et al., 1985; Schiff et al., 2006). Therefore, in Experiment 5, single-trial P300 parameters, obtained by means of a single-trial Bayesian estimation technique (D’Avanzo et al., 2011), were estimated to investigate the electrophysiological correlates of IIV of response speed and the relation between P300 parameters and RTs in normal individuals and in a population of patients with and without MHE. Experiment 3 and 4: The ICT as a suitable tool for detecting cognitive and ERP alterations in patients with liver cirrhosis. In Experiment 3, seventy-five patients with cirrhosis and 55 healthy controls underwent the ICT in 2 reference centers for the study of hepatic encephalopathy. Patients were evaluated for MHE by psychometric hepatic encephalopathy score (PHES) and spectral electroencephalogram analyses. Performance on go and nogo trials was compared between the two groups. Patients with cirrhosis exhibited a higher number of errors in nogo trials (i.e., lures), and lower accuracy in go trials, as compared with controls. However, the number of lures was comparable among patients with and without MHE. Importantly, an inverse relation between accuracy in go trials and number of lures was shown when the go accuracy was particularly low. However this is not surprising: a low accuracy in go trials indicates that many trials had a missing response (in go trial an error is a missed response), but if a participant commits many missing responses, he/she is more likely to “perform” correctly on nogo trials (hence to not respond when actually it is required to not respond). In light of this, the low number of error in nogo trials is a spurious effect. Hence, a new variable (weighted lures) was codified, adjusting the number of lures based on go accuracy. This variable distinguished between patients with and without MHE. However, accuracy in go trials alone was as effective as a stand-alone variable. Therefore, testing inhibition (lures) does not seem to be superior to testing attention and working memory updating (go accuracy) for the detection of MHE. In Experiment 4 the electrophysiological alterations related to cirrhosis were investigated in the ICT task by comparing ERPs in cirrhotic patients with MHE (N=13), without MHE (N=18) with ERPs in healthy controls (N=17). Specifically, the ERPs in detect, go and nogo trials were measured, reflecting processes of selective attention, working memory updating, and inhibition, respectively. Data were further analysed by means of a PLS analysis, was particularly suited to dissociate the ERP correlates of the different subprocesses. Findings from ANOVA and PLS analysis converged in showing selective alterations of the ERPs on detect trials in patients with MHE. Specifically these included a reduction in P3a amplitude over frontocentral sites and a delay in the P3b latency. Since detect trials involve principally attentional processes, alterations on these trials may indicate that MHE is associated with an impairment of low-level cognitive abilities, such as attention. This result corroborated the claim of Experiment 3, concerning the appropriateness to test for low-level abilities (i.e., attention) before, or together with, testing for high-level abilities (i.e., inhibition) for the diagnosis of MHE (Amodio et al., 2010). The second main, and unexpected, finding was the enhancement of several ERP components (namely, the N2 and nogo-P3) in cirrhotic patients without MHE. These electrophysiological changes might be a compensatory mechanism, reflecting the allocation of additional executive resources for overcoming the difficulties of the task (indeed, also patients without MHE had a reduction of P3a, which is an index of attentional processes). Experiment 5: The IIV of P300 as an index for detecting neural dysfunctions in patients with liver cirrhosis In patients with cirrhosis, an increased intra-individual variability of RTs has been described and qualified as a potential early sign of brain dysfunction (Schiff et al., 2006). Unfortunately, a neural counterpart of this phenomenon was not obtained yet. However, since a reduction in the amplitude of P300 has been observed in this patient population, it is possible to hypothesize that P300 amplitude reduction depends, at least in part, on the increased variability of single-trial P300 latency (as evidenced in other pathologies; e.g., Hultsch et al., 2000). Moreover, single-trial analysis might clarify the relation between RTs and P300 parameters, and evidence how this relation changed under pathological conditions, such as MHE. EEG was recorded during the execution of a choice reaction time task (i.e., Simon task) in 14 cirrhotic patients with MHE (diagnosed on paper & pencil tests plus EEG), 15 cirrhotic patients without MHE and 14 healthy controls matched for age and educational level. Single-trial P300 amplitude and latency, together with their standard deviation, were obtained using a non-parametric bayesian estimation method. P300 was also measured with the classical method of averaging. RTs distribution and its relation with single-trial P300 amplitude and latency were analysed. In cirrhotic patients, RTs were slower and more variable compared to those of controls. An increased variability in P300 latency was also detected. Linear multiple regression analysis revealed that average-based P300 amplitude reduction was predicted both by standard deviation of single-trial P300 latency and by single-trial P300 mean amplitude. These results indicate that average-based P300 amplitude reduction in cirrhotic patients with MHE depends on both an increased variability of single-trial P300 latency, and a reduction in single-trial P300 amplitude. Interestingly, we also found that P300 latency increased and amplitude decreased in parallel with increasing RTs in normal participants, but not in cirrhotic patients with MHE. Thus, another sign of neural alteration might be the weaker relationship between RTs and P300 parameters observed in patients with MHE. In summary, the present study suggests that, under normal conditions, a relation between P300 and RTs is detectable and the P300 is stable across trials; in contrast, when the brain does not function properly, as observed in patients with MHE, the relation between P300 and RTs vanishes, and neural responses become more variable. 2° Part: Conclusions The use of ICT task provided several insights concerning the neural markers of MHE. Specifically, patients with MHE showed a prolongation and a reduction of the P300 components elicited in the detect trials of ICT task, reflecting deficits in selective and sustained attention. On the other side, patients without MHE displayed an enhancement of several ERP components (i.e., N2 and P3-nogo), which might reflect a compensatory neural mechanism. The Experiment 5 better clarified the profile of P300 in cirrhotic patients. Indeed, such patients, especially those with MHE, showed an increased intra-individual variability of the P300 latency, which may contribute to the reduction of its amplitude. GENERAL CONCLUSIONS The ERP technique was revealed to be a powerful tool to explore neural alterations underlying both the healthy and pathological aging. Interestingly, several patterns of ERP alterations were shared by older individuals and cirrhotic patients (e.g., the delay in several ERPs, or a ‘paradoxical’ enhancement of other components, such as N2). Such ERP alterations highlighted that 1) age- and MHE-related deficits in higher-level cognitive tasks might be due to alterations in lower-level functions or mechanisms, including attention deficits, the reduction of available resources or processing speed; 2) brain activity of older people and cirrhotic patients without MHE was similarly characterized by compensatory mechanisms, recruited to cope with the difficulties of the tasks
La presente tesi si compone di due parti principali. Nella prima parte è stato studiato l’effetto dell’età sulla performance e sui potenziali evento-relati (ERP) elicitati in differenti compiti cognitivi. Nella seconda parte sono stati esplorati i cambiamenti elettrofisiologici (i.e., alterazioni a livello di ERP) e cognitivi che caratterizzano l’encefalopatia epatica minima (MHE), una sindrome neuropsichiatrica conseguente a cirrosi epatica. 1° PARTE: ALTERAZIONI COGNITIVE ED ELETTROFISIOLOGICHE ASSOCIATE ALL’INVECCHIAMENTO SANO. All’avanzare dell’età, le persone mostrano difficoltà in diversi compiti cognitivi. Tali compiti comprendono ad esempio compiti di tempi di reazione (TR) semplice o di scelta, test di memoria episodica, compiti di working memory o che coinvolgono funzioni esecutive, abilità spaziali e di ragionamento, test di rotazione mentale (e.g., Kausler, 1991; Salthouse, 1991). Dato che tali deficit sono così diffusi tra i diversi domini cognitivi, è ragionevole assumere che essi dipendano da un’alterazione a carico di un ristretto numero di meccanismi. Diverse teorie si sono occupate di rispondere a tale questione. Alcune di queste hanno suggerito, ad esempio, che l’invecchiamento cognitivo sia associato ad una riduzione nella quantità di risorse attenzionali disponibili (Craik, 1986; Craik & Byrd, 1982), ad un rallentamento nella velocità di elaborazione (Salthouse, 1996), o ad un declino nel controllo inibitorio delle informazioni contenute nella working memory (Hasher & Zacks, 1988). Una spiegazione cha ha recentemente ricevuto largo consenso sostiene che alla base delle alterazioni cognitive legate all’età vi sia una disfunzione a livello di controllo esecutivo, probabilmente dovuta a cambiamenti a carico della corteccia prefrontale (“teoria del controllo cognitivo” conosciuta anche come “ipotesi del mantenimento degli obiettivi”; Braver & West, 2008; Raz, 2000; West, 1996). Per controllo esecutivo si intende la capacità di rappresentare, mantenere e aggiornare gli obiettivi in memoria al fine di esercitare un controllo sui pensieri e sul comportamento (Cohen et al., 1996). Sulla base del lavoro di Miyake e collaboratori (2000), il controllo non sembra essere una funzione unitaria, ma è composta da diversi sotto-processi cognitivi, quali lo shifting, l’aggiornamento nella working memory e l’inibizione. Per esaminare il ruolo che ha il controllo esecutivo nello spiegare il declino cognitivo legato dell’invecchiamento, è stato testato l’effetto dell’età in quei compiti che sono stati dimostrati richiere un alto coinvolgimento di controllo esecutivo. In particolare, il primo studio di questa tesi (Esperimento 1) ha esaminato i cambiamenti, legati all’età, in un compito di memoria prospettica (MP) basata sul tempo, focalizzandosi sull’analisi di quelle modulazioni ERP che rifletterebbero il declino della MP nell’invecchiamento. La memoria prospettica basata sul tempo si riferisce infatti all’abilità di ricordarsi di eseguire un’azione in un particolare momento nel futuro (ad esempio, ricordarsi di andare ad un appuntamento alle tre; Brandimonte et al., 1996; Einstein & McDaniel, 2000; Kliegel et al., 2009). Un processo che è fondamentale per eseguire appropriatamente i compiti prospettici è il mantenimento e l’aggiornamento delle intenzioni prospettiche in memoria (che rappresentano altresì gli obiettivi del compito prospettico). Tali processi di mantenimento, essendo alterati nell’invecchiamento secondo la teoria del controllo cognitivo, potrebbero essere quindi il fattore chiave nel determinare le alterazioni osservate nei compiti di MP. L’analisi degli ERP elicitati dal compito prospettico si è rivelata utile per testare tale ipotesi, e per chiarire quali siano i meccanismi responsabili del declino in questo tipo di compiti. Il secondo studio ha indagato la relazione tra controllo esecutivo e invecchiamento cognitivo confrontando la prestazione di individui giovani e quella di individui più anziani in un compito in cui veniva variato il carico di controllo esecutivo tra le condizioni. Il compito, chiamato Inhibitory Control Task (ICT) (Bajaj et al., 2008a) è, infatti, composto da tre differenti condizioni, che differiscono per le risorse esecutive necessarie. Se il controllo esecutivo è il fattore chiave nel determinare il deterioramento cognitivo osservato nei diversi compiti, allora l’effetto dell’età sulla performance all’ICT dovrebbe essere tanto maggiore quanto più elevato è il grado di controllo esecutivo richiesto. Inoltre, l’ICT ha permesso di studiare le alterazioni legate all’età negli ERP associati ai differenti meccanismi che compongono il controllo esecutivo, ovverosia l’aggiornamento nella working memory, l’updating e l’inibizione (Miyake et al., 2000). I due studi saranno qui sotto descritti in dettaglio: Esperimento 1: Meccanismi ERP sottostanti alle alterazioni, legate all’età, nella memoria prospettica basata sul tempo. Esiste un generale consenso, tra gli studi sulla MP, riguardo all’effetto deleterio che ha l’invecchiamento sulle prestazioni in compiti di MP basata sul tempo (Bastin & Meulemans, 2002; McDaniel & Einstein, 1992; Park et al., 1997; vedere anche Henry, MacLeod, Phillips, & Crawford, 2004, per una rassegna). Secondo la teoria di Craik (1986), poiché nei compiti di MP non ci sono espliciti suggerimenti dall’ambiente che aiutano il recupero dell’intenzione, gli individui necessiterebbero di un maggior reclutamento di processi attenzionali e auto-iniziati per recuperare le intenzioni. Dato che l’invecchiamento è associato ad una riduzione nella disponibilità di tali risorse attenzioni, ciò determinerebbe un’alterazione nella prestazione dei compiti di MP negli individui più anziani. Dall’altra parte, secondo la teoria del controllo cognitivo (o anche detta “ipotesi del mantenimento degli obiettivi”; Braver & West, 2008), gli anziani avrebbero delle difficoltà nella rappresentazione e nel mantenimento degli obiettivi nel corso del tempo. Nel caso della MP basata sul tempo, i deficit nel mantenere attivi gli obiettivi (cioè le intenzioni) porterebbe ad un fallimento nell’eseguire con successo l’azione intesa. Sebbene un elevato numero di studi abbia esaminato come la MP basata sul tempo declini con l’età, tuttavia nessuno studio si è mai occupato finora di indagare l’attività neurale alla base di tale declino. Per tale motivo, il presente studio ha avuto lo scopo di esplorare le alterazioni legate all’età dei meccanismi elettrofisiologici alla base della MP basata sul tempo. A tal fine, gli ERP associati ad un compito detto ongoing (i.e., un compito eseguito simultaneamente al compito prospettico) sono stati analizzati in 18 anziani e di 15 giovani e sono stati confrontati tra due diversi blocchi: il blocco di baseline e il blocco prospettico. Nel blocco di baseline veniva chiesto ai partecipanti di eseguire solamente il compito ongoing, mentre nel blocco prospettico si chiedeva di eseguire, assieme al compito ongoing, anche il compito di MP. Il compito ongoing consisteva nel valutare, all’interno di stringhe di cinque lettere, se le lettere in seconda e quarta posizione fossero uguali o diverse premendo con la mano destra uno di due possibili tasti. Nel compito di MP basata sul tempo, ai partecipanti era richiesto di premere un tasto ogni 5 minuti a partire dall’inizio del blocco prospettico. Per aiutarli nella stima del tempo, era stata data loro la possibilità di controllare l’orologio (che sarebbe comparso sullo schermo qualora avessero premuto un ulteriore tasto). Gli ERP analizzati erano elicitati dalla comparsa dello stimolo ongoing (i.e., la stringa di lettere). I TR, l’accuratezza e gli ERP nelle prove ongoing sono stati analizzati confrontando il blocco di baseline e quello prospettico, sia nei giovani che negli anziani. Inoltre sono stati analizzati sia la percentuale di accuratezza nel compito prospettico che il numero di controlli dell’orologio. Per quanto riguarda i risultati comportamentali, gli anziani mostravano una percentuale di accuratezza inferiore nel compito prospettico rispetto ai giovani. Inoltre gli anziani hanno mostrato un aumento dei TR al compito ongoing rispetto ai giovani, sia nella baseline che nel blocco prospettico. A livello di dati elettrofisiologici, i giovani hanno mostrato delle modulazioni positive e sostenute degli ERP elicitati dagli stimoli ongoing dovute all’aggiunta del compito prospettico, che erano espresse maggiormente sopra le regioni frontali e prefrontali. Tali modulazioni riflettevano il carico nel mantenere le intenzioni attive in memoria, come recentemente suggerito (Cona et al., in press; West et al., 2011). Dall’altra parte, negli anziani, tali modulazioni erano maggiormente espresse sopra le regioni posteriori. È infatti interessante notare che i giovani, ma non gli anziani, mostravano una maggiore positività degli ERP nel blocco prospettico rispetto alla baseline a livello di siti frontopolari. Ad un primo sguardo, l’assenza della modulazione prefrontale negli anziani sembra riflettere la loro difficoltà nel mantenere in memoria le intenzioni prospettiche, in accordo con la teoria del controllo cognitivo (Braver & West, 2008). Tuttavia, l’analisi delle differenze ERP tra i due gruppi (già nella baseline) ha permesso di comprendere meglio quale fosse il meccanismo responsabile di questo peggioramento nella performance prospettica. Infatti nel blocco di baseline, se confrontati con i giovani, gli anziani mostravano una P300 meno ampia sopra le regioni parietali, e più ampia sopra le regioni prefrontali. L’anteriorizzazione della P300 negli anziani è un fenomeno già ben documentato in letteratura (Daffner et al., 2006; 2011) e sembra indicare il reclutamento di un maggior numero di risorse per compensare le difficoltà nell’eseguire il compito ongoing. In generale, tali risultati suggeriscono che gli anziani hanno difficoltà già nel blocco di baseline, e che affrontano tali difficoltà reclutando risorse frontali addizionali (come indicato dall’anteriorizzazione della P300). Se troppe risorse sono reclutate per eseguire il compito ongoing, allora ne rimarrebbero meno per mantenere adeguatamente le intenzioni in memoria e ciò determinerebbe una performance peggiore al compito prospettico. Sembra quindi più ragionevole assumere che il declino nel controllo esecutivo, richiesto per mantenere le intenzioni in memoria, non sia la causa primaria dei cambiamenti nei compiti prospettici, ma piuttosto sia a sua volta la conseguenza di una minor disponibilità di risorse cognitive, come postulato nella teoria di Craik (1986). Esperimento 2: Influenza dell’invecchiamento sugli ERP associati ai processi legati al controllo esecutivo. Secondo la teoria del controllo cognitivo (Braver & West, 2008), un declino del controllo esecutivo dovuto all’età produrrebbe deficit in quei compiti cognitivi che coinvolgono in misura maggiore proprio quella funzione. Al fine di studiare tale ipotesi, abbiamo utilizzato l’Inhibitory Control Task (ICT; Bajaj et al., 2008a). Durante l’ICT, una serie di lettere viene presentata, molto velocemente, una dopo l’altra. Nella prima parte del compito è richiesto di premere un tasto quando compare o la lettera X o la Y. Le prove in cui compaiono tali lettere vengono definite prove Detect. Nella seconda parte del compito è richiesto di premere il tasto solo quando la X e la Y si alternano (prove Go), ad esempio quando la X è preceduta da una Y, o vice versa, indipendentemente dalle lettere che vengono presentate tra le due lettere target. Quando le lettere X e Y si ripetono (ad esempio, una X è preceduta da un’altra X), allora è necessario inibire la risposta (prove Nogo). In tal modo, l’ICT include prove che richiedono un differente grado di controllo esecutivo per essere eseguite. Infatti, le prove Detect richiedono semplicemente di prestare attenzione selettiva e di rispondere a specifici stimoli, e coinvolgono per questo un basso grado di controllo esecutivo. Le prove Go implicano anche un processo di aggiornamento nella working memory. Infine, le prove Nogo richiedono il maggior carico di controllo esecutivo, coinvolgendo non solo un processo di aggiornamento ma anche l’inibizione di risposta. Sulla base della teoria del controllo cognitivo, le differenze tra giovani e anziani nella prestazione all’ICT dovrebbero essere minori nelle prove detect, intermedie nelle prove go e massime nelle prove nogo. In aggiunta, questo studio aveva lo scopo di studiare l’effetto dell’età sui singoli processi che compongono il controllo esecutivo (Miyake et al., 2000). Per tale motivo, è stato studiato l’effetto dell’età sull’ampiezza e la latenza della P3b, della P3-nogo e della RON (reorienting negativity) che riflettono rispettivamente i processi di aggiornamento, inibizione e shifting. Al fine di dissociare meglio quali fossero le componenti ERP legate ai differenti processi studiati, è stata condotta la partial least square (PLS) analisi. Diciassette giovani e sedici anziani hanno partecipato all’esperimento ed eseguito l’ICT. Contro le predizioni formulate, i dati comportamentali hanno rivelato come gli anziani avessero una performance peggiore rispetto ai giovani in tutti i tipi di prove, quindi dalle prove detect alle prove nogo. È importante notare che l’effetto dell’età non interagiva con il tipo di prova, ed era quindi indipendente dal grado di controllo esecutivo necessario per eseguire quella data prova. Ciò indica che il controllo esecutivo, quando inteso come costrutto unitario, non sembra essere il fattore elettivo responsabile dei deficit mostrati dagli anziani nell’ICT. In linea con i risultati comportamentali, gli anziani hanno mostrato un ritardo in tutte le componenti ERP indagate (P3b, N2, RON, P3-nogo), indipendentemente dal tipo di prova esaminata. Questo ritardo nella latenza degli ERP legato all’età sembra riflettere un generale rallentamento dei processi cognitivi. Tale idea offre supporto alla teoria di Salthouse (1996), la quale assume che il declino cognitivo legato all’età sia dovuto ad una generale riduzione nella velocità di elaborazione. Un altro risultato rilevante consiste nel fatto che le componenti RON sono risultate particolarmente sensibili all’invecchiamento. Tali componenti, che riflettono lo shifting attenzionale (Berti et al., 2008), erano ritardate e meno ampie negli anziani rispetto ai giovani. Solamente uno studio finora ha indagato le alterazioni, legate all’età, a carico delle componenti RON, ma utilizzando un paradigma uditivo di distrazione (Horváth et al., 2009). In questo senso il presente studio ha esteso i risultati ottenuti nello studio di Horváth, suggerendo che un declino nello shift attenzionale non avviene solo dopo stimoli distraenti (come evidenziato da Horváth) ma anche dopo stimoli rilevanti per il compito. Sembra, infatti, che negli anziani il meccanismo di shifting dell’attenzione sia più lento e dispendioso, probabilmente a causa del fatto che essi sono ancora occupati ad elaborare lo stimolo precedente. Riassumendo, i dati elettrofisiologici e comportamentali convergono nel rivelare che il peggioramento nei compiti cognitivi associato all’invecchiamento potrebbe essere, almeno parzialmente, spiegabile da un rallentamento generale di elaborazione delle informazioni. Infatti, coerentemente con le conclusioni formulate nella rassegna di Verheagen (2011), una riduzione nella velocità dei processi sembra spiegare meglio i deficit cognitivi dell’anziano, rispetto ad un possibile deterioramento nel controllo esecutivo (quando inteso come processo unitario). Dall’altra parte, un sottoprocesso del controllo esecutivo, lo shifting attenzionale, sembra essere particolarmente sensibile all’età, e potrebbe quindi rappresentare un possibile candidato per spiegare la molteplicità di deficit nell’anziano. 1° Parte: Conclusioni Sebbene i presenti studi abbiano utilizzato differenti paradigmi e compiti, tuttavia convergono nel mostrare come il controllo esecutivo non giochi un ruolo cruciale nel determinare i deficit cognitivi evidenziati in questi compiti. Piuttosto, un declino nei processi più di base sembra essere il fattore chiave per spiegare la molteplicità dei deficit cognitivi nell’invecchiamento. In particolare, l’analisi degli ERP ha permesso di evidenziare che i cambiamenti legati all’età sono più probabilmente dovuti ad una riduzione: 1) nella disponibilità delle risorse cognitive, 2) nella velocità di elaborazione. Le alterazioni elettrofisiologiche legate all’età sembrano interessare in misura maggiore le modulazioni ERP osservate a livello di siti prefrontali, ed sono particolarmente espresse in termini di ritardo delle latenze. È interessante notare la presenza di meccanismi compensatori negli anziani, riflessi in un aumento nell’ampiezza di diverse componenti (rispetto ai giovani). Ciò suggerisce che l’invecchiamento non solo implica un declino cognitivo e neurale, ma coinvolge anche risposte cognitive e neurali adattive. 2° PARTE: ALTERAZIONI COGNITIVE AND ELETTROFISIOLOGICHE ASSOCIATE ALL’ENCEFALOPATIA EPATICA MINIMA. L’encefalopatia epatica è una sindrome neuropsichiatrica che può presentarsi in pazienti con cirrosi epatica. Il rilevamento dei primi, seppur lievi, segni dell’encefalopatia epatica è estremamente importante. Questa iniziale e subclinica condizione, chiamata encefalopatia epatica minima (MHE; Ferenci et al., 1998) ha infatti un impatto sulla qualità della vita (Groeneweg et al., 1998; Zhou et al. 2009) e sull’abilità di guida (Wein et al., 2004). Inoltre, ha un valore prognostico negativo in relazione alla probabilità di sviluppare episodi di encefalopatia conclamata, nonché di morte (Amodio et al., 1999; Romero-Gomez et al., 2007). Il profilo della MHE è caratterizzato da alterazioni cognitive che coinvolgono processi quali l’attenzione selettiva, le funzioni esecutive, l’abilità visuo-motoria, la velocità di elaborazione, l’inibizione e la selezione di risposta (Amodio et al., 2005). La MHE causa anche una disfunzione cerebrale comunemente rilevabile sia dal rallentamento dell’elettroencefalogramma (EEG) sia dal ritardo osservato nelle latenze degli ERP, tra cui la P300 (Amodio et al., 2005; Weissenborn et al., 2005). Quindi, quando possibile, la diagnosi di MHE dovrebbe essere preferibilmente basata su una combinazione di indici neuropsicologici/neurofisiologici. L’Inhibitory Control Task (ICT) è stato recentemente proposto come un semplice strumento diagnostico per la MHE (Bajaj et al. 2007; 2008a). Tuttavia, la sua applicabilità a differenti popolazioni di pazienti con cirrosi, così come la sua relazione con altre misure di MHE necessitano di essere confermate. Per tali motivi, è stato condotto un esperimento (Esperimento 3) che aveva lo scopo di valutare la specificità e la sensibilità dell’ICT per la diagnosi della MHE. L’Esperimento 4 si è invece focalizzato di indagare l’effetto della MHE sugli ERP elicitati dall’ICT, in modo tale da ottenere informazioni sulle alterazioni cognitive ed elettrofisiologiche caratteristiche della MHE. A proposito delle alterazioni elettrofisiologiche legate alla MHE, un ulteriore esperimento (Esperimento 5) ha indagato la variabilità intra-individuale dei parametri della P300 (latenza e ampiezza) nei pazienti cirrotici con MHE. C’è un crescente interesse riguardo alla variabilità nella prestazione cognitiva (e.g., nei TR) nel campo delle neuroscienze cognitive (MacDonald et al., 2006) poiché la VII è stata largamente considerata un possibile indice comportamentale di meccanismi neurali compromessi (e.g., Hultsch et al., 2000). Tuttavia gli studi che hanno stabilito un legame tra la VII delle risposte comportamentali e quella delle risposte neurali sono ancora pochi. La MHE sembra un valido modello di patologia per studiare questa relazione poiché i pazienti con MHE mostrano un aumento nella variabilità dei TR (Elsass et al., 1985; Schiff et al., 2006). Per tale motivo, nell’Esperimento 5, i parametri delle P300 misurati per ogni singola epoca, attraverso la tecnica di stima Bayesiana (D’Avanzo et al., 2011), sono stati esaminati per studiare il correlato elettrofisiologico della VII nella velocità di risposta. Inoltre sono stati esplorati i possibili cambiamenti nella relazione tra i parametri della P300 e dei TR che avvengono in pazienti con MHE. Esperimenti 3 e 4: L’ICT come strumento adatto per rilevare le alterazioni cognitive ed elettrofisiologiche in pazienti con cirrosi epatica. Nell’Esperimento 3, 75 pazienti con cirrosi e 55 controlli sani hanno eseguito l’ICT presso due centri di riferimento per lo studio dell’encefalopatia epatica. I pazienti venivano valutati per la MHE attraverso il Psychometric Hepatic Encephalopathy Score (PHES) e le analisi spettrali dell’EEG. La performance alle prove go e nogo è stata comparata tra i due gruppi. I pazienti con cirrosi presentavano un maggior numero di errori (i.e., lures) nelle prove nogo, e mostravano un’accuratezza peggiore anche nelle prove go, rispetto ai controlli. Tuttavia, il numero di lures era comparabile tra pazienti con e pazienti senza MHE. È importante notare come ci fosse una relazione inversa tra accuratezza nelle prove go e numero di errori, quando l’accuratezza nelle prove go era particolarmente bassa. Questo non è sorprendente: una bassa accuratezza alle prove go indica che molte di queste prove avevano una risposta mancante (infatti nelle prove go un errore consiste in una risposta mancante); tuttavia se un individuo commette tante risposte mancanti, allora è più probabile che “esegua” correttamente le prove nogo (le quali infatti prevedono una mancanza di risposta come ‘risposta’ corretta). In questo senso il numero basso di errori alle prove nogo è un fenomeno spurio. È stata quindi codificata una nuova variabile (weighted lures, o “lures pesati”), in cui il numero di lure veniva aggiustato per la percentuale di accuratezza nelle prove go. Tale variabile si è mostrata in grado di differenziare i pazienti con e i pazienti senza MHE. L’accuratezza nelle prove go si è rivelata comunque essere una valida misura anche quando veniva considerata da sola. Quindi, per rilevare segni di MHE, testare l’inibizione (lures) non sembra essere superiore rispetto al testare l’attenzione e l’aggiornamento nella working memory (accuratezza nelle prove go). L’Esperimento 4 ha permesso di studiare le alterazioni elettrofisiologiche legate alla cirrosi epatica ed evidenziate nelle prove che compongono l’ICT. In tale studio, sono stati analizzati gli ERP confrontando pazienti cirrotici con MHE (N=13), senza MHE (N=18) e individui di controllo (N=17). In particolare sono stati esaminati gli ERP elicitati dalle prove detect, go e nogo, in quanto possono essere un indice dei processi di attenzione selettiva, working memory e inibizione, rispettivamente. I dati sono stati inoltre analizzati attraverso l’analisi PLS, la cui efficacia nell’identificare variabili latenti è particolarmente adatta per dissociare i correlati ERP dei diversi processi. I risultati ottenuti dall’ANOVA e dall’analisi PLS hanno mostrato alterazioni associate alla MHE che interessavano selettivamente gli ERP nelle prove detect. Specificatamente, queste erano rappresentate da una riduzione della P3a a livello di siti frontocentrali e da un ritardo della P3b. Poiché le prove detect coinvolgono principalmente processi attenzionali, le alterazioni evidenziate in tali prove potrebbero indicare un deterioramento delle abilità cognitive più di base, quali l’attenzione. Questo risultato corrobora la conclusione ottenuta nell’esperimento 3, che concerne l’appropriatezza di testare abilità più di base (come l’attenzione) prima, o assieme, alla valutazione delle abilità più di alto livello (i.e., l’inibizione). Il secondo principale, e inaspettato, risultato consiste nell’aumento (invece di una diminuzione) dell’ampiezza di diverse componenti (cioè la N2, la P3-nogo) in pazienti cirrotici senza MHE. Questi cambiamenti elettrofisiologici potrebbero essere un meccanismo compensatorio e riflettere l’allocazione di risorse esecutive addizionali per far fronte alle difficoltà nell’eseguire il compito (anche i pazienti senza MHE mostrano infatti una riduzione nella P3a, indice di deficit attenzionali). Esperimento 5: La VII della P300 come indice per rilevare disfunzioni neurali in pazienti con cirrosi epatica. In pazienti con cirrosi, un’aumentata VII dei TR è già stata descritta, ed è stata considerata un possibile indice precoce di disfunzione cerebrale (Schiff et al., 2006). Sfortunatamente, la controparte neurale di questo fenomeno non è stata ancora dimostrata. Tuttavia, siccome una riduzione dell’ampiezza della P300 è stata osservata in questa popolazione di pazienti, allora è possibile ipotizzare che tale riduzione dipenda, almeno in parte, da un’aumentata variabilità delle latenze della P300 tra le singole epoche (come evidenziato per altre patologie, e.g., Hultsch et al., 2000). Per tali motivi, l’aumentata variabilità della P300, se evidenziata, potrebbe essere anch’essa un valido indice di disfunzione neurale. Inoltre, l’analisi della P300 per ogni singola epoca ha permesso di indagare la relazione tra i TR e i parametri (i.e., ampiezza e latenza) della P300, e comprendere come tale relazione cambi nel caso di patologie quali MHE. L’EEG è stato misurato durante l’esecuzione di un compito di reazione di scelta (compito Simon) in 14 pazienti con MHE (diagnosticata sulla base di test e alterazioni all’EEG), 15 pazienti senza MHE e 14 individui sani di controlli. L’ampiezza e la latenza della P300, assieme alla loro rispettiva deviazione standard, sono state ottenute attraverso un metodo non parametrico di stima bayesiana. La P300 è stata anche misurata con il classico metodo dell’averaging. Infine sono state analizzate la distribuzione dei TR e la sua relazione con i parametri della P300. Nei pazienti con cirrosi, i TR erano più lenti e più variabili rispetto ai controlli. Un aumento nella variabilità della latenza della P300 è stato anche mostrato in tali pazienti. La regressione lineare multipla ha evidenziato come l’ampiezza della P300 – misurata con il metodo dell’averaging – era predetta sia dalla deviazione standard della latenza della P300, che dalla sua ampiezza (entrambe misurate con il metodo bayesiano). Ciò indica che una ridotta P300 nei pazienti con MHE potrebbe anche dipendere da un’aumentata variabilità nella latenza della stessa. Inoltre, è stato mostrato come la latenza della P300 aumentava e l’ampiezza diminuiva all’aumentare dei TR nei controlli, ma non nei pazienti con MHE. Un altro segno di alterazione sembra quindi essere la più debole relazione tra parametri comportamentali e la P300, come osservato nei pazienti con MHE. Riassumendo, il presente studio ha suggerito come in condizioni normali vi sia una stretta relazione tra TR e P300, e la P300 sia stabile tra le diverse prove. In contrasto, quando vi è una disfunzione cerebrale, come nel caso della MHE, la relazione tra i diversi parametri è meno forte, e le risposte neurali diventano più variabili. 2° Parte: Conclusioni L’utilizzo dell’ICT ha fornito diverse evidenze riguardo ai marker cognitivi e neurali della MHE. Specificatamente, i pazienti con MHE hanno mostrato un rallentamento e un’attenuazione delle componenti della P300 nelle prove detect. Ciò sembra indicare deficit a carico dell’attenzione selettiva e sostenuta. Dall’altra parte, i pazienti senza MHE hanno evidenziato un aumento nelle ampiezze di alcune componenti (N2 e P3-nogo), che potrebbe riflettere un meccanismo neurale compensatorio. Infine l’esperimento 5 ha evidenziato il profilo della P300 nei pazienti con cirrosi. Infatti, tali pazienti, e specialmente coloro che presentavano MHE, hanno mostrato un aumento nella variabilità della latenza della P300, che può aver contribuito alla riduzione della sua ampiezza. CONCLUSIONI GENERALI La tecnica dell’analisi ERP si è rivelata uno strumento utile per esplorare le alterazioni cognitive e neurali sottostanti sia all’invecchiamento sano sia a una condizione patologica, quale la MHE. Sono stati osservati alcuni pattern di alterazioni elettrofisiologiche comuni tra le persone anziane e pazienti con cirrosi epatica (e.g., rallentamento delle componenti ERP, aumento di alcune componenti, quali la N2). Tali alterazioni hanno evidenziato come 1) i deficit legati all’invecchiamento o alla MHE evidenziati in compiti cognitivi complessi sembrano dipendere da alterazioni a carico di meccanismi più di base (come deficit attentivi, o rallentamento nell’elaborazione degli stimoli); 2) l’attività neurale sia di individui anziani sia di pazienti senza MHE è similmente caratterizzata da meccanismi compensatori, reclutati per affrontare le difficoltà nell’eseguire i compiti

Dans ce travail, nous étudions les mécanismes du changement de langue lors de la reconnaissance visuelle de mots chez des trilingues français /anglais /espagnol. Dans un premier temps, nous avons examiné les processus d’accès pour chacune des langues étudiées, indépendamment de la présentation des autres langues. Nous nous sommes ensuite interrogés sur les relations entre les langues et l’organisation lexicale sous-jacente dans la mémoire multilingue, ainsi que la mise en place des mécanismes cognitifs permettant de passer d’une langue à une autre. Dans cette perspective, nous avons réalisé trois séries d’expériences afin d’examiner l’influence mutuelle des langues et le coût cognitif consécutif à un changement de langue lors de la reconnaissance visuelle de mots isolés. Nous avons comparé le traitement de mots spécifiques à différentes langues (ayant un degré de recouvrement orthographique minimal) en faisant varier les situations de changement et en recueillant des données comportementales et chronométriques dans des tâches de décision lexicale, de catégorisation sémantique et d’amorçage sémantique par traduction. Les résultats mettent en évidence un ralentissement global du traitement dû au changement pour les trois langues. Nous avons également observé un coût cognitif suite à un changement de langue pour les trois langues, mais plus important lorsqu’il s’opère entre les deux langues les moins maîtrisées (L2 vers L3 et L3 vers L2). Les données obtenues confirment l’hypothèse d’unités lexicales intégrées au sein d’un même lexique dans la mémoire multilingue. Les résultats sont interprétés dans leur ensemble dans le cadre des principaux modèles de la mémoire bilingue/multilingue
The present work focuses on language switching mechanisms during visual word recognition in French / English / Spanish trilinguals. First, we examined access to processing for each language, independently from the presentation of other languages. Then, our concern was to determine the different relations between languages and the underlying lexical organization inside the multilingual memory, as well as the activation of cognitive mechanisms allowing language switching. With this goal in mind, we performed three series of experiments to examine the influences between the languages, and the cognitive cost subsequent to a language switching during visual word recognition. We compare the processing of non-cognate words belonging to the three languages, manipulating the language switching situations and recording behavioral and electrophysiological data during lexical decision, semantic categorization and semantic translation priming. Results of these experiments highlight a general slowdown of processing consecutive to a language switch for all languages. Moreover, we observed a cognitive cost related to language switching for all the three languages, but bilaterally larger when it concerns the two non-dominant languages (L2 to L3 and L3 to L2). The recording data confirms the hypothesis of lexical representations integrated into a shared lexicon of multilingual memory. The results are interpreted in the light of the main models accounting for bilingual memory

Judgments of Learning (JOLs) are judgments of the likelihood of remembering recently studied material on a future test. Although JOLs have been extensively studied, particularly due to their important applications in education, relatively little is known about the cognitive and neural processes supporting JOLs and how these processes relate to actual memory processing. Direct access theories describe JOLs as outputs following direct readings of memory traces and hence predict that JOLs cannot be distinguished from objective memory encoding operations. Inferential theories, by contrast, claim JOLs are products of the evaluation of a number of cues, perceived by learners to carry predictive value. This alternative account argues that JOLs are made on the basis of multiple underlying processes, which do not necessarily overlap with memory encoding. In this thesis, the neural and cognitive bases of JOLs were examined in a series of four ERP experiments. Across experiments the study phase ERP data showed that JOLs produce neural activity that is partly overlapping with, but also partly distinct from, the activity that predicts successful memory encoding. Furthermore, the neural correlates of successful memory encoding appear sensitive to the requirements to make a JOL, emphasising the close interaction between subjective and objective measures of memory encoding. Finally, the neural correlates of both JOLs and successful memory encoding were found to vary depending on the nature of the stimulus materials, suggesting that both phenomena are supported by multiple cognitive and neural systems. Although the primary focus was on the study phase ERP data, the thesis also contains two additional chapters reporting the ERP data acquired during the test phases of three of the original experiments. These data, which examined the relative engagements of retrieval processes for low and high JOL items, suggest that encoding processes specifically resulting in later recollection (as opposed to familiarity) form one reliable basis for making JOLs. Overall, the evidence collected in this series of ERP experiments suggests that JOLs are not pure products of objective memory processes, as suggested by direct access theories, but are supported by neural systems that are at least partly distinct from those supporting successful memory encoding. These observations are compatible with inferential theories claiming that JOLs are supported by multiple processes that can be differentially engaged across stimulus contents.

We examined relations between eye movements (single-fixation durations) and RSVP-based event-related potentials (ERPs; N400’s) recorded during reading the same sentences in two independent experiments. Longer fixation durations correlated with larger N400 amplitudes. Word frequency and predictability of the fixated word as well as the predictability of the upcoming word accounted for this covariance in a path-analytic model. Moreover, larger N400 amplitudes entailed longer fixation durations on the next word, a relation accounted for by word frequency. This pattern offers a neurophysiological correlate for the lag-word frequency effect on fixation durations: Word processing is reliably expressed not only in fixation durations on currently fixated words, but also in those on subsequently fixated words.

Cette thèse explore l'analyse de l'activité électrique du cerveau. Un défi important de ces signaux est leur grande variabilité à travers différents essais et/ou différents sujets. Nous proposons une nouvelle méthode appelée "adaptive waveform learning" (AWL). Cette méthode est suffisamment générale pour permettre la prise en compte de la variabilité empiriquement rencontrée dans les signaux neuroélectriques, mais peut être spécialisée afin de prévenir l'overfitting du bruit. La première partie de ce travail donne une introduction sur l'électrophysiologie du cerveau, présente les modalités d'enregistrement fréquemment utilisées et décrit l'état de l'art du traitement de signal neuroélectrique. La principale contribution de cette thèse consiste en 3 chapitres introduisant et évaluant la méthode AWL. Nous proposons d'abord un modèle de décomposition de signal général qui inclut explicitement différentes formes de variabilité entre les composantes de signal. Ce modèle est ensuite spécialisé pour deux applications concrètes: le traitement d'une série d'essais expérimentaux segmentés et l'apprentissage de structures répétées dans un seul signal. Deux algorithmes sont développés pour résoudre ces problèmes de décomposition. Leur implémentation efficace basée sur des techniques de minimisation alternée et de codage parcimonieux permet le traitement de grands jeux de données.Les algorithmes proposés sont évalués sur des données synthétiques et réelles contenant des pointes épileptiformes. Leurs performances sont comparées à celles de la PCA, l'ICA, et du template-matching pour la détection de pointe
This thesis investigates the analysis of brain electrical activity. An important challenge is the presence of large variability in neuroelectrical recordings, both across different subjects and within a single subject, for example, across experimental trials. We propose a new method called adaptive waveform learning (AWL). It is general enough to include all types of relevant variability empirically found in neuroelectric recordings, but can be specialized for different concrete settings to prevent from overfitting irrelevant structures in the data. The first part of this work gives an introduction into the electrophysiology of the brain, presents frequently used recording modalities, and describes state-of-the-art methods for neuroelectrical signal processing. The main contribution of this thesis consists in three chapters introducing and evaluating the AWL method. We first provide a general signal decomposition model that explicitly includes different forms of variability across signal components. This model is then specialized for two concrete applications: processing a set of segmented experimental trials and learning repeating structures across a single recorded signal. Two algorithms are developed to solve these models. Their efficient implementation based on alternate minimization and sparse coding techniques allows the processing of large datasets. The proposed algorithms are evaluated on both synthetic data and real data containing epileptiform spikes. Their performances are compared to those of PCA, ICA, and template matching for spike detection

Bei altersbedingt abnehmender kognitiver Funktion stellt das steigende Renteneintrittsalter Arbeitgeber und -nehmer vor wachsende Herausforderungen. Der Aufbau der kognitiven Reserve (CR) durch geistig stimulierende Aktivitäten verspricht eine Resilienz gegenüber neuropathologisch bedingten kognitiven Defiziten. In der vorliegenden Arbeit wird die Rolle der CR in Bezug auf die kognitive Leistungsfähigkeit und die neuronale Informationsverarbeitung gesunder Erwachsener im Berufsalter untersucht. Unter Ableitung des Elektroenzephalogramms bearbeiteten Probanden mittleren und hohen Erwerbsalters (34-45 J. und 46-62 J.) im 2-Jahres-Abstand Aufgaben zu drei Domänen exekutiver Funktionen: Arbeitsgedächtnis (AG), kognitive Flexibilität und Inhibitionskontrolle. Hoch-CR-Probanden wiesen aufgabenübergreifend schnellere Reaktionen und geringere Fehlerraten auf. Reduzierte Leistung ließ sich in der Gering-CR-Gruppe tendenziell bei älteren Probanden und in anspruchsvollen Aufgabenbedingungen beobachten. Nach 2 Jahren zeigten Gering-CR-Ältere eine numerisch abnehmende AG-Kapazität, während Hoch-CR-Ältere ihre hohe Leistung steigern konnten. Die P3-Amplitude variierte in Abhängigkeit von der CR und dem Alter. Hoch-CR-Jüngere wiesen im Vergleich zu Gering-CR-Jüngeren höhere P3-Amplituden auf, während Hoch-CR-Ältere im Gegensatz zu Gering-CR-Älteren kleinere P3-Amplituden generierten. Zudem legten kürzere P3-Latenzen in der Hoch-CR-Gruppe eine schnellere neuronale Verarbeitungsgeschwindigkeit nahe. In der Aufgabe zur kognitiven Flexibilität ließ sich bei Gering-CR-Probanden ein Anterior-Shift der P3 beobachten. Die Untersuchungsergebnisse konnten nach 2 Jahren repliziert werden. Alterungsrelevante Leistungsvariablen und neuronale Informationsverarbeitungsprozesse zeigten sich bereits im Berufsalter sensitiv gegenüber der CR. Das mittlere Erwachsenenalter sollte bei der Erarbeitung und Evaluation CR-basierter Maßnahmen zur Prävention kognitiver Defizite stärker berücksichtigt werden.
The increasing retirement date accompanied by an age-associated decline of cognitive functions poses growing challenges to employers and employees. The cognitive reserve (CR) promises a resilience to brain damage-associated cognitive deficits through intellectually stimulating lifestyle activities. The present study examines the role of CR relating to cognitive performance and neuronal information processing of healthy adults in working age. Using an electroencephalogram, subjects of middle and high working age (34-45 years and 46-62 years of age, respectively) completed tasks on three domains of executive functions: working memory, cognitive flexibility and inhibition control. Follow-up assessments were conducted after two years. High-CR subjects performed better across tasks than Low-CR subjects, with faster reaction times and lower error rates. Reduced performance in the Low-CR group tended to be more common among older participants and during the more challenging task conditions. In addition, after two years, Low-CR older workers showed a decreased working memory capacity while older High-CR individuals improved their higher performance. The P3 amplitude of the event-related brain potential varied systematically as a function of CR and age. High-CR younger individuals revealed higher P3 amplitudes compared to Low-CR younger individuals, while High-CR older individuals generated smaller P3 amplitudes than Low-CR older individuals. The shorter P3 peak-latencies of the High-CR group suggested moreover a difference in neural processing speed. When testing cognitive flexibility an anterior shift of the P3 was observed in older Low-CR subjects. The results were almost completely replicated after two years. Age-related performance variables and neuronal information processes revealed to be sensitive to CR already at working age. These findings recommend more research on early adulthood in the development and evaluation of CR-based programs to prevent cognitive deficits.

L’objectiu d’aquesta tesi ha estat caracteritzar els processos d’activació léxica i semàntica que es produeixen durant el reconeixement de traduccions en bilingües de Català i Castellà. Aquests bilingües són molt competents i balancejats i viuen immersos en un context on les dues llengües estan molt presents, fent un ús regular de les dues. La tesi es composa de quatre estudis. En un d’ells s’ha desenvolupat una base de parells de paraules relacionades semànticament, i que no tenen relació associativa entre elles. Aquesta base s’há utilitzat per obtenir els materials experimentals d’alguns dels estudis inclosos a la tesi. En els altres tres estudis s’ha avaluat als participants en una tasca de reconeixement de traduccions en la qual s’ha manipulat el tipus de parells de paraules que es presenten. Aquestes poden ser traduccions correctes (p.ex., ruc-burro), o poden ser paraules relacionades formalment o semànticament entre llengües. Pel que fa a les relacions formals, s’han avaluat parells que són veïns lèxics (p.ex., ruc-ruso) i parells que són veïns de traducció (p.ex., ruc-berro). Pel que fa a les relacions semàntiques, s’han avaluat parells amb una forta relació semàntica (p.ex., ruc-caballo) i parells amb una relació no tan forta (p.ex., ruc-oso). En dos dels estudis s’há manipulat la direcció de traducció i s’han registrat mesures conductuals (temps de resposta i errades). En l’altre estudi, s’han enregistrat també potencials evocats cerebrals (ERPs). Els resultats han mostrat que els processos d’activació lèxica i semàntica poden estar modulats per les característiques de les paraules (com la seva semblança entre llengües) i dels bilingües (com l’ús i exposició a les dues llengües). Aquests resultats es discuteixen en relació amb els models més influients de la memòria bilingüe, com són el RHM (Kroll & Stewart, 1994), el BIA (Dijkstra & Van Heuven, 1998) o el DRM (De Groot, 1992)
La tesis trata los procesos de activación léxica y semántica durante el reconocimiento de traducciones en bilingües muy competentes y balanceados de catalán y castellano, inmersos en un contexto en el que las dos lenguas se usan de forma regular. La tesis consta de cuatro estudios. Uno de ellos, es una base de datos de pares de palabras relacionadas semánticamente, y sin relación asociativa. En los otros tres estudios se ha evaluado a los participantes en una tarea de reconocimiento de traducciones en cual se les presentaban pares de palabras y ellos deberían decidir si la segunda palabra del par era la traducción correcta de la primera (p.ej., ruc-burro). Además de las traducciones correctas se utilizaron pares críticos: a) relaciones formales (p.ej., vecinos léxicos: ruc-ruso y vecinos de traducción: ruc-berro) y b) relaciones semánticas (p.ej., mas semejante: ruc-caballo y menos semejante en el significado: ruc-oso). Las medidas fueron conductuales (tiempos de respuesta y errores) y registrado de potenciales evocados cerebrales (ERPs). Los resultados muestran que los procesos de activación léxica y semántica pueden ser modulados por las características de las palabras (como la semejanza entre lenguas) y de los bilingües (como el uso y exposición a las dos lenguas). Estos resultados se discuten en relación con los modelos más influyentes de la memoria bilingüe, como son el RHM (Kroll & Stewart, 1994), el BIA (Dijkstra & Van Heuven, 1998) o el DRM (De Groot, 1992).
The present thesis approach the lexical and semantic processing during translation recognition in highly proficient and balanced Catalan-Spanish bilinguals who use both languages on a regular basis. The thesis includes four studies. One study provides normative ratings for a set of semantically (and non-associatively) related pairs. In the other three studies, the performance of Catalan-Spanish bilinguals was assessed in a translation recognition task. In this task, the participants were presented with pairs of words and they had to decide where the second word of the pair was the correct translation of the first one (e.g., ruc-burro [donkey]). Additionally, there were critical pairs: a) form relatedness (e.g., lexical neighbors: ruc-ruso [Russian] and translation neighbors: ruc-berro [watercress] as well semantically related words (e.g., highly similar: ruc-caballo [horse] and less similar in meaning: ruc-oso [bear]). Behavioral measures (response times and percentage of errors) and event related potentials (ERPs) were recorded. The results show that lexical and semantic activation can be modulated by words’ characteristics (i.e., semantic similarity) as well as by bilinguals’ characteristics (such as languages use). These results are discussed within the framework of the most influential models of bilingual memory, such as the RHM (Kroll & Stewart, 1994), the BIA model (Dijkstra & Van Heuven, 1998) or the DRM (De Groot, 1992).

Affect and cognition have traditionally been considered mutually exclusive domains and their study has evolved into two separate research fields. In recent years, however, there is increasing evidence of affective modulations of cognitive processes and interest in the study of affective cognition has grown. This thesis presents analyses of data collected in four mixed-design experiments between 2009 and 2011, which were designed to investigate affective memory and its electrophysiological correlates, individual differences in said affective memory and electrophysiological correlates, the time-course of affective memory and attentional disengagement from affective stimuli respectively. The first aim of the research presented here was to further understanding of how affective content influences picture processing and memory. Event-related potentials (ERPs) provide a valuable tool for the investigation of modulations of cognitive processes, as their excellent temporal resolution allows for the dissociation between different processes contributing to behavioural outcomes. Several important results for the study of affective cognition are reported: The late positive potential (LPP) was shown to be modulated differentially by affective content when compared to a behavioural attentional disengagement task. While the behavioural measure of attention replicated findings from participants’ self-report of arousal, LPP enhancement did not. This novel finding demonstrates that the affective modulation of the LPP cannot be used as an electrophysiological marker of slowed attentional disengagement as is common in the literature. In the domain of recognition memory, affective modulation of performance was shown to be time-sensitive, with effects developing faster for negative than for positive picture content. Affective pictures were associated with a less conservative response bias than neutral pictures but only negative pictures elicited better discrimination performance, driven by an increased in the rate of “remembered” as compared to merely familiar pictures. This was reflected in an increase of the ERP old/new effect for negative pictures in the 500 to 800ms time window, the purported correlate of recollection. The late right-frontal old/new effect between 800 and 1500 ms post stimulus onset was shown to be attenuated by affective content, supporting the interpretation of the late right-frontal effect as a correlate of relevance detection over a retrieval success interpretation. In combination, the findings add weight to the conclusion that affective content enhances memory through selective memory sparing for affective stimuli. Novel evidence for gender differences in affective cognition was found. Comparisons between female and male participants revealed that the affective modulation of the late right-frontal effect differs between the genders, underlining the importance of assessing and understanding gender differences as part of the study of affective cognition. Brain-derived neurotrophic factor (BDNF) gene val66met single nucleotide polymorphism (SNP), a small genetic change that affects the functioning of BDNF, a protein that plays an important role in neuron growth, differentiation and survival, is shown here to also affect the interaction of affect and cognition. BDNF val66met genotype modulated the early “familiarity” old/new effect selectively in response to positive pictures. The present study clearly demonstrates the value of the ERP technique in the investigation of individual differences in affective and cognitive processing and the need to take such individual differences into account as part of the endeavour to fully understand the mechanisms of affective processing, cognition and affective cognition. A better understanding of the role of gender and genetic differences in the affective modulation of affective processing and memory will have important practical implications in fields where affect and cognition interact.

It is a common practice to study the dynamics of sensory and cognitive processes using event-related potentials (ERPs) measured by placing electrodes on the scalp. These ERPs are very small in comparison with the on-going electroencephalogram (EEG) and are barely visible in the individual trials. Therefore, most ERP research relies on the identification of different waves after averaging several presentations of the same stimulus pattern. Although ensemble averaging improves the signal-to-noise-ratio, it implies a loss of information related to variations between the single-trials. In this thesis, I present an automatic denoising method based on the wavelet transform to obtain single-trial evoked potentials. The method is based on the inter- and intra-scale variability of the wavelet coefficients and their deviations from baseline values. The performance of the method is tested with simulated ERPs and with real visual and auditory ERPs. For the simulated data the method gives a significant improvement in the visualisation of single-trial ERPs as well as in the estimation of their amplitudes and latencies in comparison with the standard denoising technique (Donoho’s thresholding) and in comparison with the noisy single-trials. For the real data, the proposed method helps the identification of single-trial ERPs, providing a simple, automatic and fast tool that allows the study of single-trial responses and their correlations with behaviour. We used our proposed denoising algorithm to study the amplitude modulation of the ERP responses to the flashes of faces and to investigate whether the ERP responses in a visual and an auditory oddball paradigm were due to phase-resetting of on-going EEG (phase-resetting model) or due to additive neural responses adding to the background EEG in response to the stimulus presentation (additive model).

The use of P3 as a diagnostic marker for schizophrenia was examined in a qualitative and quantitative review of the literature, as well as with an auditory discrimination task involving 21 schizophrenics, 16 patients with idiopathic Parkinson's disease and 50 matched controls. Although some studies have reported a lack of significant group differences between schizophrenics (or Parkinson's disease) and controls, both the quantitative reviews and the experimental studies suggest that this is probably due to a type 2 error. The band pass employed in experimental studies modifies results in that high pass filters with high frequency cut-off are usually associated with a greater effect size. This hypothesis was confirmed by meta-analytic techniques, by filtering of wave forms with analogue and digital filters, and can be modelled by simple compound sine-wave forms. Such a simple model for wave forms observed in schizophrenics involves the reduction of a low frequency (slow) wave, super-imposed with a higher frequency sine wave. Neither the putative genetic marker impaired smooth eye pursuit, nor a positive family history of psychiatric illness were associated with abnormal P3 in schizophrenics. In controls, abnormal P3 was associated with a positive family history. In Parkinsonian patients P3 latency was correlated with clinical markers of dopaminergic hypofunction like rigidity and bradykinesia. This is in agreement with more recent studies suggesting that delayed P3 in Parkinson's disease normalises with treatment with L-DOPE. In the absence of accurate clinical markers of dopaminergic activity in schizophrenics, no direct comparisons have been made. The role of dopaminergic alterations in the generation of P3 changes in schizophrenics can be examined with in-vivo imaging of receptor binding.

A meta-analysis of event-related potential (ERP) studies between controls and high-OCD groups was conducted to examine whether there is a consistent relationship between differences in P300 amplitude and latency following exposure to OCD-related stimuli.After applying exclusion and inclusion criteria, 10 studies remained. The overall effect size for amplitudinal P300 differences was non-significant and results were heterogeneous, while the overall findings for latency were significant. There is therefore tentative evidence from this meta-analysis that reduced P300 latency is a neural correlate for late onset attentional bias in OCD. In the large scale study, a control group of low OCS participants ,was compared to nonclinical high OCS participants on dependent variables of event-related potential amplitude and response time. EEG differences in P100 and ipsilateral invalid negativity (IIN) were investigated as neural correlates of the facilitated attention and disengagement biases respectively. Significant differences were found between groups across IIN amplitude only, suggesting effortful disengagement only occurred in the high OCD groups under selected conditions. The implication is that delayed disengagement is the main attentional bias associated with OCD symptomatology.