July 12, 2023 | by Lindsay Ejoh, PennNeuroKnow and IAES Collaboration

A message from IAES Blog Staff:

The staff at IAES is proud to present to all of you another wonderful article/blog from the amazing team at PennNeuroKnow. Since 2019 IAES has been extremely lucky to be in partnership with the PennNeuroKnow(PNK) team to help us all better understand complex medical issues related to AE and neurology in general. The talented PNK team continues to keep us up-to-date and help clarify the complexities we face each day along our AE journey, and we are eternally grateful! You can find out much more about this stellar group at: https://pennneuroknow.com/

For all of us with AE, sleep can be an ongoing issue whether it be too little, too much, interrupted sleep cycles and everything in-between! Sleep issues often go hand in hand with an AE diagnosis. PNK author Lindsay Ejoh wrote this piece for the PNK weekly series and graciously gave IAES permission to publish it in our monthly series. We hope you find this as informative as we have!

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Introduction

Sleep experts recommend that most adults get 7-9 hours of good-quality sleep each day^1,2 to avoid the myriad of issues that can occur when the brain and body are sleep-deprived. We all know what it is like to be tired. We may feel cranky and sluggish, as well as physically and mentally exhausted. We may also face issues with memory and attention³, emotional regulation, and diminished sex drive^4,11. It is hard to feel like yourself when sleep-deprived- so what occurs in the brain during sleep deprivation, and how does it affect our daily lives?

Memory

As a child, I remember learning to trick my mother, a sleep-deprived emergency room nurse that worked the night shift, by asking her for permission to do things while she was coming home from work in the mornings, half-asleep. When I’d approach her in bed to ask for permission to go on a sleepover across town or to eat food we were saving for an occasion, she would always say yes. Eventually, she caught on, and warned me against waiting until she was sleepy to get my way, but the reason it worked at first is because sleep deprivation impacts decision-making⁵.

It also affects short-term memory, so as a result, my mother would never remember giving her approval. Long-term memory is affected as well, as sleep is very important for consolidation, or storage of memories. This is also why you may not remember everything you studied after cramming for an exam all night.

Reaction time

Being awake is not the same thing as being alert. When we are sleepy, we tend to have slow reaction times, or time to respond to a change in our environment. This can have devastating effects for those who operate cars and other heavy machinery while sleepy and can be dangerous for people who work with under these conditions. Sleep deprivation can make you 70% more likely to get into work-place accidents, which happen at higher rates in people with insomnia⁶. Additionally, missing just a couple hours of sleep can substantially increase the risk of having a car accident⁷. It may seem in the moment like you can stay awake while driving, but as explained in a previous NeuroKnow article, going 24 hours without sleep can be just as dangerous as driving drunk.

Changes in the brain

Sleep deprivation impacts many regions of your brain, but two are of notable importance: amygdala and prefrontal cortex.

Amygdala

Scientists can measure brain activity by taking functional magnetic resonance imaging (fMRI) scans. Using this method, researchers found that sleep deprivation leads to a hyperactive amygdala³. The amygdala is critical for emotional regulation, and its dysfunction may be related mood issues that occur from sleep deprivation. A single sleepless night can trigger a 30% increase in anxiety levels⁹, due to the loss of ability to regulate emotions or deal with stress, and people with anxiety disorders also have hyperactive amygdalae when faced with unpleasant changes in their environment¹⁰. In other words, sleep deprivation causes disruption in emotional centers in the brain, which is linked to increased anxiety.

Prefrontal Cortex

Another brain region with altered activity during sleep deprivation is the prefrontal cortex, which is important for rational thinking and decision-making³.  This region has decreased activity during sleep deprivation, and these activity patterns are associated with impaired judgment, a common symptom of sleep deprivation.  

Chronic sleep deprivation and sleep apnea

Most of us have experienced sleep-deprivation in our lives, but for some, it is the norm. People who suffer from inadequate sleep for a prolonged period of time (weeks to years) are in a state of chronic sleep deprivation⁶. Many people wake up in the mornings feeling symptoms of sleep deprivation despite getting a long night of sleep, which may be indicative of a sleep disorder known as sleep apnea. Patients with sleep apnea wake up over a hundred times throughout the night, due to difficulty breathing¹². A research lab in Australia found that sleep apnea patients have altered brain activity during wakefulness¹³. Certain parts of their brains “go offline” briefly, despite being awake, and brain activity resembles that of a sleeping person^14. Sleep disorder patients aren’t the only ones that experience this- it can occur from other forms of sleep deprivation. When sleep intrudes into the waking brain, this can lead to errors in tasks like driving. Despite being abnormal for humans, this brain activity phenomenon is not uncommon in the animal kingdom. Some animals like seals and dolphins sleep with half of their brains “awake” while the other halves are “asleep.”

Conclusion

Neuroscientists are working to understand the neurobiological consequences of sleep deprivation, so that we can inform and treat people who must continue to perform daily tasks despite running on little sleep. Though harmful for the brain, sleep deprivation is a normal part of daily life for 30-40% of US adults¹⁵, including parents of newborns, procrastinating college students, night-shift workers, military and medical personnel, sleep disorder patients, and many others. We live in a sleep-deprived society, where people are often celebrated for trading rest for productivity. I encourage you to take this as your sign to go to bed early tonight- you are not yourself when you’re sleepy!

References

1. Watson NF, Badr MS, Belenky G, et al. Recommended amount of sleep for a healthy adult: a joint consensus statement of the American Academy of Sleep Medicine and Sleep Research Society. Sleep. 2015;38(6):843–844.
2. Consensus Conference Panel, Watson, N. F., Badr, M. S., Belenky, G., Bliwise, D. L., Buxton, O. M., Buysse, D., Dinges, D. F., Gangwisch, J., Grandner, M. A., Kushida, C., Malhotra, R. K., Martin, J. L., Patel, S. R., Quan, S. F., Tasali, E., Non-Participating Observers, Twery, M., Croft, J. B., Maher, E., … Heald, J. L. (2015). Recommended Amount of Sleep for a Healthy Adult: A Joint Consensus Statement of the American Academy of Sleep Medicine and Sleep Research Society. Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, 11(6), 591–592. https://doi.org/10.5664/jcsm.4758
3. Krause, A. J., Simon, E. B., Mander, B. A., Greer, S. M., Saletin, J. M., Goldstein-Piekarski, A. N., & Walker, M. P. (2017). The sleep-deprived human brain. Nature reviews. Neuroscience, 18(7), 404–418. https://doi.org/10.1038/nrn.2017.55
4. Chen, K. F., Liang, S. J., Lin, C. L., Liao, W. C., & Kao, C. H. (2016). Sleep disorders increase risk of subsequent erectile dysfunction in individuals without sleep apnea: a nationwide population-base cohort study. Sleep medicine, 17, 64–68. https://doi.org/10.1016/j.sleep.2015.05.018
5. Rasch, B., & Born, J. (2013). About sleep’s role in memory. Physiological reviews, 93(2), 681–766. https://doi.org/10.1152/physrev.00032.2012
6. Suni, E. (2023, April 5). The relationship between sleep and workplace accidents. Sleep Foundation. Retrieved April 26, 2023, from https://www.sleepfoundation.org/excessive-sleepiness/workplace-accidents#references-197012
7. AAA. (2016, December 6). Missing 1-2 hours of sleep doubles crash risk: Study reveals the dangers of getting less than 7 hours of sleep. ScienceDaily. Retrieved April 26, 2023 from www.sciencedaily.com/releases/2016/12/161206110235.htm
8. Wong, M. M., Robertson, G. C., & Dyson, R. B. (2015). Prospective relationship between poor sleep and substance-related problems in a national sample of adolescents. Alcoholism, clinical and experimental research, 39(2), 355–362. https://doi.org/10.1111/acer.12618
9. Ben Simon, E., Rossi, A., Harvey, A. G., & Walker, M. P. (2020). Overanxious and underslept. Nature human behaviour, 4(1), 100–110. https://doi.org/10.1038/s41562-019-0754-8
10. Etkin, A., & Wager, T. D. (2007). Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia. The American journal of psychiatry, 164(10), 1476–1488. https://doi.org/10.1176/appi.ajp.2007.07030504
11. Sleep Center of Middle Tennessee. (2022, June 22). Sleep deprivation and its effects on the brain. Sleep Centers of Middle Tennessee. Retrieved April 26, 2023, from https://sleepcenterinfo.com/blog/sleep-deprivation-effects-on-brain/
12. Slowik, J. M., Sankari, A., & Collen, J. F. (2022). Obstructive Sleep Apnea. In StatPearls. StatPearls Publishing.
13. Hung, C. S., Sarasso, S., Ferrarelli, F., Riedner, B., Ghilardi, M. F., Cirelli, C., & Tononi, G. (2013). Local experience-dependent changes in the wake EEG after prolonged wakefulness. Sleep, 36(1), 59–72. https://doi.org/10.5665/sleep.2302
14. Mannix, L. (2019, January 27). Your brain could be sleeping … even while you’re awake. The Sydney Morning Herald. Retrieved April 26, 2023, from https://www.smh.com.au/national/your-brain-could-be-sleeping-even-while-you-re-awake-20190124-p50tgg.html
15. Centers for Disease Control and Prevention. (2022, November 2). Adults – sleep and sleep disorders. Centers for Disease Control and Prevention. Retrieved April 26, 2023, from https://www.cdc.gov/sleep/data-and-statistics/adults.html

Cover image by Karollyne Videira Hubert on Unsplash

References

1. Zeng, J. & James, L. C. Intracellular antibody immunity and its applications. PLOS Pathog. 16, e1008657 (2020).
2. CDC. COVID-19 and Your Health. Centers for Disease Control and Preventionhttps://www.cdc.gov/coronavirus/2019-ncov/your-health/about-covid-19/antibodies.html (2020).
3. Elkon, K. & Casali, P. Nature and functions of autoantibodies. Nat. Clin. Pract. Rheumatol. 4, 491–498 (2008).
4. Hermetter, C., Fazekas, F. & Hochmeister, S. Systematic Review: Syndromes, Early Diagnosis, and Treatment in Autoimmune Encephalitis. Front. Neurol. 9, 706 (2018).
5. Graus, F. et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. 15, 391–404 (2016).
6. Anti-NMDA receptor encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/anti-nmda-receptor-encephalitis/.
7. Anti-AMPAR encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/anti-ampar-encephalitis/.
8. Anti-GABAA receptor encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/anti-gabaa-receptor-encephalitis/.
9. Anti-GABAB receptor encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/anti-gabab-receptor-encephalitis/.
10. LGI1-antibody encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/lgi1-antibody-encephalitis/.
11. CASPR2-antibody encephalitis. Autoimmune Encephalitis Alliance https://aealliance.org/ae-types/caspr2-antibody-encephalitis/.
12. Malter, M. P., Helmstaedter, C., Urbach, H., Vincent, A. & Bien, C. G. Antibodies to glutamic acid decarboxylase define a form of limbic encephalitis. Ann. Neurol. 67, 470–478 (2010).
13. Voltz, R. & Eichen, J. A Serologic Marker of Paraneoplastic Limbic and Brain-Stem Encephalitis in Patients with Testicular Cancer. N. Engl. J. Med. (1999).
14. Graus, F. & Dalmau, J. Paraneoplastic neurological syndromes in the era of immune-checkpoint inhibitors. Nat. Rev. Clin. Oncol. 16, 535–548 (2019).
15. Lancaster, E. Encephalitis and antibodies to synaptic and neuronal cell surface proteins. (2011).

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