title: Neural correlates and neural stimulation of temporal recalibration mechanisms in sensorimotor and inter-sensory contexts
title: Neurale Korrelate und neurale Stimulation von zeitlichen Rekalibrierungsmechanismen in sensomotorischen und inter-sensorischen Kontexten
titleType: AlternativeTitle
Creators: name: Schmitter, Christina Victoria
Publisher: name: Philipps-Universität Marburg
Year: 2024
Subjects: schizophrenia
cerebellum
Medical sciences Medicine
Medizin
fMRI
temporal recalibration
tDCS
sensorimotor adaptation

description: The sensory outcomes of our actions typically follow at a characteristic, predictable time shortly after the action. Predictions about sensory action-outcomes and their timing are believed to be generated by internal forward models based on the actions’ motor commands. The comparison between predictions and re-afferent sensory feedback helps distinguish self- from externally generated sensory input. Importantly, in the complex and dynamically changing environment we can be exposed to, and must be able to adapt to, varying delays between our actions and the corresponding sensory outcomes. Therefore, forward models need to be capable of flexibly recalibrating their predictions to account for additional action-outcome delays and thereby maintain our ability of self-other distinction. This process, known as sensorimotor temporal recalibration, has been linked to neural processing in various brain regions, most prominently to the cerebellum. However, until now, it remains unclear whether the neural correlates associated with the adaptation to action-outcome delays can indeed be attributed to the recalibration of forward model predictions, or whether they may partially be explained by the recalibration of the expected inter-sensory timing, such as the timing between the tactile sensations during the movement and a visual or auditory sensory outcome. Moreover, while impairments in self-other distinction in patients with schizophrenia spectrum disorders (SSD) have often been linked to dysfunctional predictive mechanisms of the forward model, it remains elusive whether this could be partly due to the dysfunctional recalibration of these predictions to changing environmental conditions.
 In this dissertation, three studies were conducted to fill these knowledge gaps. Firstly, the neural correlates of sensorimotor temporal recalibration were investigated using functional magnetic resonance imaging (fMRI) by controlling for the impact of inter-sensory temporal recalibration mechanisms (study I). It was further assessed whether transcranial direct current stimulation (tDCS) applied to the cerebellum can modulate temporal recalibration effects (study II). Additionally, this research aimed to investigate whether tDCS can be used to facilitate potentially impaired sensorimotor temporal recalibration mechanisms in SSD (study III).
 In all studies, a temporal recalibration paradigm was applied which exposed subjects to delayed or undelayed visual or auditory outcomes elicited by actively performed (sensorimotor context) or passively induced (inter-sensory context) button press movements. The effects of this adaptation procedure on subjects’ temporal perception were tested in a subsequent delay detection task. This paradigm was applied in healthy subjects during fMRI data acquisition (study I) and with different configurations of cerebellar tDCS (study II). Furthermore, it was applied in patients with SSD and matched healthy control subjects while they received anodal tDCS of the bilateral cerebellum, right temporo-parietal junction, or right supplementary motor area 
(study III).
 The findings of study I demonstrated important contributions of the hippocampus and the cerebellum to temporal recalibration. As both regions were engaged across active and passive movement conditions, they may play a general role in responding to violations of the expected inter-sensory stimulus timing, regardless of the involvement of forward model predictions. Importantly, the availability of forward model predictions also had an influence on neural processing by differentially modulating the activity pattern in frontal, sensory, and posterior cerebellar regions in sensorimotor and inter-sensory contexts. These findings were further supported by study II, which showed that anodal stimulation of the cerebellum via tDCS had a faciliatory impact on temporal recalibration, and this effect manifested differently in inter-sensory and sensorimotor contexts. Finally, the results of study III demonstrated similar sensorimotor temporal recalibration effects in patients with SSD and healthy control subjects and emphasized again that anodal cerebellar tDCS holds the potential to facilitate temporal recalibration mechanisms, specifically in the sensorimotor context.
 This dissertation shows for the first time that, in addition to the cerebellum, the hippocampus plays a critical role in temporal recalibration in both sensorimotor and inter-sensory contexts, potentially by encoding and retrieving the newly learned inter-sensory temporal stimulus associations. It also extends previous research by demonstrating that recalibration-related processes in a range of brain regions, including parts of the cerebellum as well as frontal and sensory processing regions, may depend on whether forward model predictions contribute to recalibration or whether it solely relies on inter-sensory recalibration mechanisms. Finally, the comparable effects of temporal recalibration for both patients and healthy subjects indicate that sensorimotor temporal recalibration mechanisms may be preserved in SSD. The faciliatory impact that cerebellar tDCS had not only on healthy subjects but also on patients further confirms the importance of the cerebellum in temporal recalibration. It also suggests that cerebellar tDCS may be an interesting tool for future research to mitigate known deficits in forward model-based prediction mechanisms in the cerebellum in SSD, even though these deficits may not be explained by the dysfunctional temporal recalibration of these predictions. 
Taken together, the findings of this dissertation contribute to a more advanced understanding of the neural correlates of sensorimotor and inter-sensory temporal recalibration mechanisms and provide new insights into the benefits of cerebellar tDCS to promote these mechanisms in healthy subjects and patients with SSD.