New insight into the neural mechanisms of migraine in adolescents: Relationships with sleep

Objective: This case-control study examines if measures of subjective and objective (actigraphic) sleep difficulties mediate alterations in amygdalar connectivity in adolescents with migraine compared to healthy adolescents. Background: Adolescents with migraine have different functional connectivity of the amygdala compared to individuals without migraine. Sleep is often disturbed in adolescents with migraine, and could contribute to the alterations in functional connectivity. Methods: Twenty adolescents with migraine and 20 healthy controls were recruited from Cincinnati Children’s Hospital. Participants completed surveys about their headaches and overall sleep quality, sleep hygiene, and perceived sleep difficulties (Insomnia Severity Scale [ISI]); completed wrist-worn actigraphy; and underwent a magnetic resonance imaging scan. Results: Adolescents with migraine differed from healthy controls only in perceived difficulty in sleep initiation and maintenance (ISI: 8.5 ± 4.7 and 4.5 ± 3.7 [mean ± standard deviation], −4.00 [95% confidence: −6.7 to −1.3], p = 0.005) and had greater functional connectivity between the amygdala and the posterior cingulate cortex, precuneus, dorsolateral prefrontal, sensorimotor, and the occipital cortexes. The differences in functional connectivity of the amygdala were not mediated by the subjective/objective sleep measures (ISI/wake minutes after sleep onset). Conclusions: Adolescents with migraine have greater connectivity between the amygdala and areas involved in sensory, affective, and cognitive aspects of pain. These alterations may not be due to higher levels of sleep difficulties in adolescents with migraine, suggesting that both amygdala and sleep alterations may play an independent role in migraine pathophysiology. This advances the understanding of the mechanisms underlying pediatric migraine and can potentially advance migraine management.