Functional reorganization in obstructive sleep apnoea and insomnia: A systematic review of the resting-state fMRI

Abstract

Functional neuroimaging techniques have accelerated progress in the study of sleep disorders. Considering the striking prevalence of these disorders in the general population, however, as well as their strong bidirectional relationship with major neuropsychiatric disorders, including major depressive disorder, their numbers are still surprisingly low. This review examines the contribution of resting state functional MRI to current understanding of two major sleep disorders, insomnia disorder and obstructive sleep apnoea. An attempt is made to learn from parallels of previous resting state functional neuroimaging findings in major depressive disorder. Moreover, shared connectivity biomarkers are suggested for each of the sleep disorders. Taken together, despite some inconsistencies, the synthesis of findings to date highlights the importance of the salience network in hyperarousal and affective symptoms in insomnia. Conversely, dysfunctional connectivity of the posterior default mode network appears to underlie cognitive and depressive symptoms of obstructive sleep apnoea.

Keywords: Insomnia disorder; Major depressive disorder; Obstructive sleep apnea; Resting-state fMRI; Sleep disorders.

Fig 1

Short description of the most important analyses method for investigation of resting state functional MRI (rs-fMRI) findings (adapted from Tahmasian et al. (2015a)).

Fig. 2

Paper selection strategy flow chart.

Fig. 3

The schematic presentation of symptoms observed in patients with obstructive sleep apnoea (OSA) and insomnia disorder, and their correlations with the aberrant functional connectivity in hubs of three major intrinsic networks, as suggested by resting state functional MRI (rs-fMRI). Three major intrinsic brain networks are shown (from right to left): The aberrant connectivity of the frontoparietal network (including central executive network (CEN); green) has been linked to severity of OSA. It has key nodes in the dorsolateral prefrontal cortex (DLPFC) and the posterior parietal cortex (PPC). Its major task is in attentional selection of the relevant stimuli, and any disturbance in this network is likely to have a domino effect on other three major intrinsic networks. Its malfunctioning could lead to executive deficits in some patients with OSA. On the other hand, salience signals are integrated in the salience network (blue), which has been affected in both OSA and insomnia. This network has a central role in the detection of behaviorally relevant stimuli and the coordination of neural resources. It includes the insular cortices (IC) and the anterior cingulate cortex (ACC). In OSA, links between this network and increased sympathetic outflow have been reported. Similarly, in insomnia, correlation with hyperarousal and affective symptoms has been suggested. The salience network via IC mediates the ‘switching' between activation of the CEN and final major intrinsic the default-mode network (DMN; yellow) to guide appropriate responses to salient stimuli (adapted from Uddin (2015)). The DMN has key nodes in the posterior cingulate cortex (PCC) and the ventromedial prefrontal cortex (VMPFC). The DMN and CEN support self-related (or internally directed) and goal-oriented (or externally directed) cognition, respectively. In OSA, link between affective and cognitive symptoms (e.g. deficits in working and declarative memory) and aberrant connectivity of the posterior DMN has been shown. In insomnia, in contrast, the connectivity within this network is more closely correlated with objective sleep disturbance parameters. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).

Fig. 4

Comparison of the blueprint fingerprint of within- and between-network connectivity changes in sleep disorders, obstructive sleep apnoea and insomnia disorder, with their major neuropsychiatric comorbidity, major depressive disorder (adapted from (Mulders et al. (2015)). A within-network increase/decrease in connectivity is presented with pink/blue outlines; lines (pink/blue) between networks represent a between-network increase/decrease in connectivity. Grey lines correspond to inconsistent or unclear findings. Black ellipses represent key nodes related to connectivity. Numbers represent main findings previously reported for the major depressive disorder: (1): increase in the anterior DMN connectivity and inclusion of sgACC within the anterior DMN, (2): increased connectivity between the anterior DMN and SN, (3): changed connectivity between the anterior and posterior DMN, (4): decreased connectivity between the posterior DMN and CEN (Mulders et al., 2015). Abbreviations: CEN: central executive network; DMN: default-mode network; MTL: medial temporal lobe; PMC: premotor cortex; SN: salience network; sgACC: subgenual anterior cingulate cortex. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.).