It’s About Understanding the Brain
In this project, we investigate brain function in patients with sleep disorders. The present study is about brain function and structure and their relation to clinical symptoms in adolescents with narcolepsy.
Narcolepsy is characterized by daytime sleep attacks, poor nighttime sleep, and sudden loss of muscle tonus (cataplexy) caused by the loss of certain neurons in the hypothalamus: a central structure in the brain. These neurons produce a specific neurotransmitter called orexin, that takes part in the regulation of sleep and wakefulness, and also body metabolism. Orexin deficiency is therefore one hypothesis behind weight gain at narcolepsy onset.
To investigate the relation between brain function and clinical symptoms in narcolepsy, we use functional MRI (fMRI) and simultaneous electroencephalography (EEG), quantitative MRI and body fat imaging.
Working Memory, Attention and Rest
We have shown that adolescents with narcolepsy have altered resting state brain dynamics. Compared to healthy controls, they are less likely to stay in a specific brain microstate, related to the default mode network, which is active when the brain is at wakeful rest. We concluded that narcolepsy might be accompanied with a disruption in the default mode network that is disease specific. This conclusion was supported by our second study where we investigated working memory function.
Many patients with narcolepsy complain about subjective working memory problems, but research has not found objective evidence. In our study, we neither found signs of working memory performance deficits nor specific brain dysfunction related to working memory. However, we did find an imbalance in cognitive resources manifested by decreased activation of the default mode network. This is pointing to a dysregulation within the sustained attention system, which could be the origin behind self-reported cognitive difficulties in narcolepsy.
Differences in Fat Distribution
Body muscle and fat visualization. The left image shows segmented tight muscles and the right image shows belly fat where inner fat is red and subcutaneous fat is blue.
In line with previous reports we recently showed that that narcolepsy patients had more belly fat compared to their healthy controls (Fig. 1). However, we also found that they had lower ratio between inner fat and total belly fat indicating a relative increase of subcutaneous fat. This relationship between inner and subcutaneous fat has been associated with a lower risk for metabolic disease.
Quantitative MRI of the Brain Stem
Structural anomaly in the brain stem's reticular formation in narcolepsy. A) Lower R2 in the brain stem in narcolepsy. B) Mean R2 in all participants. C) Average difference in R2 between narcolepsy patients and healthy peers. D) The significance of the R2 difference. E) Functional connectivity related to the orexin network.
Preliminary data (submitted manuscript) from quantitative MRI show structural changes in the brain stem's reticular formation in patients with narcolepsy. Figures 2A–D show areas with lower R2 relaxation rate, a finding that could be related to lower levels of neuromelanin in the locus coeruleus of narcolepsy patients. We also observed that the R2 deviant region was functionally connected to the cerebellum and the thalamus together with other subcortical areas involved in the orexin network (Fig. 2E).