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.

La personnalité et les émotions sont des concepts étroitement liés théoriquement comme empiriquement, cependant, la question de savoir quels aspects de la réactivité émotionnelle modulent la personnalité a été peu étudiée en soi. Cette question est abordée dans ce travail au moyen de méthodes psychophysiologiques (en particulier la réponse électrodermale et les potentiels évoqués), afin disoler les différents éléments de la réponse émotionnelle. Les résultats montrent que la personnalité module à la fois les aspects somatique et cognitif de la réponse émotionnelle. Finalement, le présent travail fait état de possibles implications de ces différences de réactivité émotionnelle liées à la personnalité sur le fonctionnement psychologique en situation de prise de décision, ainsi que dans lépisode dépressif. Personality and emotions are theoretically and empirically related concepts; however which emotional responsiveness aspect is modulated by personality has been hardly addressed. This issue is thus investigated here with psychophysiological methods (namely skin conductance response and event-related potentials), in order to separately focus on different parts of the emotional response. The results show that both somatic and cognitive aspects of the emotional response are modulated by personality. Finally, the present work reports that personality-related differences regarding emotional responsiveness might be implicated in psychological functioning in a decision-making task, as well as in depression.

Nikotin in den unterschiedlichsten Darreichungsformen verringert bei verschiedenen Spezies im räumlichen Hinweisreizparadigma die Kosten invalider Hinweisreize. Welcher Teilprozess genau durch Nikotin beeinflusst wird, ist bislang nicht untersucht worden. Die gängige Interpretation ist, daß Nikotin das Loslösen von Aufmerksamkeit von einem bisher beachteten Ort erleichtert. In fünf Studien, drei elektrophysiologischen und zwei behavioralen wurden drei mögliche Mechanismen der Nikotinwirkung an Nichtrauchern untersucht. Experiment 1 und 2 gingen der Frage nach, ob Nikotin eine Modulation sensorischer gain Kontrolle bewirkt. Dazu wurden ereigniskorrelierte Potentiale (EKP) im Posner-Paradigma erhoben und die Wirkung von Nikotin auf die aufmerksamkeitsassoziierten Komponenten P1 und N1 betrachtet. Nikotin verringerte die Kosten invalider Hinweisreize bei Aufmerksamkeitslenkung durch endogene Hinweisreize, nicht aber bei exogenen Hinweisreizen. Die P1 und N1 Komponenten zeigten sich unbeeinflusst von Nikotin, damit findet also die Annahme einer Wirkung auf sensorische Suppression keine Unterstützung. In Experiment 3 und 4 wurde untersucht, ob Nikotin einen Effekt auf kostenträchtige unwillkürliche Aufmerksamkeitsverschiebungen, Distraktionen, hat. In Experiment 3 wurden in einem räumlichen Daueraufmerksamkeitsparadigma Distraktionen durch deviante Stimulusmerkmale ausgelöst und die Wirkung von Nikotin auf eine distraktionsassoziierte Komponente des EKP, die P3a, betrachtet. <br>In Experiment 4 wurde in einem Hinweisreizparadigma durch zusätzliche Stimuli eine Distraktion ausgelöst und die Nikotinwirkung auf die Reaktionszeitkosten untersucht. Nikotin zeigte keinen Einfluss auf Distraktionskosten in beiden Studien und auch keine Wirkung auf die P3a Komponente in Experiment 3. In Experiment 4 wurde zusätzlich die Wirkung von Nikotin auf das Loslösen von Aufmerksamkeit untersucht, indem die Schwierigkeit des Loslösens variiert wurde. Auch hier zeigte sich keine Nikotinwirkung. Allerdings konnte in beiden Studien weder die häufig berichtete generelle Reaktionszeitverkürzung noch die Verringerung der Kosten invalider Hinweisreize repliziert werden, so dass zum Einen keine Aussage über die Wirkung von Nikotin auf Distraktionen oder den Aufmerksamkeitsloslöseprozess gemacht werden können, zum Anderen sich die Frage stellte, unter welchen Bedingungen Nikotin einen differentiellen Effekt überhaupt zeigt.<br><br> Im letzten Experiment wurde hierzu die Häufigkeit der Reaktionsanforderung einerseits und die zeitlichen Aspekte der Aufmerksamkeitslenkung andererseits variiert und der Effekt des Nikotins auf den Validitätseffekt, die Reaktionszeitdifferenz zwischen valide und invalide vorhergesagten Zielreizen, betrachtet. Nikotin verringerte bei Individuen, bei denen Aufmerksamkeitslenkung in allen Bedingungen evident war, in der Tendenz den Validitätseffekt in der ereignisärmsten Bedingung, wenn nur selten willentliche Aufmerksamkeitsausrichtung notwendig war. Dies könnte als Hinweis gedeutet werden, dass Nikotin unter Bedingungen, die große Anforderungen an die Vigilanz stellen, die top-down Zuweisung von Aufmerksamkeitsressourcen unterstützt. / Nicotine has consistently been shown to improve performance on a range of attentional tasks. In spatial cueing (Posner-type) paradigms, where a cue indicates the likely location of a subsequent target stimulus, nicotine influences the ability to react to invalidly cued targets across different species and ways of administration. Previous research suggested that the cholinergic effect is due to a facilitated disengagemant of attention from the cued location. In five studies with nonsmoking subjects, three candidate mechanisms of nicotinic action were examined. <br><br> Experiment 1 and experiment 2 investigated whether nicotine modulates attentional processes of sensory gain control. In a Posner-paradigm event-related potentials (ERP) were measured and the effect of nicotine on the attention-related components P1 and N1 was assessed. Behaviorally, nicotine reduced the costs of invalid cueing when cues were endogenous, but not with exogenous cues. Electrophysiologically, the P1 and N1 components were not affected by nicotine. These data provide therefore no support for the notion of a nicotine-modulated attentional suppression. <br><br> In experiment 3 and 4 the effect of nicotine on involuntary distracting attention shifts was investigated. In experiment 3 ERPs were measured in a spatial sustained attention paradigm, where rare changes in a target stimulus attribute were used as distractors. The effect of nicotine on the distraction-associated P3a component was assessed. In experiment 4 the effect of nicotine on the reaction time costs of additional distracting stimuli was studied in a Posner paradigm. In both studies nicotine did not show an effect on distractions, neither in the reaction time costs nor in the parameters of the P3a component. Experiment 4 also investigated whether nicotine has an effect on the disengagement of attention by varying the difficulty of disengaging one's focus from the cued location. Again, nicotine did not show an effect. However, experiment 3 and 4 also neither replicated the commonly reported general nicotinic reduction of reaction times nor the differential reduction of the costs of invalid cueing. Therefore, regarding the effect of nicotine on distraction and on the disengagement of attention the data remain inconclusive. However, these data suggest that there are conditions and mechanisms moderating nicotinic action, that are still unknown. <br><br> Accordingly, experiment 5 made the attempt to determine such conditions. Response frequency and temporal characteristics of attention orientation were varied. In individuals, who evidently had shifted their attention, nicotine reduced the validity effect under uneventful conditions, when attention was not to be shifted in each trial. This might suggest that nicotine facilitates the top-down allocation of attentional resources in vigilance-demanding situations.

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 direction in which another is looking at triggers a spontaneous orienting of attention towards gaze direction in the viewer. However, whether the facial expression displayed by the gazing individual modulates this attention orienting is unclear. In this thesis, the modulation of gaze-oriented attention with facial expressions was explored in non-anxious individuals at the behavioral level and at the neural level using Event-Related Potentials (ERP). In the gaze-cueing paradigm used, a dynamic face cue averting gaze and expressing an emotion was presented, followed by a lateral, to-be-localized target. At the behavioral level, a faster response to targets appearing at the gazed-at location (congruent targets) than to targets appearing opposite to the gazed-at location (incongruent targets) was observed (Chapters 3-5). This so-called Gaze Orienting Effect (GOE) was enhanced with fearful, angry and surprised expressions relative to neutral and happy expressions and was driven by emotional differences in response speed to congruent targets (Chapters 3-5). These effects could not be attributed to better discrimination of those emotions when presented with an averted gaze (Chapter 2). These results confirm the impact of fear and surprise on gaze-oriented attention in non-anxious individuals and demonstrate, for the first time, a similar impact for angry expressions. All the emotions enhancing the GOE signal an evolutionary relevant stimulus in the periphery, are threat-related and carry a negative valence, which suggests that one of these attributes (or all combined) is driving the emotional modulation of gaze-oriented attention (surprise is treated like fear in the context of fearful expressions). In Chapter 4, the effect of the dynamic cue sequence on these GOE modulations was investigated. An emotional modulation of the GOE was found only when the gaze shift preceded the emotional expression, but not when the emotion was expressed before gaze shift or when expression and gaze shift were simultaneous. These results highlight the importance of using a sequence closer to real life situations (we usually orient attention before reacting to an object in the environment) in studying the modulation of the GOE with emotions. At the neural level, we investigated the ERPs associated with gaze-oriented attention at target presentation and at cue presentation (Chapters 3 and 5). Confirming previous reports, the amplitude of a target-triggered P1 ERP component was larger in the congruent than in the incongruent condition, reflecting enhanced processing of gaze-congruent targets. In addition, cue-triggered ERPs previously observed in response to arrow cues, were investigated. An Early Directing Attention Negativity (EDAN) and an Anterior Directing Attention Negativity (ADAN) were found, indexing respectively attention-orienting to the cued location and maintenance of attention at the cued location. This is the first study to report both EDAN and ADAN components in response to gaze cues. These results show clear markers of attention orienting by gaze at the neural level, during both cue and target processing. Neither EDAN nor ADAN was modulated by emotion. The congruency effect on P1 was enhanced for fearful, surprised and happy faces compared to neutral faces in Chapter 3 but no differences between the emotions were found in Chapter 5. Thus, the emotional modulation of the brain processes involved in gaze-oriented attention is very weak and protracted or occurs mainly between target onset and response to target. The relationships between participants’ autistic traits and their emotional modulation of gaze-oriented attention were also investigated. Results showed a negative correlation with the GOE to happy upright faces and with the P1 congruency effect, which suggests that individuals with more severe autistic traits are less sensitive to the impact of social emotions like joy. The implication of these results for attention orienting in general and for individuals with Autism Spectrum Disorder is discussed. Together, the findings reported in this thesis clarify the behavioral and neural processes involved in gaze oriented attention and its modulation by facial expression in addition to demonstrating a relationship between gaze oriented attention, its modulation with social emotions and autistic traits.

When multiple objects are present in a visual scene, salient and behaviorally relevant objects are selectively processed at the expense of less salient or irrelevant objects. Here I used three lateralized components of the event-related potential â " the N2pc, Ptc, and SPCN â " to examine how objects compete for representation in our limited capacity visual system, and how task-relevant objects are selectively processed. Participants responded to the orientation of a color singleton target while ignoring a color singleton distractor. Competition between the objects was manipulated by presenting visual search arrays that contained only a target, only a distractor, or both objects together. In Experiment 1, observers did not know the color of the target in advance, whereas in Experiment 2 this information was provided. Experiment 3 was a control experiment to rule out low-level sensory explanations of the effects. The results suggest that the N2pc component indexes capture of attention by salient objects which is modulated both by competition between the objects and top-down knowledge. The Ptc component may index inhibition of return so that once an object is processed it is not selected again. The SPCN component may index enhancement of goal-relevant objects once task-irrelevant objects have been suppressed. Together these lateralized event-related potentials reveal the temporal dynamics of competition and selectivity in the human visual system.

Investigations of the anticipated effects of alcohol indicate that cognitive frameworks are highly correlated with drinking and other variables associated with alcohol use, explaining up to 50% of the variance in drinking outcomes (Goldman, Darkes, & Del Boca, 1999; Goldman, 2002; Goldman et al., 2006; Goldman, Reich, & Darkes, 2006). Furthermore, alcohol expectancies appear to mediate the relationship between a variety of risk factors, such as sensation seeking, and alcohol outcomes (Darkes, Greenbaum, & Goldman, 2004). The current study examined the relationship of these cognitive networks with a physiological index of expectancy violation Participants were presented with statements reflecting a wide range of alcohol outcome effects, which either violated or confirmed the participant’s own set of alcohol expectancies, while the ERPs evoked by these stimuli were recorded. As predicted, the P300 amplitude elicited by negative alcohol expectancy stimuli was positively correlated with the degree of endorsement of positive/arousing expectancies on the self-report measure. That is, the higher the individual’s positive/arousing expectancies, the larger the P300 elicited by stimuli asserting the negative effects of alcohol. There was no significant correlation, however, between P300 amplitude elicited by positive alcohol expectancy stimuli and the degree of endorsement of negative/sedating expectancies on the selfreport measure. In addition, individual differences relating to alcohol expectancies were examined as well. These results were able to identify specific stimuli that violated expectancies for each individual, as well as those that tended to violate expectancies in systematic ways across subjects. These findings provide a way forward for more precise assessment and prediction based on the well developed cognitive model of Alcohol Expectancies. In sum, variations in the amplitude of the P300 were consistent with the model of Alcohol Expectancies. Words imputing negative/sedating effects of alcohol elicited a large P300 in individuals with higher positive alcohol expectancies. By indexing the brain’s electrophysiological response sensitive to expectancy violations, these findings demonstrate concordance between verbal measures of alcohol expectancies, which by their very nature are introspective, and a psychophysiological index of expectancy thought to operate automatically and to be independent of overt responding.

Events that violate expectations are biologically significant and accordingly elicit various physiological responses. We investigated the functional relationship between three of these responses: the P300, the Novelty P3 and the pupil dilation response (PDR), with a particular focus on their co-variance with reaction time and measures of subsequent memory. In a modified Novelty P3 oddball paradigm, participants semantically categorized a sequence of stimuli including (1) words of a frequent category, (2) words of an infrequent category (14% of the trials) and (3) pictures of the frequent category (14% of the trials). The Novelty P3 oddball task was followed by a recall- and a recognition test. Larger amplitudes of the P300, identified by a spatial principal component analysis (PCA), were associated with enhanced subsequent recall as well as faster reaction times during the recognition test, suggesting a close relationship between the cognitive process indexed by the P300 and memory encoding. The PDR was larger for infrequents (which required a response switch) than both frequents and pictures (which did not require a switch). Furthermore, its latency was correlated with reaction time on the same trial and with reaction time on the immediately following trial. There was only weak evidence for a correlation with subsequent memory, suggesting that the cognitive process associated with the PDR might be a direct link in the stimulus-response stream. Larger Novelty P3 amplitudes were associated with both faster reaction times on the same trial and stronger memory traces, suggesting that its amplitude might index resource allocation. These findings suggest that each of the physiological responses carries a distinct functional significance in detecting, processing, or responding to novel events, and we discuss the findings in the light of the prevalent theories of the functional significance of each response.

Research on addictive behavior has traditionally emphasized the role that primary reinforcing effects of drugs of abuse plays in the development and maintenance of dependence. However, contemporary behavioral economic theory and animal models of nicotine dependence suggest the need for greater attention to the impact that response to alternative rewards may have on smoking behavior. The present study sought to investigate the impact of nicotine withdrawal on self-report, behavioral and neural indices of motivation, immediate response to rewards and the capacity to learn and modify behavior in response to positive and negative feedback. Heavy smokers (n = 48) completed two laboratory sessions following overnight deprivation, during which they smoked either nicotinized or denicotinized cigarettes. At each session, they completed a reward prediction and feedback learning task while electro-encephalographic recordings were obtained, as well as resting state recordings which were used to extract global indices of motivational state. Results confirmed that nicotine withdrawal produced an avoidant motivational state. This effect was strongly related to numerous indices of smoking motivation. Exploratory analyses also revealed numerous moderators of these effects. Behavioral data from tasks provided some support for the impact of nicotine withdrawal on reward and feedback processing, though minimal impact was observed for neural indices. Together, results confirm the manifestation of a broad-spanning impact of nicotine withdrawal on motivational state, but effects on specific reward systems remains unknown. Future research should examine the impact of nicotine withdrawal on other reward-related constructs to better delineate these effects.

Objective: A neuroscientific picture-word task was used to investigate semantic and phonological activation spreading in adults who stutter (AWS). Method: Fourteen AWS and 14 adults who do not stutter (AWNS) participated. On each trial, a picture was named at a delay. Sometimes, an attended probe word was heard before naming. Some probes were Semantically-Related to the labels. Those same probes also appeared following pictures with Unrelated labels. N400 ERPs recorded to these two probe types were compared (Semantically-Related versus Unrelated). Other probes were Phonologically-Related to the labels. Those same probes also appeared following pictures with unrelated labels (P-Unrelated). N400 ERPs recorded to these two probe types were compared (Phonologically-Related versus P-Unrelated). Results: AWNS exhibited typical N400 priming effects. AWS exhibited non-robust Semantic N400 priming, and a reverse Phonological N400 priming effect. Conclusions: Results suggest that AWS use attentional control strategies to influence the activation of words in the mental lexicon.