Connectomic disturbances underlying insomnia disorder and predictors of treatment response

Background. Despite its prevalence, insomnia disorder (ID) remains poorly understood. In this study, we used machine learning to analyze the functional connectivity (FC) disturbances underlying ID, and identify potential predictors of treatment response through recurrent transcranial magnetic stimulation (rTMS) and pharmacotherapy. Methods. 51 adult patients with chronic insomnia and 42 healthy age and education matched controls underwent baseline anatomical T1 magnetic resonance imaging (MRI), resting-stage functional MRI (rsfMRI), and diffusion weighted imaging (DWI). Imaging was repeated for 24 ID patients following four weeks of treatment with pharmacotherapy, with or without rTMS. A recently developed machine learning technique, Hollow Tree Super (HoTS) was used to classify subjects into ID and control groups based on their FC, and derive network and parcel-based FC features contributing to each model. The number of FC anomalies within each network was also compared between responders and non-responders using median absolute deviation at baseline and follow-up. Results. Subjects were classified into ID and control with an area under the receiver operating characteristic curve (AUC-ROC) of 0.828. Baseline FC anomaly counts were higher in responders than non-responders. Response as measured by the Insomnia Severity Index (ISI) was associated with a decrease in anomaly counts across all networks, while all networks showed an increase in anomaly counts when response was measured using the Pittsburgh Sleep Quality Index. Overall, responders also showed greater change in all networks, with the Default Mode Network demonstrating the greatest change. Conclusions. Machine learning analysis into the functional connectome in ID may provide useful insight into diagnostic and therapeutic targets.