3,112 research outputs found

    Exploring missing heritability in neurodevelopmental disorders:Learning from regulatory elements

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    In this thesis, I aimed to solve part of the missing heritability in neurodevelopmental disorders, using computational approaches. Next to the investigations of a novel epilepsy syndrome and investigations aiming to elucidate the regulation of the gene involved, I investigated and prioritized genomic sequences that have implications in gene regulation during the developmental stages of human brain, with the goal to create an atlas of high confidence non-coding regulatory elements that future studies can assess for genetic variants in genetically unexplained individuals suffering from neurodevelopmental disorders that are of suspected genetic origin

    Gait sonification for rehabilitation: adjusting gait patterns by acoustic transformation of kinematic data

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    To enhance motor learning in both sport and rehabilitation, auditory feedback has emerged as an effective tool. Since it requires less attention than visual feedback and hardly affects the visually dominated orientation in space, it can be used safely and effectively in natural locomotion such as walking. One method for generating acoustic movement feedback is the direct mapping of kinematic data to sound (movement sonification). Using this method in orthopedic gait rehabilitation could make an important contribution to the prevention of falls and secondary diseases. This would not only reduce the individual suffering of the patients, but also medical treatment costs. To determine the possible applications of movement sonification in gait rehabilitation in the context of this work, a new gait sonification method based on inertial sensor technology was developed. Against the background of current scientific findings on sensorimotor function, feedback methods, and gait analysis, three studies published in scientific journals are presented in this thesis: The first study shows the applicability and acceptance of the feedback method in patients undergoing inpatient rehabilitation after unilateral total hip arthroplasty. In addition, the direct effect of gait sonification during ten gait training sessions on the patients’ gait pattern was revealed. In the second study, the immediate follow-up effect of gait sonification on the kinematics of the same patient group is examined at four measurement points after gait training. In this context, a significant influence of sonification on the gait pattern of the patients was shown, which, however, did not meet the previously expected effects. In view of this finding, the effect of the specific sound parameter loudness of gait sonification on the gait of healthy persons was analyzed in a third study. Thus, an impact of asymmetric loudness of gait sonification on the ground contact time could be detected. Considering this cause-effect relationship can be a component in improving gait sonfication in rehabilitation. Overall, the feasibility and effectiveness of movement sonification in gait rehabilitation of patients after unilateral hip arthroplasty becomes evident. The findings thus illustrate the potential of the method to efficiently support orthopedic gait rehabilitation in the future. On the basis of the results presented, this potential can be exploited in particular by an adequate mapping of movement to sound, a systematic modification of selected sound parameters, and a target-group-specific selection of the gait sonification mode. In addition to a detailed investigation of the three factors mentioned above, an optimization and refinement of gait analysis in patients after arthroplasty using inertial sensor technology will be beneficial in the future.Akustisches Feedback kann wirkungsvoll eingesetzt werden, um das Bewegungslernen sowohl im Sport als auch in der Rehabilitation zu erleichtern. Da es weniger Aufmerksamkeit als visuelles Feedback erfordert und die visuell dominierte Orientierung im Raum kaum beeintrĂ€chtigt, kann es wĂ€hrend einer natĂŒrlichen Fortbewegung wie dem Gehen sicher und effektiv genutzt werden. Eine Methode zur Generierung akustischen Bewegungsfeedbacks ist die direkte Abbildung kinematischer Daten auf Sound (Bewegungssonifikation). Ein Einsatz dieser Methode in der orthopĂ€dischen Gangrehabilitation könnte einen wichtigen Beitrag zur PrĂ€vention von StĂŒrzen und Folgeerkrankungen leisten. Neben dem individuellen Leid der Patienten ließen sich so auch medizinische Behandlungskosten erheblich reduzieren. Um im Rahmen dieser Arbeit die Einsatzmöglichkeiten der Bewegungssonifikation in der Gangrehabilitation zu bestimmen, wurde eine neue Gangsonifikationsmethodik auf Basis von Inertialsensorik entwickelt. Zu der entwickelten Methodik werden, vor dem Hintergrund aktueller wissenschaftlicher Erkenntnisse zur Sensomotorik, zu Feedbackmethoden und zur Ganganalyse, in dieser Thesis drei in Fachzeitschriften publizierte Studien vorgestellt. Die erste Studie beschreibt die Anwendbarkeit und Akzeptanz der Feedbackmethode bei Patienten in stationĂ€rer Rehabilitation nach unilateraler HĂŒftendoprothetik. DarĂŒber hinaus wird der direkte Effekt der Gangsonifikation wĂ€hrend eines zehnmaligen Gangtrainings auf das Gangmuster der Patienten deutlich. In der zweiten Studie wird der unmittelbare Nacheffekt der Gangsonifikation auf die Kinematik der gleichen Patientengruppe zu vier Messzeitpunkten nach dem Gangtraining untersucht. In diesem Zusammenhang zeigte sich ein signifikanter Einfluss der Sonifikation auf das Gangbild der Patienten, der allerdings nicht den zuvor erwarteten Effekten entsprach. Aufgrund dieses Ergebnisses wurde in einer dritten Studie die Wirkung des spezifischen Klangparameters LautstĂ€rke der Gangsonifikation auf das Gangbild von gesunden Personen analysiert. Dabei konnte ein Einfluss von asymmetrischer LautstĂ€rke der Gangsonifikation auf die Bodenkontaktzeit nachgewiesen werden. Die BerĂŒcksichtigung dieses Ursache-Wirkungs-Zusammenhangs kann einen Baustein bei der Verbesserung der Gangsonifikation in der Rehabilitation darstellen. Insgesamt wird die Anwendbarkeit und Wirksamkeit von Bewegungssonifikation in der Gangrehabilitation bei Patienten nach unilateraler HĂŒftendoprothetik evident. Die gewonnenen Erkenntnisse verdeutlichen das Potential der Methode, die orthopĂ€dische Gangrehabilitation zukĂŒnftig effizient zu unterstĂŒtzen. Ausschöpfen lĂ€sst sich dieses Potential auf Grundlage der vorgestellten Ergebnisse insbesondere anhand einer adĂ€quaten Zuordnung von Bewegung zu Sound, einer systematischen Modifikation ausgewĂ€hlter Soundparameter sowie einer zielgruppenspezifischen Wahl des Modus der Sonifikation. Neben einer differenzierten Untersuchung der genannten Faktoren, erscheint zukĂŒnftig eine Optimierung und Verfeinerung der Ganganalyse bei Patienten nach Endoprothetik unter Einsatz von Inertialsensorik notwendig

    Neural generators of the frequency-following response elicited to stimuli of low and high frequency: a magnetoencephalographic (MEG) study

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    The frequency-following response (FFR) to periodic complex sounds has gained recent interest in auditory cognitive neuroscience as it captures with great fidelity the tracking accuracy of the periodic sound features in the ascending auditory system. Seminal studies suggested the FFR as a correlate of subcortical sound encoding, yet recent studies aiming to locate its sources challenged this assumption, demonstrating that FFR receives some contribution from the auditory cortex. Based on frequency-specific phase-locking capabilities along the auditory hierarchy, we hypothesized that FFRs to higher frequencies would receive less cortical contribution than those to lower frequencies, hence supporting a major subcortical involvement for these high frequency sounds. Here, we used a magnetoencephalographic (MEG) approach to trace the neural sources of the FFR elicited in healthy adults (N = 19) to low (89 Hz) and high (333 Hz) frequency sounds. FFRs elicited to the high and low frequency sounds were clearly observable on MEG and comparable to those obtained in simultaneous electroencephalographic recordings. Distributed source modeling analyses revealed midbrain, thalamic, and cortical contributions to FFR, arranged in frequency-specific configurations. Our results showed that the main contribution to the highfrequency sound FFR originated in the inferior colliculus and the medial geniculate body of the thalamus, with no significant cortical contribution. In contrast, the low-frequency sound FFR had a major contribution located in the auditory cortices, and also received contributions originating in the midbrain and thalamic structures. These findings support the multiple generator hypothesis of the FFR and are relevant for our understanding of the neural encoding of sounds along the auditory hierarchy, suggesting a hierarchical organization of periodicity encoding

    Principles of generalization for sensorimotor cerebellar learning

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    Linking language and emotion: how emotion is understood in language comprehension, production and prediction using psycholinguistic methods

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    Emotions are an integral part of why and how we use language in everyday life. We communicate our concerns, express our woes, and share our joy through the use of non-verbal and verbal language. Yet there is a limited understanding of when and how emotional language is processed differently to neutral language, or of how emotional information facilitates or inhibits language processing. Indeed, various efforts have been made to bring back emotions into the discipline of psycholinguistics in the last decade. This can be seen in many interdisciplinary models focusing on the role played by emotion in each aspect of linguistic experience. In this thesis, I answer this call and pursue questions that remain unanswered in psycholinguistics regarding its interaction with emotion. The general trend that I am using to bring emotion into psycholinguistic research is straightforward. Where applicable and relevant, I use well-established tasks or paradigms to investigate the effects of emotional content in language processing. Hence, I focused on three main areas of language processing: comprehension, production and prediction. The first experimental chapter includes a series of experiments utilising the Modality Switching Paradigm to investigate whether sentences describing emotional states are processed differently from sentences describing cognitive states. No switching effects were found consistently in my 3 experiments. My results suggest that these distinct classes of interoceptive concepts, such as ‘thinking’ or ‘being happy’, are not processed differently from each other, suggesting that people do not switch attention between different interoceptive systems when comprehending emotional or cognitive sentences. I discuss the implications for grounded cognition theory in the embodiment literature. In my second experimental chapter, I used the Cumulative Semantic Interference Paradigm to investigate these two questions: (1) whether emotion concepts interfere with one another when repeatedly retrieved (emotion label objects), and (2) whether similar interference occurs for concrete objects that share similar valence association (emotion-laden objects). This could indicate that people use information such as valence and arousal to group objects in semantic memory. I found that interference occurs when people retrieve direct emotion labels repeatedly (e.g., “happy” and “sad”) but not when they retrieve the names of concrete objects that have similar emotion connotations (e.g., “puppy” and “rainbow”). I discuss my findings in terms of the different types of information that support representation of abstract vs. concrete concepts. In my final experimental chapter, I used the Visual World Paradigm to investigate whether the emotional state of an agent is used to inform predictions during sentence processing. I found that people do use the description of emotional state of an agent (e.g., “The boy is happy”) to predict the cause of that affective state during sentence processing (e.g., “because he was given an ice-cream”). A key result here is that people were more likely to fixate on the emotionally congruent objects (e.g., ice-cream) compared to incongruent objects (e.g., broccoli). This suggests that people rapidly and automatically inform predictions about upcoming sentence information based on the emotional state of the agent. I discuss our findings as a novel contribution to the Visual World literature. I conducted a diverse set of experiments using a range of established psycholinguistic methods to investigate the roles of emotional information in language processing. I found clear results in the eye-tracking study but inconsistent effects in both switching and interference studies. I interpret these mixed findings in the following way: emotional content does not always have effects in language processing and that effect are most likely in tasks that explicitly require participants to simulate emotion states in some way. Regardless, not only was I successful in finding some novel results by extending previous tasks, but I was also able to show that this is an avenue that can be explored more to advance the affective psycholinguistic field

    Principles of generalization for sensorimotor cerebellar learning

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    Exploring missing heritability in neurodevelopmental disorders:Learning from regulatory elements

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    Neuroimaging investigations of cortical specialisation for different types of semantic knowledge

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    Embodied theories proposed that semantic knowledge is grounded in motor and perceptual experiences. This leads to two questions: (1) whether the neural underpinnings of perception are also necessary for semantic cognition; (2) how do biases towards different sensorimotor experiences cause brain regions to specialise for particular types of semantic information. This thesis tackles these questions in a series of neuroimaging and behavioural investigations. Regarding question 1, strong embodiment theory holds that semantic representation is reenactment of corresponding experiences, and brain regions for perception are necessary for comprehending modality-specific concepts. However, the weak embodiment view argues that reenactment may not be necessary, and areas near to perceiving regions may be sufficient to support semantic representation. In the particular case of motion concepts, lateral occipital temporal cortex (LOTC) has been long identified as an important area, but the roles of its different subregions are still uncertain. Chapter 3 examined how different parts of LOTC reacted to written descriptions of motion and static events, using multiple analysis methods. A series of anterior to posterior sub-regions were analyzed through univariate, multivariate pattern analysis (MVPA), and psychophysical interaction (PPI) analyses. MVPA revealed strongest decoding effects for motion vs. static events in the posterior parts of LOTC, including both visual motion area (V5) and posterior middle temporal gyrus (pMTG). In contrast, only the middle portion of LOTC showed increased activation for motion sentences in univariate analyses. PPI analyses showed increased functional connectivity between posterior LOTC and the multiple demand network for motion events. These findings suggest that posterior LOTC, which overlapped with the motion perception V5 region, is selectively involved in comprehending motion events, while the anterior part of LOTC contributes to general semantic processing. Regarding question 2, the hub-and-spoke theory suggests that anterior temporal lobe (ATL) acts as a hub, using inputs from modality-specific regions to construct multimodal concepts. However, some researchers propose temporal parietal cortex (TPC) as an additional hub, specialised in processing and integrating interaction and contextual information (e.g., for actions and locations). These hypotheses are summarized as the "dual-hub theory" and different aspects of this theory were investigated in in Chapters 4 and 5. Chapter 4 focuses on taxonomic and thematic relations. Taxonomic relations (or categorical relations) occur when two concepts belong to the same category (e.g., ‘dog’ and ‘wolf’ are both canines). In contrast, thematic relations (or associative relations) refer to situations that two concepts co-occur in events or scenes (e.g., ‘dog’ and ‘bone’), focusing on the interaction or association between concepts. Some studies have indicated ATL specialization for taxonomic relations and TPC specialization for thematic relations, but others have reported inconsistent or even converse results. Thus Chapter 4 first conducted an activation likelihood estimation (ALE) meta-analysis of neuroimaging studies contrasting taxonomic and thematic relations. This found that thematic relations reliably engage action and location processing regions (left pMTG and SMG), while taxonomic relations only showed consistent effects in the right occipital lobe. A primed semantic judgement task was then used to test the dual-hub theory’s prediction that taxonomic relations are heavily reliant on colour and shape knowledge, while thematic relations rely on action and location knowledge. This behavioural experiment revealed that action or location priming facilitated thematic relation processing, but colour and shape did not lead to priming effects for taxonomic relations. This indicates that thematic relations rely more on action and location knowledge, which may explain why the preferentially engage TPC, whereas taxonomic relations are not specifically linked to shape and colour features. This may explain why they did not preferentially engage left ATL. Chapter 5 concentrates on event and object concepts. Previous studies suggest ATL specialization for coding similarity of objects’ semantics, and angular gyrus (AG) specialization for sentence and event structure representation. In addition, in neuroimaging studies, event semantics are usually investigated using complex temporally extended stimuli, unlike than the single-concept stimuli used to investigate object semantics. Thus chapter 5 used representational similarity analysis (RSA), univariate analysis, and PPI analysis to explore neural activation patterns for event and object concepts presented as static images. Bilateral AGs encoded semantic similarity for event concepts, with the left AG also coding object similarity. Bilateral ATLs encoded semantic similarity for object concepts but also for events. Left ATL exhibited stronger coding for events than objects. PPI analysis revealed stronger connections between left ATL and right pMTG, and between right AG and bilateral inferior temporal gyrus (ITG) and middle occipital gyrus, for event concepts compared to object concepts. Consistent with the meta-analysis in chapter 4, the results in chapter 5 support the idea of partial specialization in AG for event semantics but do not support ATL specialization for object semantics. In fact, both the meta-analysis and chapter 5 findings suggest greater ATL involvement in coding objects' associations compared to their similarity. To conclude, the thesis provides support for the idea that perceptual brain regions are engaged in conceptual processing, in the case of motion concepts. It also provides evidence for a specialised role for TPC regions in processing thematic relations (pMTG) and event concepts (AG). There was mixed evidence for specialisation within the ATLs and this remains an important target for future research
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