Cerebral electrometabolic coupling in disordered and normal states of consciousness.

We assess cerebral integrity with cortical and subcortical FDG-PET and cortical electroencephalography (EEG) within the mesocircuit model framework in patients with disorders of consciousness (DoCs). The mesocircuit hypothesis proposes that subcortical activation facilitates cortical function. We find that the metabolic balance of subcortical mesocircuit areas is informative for diagnosis and is associated with four EEG-based power spectral density patterns, cortical metabolism, and α power in healthy controls and patients with a DoC. Last, regional electrometabolic coupling at the cortical level can be identified in the θ and α ranges, showing positive and negative relations with glucose uptake, respectively. This relation is inverted in patients with a DoC, potentially related to altered orchestration of neural activity, and may underlie suboptimal excitability states in patients with a DoC. By understanding the neurobiological basis of the pathophysiology underlying DoCs, we foresee translational value for diagnosis and treatment of patients with a DoC.

Sleep and Circadian Disturbance in Disorders of Consciousness: Current Methods and the Way towards Clinical Implementation.

The investigation of sleep in disorders of consciousness (DoC) has shown promising diagnostic and prognostic results. However, the methods employed in this field of research are diverse. This leads to confusion in the way forward for both scientific and clinical purposes. We review the literature that has investigated sleep in DoC patients and specifically outline the methodologies used next to the presented results. We highlight what knowledge we currently have and where increased efforts are needed before further clinical implementation. Specifically, the review shows that successful methods may employ a two-stage approach to sleep scoring, where one is the application of loosened standard criteria and the other a more general factor describing closeness of the electroencephalography to a healthy pattern, including a score that describes the extent to which sleep scoring criteria can be applied. This should be performed as part of a multimodal approach that also includes investigations of eye-opening/closure and that of circadian (24-hour) rhythmicity. Taken together, this puts the most promising methodologies in the field together for a comprehensive investigation. Large-scale approaches, incorporating multiple modalities and looking at individual variation, are now needed to advance our understanding of sleep in DoC and its role in diagnosis, treatment, and recovery.

Treating Insomnia with High Risk of Depression Using Therapist-Guided Digital Cognitive, Behavioral, and Circadian Rhythm Support Interventions to Prevent Worsening of Depressive Symptoms: A Randomized Controlled Trial.

INTRODUCTION: The global disease burden of major depressive disorder urgently requires prevention in high-risk individuals, such as recently discovered insomnia subtypes. Previous studies targeting insomnia with fully automated eHealth interventions to prevent depression are inconclusive: dropout was high and likely biased, and depressive symptoms in untreated participants on average improved rather than worsened. OBJECTIVE: This randomized controlled trial aimed to efficiently prevent the worsening of depressive symptoms by selecting insomnia subtypes at high risk of depression for internet-based circadian rhythm support (CRS), cognitive behavioral therapy for insomnia (CBT-I), or their combination (CBT-I+CRS), with online therapist guidance to promote adherence. METHODS: Participants with an insomnia disorder subtype conveying an increased risk of depression (n = 132) were randomized to no treatment (NT), CRS, CBT-I, or CBT-I+CRS. The Inventory of Depressive Symptomatology - Self Report (IDS-SR) was self-administered at baseline and at four follow-ups spanning 1 year. RESULTS: Without treatment, depressive symptoms indeed worsened (d = 0.28, p = 0.041) in high-risk insomnia, but not in a reference group with low-risk insomnia. Therapist-guided CBT-I and CBT-I+CRS reduced IDS-SR ratings across all follow-up assessments (respectively, d = -0.80, p = 0.001; d = -0.95, p < 0.001). Only CBT-I+CRS reduced the 1-year incidence of clinically meaningful worsening (p = 0.002). Dropout during therapist-guided interventions was very low (8%) compared to previous automated interventions (57-62%). CONCLUSIONS: The findings tentatively suggest that the efficiency of population-wide preventive strategies could benefit from the possibility to select insomnia subtypes at high risk of developing depression for therapist-guided digital CBT-I+CRS. This treatment may provide effective long-term prevention of worsening of depressive symptoms. TRIAL REGISTRATION: the Netherlands Trial Register (NL7359).