Effects of Sleep Deprivation on Cortical Spreading Depolarization

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Acute sleep deprivation may cause increased frequency of cortical spreading depolarization and reduce its electrical threshold.

Acute sleep deprivation may increase cortical spreading depolarization (CSD) frequency and reduce its electrical threshold, according to study results published in The Journal of Headache and Pain.

The investigators described CSD, the electrophysiologic correlate of migraine aura, as a wave of sustained depolarization of neuronal and glial membranes that can be altered by various genetic and environmental factors. While sleep disorders are known migraine triggers, the underlying mechanism is not well understood. The goal of the current study was to explore the potential effect of sleep deprivation on CSD susceptibility.

The animal model included 58 male rats, including 30 control rats, 11 rats with 12 hours of sleep deprivation, and 17 rats with 6 hours of sleep deprivation. CSD recordings were completed twice daily by an investigator who was not aware of the rat’s sleep deprivation status. In addition, 29 rats were used to investigate the effects of chronic sleep deprivation on CSD susceptibility. The effect on sleep-wake status was assessed using electroencephalogram (EEG) and electromyogram (EMG) before and after inducing a cytotoxic lesion in the hypothalamic ventrolateral preoptic nucleus.

Recordings from 6- and 12-hour sleep-deprived rats indicated increased CSD frequency, compared with controls (16.9±3.5 and 17.9±2.1 vs 14.4±2.0 CSDs/h, respectively; P =.003 for both). Acute sleep deprivation of 12 hours, but not 6 hours, was associated with significantly reduced electrical threshold for CSD induction compared with controls (mean, 10 vs 50 µC, respectively; P <.01). There were no significant differences between sleep-deprived rats and controls for propagation speed or failure, nor for duration of first CSD or cumulative CSD duration.

As for the effects of partial chronic sleep deprivation, the researchers reported that there was no change in CSD susceptibility with chronic sleep restriction or fragmentation.

The study had several limitations, including those secondary to using animal sleep-deprived models that may not apply to patients, using an invasive method to induce and record CSD with potential alteration of CSD susceptibility, and missing data on additional migraine surrogates.

“These findings further underscore the importance of CSD as a migraine substrate, and open up new potential therapeutic avenues, suggesting that headache management should identify and treat associated sleep disorders,” concluded the researchers.


Negro A, Seidel JL, Houben T, et al. Acute sleep deprivation enhances susceptibility to the migraine substrate cortical spreading depolarization. J Headache Pain. 2020;21(1):86.