Abstract
The human cerebellum is one of the earliest brain regions to develop, but continues to grow until late adolescence and adulthood. This makes it especially vulnerable for disorder and disease, specifically affecting neurodevelopmental disorders such as obsessive compulsive disorder (OCD) and autism spectrum disorder (ASD). Cerebellocortical loops further allow the cerebellum to interact with the neocortex, enabling changes in the cerebellum to influence cortical structures.This thesis aimed to identify cerebellar and neurocognitive mechanisms modifying (1) typical and (2) abnormal cerebellar growth and brain development. The first aim has been addressed in a series of two studies, exploring plastic changes in cerebellar and cortical functional connectivity (Chapter 2.1), volume, shape and white matter microstructure (Chapter 2.2) in healthy adolescents after learning to drum for 8 weeks. In order to explore distinct and shared cerebellar contributions to abnormal brain development, the role of the cerebellum and brainstem to classify adult and paediatric ASD was studied (Chapter 3.1); the reshaping of cerebellar and brainstem vertex (Chapter 3.2) and neocortical thickness and surface area (Chapter 3.3) with repetitive behaviours and symptom severity was explored in paediatric ASD and OCD. As compulsive and repetitive behaviours are one of the main measurements assessing diagnostic features in psychiatric animal models, distinct brain-behaviour correlates for OCD-phenotypical compulsive and anxious behaviours were studied in context of cerebellar insulin regulation in a mouse model of diabetes mellitus (Chapter 4). The data provided underline the cerebellum’s central role in neurocognitive mechanisms and functions important for neurotypical development and functioning. While abnormal cerebellar development co-occurs with neocortical dysfunction and has been connected to a range of childhood disorders, its plastic changes to complex skill learning during adolescence also co-occur with neocortical functional and structural changes. This opens up an opportunity of the cerebellum as a target for possible early intervention for childhood disorders.
Date of Award | 29 Aug 2018 |
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Original language | English |
Awarding Institution |
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Supervisor | Steven Williams (Supervisor), Ali Amad (Supervisor) & Christine Ecker (Supervisor) |