Abstract
The sense of smell is vital for species survival in terms of food selection and detection as well as procreation. Disorders of the sense of smell are not uncommon and can have a significant effect on general health and well-being including quality of life. In Parkinson's disease (PD), the loss of sense of smell is one of the most common and earliest symptoms, appearing approximately 5 years prior to any motor symptoms. Deep brain stimulation (DBS) has proven remarkably effective in alleviating the symptoms of PD including olfactory dysfunction. This remains a difficult area to research with many unknowns, not only the normal spatiotemporal processing of olfaction in humans, but also the mechanisms underlying the dysfunction in PD and the alleviation by DBS.
This thesis aims to address these difficulties by developing the necessary tools to be able to study spatiotemporal aspects of olfactory function in PD patients with DBS. The first two studies in this dissertation are reviews of the olfactory system and one of its most vital roles in eating behaviour. These studies indicate the extent of the olfactory system in terms of anatomy and implication in certain behaviours. In the third study the long-term effects of DBS for PD are investigated. The results show that after five months of continuous DBS, olfactory areas known to be affected in PD show significant structural changes. The fourth study uses advanced whole-brain computational modeling to uncover the mechanisms of continuous DBS of the subthalamic nucleus which leads to significant changes in brain regions including the thalamus, suggestive of long-term Hebbian long-term structural changes. In the fifth study, I return to olfaction to explore a new paradigm regarding the use of magnetoencephalography (MEG) to investigate the spatiotemporal aspects of olfactory functioning in healthy subjects. The results show significant differences between pleasant and unpleasant odours in the orbitofrontal cortex early after stimulus onset. This novel paradigm indicates the possibility to unravel the spatiotemporal aspects of normal olfaction as well as the underlying mechanisms of olfactory dysfunction in PD patients with DBS, where magnetic imaging techniques are not readily available due to the severe risk related to the electrodes.
This thesis aims to address these difficulties by developing the necessary tools to be able to study spatiotemporal aspects of olfactory function in PD patients with DBS. The first two studies in this dissertation are reviews of the olfactory system and one of its most vital roles in eating behaviour. These studies indicate the extent of the olfactory system in terms of anatomy and implication in certain behaviours. In the third study the long-term effects of DBS for PD are investigated. The results show that after five months of continuous DBS, olfactory areas known to be affected in PD show significant structural changes. The fourth study uses advanced whole-brain computational modeling to uncover the mechanisms of continuous DBS of the subthalamic nucleus which leads to significant changes in brain regions including the thalamus, suggestive of long-term Hebbian long-term structural changes. In the fifth study, I return to olfaction to explore a new paradigm regarding the use of magnetoencephalography (MEG) to investigate the spatiotemporal aspects of olfactory functioning in healthy subjects. The results show significant differences between pleasant and unpleasant odours in the orbitofrontal cortex early after stimulus onset. This novel paradigm indicates the possibility to unravel the spatiotemporal aspects of normal olfaction as well as the underlying mechanisms of olfactory dysfunction in PD patients with DBS, where magnetic imaging techniques are not readily available due to the severe risk related to the electrodes.
| Original language | English |
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| Number of pages | 158 |
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| Publication status | Published - Aug 2014 |