Alterations of Resting-State Locus Coeruleus Functional Connectivity After Transdermal Trigeminal Electrical Neuromodulation in Insomnia

Abstract

BackgroundTransdermal trigeminal electrical neuromodulation (TTEN) is a novel treatment modality that is known for noradrenergic modulation through the trigeminal nerve and locus coeruleus (LC). This study aimed to demonstrate the alterations of LC functional connectivity (FC) in patients with insomnia after a 4-week TTEN.MethodsThe Cefaly device targeting the ophthalmic division of the trigeminal nerve was applied to a total of 12 patients with insomnia to monitor for the effects of TTEN. All the patients went through a 4-week daily 20 min TTEN sessions before bedtime. Baseline and post-TTEN demographic data, polysomnography (PSG) parameters, and insomnia severity index (ISI) were attained. Data from pre- and post-intervention resting-state functional magnetic resonance imaging (MRI) were collected. LC FC differences were measured between the pre-and post-TTEN groups through seed-to-voxel analysis. Correlation analyses were conducted between LC FC changes after TTEN, ISI score changes, and PSG parameter changes.ResultsThere was a significantly decreased LC FC with occipital and temporal cortices after a 4-week TTEN. However, there was no significant correlation between LC FC, ISI score changes, and PSG parameter changes.ConclusionBy targeting hyperarousal symptoms of insomnia, TTEN can be a promising intervention that can modulate LC FC in patients with insomnia patients. The data presented in the study are from a study exploring the effect of TTEN on insomnia (www.clinicaltrials.gov, NCT04838067).

No alterations in potential indirect markers of locus coeruleus–norepinephrine function in insomnia disorder

“…Directly targeting norepinephrine hyperarousal by medication (Bamgbade et al, 2022) or technical interventions (Um et al, 2022) represents a promising, but challenging approach in ID treatment. Specifically the LC NE system remains a potential target due to its well understood links to arousal and sleep regulation (Broese et al, 2012).…”

“…Directly targeting norepinephrine hyperarousal by medication (Bamgbade et al, 2022) or technical interventions (Um et al, 2022) represents a promising, but challenging approach in ID treatment.…”