Lack of structural brain alterations associated with insomnia: findings from the ENIGMA-Sleep Working Group.

Existing neuroimaging studies have reported divergent structural alterations in insomnia disorder (ID). In the present study, we performed a large-scale coordinated meta-analysis by pooling structural brain measures from 1085 subjects (mean [SD] age 50.5 [13.9] years, 50.2% female, 17.4% with insomnia) across three international Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA)-Sleep cohorts. Two sites recruited patients with ID/controls: Freiburg (University of Freiburg Medical Center, Freiburg, Germany) 42/43 and KUMS (Kermanshah University of Medical Sciences, Kermanshah, Iran) 42/49, while the Study of Health in Pomerania (SHIP-Trend, University Medicine Greifswald, Greifswald, Germany) recruited population-based individuals with/without insomnia symptoms 75/662. The influence of insomnia on magnetic resonance imaging-based brain morphometry using an insomnia brain score was then assessed. Within each cohort, we used an ordinary least-squares linear regression to investigate the link between the individual regional cortical and subcortical volumes and the presence of insomnia symptoms. Then, we performed a fixed-effects meta-analysis across cohorts based on the first-level results. For the insomnia brain score, weighted logistic ridge regression was performed on one sample (Freiburg), which separated patients with ID from controls to train a model based on the segmentation measurements. Afterward, the insomnia brain scores were validated using the other two samples. The model was used to predict the log-odds of the subjects with insomnia given individual insomnia-related brain atrophy. After adjusting for multiple comparisons, we did not detect any significant associations between insomnia symptoms and cortical or subcortical volumes, nor could we identify a global insomnia-related brain atrophy pattern. Thus, we observed inconsistent brain morphology differences between individuals with and without insomnia across three independent cohorts. Further large-scale cross-sectional/longitudinal studies using both structural and functional neuroimaging are warranted to decipher the neurobiology of insomnia.

Discriminating Paradoxical and Psychophysiological Insomnia Based on Structural and Functional Brain Images: A Preliminary Machine Learning Study.

Insomnia disorder (ID) is a prevalent mental illness. Several behavioral and neuroimaging studies suggested that ID is a heterogenous condition with various subtypes. However, neurobiological alterations in different subtypes of ID are poorly understood. We aimed to assess whether unimodal and multimodal whole-brain neuroimaging measurements can discriminate two commonly described ID subtypes (i.e., paradoxical and psychophysiological insomnia) from each other and healthy subjects. We obtained T1-weighted images and resting-state fMRI from 34 patients with ID and 48 healthy controls. The outcome measures were grey matter volume, cortical thickness, amplitude of low-frequency fluctuation, degree centrality, and regional homogeneity. Subsequently, we applied support vector machines to classify subjects via unimodal and multimodal measures. The results of the multimodal classification were superior to those of unimodal approaches, i.e., we achieved 81% accuracy in separating psychophysiological vs. control, 87% for paradoxical vs. control, and 89% for paradoxical vs. psychophysiological insomnia. This preliminary study provides evidence that structural and functional brain data can help to distinguish two common subtypes of ID from each other and healthy subjects. These initial findings may stimulate further research to identify the underlying mechanism of each subtype and develop personalized treatments for ID in the future.