Resting state functional connectivity in primary insomnia, generalized anxiety disorder and controls

Abstract

Sleep abnormalities are extremely common in anxiety disorders and may contribute to their development and persistence. Their shared pathophysiological mechanisms could thus serve as biomarkers or targets for novel therapeutics. Individuals with Primary Insomnia were age- and sex-matched to controls and to persons with Generalized Anxiety Disorder. All underwent fMRI resting-state scans at 3-T. In Primary Insomnia and controls, sleep was recorded for 2 weeks using diaries and actigraphy. All participants completed state-anxiety and neuroticism inventories. Whole-brain connectivity of 6 fear- and extinction-related seeds were compared between the 3 groups using ANOVA. The only significant between-group main effect was seen for connectivity between the left amygdala seed and a bilateral cluster in the rostral anterior cingulate cortex. The latter is believed to exert top-down control over amygdala activity and their interaction may thus constitute an emotion regulatory circuit. This connectivity was significantly greatest in controls while Primary Insomnia was intermediate between that of controls and Generalized Anxiety Disorder. Across Primary Insomnia and control subjects, mean connectivity decreased with poorer sleep. Across all 3 groups, connectivity decreased with greater neuroticism and pre-scan anxiety. Decreased top-down control of the amygdala may increase risk of developing an anxiety disorder with preexisting Primary Insomnia.

Self-Reported Sleep Quality Modulates Amygdala Resting-State Functional Connectivity in Anxiety and Depression

“…That is, more not less coupling between amygdala and sgACC was predicted by worse sleep when controlling for anxiety and depression symptoms. Findings are generally in line with a sleep deprivation resting-state study that reported increased FC between centromedial amygdala and rostral ACC in healthy individuals relative to rested wakefulness ( 65 ) and evidence of increased amygdala-rostral ACC FC in insomnia disorder when compared to generalized anxiety disorder ( 47 ). Notably, primate and effective connectivity studies indicate the amygdala has direct connections to sgACC ( 66 , 67 ), a region implicated in the modulation of emotional behavior ( 68 ) and known to be dysfunctional in IPs [e.g., depression; ( 69 )].…”

“…For example, individuals with insomnia disorder (without concurrent psychiatric illness) exhibit altered rsFC between amygdala and the inferior frontal gyrus, subcortical structures (e.g., caudate, thalamus), temporal, parietal, and occipital regions relative to healthy controls ( 46 ). Also, limited research comparing insomnia disorder to an IP reported relatively more amygdala-rostral anterior cingulate cortex (ACC) rsFC in primary insomnia compared to generalized anxiety disorder ( 47 ). Though findings suggest a compensatory response in insomnia, both groups exhibited less amygdala-rostral ACC coupling than good sleepers signifying diminished top-down control of emotion regulation in these disorders ( 47 ).…”

“…Also, limited research comparing insomnia disorder to an IP reported relatively more amygdala-rostral anterior cingulate cortex (ACC) rsFC in primary insomnia compared to generalized anxiety disorder ( 47 ). Though findings suggest a compensatory response in insomnia, both groups exhibited less amygdala-rostral ACC coupling than good sleepers signifying diminished top-down control of emotion regulation in these disorders ( 47 ). Similar dysfunction has been observed in IPs.…”

Changes in subcortical resting-state functional connectivity in patients with psychophysiological insomnia after cognitive–behavioral therapy

“…Previous studies observed disruptions in FC within the DMN and in regions associated with executive function ( Li et al, 2014 , Nie et al, 2015 ), sensorimotor functions, and limbic regions ( Chen et al, 2014 , Killgore et al, 2013 , Huang et al, 2012 ), supporting previous physiological and emotional arousal findings associated with insomnia patients. A recent study found the resting-state FC between the amygdala and rostral anterior cingulate cortex to be intermediate in patients with primary insomnia compared to those with generalized anxiety disorder and controls, indicating that the emotional circuit is disrupted by insomnia ( Pace-Schott et al, 2017 ). Intrinsic resting-state activity, identified by brain entropy or regional homogeneity analyses, has also been introduced as a variable in insomnia studies, resulting in consistent evidence for hyperarousal in related structures such as the hippocampus, DMN, basal ganglia (BG) ( Zhou et al, 2016 ), and temporal cortex ( Dai et al, 2014 ).…”

Rest but busy: Aberrant resting‐state functional connectivity of triple network model in insomnia

“…Resting‐state fMRI studies of insomnia disorder have highlighted the importance of the salience network in hyperarousal and affective symptoms (Khazaie et al., ). Specifically, researches revealed decreased functional connectivity between the amygdala and insula, striatum, thalamus, and bilateral ACC, and increased functional connectivity between the amygdala and premotor cortex, sensorimotor cortex in patients with primary insomnia, suggesting a potential neurological mechanism for dysfunction of emotional control and affective disorder in insomniacs (Huang et al., ; Pace‐Schott et al., ). Findings from another study showed that activation of the insula within the salience network was increased in insomniacs, which could be indicative of subthreshold anxiety, worry, and rumination (Chen, Chang, Glover, & Gotlib, ).…”