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Pathophysiology of narcolepsy - a multimodal approach

English title Pathophysiology of narcolepsy - a multimodal approach
Applicant Bassetti Claudio L.
Number 118272
Funding scheme Project funding (Div. I-III)
Research institution Neurologische Klinik Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Neurology, Psychiatry
Start/End 01.11.2007 - 31.07.2009
Approved amount 141'667.00
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Keywords (8)

narcolepsy; cataplexy; emotions; amygdala; hypothalamus; emotional learning; motor control; REM-sleep

Lay Summary (English)

Lead
Lay summary
Narcolepsy is a chronic sleep-wake disorder characterized by excessive daytime sleepiness, cataplexy and other rapid-eye movement (REM) sleep associated symptoms. Narcolepsy is thought to be caused by a destruction of hypocretin/orexin neurons, which are located in the hypothalamus. The hypothalamus is an integrative centre in the brain that mediates a number of basic functions such as energy homeostasis, feeding, sleep-wake regulation, and motivation. Cataplexy refers to a sudden bilateral loss of muscle tone triggered by emotions. The most commonly involved emotions are laughing, excitement, surprise, fear, and embarrassment. The mechanisms of how emotions induce a transient loss of muscle tone are not well understood. Our previous data using functional magnetic resonance (fMRI) and electrophysiology suggest amygdala dysfunction in narcoleptic patients. The amygdalae represent groups of neurons located deep in the brain which are primarily involved in emotional processing and emotional memory. To further investigate the role of emotional memory in NC and to see how impaired amygdala functioning affects motor activity we plan to perform two experiments. In the first experiment we use aversive conditioning to test whether hypocretin-deficient narcolepsy-cataplexy (NC) patients might fail to show associative emotional learning. The lack of emotional learning in NC patients would fit animal models of hypocretin function in learning. To assess the association between emotional learning and physiological body functions we plan to collect measures of autonomic function including heart rate, skin conductions and pupil diameter. In the second experiment we apply an emotional stop-signal task to test the effect of emotions on voluntary motor control. We measure the time needed to stop an initiated motor action under different emotional conditions (neural and fear). This task provides us with the possibility to dissect inhibitory motor control from motor execution and other (unspecific) cognitive functions that critically depend on the speed of reaction time. Both experiments will help to understand the impact of hypothalamic hypocretin deficiency on amygdala activity, emotional modulation of motor control, and emotional learning in narcolepsy-cataplexy
Direct link to Lay Summary Last update: 21.02.2013

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Associated projects

Number Title Start Funding scheme
185362 Swiss Primary Hypersomnolence and Narcolepsy Cohort Study 01.09.2019 Project funding (Div. I-III)
104100 Pathophysiology of narcolepsy - a multimodal approach 01.08.2004 Project funding (Div. I-III)

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