No description available.

Neurotrophine beeinflussen durch die Modulation von Prozessen wie Zellproliferation, -migration, Apoptose und Synapsenbildung entscheidend die neuronale Plastizität. Sie gelten deshalb als Kandidatengene neuronaler Entwicklungsstörungen wie Autismus-Spektrum-Störungen (ASS). Die vorgelegte Arbeit zielt auf die weitere Klärung der Rolle von Brain Derived Neurotrophic Factor (BDNF) bei der Ätiopathophysiologie der ASS durch Expressionsanalysen im Blut als potenziellem Surrogat zentralnervöser Prozesse. In gut charakterisierten ASS-Stichproben und - neben gesunden Kontrollprobanden - einer klinischen Kontrollgruppe von Patienten mit Aufmerksamkeitsdefizit-/ Hyperaktivitätsstörung (ADHS) wurde die BDNF-mRNA-Expression in Vollblut sowie BDNF-Proteinserumkonzentrationen untersucht. Zusätzlich wurden mögliche Einflussfaktoren auf die BDNF-Werte wie Alter, IQ, autismusspezifische Symptomatik, Komorbidität und Medikation analysiert. In einer ersten Stichprobe (ASS-Patienten versus gesunde Kontrollen) wurden signifikant erniedrigte BDNF-Serumkonzentrationen in der Patientengruppe mittels Enzyme-Linked-Immunosorbent-Assay gemessen (p = 0,040). In einer zweiten unabhängigen Stichprobe (Patienten mit ASS, Patienten mit ADHS und gesunde Kontrollen) wurde auf mRNA-Ebene mittels quantitativer Real-Time-Polymerasekettenreaktion ebenfalls ein signifikanter Gruppenunterschied ermittelt mit erniedrigter BDNF-Expression in der ASS-Gruppe im Vergleich zu gesunder Kontrollgruppe (p = 0,011), sowie einem Trend zu erniedrigten BDNF-Werten bei ADHS-Patienten im Vergleich zu gesunden Probanden (p = 0,097). Des Weiteren wurde eine signifikante negative Korrelation zwischen Alter und BDNF-mRNA-Expression bei Patienten mit ASS sowie eine positive Korrelation von Alter und BDNF-Serumkonzentrationen bei gesunden Kontrollen gemessen. Auch korrelierten die BDNF-Werte im Serum mit der Ausprägung des autistischen Phänotyps. In einer Subgruppe der ADHS-Patienten wurde kein Einfluss von Psychostimulanzien auf die BDNF-mRNA-Expression gemessen. Der Einbezug größerer Stichproben sowie die systematische Erfassung weiterer potenzieller Einflussfaktoren auf die BDNF-Expression (wie pubertärer Entwicklungsstand bzw. Geschlechtshormonkonzentrationen) könnten in zukünftigen Studien zu einer weiteren Klärung der pathophysiologischen Rolle von BDNF bei Kindern und Jugendlichen mit ASS beitragen. / Neurotrophins impact on neuronal plasticity by modulating processes such as cell proliferation, cell migration, apoptosis and synaptic plasticity. Therefore, they are regarded as candidate genes for neurodevelopmental disorders such as autism spectrum disorders (ASD). The following work aims at further clarifying the role of brain derived neurotrophic factor (BDNF) in the pathophysiology of ASD by expression analyses in blood as a potential surrogate for BDNF effects observed in the central nervous system. BDNF mRNA expression in whole blood and BDNF serum concentrations were analyzed in well characterized samples of ASD patients, healthy controls, and a clinical control group of patients with attention deficit hyperactivity disorder (ADHD). In addition, potential modulating factors such as age, IQ, autistic phenotype, comorbidity and medication were further investigated. In a first project (ASD patients vs. healthy controls) significantly lower BDNF serum concentrations in the ASD group were observed via enzyme-linked immunosorbent assay (p = 0.040). In a second independent sample and project (patients with ASS, patients with ADHD, and healthy controls), BDNF mRNA expression was analyzed using quantitative real time polymerase chain reaction. Also in this sample, a significant group difference was found with lower BDNF expression in the ASD group compared to the health controls (p = 0.011). Moreover, a trend of decreased BDNF mRNA levels was observed for patients with ADHD in comparison to the normally developing controls (p = 0.097). Furthermore, with regard to potential influencing factors, we found a significant negative correlation between age and BDNF mRNA expression in patients with ASD, as well as a positive correlation between age and BDNF serum concentrations in healthy controls. A positive correlation was moreover detected between the serum BDNF concentrations and autistic phenotype. Testing a sub-group of ADHD patients, no significant influence of stimulants was observed on BDNF mRNA expression. In future studies, bigger sample sizes as well as a systematic assessment of other factors that potentially influence BDNF expression (like pubertal developmental status or concentration of sex hormones) could further clarify the pathophysiological role of BDNF in children and adolescents with ASD.

Neurotrophine beeinflussen durch die Modulation von Prozessen wie Zellproliferation, -migration, Apoptose und Synapsenbildung entscheidend die neuronale Plastizität. Sie gelten deshalb als Kandidatengene neuronaler Entwicklungsstörungen wie Autismus-Spektrum-Störungen (ASS). Die vorgelegte Arbeit zielt auf die weitere Klärung der Rolle von Brain Derived Neurotrophic Factor (BDNF) bei der Ätiopathophysiologie der ASS durch Expressionsanalysen im Blut als potenziellem Surrogat zentralnervöser Prozesse. In gut charakterisierten ASS-Stichproben und - neben gesunden Kontrollprobanden - einer klinischen Kontrollgruppe von Patienten mit Aufmerksamkeitsdefizit-/ Hyperaktivitätsstörung (ADHS) wurde die BDNF-mRNA-Expression in Vollblut sowie BDNF-Proteinserumkonzentrationen untersucht. Zusätzlich wurden mögliche Einflussfaktoren auf die BDNF-Werte wie Alter, IQ, autismusspezifische Symptomatik, Komorbidität und Medikation analysiert. In einer ersten Stichprobe (ASS-Patienten versus gesunde Kontrollen) wurden signifikant erniedrigte BDNF-Serumkonzentrationen in der Patientengruppe mittels Enzyme-Linked-Immunosorbent-Assay gemessen (p = 0,040). In einer zweiten unabhängigen Stichprobe (Patienten mit ASS, Patienten mit ADHS und gesunde Kontrollen) wurde auf mRNA-Ebene mittels quantitativer Real-Time-Polymerasekettenreaktion ebenfalls ein signifikanter Gruppenunterschied ermittelt mit erniedrigter BDNF-Expression in der ASS-Gruppe im Vergleich zu gesunder Kontrollgruppe (p = 0,011), sowie einem Trend zu erniedrigten BDNF-Werten bei ADHS-Patienten im Vergleich zu gesunden Probanden (p = 0,097). Des Weiteren wurde eine signifikante negative Korrelation zwischen Alter und BDNF-mRNA-Expression bei Patienten mit ASS sowie eine positive Korrelation von Alter und BDNF-Serumkonzentrationen bei gesunden Kontrollen gemessen. Auch korrelierten die BDNF-Werte im Serum mit der Ausprägung des autistischen Phänotyps. In einer Subgruppe der ADHS-Patienten wurde kein Einfluss von Psychostimulanzien auf die BDNF-mRNA-Expression gemessen. Der Einbezug größerer Stichproben sowie die systematische Erfassung weiterer potenzieller Einflussfaktoren auf die BDNF-Expression (wie pubertärer Entwicklungsstand bzw. Geschlechtshormonkonzentrationen) könnten in zukünftigen Studien zu einer weiteren Klärung der pathophysiologischen Rolle von BDNF bei Kindern und Jugendlichen mit ASS beitragen. / Neurotrophins impact on neuronal plasticity by modulating processes such as cell proliferation, cell migration, apoptosis and synaptic plasticity. Therefore, they are regarded as candidate genes for neurodevelopmental disorders such as autism spectrum disorders (ASD). The following work aims at further clarifying the role of brain derived neurotrophic factor (BDNF) in the pathophysiology of ASD by expression analyses in blood as a potential surrogate for BDNF effects observed in the central nervous system. BDNF mRNA expression in whole blood and BDNF serum concentrations were analyzed in well characterized samples of ASD patients, healthy controls, and a clinical control group of patients with attention deficit hyperactivity disorder (ADHD). In addition, potential modulating factors such as age, IQ, autistic phenotype, comorbidity and medication were further investigated. In a first project (ASD patients vs. healthy controls) significantly lower BDNF serum concentrations in the ASD group were observed via enzyme-linked immunosorbent assay (p = 0.040). In a second independent sample and project (patients with ASS, patients with ADHD, and healthy controls), BDNF mRNA expression was analyzed using quantitative real time polymerase chain reaction. Also in this sample, a significant group difference was found with lower BDNF expression in the ASD group compared to the health controls (p = 0.011). Moreover, a trend of decreased BDNF mRNA levels was observed for patients with ADHD in comparison to the normally developing controls (p = 0.097). Furthermore, with regard to potential influencing factors, we found a significant negative correlation between age and BDNF mRNA expression in patients with ASD, as well as a positive correlation between age and BDNF serum concentrations in healthy controls. A positive correlation was moreover detected between the serum BDNF concentrations and autistic phenotype. Testing a sub-group of ADHD patients, no significant influence of stimulants was observed on BDNF mRNA expression. In future studies, bigger sample sizes as well as a systematic assessment of other factors that potentially influence BDNF expression (like pubertal developmental status or concentration of sex hormones) could further clarify the pathophysiological role of BDNF in children and adolescents with ASD.

Background: Background of this work was the investigation of the endocannabinoid system (ECS) in the Fmr1 knock- out (KO) mouse. The Fmr1- KO mouse is a mouse model for fragile X syndrome (FXS). FXS is the leading monogenic cause for autism spectrum disorders (ASD) in humans. The Fmr1- KO mouse displays autistic behavior such as an impaired social interaction, repetitive behavior, cognitive deficits, increased anxiety and aggressiveness. Alterations of the ECS have been suggested to play a key role in the etiopathology of a variety of neuropsychiatric disorders. Until today, little has been described about the involvement of the ECS in ASD. Interrogation: 1. Evaluating the manifestation of typical cannabinoid- induced effects in the Fmr1- KO mouse 2. Investigating the influenceability of autistic symptoms with THC treatment in the Fmr1- KO mouse 3. Analyzing the signaling cascade of the stimulated and unstimulated ECS in different brain regions of the Fmr1- KO mouse Material and Methods: Experiments were carried out on adult (12±1 weeks old) male Fmr1- KO and Fmr1- wild- type (WT) mice from the C57BL/6J- (B6)- background. N= 15 mice received THC (10mg/kg bodyweight) and N= 16 received WIN55,212 (3mg/kg bodyweight). 30min after injection, the body temperature was measured and the distance animals moved in an open field during 15min was recorded (locomotion). Then, animals were placed with their forepaws onto a horizontally fixed bar and the time remaining in this position (catalepsy) was measured. Finally animals were placed on a preheated plate and the temperature at which a pain stimulus occurred was determined (testing analgesia). All 4 experiments are called tetrad experiment. Afterwards changes in body temperature, locomotion, catalepsy and analgesia of the animals was evaluated. To explore long-term effects of THC after the tetrad, N= 15 animals were tested in a social interaction test with a female contact mouse, 10 and 20 days after THC treatment. Therefore, the tested mouse and the contact mouse were placed together into a cage and the time mice spent in social interaction (nose, body and anogential sniffing, allogrooming and body contact) was manually quantified during 6min of recorded testing time. Another group of N= 19 received a premedication of rimonabant (Cannabinoid- receptor 1 (CB1) antagonist, 3mg/kg bodyweight) 30min prior to THC treatment. Rimonabant prevents THC from binding to CB1 and therefore allows the assessment of the involvement of CB1 in mediating social behavior. Furthermore the suggestibility of context-dependent fear conditioning with THC treatment has been tested on N= 13 mice. Animals were placed into a conditioning chamber that delivered 6 short electric shocks with a 30sec pause to their paws (conditioning phase). Immediately afterwards mice received THC or placebo. 24h later contextdependent fear was evaluated by quantification of the time mice spent freezing in the conditioning-chamber (fear) without receiving foot shocks. Intraneuronal signaling of the ECS was analyzed with N= 29 animals using western blots. Quantities of phosphorylated (“activated”) protein kinases (ERK, AKT and S6) from different brain homogenates (hippocampus, striatum, cortex and cerebellum) were therefore measured after THC or placebo injection (30 minutes prior to sacrificing). Results: Cannabinoids induced hypothermia, hypolocomotion, analgesia and catalepsy in WTmice. These effects were significantly less detectable in Fmr1- KO mice. Effects of both cannabinoids, THC and WIN55,212, were comparable with a slightly greater but not significant efficiency of THC. THC treated WT- mice exhibited further reduced social interaction 10 days after treatment, an effect that was partially prevented by premedication with rimonabant. THC increased social interaction in Fmr1- KO mice comparable to the level of untreated WT- mice. THC had no effect on behavior of WT- mice in context-dependent fear conditioning. Fmr1- KO mice showed significant less contextdependent fear conditioning compared to WT- mice. THC facilitated the recognition of an anxiety-correlated context in Fmr1- KO mice comparable to untreated WT- mice. In western blots significant changes in the THC- induced signaling cascade were detectable and depending on genotype, brain-region and analyzed protein-kinase. In the hippocampus there were no changes in untreated Fmr1- KO mice compared to WT- mice. THC had no effect on activation of protein-kinases in WT- and Fmr1- KO mice. In the striatum there were no changes in untreated Fmr1- KO mice compared to WTmice. THC significantly increased activity of ERK, AKT and S6 in WT-mice and not in Fmr1- KO mice. In the cortex of untreated Fmr1- KO mice AKT showed a significantly increased activity compared to WT- mice. THC significantly increased AKT activity in WT- mice without having an effect on KO- mice. In the cerebellum there were no changes in untreated Fmr1- KO mice compared to WT- mice. THC significantly increased ERK- activity in Fmr1- KO mice but had no effect on protein kinase activity in WT- mice. Conclusion: We observed physiological cannabinoid effects in WT- mice after treatment with THC and WIN55,212. These effects are significantly attenuated in Fmr1- KO mice. This may be interpreted as a desensitization of the ECS in the Fmr1- KO mouse. At the same time it was demonstrated that THC has the potential to improve context dependent memory consolidation and to increase social interaction in the Fmr1- KO mouse. In particular the influence of THC on impaired social interaction should be a target of further investigations to find possible therapeutic options for this typical symptom of Autism. Underlying molecular mechanisms remain unclear and the analysis of THC stimulated intraneuronal signaling gave no clear indication of possible molecular alterations in the Fmr1- KO mouse.

Background. In everyday life it is often required to integrate multisensory input to successfully conduct response inhibition (RI) and thus major executive control processes. Both RI and multisensory processes have been suggested to be altered in autism spectrum disorder (ASD). It is, however, unclear which neurophysiological processes relate to changes in RI in ASD and in how far these processes are affected by possible multisensory integration deficits in ASD. Method. Combining high-density EEG recordings with source localization analyses, we examined a group of adolescent ASD patients (n = 20) and healthy controls (n = 20) using a novel RI task. Results. Compared to controls, RI processes are generally compromised in adolescent ASD. This aggravation of RI processes is modulated by the content of multisensory information. The neurophysiological data suggest that deficits in ASD emerge in attentional selection and resource allocation processes related to occipito-parietal and middle frontal regions. Most importantly, conflict monitoring subprocesses during RI were specifically modulated by content of multisensory information in the superior frontal gyrus. Conclusions. RI processes are overstrained in adolescent ASD, especially when conflicting multisensory information has to be integrated to perform RI. It seems that the content of multisensory input is important to consider in ASD and its effects on cognitive control processes.

Background: Background of this work was the investigation of the endocannabinoid system (ECS) in the Fmr1 knock- out (KO) mouse. The Fmr1- KO mouse is a mouse model for fragile X syndrome (FXS). FXS is the leading monogenic cause for autism spectrum disorders (ASD) in humans. The Fmr1- KO mouse displays autistic behavior such as an impaired social interaction, repetitive behavior, cognitive deficits, increased anxiety and aggressiveness. Alterations of the ECS have been suggested to play a key role in the etiopathology of a variety of neuropsychiatric disorders. Until today, little has been described about the involvement of the ECS in ASD. Interrogation: 1. Evaluating the manifestation of typical cannabinoid- induced effects in the Fmr1- KO mouse 2. Investigating the influenceability of autistic symptoms with THC treatment in the Fmr1- KO mouse 3. Analyzing the signaling cascade of the stimulated and unstimulated ECS in different brain regions of the Fmr1- KO mouse Material and Methods: Experiments were carried out on adult (12±1 weeks old) male Fmr1- KO and Fmr1- wild- type (WT) mice from the C57BL/6J- (B6)- background. N= 15 mice received THC (10mg/kg bodyweight) and N= 16 received WIN55,212 (3mg/kg bodyweight). 30min after injection, the body temperature was measured and the distance animals moved in an open field during 15min was recorded (locomotion). Then, animals were placed with their forepaws onto a horizontally fixed bar and the time remaining in this position (catalepsy) was measured. Finally animals were placed on a preheated plate and the temperature at which a pain stimulus occurred was determined (testing analgesia). All 4 experiments are called tetrad experiment. Afterwards changes in body temperature, locomotion, catalepsy and analgesia of the animals was evaluated. To explore long-term effects of THC after the tetrad, N= 15 animals were tested in a social interaction test with a female contact mouse, 10 and 20 days after THC treatment. Therefore, the tested mouse and the contact mouse were placed together into a cage and the time mice spent in social interaction (nose, body and anogential sniffing, allogrooming and body contact) was manually quantified during 6min of recorded testing time. Another group of N= 19 received a premedication of rimonabant (Cannabinoid- receptor 1 (CB1) antagonist, 3mg/kg bodyweight) 30min prior to THC treatment. Rimonabant prevents THC from binding to CB1 and therefore allows the assessment of the involvement of CB1 in mediating social behavior. Furthermore the suggestibility of context-dependent fear conditioning with THC treatment has been tested on N= 13 mice. Animals were placed into a conditioning chamber that delivered 6 short electric shocks with a 30sec pause to their paws (conditioning phase). Immediately afterwards mice received THC or placebo. 24h later contextdependent fear was evaluated by quantification of the time mice spent freezing in the conditioning-chamber (fear) without receiving foot shocks. Intraneuronal signaling of the ECS was analyzed with N= 29 animals using western blots. Quantities of phosphorylated (“activated”) protein kinases (ERK, AKT and S6) from different brain homogenates (hippocampus, striatum, cortex and cerebellum) were therefore measured after THC or placebo injection (30 minutes prior to sacrificing). Results: Cannabinoids induced hypothermia, hypolocomotion, analgesia and catalepsy in WTmice. These effects were significantly less detectable in Fmr1- KO mice. Effects of both cannabinoids, THC and WIN55,212, were comparable with a slightly greater but not significant efficiency of THC. THC treated WT- mice exhibited further reduced social interaction 10 days after treatment, an effect that was partially prevented by premedication with rimonabant. THC increased social interaction in Fmr1- KO mice comparable to the level of untreated WT- mice. THC had no effect on behavior of WT- mice in context-dependent fear conditioning. Fmr1- KO mice showed significant less contextdependent fear conditioning compared to WT- mice. THC facilitated the recognition of an anxiety-correlated context in Fmr1- KO mice comparable to untreated WT- mice. In western blots significant changes in the THC- induced signaling cascade were detectable and depending on genotype, brain-region and analyzed protein-kinase. In the hippocampus there were no changes in untreated Fmr1- KO mice compared to WT- mice. THC had no effect on activation of protein-kinases in WT- and Fmr1- KO mice. In the striatum there were no changes in untreated Fmr1- KO mice compared to WTmice. THC significantly increased activity of ERK, AKT and S6 in WT-mice and not in Fmr1- KO mice. In the cortex of untreated Fmr1- KO mice AKT showed a significantly increased activity compared to WT- mice. THC significantly increased AKT activity in WT- mice without having an effect on KO- mice. In the cerebellum there were no changes in untreated Fmr1- KO mice compared to WT- mice. THC significantly increased ERK- activity in Fmr1- KO mice but had no effect on protein kinase activity in WT- mice. Conclusion: We observed physiological cannabinoid effects in WT- mice after treatment with THC and WIN55,212. These effects are significantly attenuated in Fmr1- KO mice. This may be interpreted as a desensitization of the ECS in the Fmr1- KO mouse. At the same time it was demonstrated that THC has the potential to improve context dependent memory consolidation and to increase social interaction in the Fmr1- KO mouse. In particular the influence of THC on impaired social interaction should be a target of further investigations to find possible therapeutic options for this typical symptom of Autism. Underlying molecular mechanisms remain unclear and the analysis of THC stimulated intraneuronal signaling gave no clear indication of possible molecular alterations in the Fmr1- KO mouse.

Diese qualitative Studie untersucht den schulischen Alltag von drei Jungen mit Fragilem-X- Syndrom. Das Fragile-X-Syndrom ist die häufigste bekannte erbliche Ursache von geistiger Behinderung und wird mit einer Reihe von charakteristischen Eigenschaften assoziiert. Dazu zählen vor allem physische, kognitive und psychosoziale Merkmale. Mithilfe der Ethnografie mit teilnehmender Beobachtung im schulischen Umfeld der Schüler werden die Bedingungen herausgearbeitet, die das Fragile-X-Syndrom der Schüler „sichtbar“ machen. Diese Bedingungen sind vor allem durch den jeweiligen Kontext geprägt, welcher sich aus dem Ausmaß der Hilfestellungen, der Struktur der Anforderungen und der räumlichen und organisatorischen Gestaltung der Umgebung zusammensetzt. Menschen mit Fragilem-X-Syndrom dürfen nicht nur als Träger eines genetischen Syndroms angesehen werden, sondern auch als Mitglieder sozialer Gruppen und Gemeinschaften, an deren immanenten Regeln sie ihr Handeln ausrichten. Die institutionellen und sozialen Bedingungen auf der Ebene des Klassenraums mit seinen jeweiligen Teilnehmerinnen und Teilnehmern bilden die Grundlage für eine soziale Konstruktion des Fragilen-X- Syndroms in der Schule. Diese Annahme ist die Voraussetzung für einen Verstehensprozess, der das Syndrom nicht nur als Ursache einer Behinderung ansieht, sondern vielmehr die Handlungen und performativen Äußerungen der Schüler als individuellen, kompetenten Teil ihrer Kommunikation deutet. Das gegenseitige Verstehen führt dazu, dass die Bedingungen des Fragilen-X-Syndroms, der Verhaltensphänotyp des Schülers sowie die jeweilige soziale Umgebung, in einen angemessenen Kontext gesetzt werden können. Erst dadurch kann der Schulalltag erfolgreich gestaltet und ein Scheitern des Schülers minimiert werden. / This qualitative research project examines the everyday life of three boys with Fragile X syndrome in their special education classrooms. Fragile X syndrome is the leading inherited cause of intellectual disability and is associated with a specific behavioral phenotype and cognitive and physical characteristics. Utilizing ethnographic participant observation, the specific context in which the Fragile X syndrome becomes “visible” will be analyzed. This context is mainly shaped by the institutional and social conditions on the level of the classroom with its participants (peers and educators). Individuals with Fragile X syndrome need to be viewed not only as living under a genetic condition, but as members of social groups and communities who act in relation to socially and culturally ordered expectations. The understanding of the students’ performative acts as part of their communication abilities can initiate the understanding of the behavioral phenotype within its context. This understanding of Fragile X syndrome as a social category may lead to a successful organization of everyday school life.

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.

Kommunikation ist allgegenwärtig in unserem Alltag. Personen mit einer Autismus-Spektrum-Störung (ASS) zeigen soziale Schwierigkeiten und beim Erkennen von Kommunikationssignalen von Gesicht und Stimme. Da derartige Schwierigkeiten die Lebensqualität beeinträchtigen können, ist ein tiefgreifendes Verständnis der zugrundeliegenden Mechanismen von großer Bedeutung. In der vorliegenden Dissertation befasste ich mich mit sensorischen Gehirnmechanismen, die der Verarbeitung von Kommunikationssignalen zugrunde liegen und, die in der Forschung zu ASS bisher wenig Beachtung fanden. Erstens untersuchte ich, ob eine intranasale Gabe von Oxytocin die Erkennung der Stimmenidentität beeinflussen, und ihre Auffälligkeiten bei Personen mit ASS mildern kann. Zweitens erforschte ich, welche neuronalen Prozesse den Schwierigkeiten in der Wahrnehmung visueller Sprache in ASS zugrunde liegen, da bisherige Evidenz nur auf Verhaltensdaten basierte. Diese Fragestellungen beantwortete ich mit Hilfe von funktioneller Magnetresonanztomographie, Eyetracking und Verhaltenstestungen. Die Ergebnisse der Dissertation liefern neuartige Erkenntnisse, die für Personen mit ASS und typisch entwickelte Personen von hoher Relevanz sind. Erstens bestätigen sie die Annahmen, dass atypische sensorische Mechanismen für unser Verständnis der sozialen Schwierigkeiten in ASS grundlegend sind. Sie zeigen, dass atypische Funktionen sensorischer Gehirnregionen den Kommunikationseinschränkungen in ASS zugrunde liegen und die Effektivität von Interventionen beeinflussen, die jene Schwierigkeiten vermindern sollen. Zweitens liefern die Ergebnisse empirische Evidenz für theoretische Annahmen darüber, wie das typisch entwickelte Gehirn visuelle Kommunikationssignale verarbeitet. Diese Erkenntnisse erweitern maßgeblich unser aktuelles Wissen und zukünftige Forschungsansätze zur zwischenmenschlichen Kommunikation. Außerdem können sie neue Interventionsansätze zur Förderung von Kommunikationsfähigkeiten hervorbringen. / Communication is ubiquitous in our everyday life. Yet, individuals with autism spectrum disorder (ASD) have difficulties in social interactions and to recognize socially relevant signals from the face and the voice. Such impairments can vastly affect the quality of life - a profound understanding of the mechanisms behind these difficulties is thus strongly required. In the current dissertation, I focused on sensory brain mechanisms that underlie the perception of emotionally neutral communication signals that so far have gained little attention in ASD research. I studied the malleability of voice-identity processing using intranasal administration of oxytocin, and thus the potential to alleviate voice-identity recognition impairments in ASD. Furthermore, I investigated brain mechanisms that underlie recognition difficulties for visual speech in ASD, as until now evidence on visual-speech recognition in ASD was limited to behavioral findings. I applied methods of functional magnetic resonance imaging, eye tracking, and behavioral testing. The contribution of the present dissertation is twofold. First, the findings corroborate the view that atypical sensory perception is a critical cornerstone for understanding of social difficulties in ASD. Dysfunction of visual and auditory sensory brain regions might contribute to difficulties in processing aspects of communication signals in ASD and modulate the efficacy of interventions for improving the behavioral deficits. Second, the findings deliver empirical support for a recent theoretical model of how the typically developing brain perceives dynamic faces. This improved our current knowledge about brain processing of visual communication signals in the typically developing population. Advanced scientific knowledge about human communication, as provided in the current dissertation, propels further empirical research and development of clinical interventions that aim to promote communication abilities in affected individuals.

Autism spectrum disorder (ASD) is characterised by social communication difficulties. These difficulties have been mainly explained by cognitive, motivational, and emotional alterations in ASD. The communication difficulties could, however, also be associated with altered sensory processing of communication signals. Here, we assessed the functional integrity of auditory sensory pathway nuclei in ASD in three independent functional magnetic resonance imaging experiments. We focused on two aspects of auditory communication that are impaired in ASD: voice identity perception, and recognising speech-in-noise. We found reduced processing in adults with ASD as compared to typically developed control groups (pairwise matched on sex, age, and full-scale IQ) in the central midbrain structure of the auditory pathway (inferior colliculus [IC]). The right IC responded less in the ASD as compared to the control group for voice identity, in contrast to speech recognition. The right IC also responded less in the ASD as compared to the control group when passively listening to vocal in contrast to non-vocal sounds. Within the control group, the left and right IC responded more when recognising speech-in-noise as compared to when recognising speech without additional noise. In the ASD group, this was only the case in the left, but not the right IC. The results show that communication signal processing in ASD is associated with reduced subcortical sensory functioning in the midbrain. The results highlight the importance of considering sensory processing alterations in explaining communication difficulties, which are at the core of ASD.