Below the surface
Authors:   , Bresser Tom 
Published: May 2024

Insomnia disorder is a common and complex mental health problem that also is a risk factor for the development of major depressive disorder. Despite its high prevalence, the neurobiological mechanism underlying insomnia disorder remains elusive. Advancing our understanding of the mechanisms could ultimately contribute to the development of more effective treatments. White matter, comprising myelinated axons, connects brain regions into functional brain circuits. Investigating deviations in people with insomnia could advance our understanding of the brain circuits involved in the disorder. This thesis examined the role of white matter in insomnia disorder and its ensuing risk of depression.
In Chapter 2, a comparative analysis of whole-brain structural connectivity revealed hyperconnectivity within a subnetwork anchored at the right angular gyrus. This subnetwork overlapped with multiple resting-state functional networks, including the frontoparietal control network, cinguloopercular network, default-mode network, and right-lateralized ventral attention network. Furthermore, connectivity strength within this subnetwork correlated with reactive hyperarousal, a key insomnia symptom. Chapter 3 delves into white matter microstructure, focusing on fractional anisotropy (FA) in the anterior limb of the internal capsule. Using data from three independent studies, lower FA in the right internal capsule was replicated in insomnia patients. In addition, correlation analysis showed more severe insomnia symptoms in people with a lower fractional anisotropy in the right internal capsule. Exploratory whole brain analysis did not detect additional spatial clusters where fractional anisotropy was significantly associated with insomnia or insomnia severity. Chapter 4 uses longitudinal data from a randomized controlled trial on insomnia interventions to determine if deviations in white matter microstructure precede insomnia or follow as a consequence. Results indicated that lower FA in the left retrolenticular part of the internal capsule at baseline predicted worse progression of depressive symptoms in untreated participants and a more pronounced alleviation of symptoms in treated participants. Additionally, combined cognitive behavioral therapy for insomnia with circadian rhythm support led to a small decrease in mean diffusivity in the right superior corona radiata. Across all participants, changes in mean diffusivity in this white matter tract correlated with changes in insomnia severity. Chapter 5 investigates the heterogeneity within insomnia disorder by examining structural connectivity in different insomnia subtypes. The study showed different patterns of deviating structural connectivity in subtypes, predominantly in the ventral attention network, limbic network, and default mode network. Subtype connectivity deviation profiles differed significantly compared to random subsamples of the entire insomnia group disregarding subtype. This study provided the first indication that insomnia subtypes show different profiles of altered structural connectivity.
In conclusion, the research in this thesis shows that insomnia disorder is linked to altered structural connectivity, particularly in frontal-subcortical circuits and networks related to limbic network, default mode network, and salience network. The diverging patterns in structural connectivity deviations between different insomnia subtypes highlight the possibility of multiple neural correlates contributing to the same single diagnostic label. Future research will benefit from larger samples, deeper phenotyping, examining dysfunctional brain networks, and advanced neuroimaging methods to further disentangle the neural correlates underlying insomnia disorder.