Sleep Deprivation Leaves a Mark on the Human Brain

From tiny squirrels and sluggish tortoises to giant elephants and agile cheetahs, one thing unites virtually all animals: the need to sleep. One of the theories for the need to sleep suggests that it restores homeostasis in the brain after wakefulness.

Synaptic connections between brain cells become stronger when an animal is awake, raising energy consumption and causing the buildup of proteins, which limits the capacity for learning.¹ While scientists believe that sleep fixes this imbalance, they didn’t have much human evidence to support this hypothesis.

Now, David Elmenhorst, a neuroimaging and sleep scientist at Jülich Research Center, used positron emission tomography (PET) to test whether the synaptic hypothesis of sleep holds true in humans.² The findings, published in PLoS Biology, indicate that wakefulness does strengthen synaptic connections in human brains, providing molecular evidence behind the neurobiology of sleep.

For their study, Elmenhorst and his team recruited 40 healthy participants, who underwent PET scans to measure the amount of synaptic vesicle glycoprotein 2A (SV2A), an established proxy marker of synaptic density, in their brains.³ The control group, comprising of half the participants, underwent a second scan after sleeping for nine hours, while the others remained awake for 28 hours before completing their second PET scan.

Comparing the brains of people in the control and sleep deprivation groups revealed that the latter had significantly higher SV2A levels. While these elevations were relatively small, according to the authors, the results support the synaptic homeostasis model of sleep.

Focusing on different brain regions, the researchers observed raised SV2A levels in the thalamus, which relays sensory and motor signals; the hippocampus, which influences learning and memory; and the parietal cortex, which helps process sensory information.

Finally, Elmenhorst and his team used sleep-electroencephalograms to assess the brain activity of the sleep deprived participants when they took a two-hour recovery nap. These results revealed that the people who had higher levels of SV2A showed more slow wave activity, a physiolog­ical indicator of sleep need. These findings indicated that the increased density of synapses correlated with increased pressure to sleep.

In a statement, the authors said, “During sleep deprivation, the brain remains awake longer and continues to process stimuli and information. Our study shows that after approximately 28.5 hours of wakefulness, a marker for synaptic density increases in several brain regions. This suggests that sleep deprivation not only causes fatigue but is also accompanied by measurable changes in neural connections.”