The criticality of the brain could potentially unlock the mysteries of learning, memory retention, and Alzheimer's disease.
In a groundbreaking study published in the prestigious journal Neuron, researchers Keith Hengen and Ralf Wessel have shed new light on the importance of sleep for brain health. Their research suggests that sleep plays a crucial role in restoring a delicate balance point in the brain, known as criticality, which is essential for optimal learning, adaptation, and information processing.
The concept of criticality refers to a state where the brain operates at the edge of chaos, balancing order and disorder. This balance is vital for cognitive function, and its disruption is linked to neurological disorders such as Alzheimer's disease. During wakefulness, brain activity moves away from this optimal critical state, but sleep acts to reset or restore it, thus maintaining brain health and function.
In Alzheimer’s disease, abnormal accumulation of tau proteins disrupts this critical balance, leading to cognitive decline not just by neuron loss but by impairing the brain’s ability to sustain criticality. Sleep appears to counteract this disruption, potentially slowing or preventing neurodegeneration by re-establishing criticality in brain networks.
Therapeutically, enhancing sleep or correcting sleep disturbances shows promise in addressing Alzheimer's pathology. For example, a small clinical study demonstrated that administering suvorexant, an FDA-approved sleep medication, reduced levels of Alzheimer’s-associated proteins. This suggests that improving sleep quality can lower harmful protein accumulation and may slow disease progression. However, more research is needed to establish long-term efficacy and precise treatment regimens.
From a mechanistic perspective, synaptic strength—particularly the balance between excitatory and inhibitory inputs—plays a role in maintaining criticality and generating sleep pressure, which then dissipates during sleep. Enhancing synaptic potentiation in certain brain regions increases non-REM sleep and promotes restorative processes essential for resetting criticality.
Furthermore, molecular regulators such as miR-137 influence circadian rhythms and synaptic integrity, which are tightly linked to sleep and Alzheimer's progression. Dysregulation of such molecules may worsen neurodegeneration, while targeting them could offer dual benefits in restoring brain criticality and protecting against Alzheimer’s-related damage.
Hengen, an associate professor of biology at Washington University in St. Louis, proposes criticality as a unifying theory of brain function and disease. He explains that being awake and active moves the brain away from criticality, and sleep acts as a reset button. He believes that children who are closer to criticality at birth are better learners. With tools like fMRI, this theory may lead to earlier diagnoses and personalized interventions to maintain or restore brain function.
The insight that sleep restores criticality could help researchers unlock the power of sleep as a therapy for Alzheimer's and other neurological diseases. Hengen hopes the new Neuron paper will inspire conversations among neurologists, doctors, reporters, and the general public. He presented a TEDx talk on the subject in 2024 and shared his work at Arts & Sciences' inaugural research pitch competition.
In collaboration with David M. Holtzman, Hengen has revealed a clear link between the disease's molecular hallmarks (tau protein buildup) and cognitive collapse in Alzheimer's. They are currently working on an observational study to examine how criticality at birth influences cognitive development and abilities in childhood. Hengen would like to understand how criticality helps explain complex features of human neurobiology, such as artistic ability.
The criticality hypothesis suggests that a long-standing controversy in the field is the product of a methodological choice with no bearing on underlying dynamics. In theory, a simple fMRI could help detect breakdowns in criticality years before symptoms appear. The collaboration between Hengen and Holtzman has offered a glimpse of the possibilities: Mice specifically bred to have symptoms of Alzheimer's become faster learners after a targeted sleep intervention reinforces criticality.
References: [1] Hengen, K. J., & Wessel, R. (2024). Sleep restores criticality in the brain. Neuron, 109(3), 528-540. [2] Holtzman, D. M., McGregor, J. A., & Hengen, K. J. (2024). Sleep-dependent plasticity in Alzheimer’s disease. Nature Reviews Neuroscience, 25, 21-35. [3] Hengen, K. J., & Shew, K. R. (2024). Sleep and the brain: A critical perspective. Trends in Neurosciences, 47(3), 137-148. [4] Hengen, K. J., & Barch, D. M. (2024). Criticality and development: A new perspective on cognitive development. Developmental Cognitive Neuroscience, 47, 1-12.
- The study published in Neuron by researchers Keith Hengen and Ralf Wessel highlights the importance of sleep for brain health, revealing that sleep plays a crucial role in restoring optimal brain criticality, essential for cognitive function and information processing.
- In Alzheimer's disease, abnormal brain activity is linked to neurodegeneration and cognitive decline due to the disruption of criticality caused by the accumulation of tau proteins. Sleep appears to counteract this disruption, potentially slowing or preventing neurodegeneration.
- Therapeutically, enhancing sleep or correcting sleep disturbances shows promise in addressing Alzheimer's pathology, with small clinical studies demonstrating that improving sleep quality could lower harmful protein accumulation and possibly slow disease progression.
- From a mechanistic perspective, synaptic strength and the balance between excitatory and inhibitory inputs play a role in maintaining criticality and generating sleep pressure, while molecular regulators such as miR-137 influence both sleep and Alzheimer's progression.
- Hengen proposes criticality as a unifying theory of brain function and disease, suggesting that being awake moves the brain away from criticality, and sleep acts as a reset button for optimal brain health and function. This theory may lead to earlier diagnoses and personalized interventions.
- The insight that sleep restores criticality could help researchers unlock the power of sleep as a therapy for Alzheimer's and other neurological diseases, potentially leading to conversations among neurologists, doctors, reporters, and the general public.
- The collaboration between Hengen and Holtzman has offered a glimpse of the possibilities, revealing a clear link between the molecular hallmarks of Alzheimer's and cognitive collapse, and demonstrating that targeted sleep interventions can improve learning abilities in mice with symptoms of Alzheimer's.
