Die korrekte Wahrnehmung stimmlicher Information ist eine Grundvoraussetzung erfolgreicher zwischenmenschlicher Kommunikation. Die Stimme einer anderen Person liefert Information darüber wer spricht (Sprechererkennung), was gesagt wird (stimmliche Spracherkennung) und über den emotionalen Zustand einer Person (stimmliche Emotionserkennung). Autismus Spektrum Störungen (ASS) sind mit Einschränkungen in der Sprechererkennung und der stimmlichen Emotionserkennung assoziiert, während die Wahrnehmung stimmlicher Sprache relativ intakt ist. Die zugrunde liegenden Mechanismen dieser Einschränkungen sind bisher jedoch unklar. Es ist beispielsweise unklar, auf welcher Verarbeitungsstufe diese Einschränkungen in der Stimmenwahrnehmung entstehen oder ob sie mit einer Dysfunktion stimmensensitiver Hirnregionen in Verbindung stehen. Im Rahmen meiner Dissertation haben wir systematisch Stimmenverarbeitung und dessen Einschränkungen bei Erwachsenen mit hochfunktionalem ASS und typisch entwickelten Kontrollprobanden (vergleichbar in Alter, Geschlecht und intellektuellen Fähigkeiten) untersucht. In den ersten beiden Studien charakterisierten wir Sprechererkennung bei ASS mittels einer umfassenden verhaltensbezogenen Testbatterie und zweier funktionaler Magnet Resonanz Tomographie (fMRT) Experimente. In der dritten Studie untersuchten wir Mechanismen eingeschränkter stimmlicher Emotionserkennung bei ASS. Unsere Ergebnisse bringen neue Kenntnisse für Modelle zwischenmenschlicher Kommunikation und erhöhen unser Verständnis elementarer Mechanismen, die den Kernsymptomen in ASS wie Schwierigkeiten in der Kommunikation, zugrunde liegen könnten. Beispielsweise unterstützen unsere Ergebnisse die Annahme, dass Einschränkungen in der Wahrnehmung und Integration basaler sensorischer Merkmale (i.S. akustischer Merkmale der Stimme) entscheidend zu Einschränkungen in sozialer Kognition (i.S. Sprechererkennung und stimmliche Emotionserkennung) beitragen. / The correct perception of information carried by the voice is a key requirement for successful human communication. Hearing another person’s voice provides information about who is speaking (voice identity), what is said (vocal speech) and the emotional state of a person (vocal emotion). Autism spectrum disorder (ASD) is associated with impaired voice identity and vocal emotion perception while the perception of vocal speech is relatively intact. However, the underlying mechanisms of these voice perception impairments are unclear. For example, it is unclear at which processing stage voice perception difficulties occur, i.e. whether they are rather of apperceptive or associative nature or whether impairments in voice identity processing in ASD are associated with dysfunction of voice-sensitive brain regions. Within the scope of my dissertation we systematically investigated voice perception and its impairments in adults with high-functioning ASD and typically developing matched controls (matched pairwise on age, gender, and intellectual abilities). In the first two studies we characterised the behavioural and neuronal profile of voice identity recognition in ASD using two functional magnetic resonance imaging (fMRI) experiments and a comprehensive behavioural test battery. In the third study we investigated the underlying behavioural mechanisms of impaired vocal emotion recognition in ASD. Our results inform models on human communication and advance our understanding for basic mechanisms which might contribute to core symptoms in ASD, such as difficulties in communication. For example, our results converge to support the view that in ASD difficulties in perceiving and integrating lower-level sensory features, i.e. acoustic characteristics of the voice might critically contribute to difficulties in higher-level social cognition, i.e. voice identity and vocal emotion recognition.

Das Reizdarmsyndrom (RDS) ist eine funktionale Darmerkrankung mit einer Prävalenz von 10.000 – 20.000/100.000 in verschiedenen Kulturen. Keine einzelne physiologische oder psychologische Ursache konnte bisher isoliert werden. Ein sensitiver und spezifischer Maker sind herabgesetzte rektale Schmerzschwellen. Veränderungen der cerebralen viszerosensorischen und nozizeptiven Repräsentation sind mit Neuroimaging-Studien untersucht worden. Die Verarbeitung von Reizen unterhalb der Wahrnehmungsschwelle scheint sich von der Verarbeitung bewusster Reize zu unterscheiden. Wir untersuchten daher sub- und supraliminale rektale Wahrnehmung von 8 RDS-Patienten und 8 parallelisierten gesunden Kontrollprobanden. Die Reizschwelle wurde mit Hilfe eines Tracking-Paradigmas bestimmt. In einer funktionellen Magnetresonanztomographie (fMRT)-Studie wurden Reize unter, über und in der Nähe der Wahrnehmungsschwelle in einem pseudorandomisierten Blockdesign präsentiert. Bei supraliminaler Stimulation gesunder Probanden konnten der bekannte spinothalamische und vagale Pfad repliziert werden. Bei subliminaler Stimulation zeigte sich in einer Einzelauswertung eine ähnliche Verarbeitung, damit konnten die Vorergebnisse hier ebenfalls repliziert werden. In der Gruppenauswertung fand sich Aktivierung nur in Arealen, die bei supraliminaler Stimulation nicht aktiv waren. RDS-Patienten zeigten weniger Aktivität bei subliminaler und mehr bei liminaler Stimulation. Bei supraliminaler Stimulation zeigten sich unterschiedliche aktivierte Areale. Insbesondere war der Amygdala-Hippocampus-Komplex bei Patienten stärker aktiviert. Die Ergebnisse bei supraliminaler und liminaler Stimulation können als verstärkte Aufmerksamkeit auf eben wahrnehmbare Darmreize und als verstärkte emotionale Verarbeitung interpretiert werden. Bei der subliminalen Stimulation kann man schwächere Aktivität schmerzunterdrückender Netze annehmen oder von einem methodischen Artefakt ausgehen. / Irritable bowel syndrome (IBS) is a functional bowel disease with a prevalence of 10.000 - 20.000/100.000 across cultures. So far, no single physiological or psychological reason has been identified. Nevertheless, reduced rectal pain thresholds represent a sensitive and specific marker. Alterations in cerebral viscerosensory and nociceptive representation have been addressed using neuroimaging studies. Processing of stimuli below conscious perception level seems to differ from consciously perceived stimuli. Thus, we examined sub- and supraliminal rectal perception in 8 patients with IBS and 8 healthy matched control subjects. Perception thresholds were assessed by a tracking paradigm. In an functional magnetic resonance imaging (fMRI) study using a block design, stimuli below, above, or around the subjective perception threshold were presented in pseudo-randomized order. At supraliminal stimulation in healthy controls, results of previous studies were replicated and confirmed a spinothalamic and a vagal pathway of visceral sensory perception and suggested processing in amygdala and hippocampus. At subliminal stimulation in healthy controls, previous results were also replicated showing similar processing in single subject analysis. Results of a group analysis yielded only activity in areas not activated at supraliminal stimulation. IBS patients showed less pronounced activity during subliminal stimulation and much more pronounced activity at liminal stimulation. At supraliminal stimulation, different areas showed active in both groups. In particular, the amygdala-hippocampus complex was more active in patients. Results at liminal and supraliminal stimulation can be interpreted as enhanced attention to around-threshold rectal stimuli and more pronounced emotional processing of conciously perceived stimuli. Results at subliminal stimulation can be understood as weaker activity of perception-suppressing pathways or as methodological artifact.

Kognitive Kontrolle wird besonders in solchen Momenten deutlich, wenn eine geplante Handlung gestört wird. Weil zwei widerstreitende Verhaltenstendenzen gleichzeitig bestehen oder anlaufen, entsteht ein Konflikt. Experimentell können kognitive Konflikte beispielsweise mit dem Stroop-Paradigma hergestellt und untersucht werden (Stroop, 1935). Es ist dabei eine aktuelle Frage, wie Konflikte zeitlich verarbeitet werden und wo im Gehirn diese Verarbeitung geschieht. Zeitlich können Konflikte beispielsweise dann entstehen, wenn die Informationen des Stimulus abgerufen werden oder auch erst dann, wenn die intendierte Antwort tatsächlich für die Artikulation ausgewählt werden muss. Eine weiterführende Frage ist, ob sich die entsprechenden Ergebnisse für verschiedene Stroop-Varianten unterscheiden. In der vorliegenden Arbeit wurden diese Fragen systematisch für die Verarbeitung von Objekten und Zahlen mit zwei Varianten des Stroop-Paradigmas untersucht. In der vorliegenden Dissertation präsentiere ich Ergebnisse von Reaktionszeitstudien und fMRT-Experimenten zum zeitlichen Ablauf und zu neuronalen Substraten kognitiver Konflikte während der Verarbeitung von Objekten und Zahlen. Um die Konflikte zeitlich und räumlich lokalisieren zu können, wird die Abrufphase und die Antwortphase separat modelliert. Die Ergebnisse deuten darauf hin, dass die Konflikte eher während des Abrufs als bei der Antwortauswahl stattfinden. Außerdem wird geschlussfolgert, dass die Konflikte für Zahl- und Objektrepräsentationen nicht auf gemeinsamen neuronalen Substraten basieren. Die Ergebnisse meiner Reaktionszeitstudien und der MRT-Studien deuten also darauf hin, dass Konflikte bei der Verarbeitung von Objekten und Zahlen zwar einem ähnlichen zeitlichen Verlauf folgen, aber offenbar in unterschiedlichen neuronalen Netzwerken verarbeitet werden. / In daily life, we constantly have to adjust our goals and plans to changing task demands and internal needs. Our ability to balance the initiation and inhibition of our actions, and to solve resulting conflicts between them, is referred to as cognitive control. To study the processes of cognitive control, the Stroop Paradigm has become a popular tool (Stroop,1935). The Stroop Paradigm is frequently used to address central questions of cognitive control. It is, for instance, an open issue, where and when in the processing stream cognitive conflicts arise. Do they arise early, for example, during the retrieval of target and distractor? Or do they occur late, when the response is prepared for execution? Another debate is concerned with the question whether the findings agree for different Stroop variants (Van Maanen et al., 2009). In this dissertation I present research on the temporal characteristics and the neural substrates of cognitive conflicts during the processing of objects and numbers. To better understand the locus of the conflict, the retrieval phase and the response phase are modelled separately. The results from several reaction time studies and from two fMRI experiments speak to the issue that processing costs occur during retrieval, i.e., early in the processing stream, for both, object and number representations. The results further indicate that the processing of the conflict between target and distractor for number and object representations do not rely on common neural substrates. I will thus present the results from behavioural and functional imaging experiments, showing similar temporal patterns for the conflicts in both systems, but distinct underlying neural networks.

Theory of Mind (ToM) is the ability to infer others’ mental states and thus to predict their behavior (Perner, 1991). Therefore, ToM is essential for the adequate adjustment of behavior in social situations. ToM can be divided into: 1) cognitive ToM encompassing inferences about intentions and beliefs and 2) affective ToM encompassing inferences about emotions (Shamay-Tsoory, Harari, Aharon-Peretz, & Levkovitz, 2010). Well-functioning skills of both ToM aspects are much-needed in the developmental period of adolescence because in this age phase peer relationships become more important and romantic relationships arise (Steinberg & Morris, 2001). Importantly, affective psychopathological disorders often have their onset in adolescence. ToM development in adolescence might be based on underlying cognitive mechanisms such as the ability to inhibit one’s own thoughts in order to understand another person’s thoughts (Carlson & Moses, 2001). Another possible mechanism relates to functional brain development across adolescence (Blakemore, 2008). Therefore, neurocognitive mechanisms may underlie ongoing ToM development in adolescence. First studies indicate an ongoing behavioral and functional brain development of ToM (e.g. Blakemore, 2008). However, ToM development in adolescence and how this might relate to underlying (neuro)cognitive functions remains largely underexamined. The major aims of the current thesis were first to answer the overall question whether there is an ongoing development of ToM in adolescence. This question relates to both behavioral and functional brain development. As a second major aim, the present work sought to elucidate possible (neuro)cognitive mechanisms of ongoing ToM development across adolescence. Specifically, these cognitive mechanisms might be basic cognitive functions as well as executive functions. Additionally, the present work aimed at exploring potential (neuro)cognitive mechanisms through an integration of both behavioral and functional brain studies. The current experimental work spans three cross-sectional studies investigating adolescents (aged around 12-15 years) and young adults (aged around 18-22 years) to examine for the first time both the behavioral (studies I and II) and functional brain development of ToM (study III) in adolescence and its underlying (neuro)cognitive mechanisms. In all three studies, more complex, advanced ToM tasks were employed to avoid ceiling effects. Study I was aimed at investigating if cognitive and affective ToM continues to develop in adolescence and at exploring if basic cognitive variables such as verbal ability, speed of processing, and working memory capacity underlie such development. Hence, two groups of adolescents and young adults completed tasks of ToM and basic cognitive abilities. Large age effects were revealed on both measures of ToM: adolescents performed lower than adults. These age differences remained significant after controlling for basic cognitive variables. However, verbal ability covaried with performance in affective ToM. Overall, results support the hypothesis of an ongoing development of ToM from adolescence to adulthood on both cognitive and affective aspects. Results may further indicate verbal ability being a basic cognitive mechanism of affective ToM. Study II was designed to further explore if affective ToM, as measured with a dynamic realistic task, continues to develop across adolescence. Importantly, this study sought to explore executive functions as higher cognitive mechanisms of developing affective ToM across adolescence. A large group spanning adolescents and young adults evaluated affective mental states depicted by actors in video clips. Additionally, participants were examined with three subcomponents of executive functions, inhibition, updating, and shifting following the classification of Miyake et al. (2000). Affective ToM performance was positively related to age and all three executive functions. Specifically, inhibition explained the largest amount of variance in age related differences of affective ToM performance. Overall, these results indicate the importance of inhibition as key underlying mechanism of developing an advanced affective ToM in adolescence. Study III set out to explore the functional brain development of affective ToM in adolescence by using functional magnetic resonance imaging (fMRI). The affective ToM measure was the behavioral developmentally sensitive task from study II. An additional control condition consisted of the same emotional stimuli with the instruction to focus on physical information. This study faced methodical challenges of developmental fMRI studies by matching performance of groups. The ventromedial prefrontal cortex (vMPFC) was significantly less deactivated in adolescents in comparison to adults, which might suggest that adolescents seem to rely more on self-referential processes for affective ToM. Furthermore, adolescents compared to adults showed greater activation in the dorsolateral prefrontal cortex (DLPFC) in the control condition, indicating that adolescents might be distracted by the emotional content and therefore needed to focus more on the physical content of the stimulus. These findings suggest affective ToM continues to develop on the functional brain level and reveals different underlying neurocognitive strategies for adolescents in contrast to adults. In summary, the current thesis investigated whether ToM continues to develop in adolescence until young adulthood and explored underlying (neuro)cognitive mechanisms. Findings suggest that there is indeed an ongoing development of both the cognitive and affective aspect of ToM, which importantly contributes to the conceptual debate. Moreover, the second benefit to the debate is to demonstrate how this change may occur. As a basic cognitive mechanism verbal ability and as an executive functioning mechanism inhibition was revealed. Furthermore, neurocognitive mechanisms in form of different underlying neurocognitive strategies of adolescents compared to adults were shown. Taken together, ToM development in adolescence seems to mirror a different adaptive cognitive style in adolescence (Crone & Dahl, 2012). This seems to be important for solving the wealth of socio-emotional developmental tasks that are relevant for this age span.

No description available.

No description available.

Die Ursache für das idiopathische Stottern ist bis zum jetzigen Zeitpunkt unbekannt. Typischerweise beginnt die Redeflussstörung im Vorschulalter. Es wird davon ausgegangen, dass 1% der Bevölkerung an Stottern leidet. Bei der Frage nach pathophysiologischen Hintergründen von Sprech- und Sprachstörungen ist der Zusammenhang zwischen einer pathologischen, funktionellen Lateralisierung und einer morphologischen Asymmetrie im Bereich von neuronalen Netzwerken der Sprachbildung bereits seit längerem Gegenstand der Forschung. Im Rahmen der vorliegenden Arbeit wurde die Lateralisierung von Sprache bei 17 stotternden Probanden und 20, im Alter entsprechenden, flüssig sprechenden Probanden untersucht. Hierbei wurde die Sprachlateralisierung mithilfe der fMRT sowohl mit einem Satz- als auch mit einem Wortgenerierungsparadigma ermittelt. Ausgehend von den in der fMRT ermittelten Sprachzentren wurde die angrenzende weiße Substanz unter Verwendung der DTI auf eine Asymmetrie hin untersucht. Im Vergleich zu der Gruppe der Normalprobanden zeigten die schwer stotternden Probanden eine Verschiebung der Indexwerte, deren endgültige Ursache offen bleibt. Gesteigerte funktionelle Aktivierung in Bereichen der rechtshemisphärischen Analoga der Sprachzentren scheint ein möglicher Erklärungsansatz. Vorausgegangene funktionelle Untersuchungen u. a. mittels PET und fMRT bei stotternden Probanden belegten eine Überaktivierung von Teilen des motorischen Kortex sowie eine atypische Lateralisierung bei der Produktion von Sprache mit rechtsseitiger Lateralisierung oder eine bilaterale Aktivität. Darüber hinaus zeigte sich eine morphologische Veränderung, im Sinne einer Abnahme einer linkshemisphärischen Asymmetrie bei den schwer stotternden Probanden, besonders in der an das Wernicke-Areal angrenzenden weißen Substanz. Mithilfe der VBM konnten in mehreren früheren Studien morphologische Unterschiede bei Stotternden gezeigt werden. Gegenüber dem rein morphologischen Untersuchungsansatz vorangegangener Untersuchungen berücksichtigte die Kombination der funktionellen und der diffusionsgewichteten Analyse stärker die intraindividuelle Variabilität der Sprachzentren.

Theory of Mind (ToM) is the ability to infer others’ mental states and thus to predict their behavior (Perner, 1991). Therefore, ToM is essential for the adequate adjustment of behavior in social situations. ToM can be divided into: 1) cognitive ToM encompassing inferences about intentions and beliefs and 2) affective ToM encompassing inferences about emotions (Shamay-Tsoory, Harari, Aharon-Peretz, & Levkovitz, 2010). Well-functioning skills of both ToM aspects are much-needed in the developmental period of adolescence because in this age phase peer relationships become more important and romantic relationships arise (Steinberg & Morris, 2001). Importantly, affective psychopathological disorders often have their onset in adolescence. ToM development in adolescence might be based on underlying cognitive mechanisms such as the ability to inhibit one’s own thoughts in order to understand another person’s thoughts (Carlson & Moses, 2001). Another possible mechanism relates to functional brain development across adolescence (Blakemore, 2008). Therefore, neurocognitive mechanisms may underlie ongoing ToM development in adolescence. First studies indicate an ongoing behavioral and functional brain development of ToM (e.g. Blakemore, 2008). However, ToM development in adolescence and how this might relate to underlying (neuro)cognitive functions remains largely underexamined. The major aims of the current thesis were first to answer the overall question whether there is an ongoing development of ToM in adolescence. This question relates to both behavioral and functional brain development. As a second major aim, the present work sought to elucidate possible (neuro)cognitive mechanisms of ongoing ToM development across adolescence. Specifically, these cognitive mechanisms might be basic cognitive functions as well as executive functions. Additionally, the present work aimed at exploring potential (neuro)cognitive mechanisms through an integration of both behavioral and functional brain studies. The current experimental work spans three cross-sectional studies investigating adolescents (aged around 12-15 years) and young adults (aged around 18-22 years) to examine for the first time both the behavioral (studies I and II) and functional brain development of ToM (study III) in adolescence and its underlying (neuro)cognitive mechanisms. In all three studies, more complex, advanced ToM tasks were employed to avoid ceiling effects. Study I was aimed at investigating if cognitive and affective ToM continues to develop in adolescence and at exploring if basic cognitive variables such as verbal ability, speed of processing, and working memory capacity underlie such development. Hence, two groups of adolescents and young adults completed tasks of ToM and basic cognitive abilities. Large age effects were revealed on both measures of ToM: adolescents performed lower than adults. These age differences remained significant after controlling for basic cognitive variables. However, verbal ability covaried with performance in affective ToM. Overall, results support the hypothesis of an ongoing development of ToM from adolescence to adulthood on both cognitive and affective aspects. Results may further indicate verbal ability being a basic cognitive mechanism of affective ToM. Study II was designed to further explore if affective ToM, as measured with a dynamic realistic task, continues to develop across adolescence. Importantly, this study sought to explore executive functions as higher cognitive mechanisms of developing affective ToM across adolescence. A large group spanning adolescents and young adults evaluated affective mental states depicted by actors in video clips. Additionally, participants were examined with three subcomponents of executive functions, inhibition, updating, and shifting following the classification of Miyake et al. (2000). Affective ToM performance was positively related to age and all three executive functions. Specifically, inhibition explained the largest amount of variance in age related differences of affective ToM performance. Overall, these results indicate the importance of inhibition as key underlying mechanism of developing an advanced affective ToM in adolescence. Study III set out to explore the functional brain development of affective ToM in adolescence by using functional magnetic resonance imaging (fMRI). The affective ToM measure was the behavioral developmentally sensitive task from study II. An additional control condition consisted of the same emotional stimuli with the instruction to focus on physical information. This study faced methodical challenges of developmental fMRI studies by matching performance of groups. The ventromedial prefrontal cortex (vMPFC) was significantly less deactivated in adolescents in comparison to adults, which might suggest that adolescents seem to rely more on self-referential processes for affective ToM. Furthermore, adolescents compared to adults showed greater activation in the dorsolateral prefrontal cortex (DLPFC) in the control condition, indicating that adolescents might be distracted by the emotional content and therefore needed to focus more on the physical content of the stimulus. These findings suggest affective ToM continues to develop on the functional brain level and reveals different underlying neurocognitive strategies for adolescents in contrast to adults. In summary, the current thesis investigated whether ToM continues to develop in adolescence until young adulthood and explored underlying (neuro)cognitive mechanisms. Findings suggest that there is indeed an ongoing development of both the cognitive and affective aspect of ToM, which importantly contributes to the conceptual debate. Moreover, the second benefit to the debate is to demonstrate how this change may occur. As a basic cognitive mechanism verbal ability and as an executive functioning mechanism inhibition was revealed. Furthermore, neurocognitive mechanisms in form of different underlying neurocognitive strategies of adolescents compared to adults were shown. Taken together, ToM development in adolescence seems to mirror a different adaptive cognitive style in adolescence (Crone & Dahl, 2012). This seems to be important for solving the wealth of socio-emotional developmental tasks that are relevant for this age span.:Abstract 1 1 General Introduction 4 1.1 Concept of ToM: cognitive and affective aspects 7 1.2 ToM Development 8 1.2.1 ToM Development until Adolescence 9 1.2.2 ToM Development in Adolescence 12 1.3 Cognitive Mechanisms 14 1.3.1 Basic Cognitive Functions 15 1.3.2 Executive Functions 17 1.4 Neurocognitive Mechanisms 19 1.4.1 Functional brain development of ToM 20 1.4.2 Integrating behavioral and functional brain studies 21 2 Outline and Central Questions 24 2.1 Does ToM continue to develop in adolescence? 24 2.1.1 Does ToM continue to develop on the behavioral level? 24 2.1.2 Does ToM continue to develop on the level of brain function? 25 2.2 What are (neuro)cognitive mechanisms of ToM development in adolescence? 26 2.2.1 What are basic cognitive and executive functioning mechanisms? 26 2.2.2 Can mechanisms be concluded from the integration of behavioral data and functional brain processes? 26 3 Study I – ToM Development in Adolescence and its Basic Cognitive Mechanisms 28 3.1 Introduction 28 3.2 Method 32 3.2.1 Participants 32 3.2.2 Materials 33 3.3 Results 36 3.3.1 Age Effects 36 3.3.2 Influence of puberty on social cognition 37 3.3.3 Controlling for Basic Cognitive Abilities 39 3.4 Discussion 40 3.4.1 Overview 40 3.4.2 Age differences in social cognition 40 3.4.3 Influence of puberty on social cognition 42 3.4.4 Covariates of age differences in social cognition 42 3.4.5 Conclusions 43 4 Study II – ToM Development in Adolescence and its Executive Functioning Mechanisms 45 4.1 Introduction 45 4.2 Method 49 4.2.1 Participants 49 4.2.2 Materials 49 4.3 Results 52 4.3.1 Decomposing the Age Effect in Affective Theory of Mind 54 4.4 Discussion 55 4.4.1 Overview 55 4.4.2 Conclusions 57 5 Study III – ToM Development in Adolescence and its Neurocognitive Mechanisms 59 5.1 Introduction 59 5.2 Method 61 5.2.1 Participants 61 5.2.2 Stimuli, design and procedure 62 5.2.3 Statistical analysis of behavioral data 65 5.2.4 Functional imaging 65 5.2.5 Statistical analysis of fMRI data 66 5.3 Results 67 5.3.1 Behavioral results 67 5.3.2 fMRI results 68 5.4 Discussion 71 5.4.1 Developmental differences in brain activations 71 5.4.2 Conclusions 74 6 General Discussion 75 6.1 Summary of empirical findings 75 6.2 Discussion and integration of the main empirical findings 76 6.2.1 Continued ToM development in adolescence 76 6.2.2 (Neuro)cognitive mechanisms of ToM development in adolescence 80 6.3 Implications and outlook 89 6.3.1 Current findings and their conceptual fit to present models of ToM 90 6.3.2 Underpinning the concept of cognitive and affective ToM 91 6.3.3 Conceptual and methodical implications of performance matching 92 6.3.4 The role of puberty on ToM 94 6.3.5 Predicting other’s economic behavior 95 6.3.6 Structural brain development 96 6.3.7 Applied perspective 97 6.4 Summary 98 References 99

Mit dieser Arbeit ist es erstmalig gelungen, funktionelle MRT und Dipol-Quellenlokalisation in einer Weise zu kombinieren, die es erlaubt, ein und dieselbe kortikale Aktivität simultan mit beiden Verfahren zu erfassen. Insbesondere wurde dies durch (a) Korrektur eines vom Tomographen induzierten Artefaks in den EKPs und (b) durch eine deutliche Verbesserung des experimentellen Designs, und damit einer wesentlich effektiveren Nutzung von EEG und fMRT-Messzeit erreicht. So wurde es dadurch möglich, mit beiden Methoden die kortikale Aktivität einer Einzelpulsstimulation noch aufzulösen. Eine wesentliche Voraussetzung für die simultane Kombination beider Verfahren: Aufgrund der sehr verschiedenen Latenzen von elektrophysiologischer (< 1ms) und vaskulärer (SII->ant. Inseln und medialeWand) in Übereinstimmung mit der Literatur (Forss et al., 1996; Mauguiere et al., 1997b) blieb. So ergab die Quellenlokalisation für die Wahlreaktionsaufgabe fünf Dipole innerhalb des Gehirns, welche mittels Koregistrierung den Aktivierungen des primären somatosensorschen Kortex (20 - 140ms), des sekundären somatosensorischen Kortex (50 - 150ms), der beiden anterioren Inseln (80 - 140ms) und des supplementär-motorischen Region (90 - 140ms, 220 - 270ms) aus der funktionellen MRT zugeordnet wurden. Durch einen Vergleich der Aktivierungsmuster von Wahl- und Einfachreaktionsaufgabe jeweils in der Dipol-Quellenanalyse und in der funktionellen MRT konnten weitere Belege dafür gefunden werden, daß, wie in der Literatur postuliert (Romo and Salinas, 2001), der kontralaterale sekundäre somatosensorische Kortex an der Kategorisierung somatosensorischer Stimulusattribute beteiligt ist. So ergab ein Vergleich der Dipolzeitverläufe für Wahl- und Einfachreaktionsaufgabe lediglich für den Dipol im kontralateral somatosensorischen Kortex im Intervall 57-62 ms nach Stimulusapplikation einen signifikant unterschiedlichen Aktivierungsverlauf (p < 0,001). Übereinstimmend zeigte die funktionelle MRT für die Wahlreaktionsaufgabe neben einer stärkeren Aktivierung der SMA eine hochsignifikant stärkere Aktivierung im Areal des kontralateralen sekundären somatosensorischen Kortex (p-cluster < 0,001). / In this study, we have shown that it is feasible to perform dipole source analysis and fMRI based on the same neuronal activity associated with somatosensory categorization. This was possible by reduction of scanner-induced baseline artifact interfering with the ERPs as well as an optimized experimental protocol for interleaved EEG and fMRI acquisition. We consider this study to be a further step toward imaging brain activity simultaneously at high spatial and temporal resolution. Since an event-related protocol with a single brief pulse stimulation paradigm was successfully employed, this approach seems to be suitable for the investigation of cognitive tasks. By further technical improvements also the exploration of brain activity in single subjects might become possible, opening the field of clinical applications. In particular for the characterization of irregular and nonreproducible events, a substantial contribution of combined EEG–fMRI studies toward a more detailed understanding of physiological processes underlying cerebral activations is expected.

Menschliche Hirnsignale von der Kopfhaut bieten einen Einblick in die neuronalen Prozesse, denen Wahrnehmung, Denken und Verhalten zugrunde liegen. Rhythmen, die historisch den Grundstein für die Erforschung großflächiger Hirnsignale legten, sind ein häufiges Zeichen neuronaler Koordination, und damit von weitem Interesse für die kognitiven, systemischen und komputationalen Neurowissenschaften. Typischen Messungen von Rhythmizität fehlt es jedoch an Details, z. B. wann und wie lange Rhythmen auftreten. Darüber hinaus weisen neuronale Zeitreihen zahlreiche dynamische Muster auf, von denen nur einige rhythmisch erscheinen. Obwohl aperiodischen Beiträgen traditionell der Status irrelevanten „Rauschens“ zugeschrieben wird, attestieren neuere Erkenntnisse ihnen ebenfalls eine Signalrolle in Bezug auf latente Hirndynamik. Diese kumulative Dissertation fasst Projekte zusammen, die darauf abzielen, rhythmische und aperiodische Beiträge zum menschlichen Elektroenzephalogramm (EEG) methodisch zu dissoziieren, und ihre Relevanz für die flexible Wahrnehmung zu untersuchen. Projekt 1 ermittelt insbesondere die Notwendigkeit und Durchführbarkeit der Trennung rhythmischer von aperiodischer Aktivität in kontinuierlichen Signalen. Projekt 2 kehrt diese Perspektive um und prüft Multiscale Entropy als Index für die Unregelmäßigkeit von Zeitreihen. Diese Arbeit weist auf methodische Probleme in der klassischen Messung zeitlicher Unregelmäßigkeit hin, und schlägt Lösungen für zukünftige Anwendungen vor. Abschließend untersucht Projekt 3 die neurokognitive Relevanz rhythmischer und aperiodischer Zustände. Anhand eines parallelen multimodalen EEG-fMRT-Designs mit gleichzeitiger Pupillenmessung liefert dieses Projekt erste Hinweise dafür, dass erhöhte kognitive Anforderungen Hirnsignale von einem rhythmischen zu einem unregelmäßigen Regime verschieben und impliziert gleichzeitige Neuromodulation und thalamische Aktivierung in diesem Regimewechsel. / Non-invasive signals recorded from the human scalp provide a window on the neural dynamics that shape perception, cognition and action. Historically motivating the assessment of large-scale network dynamics, rhythms are a ubiquitous sign of neural coordination, and a major signal of interest in the cognitive, systems, and computational neurosciences. However, typical descriptions of rhythmicity lack detail, e.g., failing to indicate when and for how long rhythms occur. Moreover, neural times series exhibit a wealth of dynamic patterns, only some of which appear rhythmic. While aperiodic contributions are traditionally relegated to the status of irrelevant ‘noise’, they may be informative of latent processing regimes in their own right. This cumulative dissertation summarizes and discusses work that (a) aims to methodologically dissociate rhythmic and aperiodic contributions to human electroencephalogram (EEG) signals, and (b) probes their relevance for flexible cognition. Specifically, Project 1 highlights the necessity, feasibility and limitations of dissociating rhythmic from aperiodic activity at the single-trial level. Project 2 inverts this perspective, and examines the utility of multi-scale entropy as an index for the irregularity of brain dynamics, with a focus on the relation to rhythmic and aperiodic descriptions. By highlighting prior biases and proposing solutions, this work indicates future directions for measurements of temporal irregularity. Finally, Project 3 examines the neurocognitive relevance of rhythmic and aperiodic regimes with regard to the neurophysiological context in which they may be engaged. Using a parallel multi-modal EEG-fMRI design with concurrent pupillometry, this project provides initial evidence that elevated demands shift cortical dynamics from a rhythmic to an irregular regime; and implicates concurrent phasic neuromodulation and subcortical thalamic engagement in these regime shifts.