In a recent article with ramifications for averting Alzheimer’s disease and other neural conditions, Keith Hengen, an associate professor of biology in the Arts & Sciences division at Washington University in St. Louis, proposes a novel comprehensive method for grasping the functionality of the brain and the principles it must adhere to achieve peak performance.
“There’s a prevalent belief that the human brain is the most intricate entity in the universe,” Hengen stated. “The brain possesses immense strength; however, that strength may emerge from a relatively straightforward collection of mathematical concepts.”
Hengen begins with the assertion that nearly everything our brains accomplish is learned or strongly influenced by experiences. In other words, we are not born with pre-configured circuits programmed to assist us in reading, driving, or any other daily activities. A functioning brain must be equipped to learn various skills and information.
But how can a cluster of neurons learn? Hengen suggests that brains transform into learning machines only when they achieve a distinctive state known as “criticality.” This concept, borrowed from the field of physics, pertains to a complex system that is on the verge of order and chaos. At this precarious threshold, brains are ready to absorb new information, Hengen said. “Brains must reach criticality to think, recall, and learn.”
Hengen introduced criticality as a comprehensive theory of brain function and illness in the prestigious journal Neuron. Woodrow Shew, a physicist at the University of Arkansas, is the co-author.
A biologist and a physicist might seem like an unusual partnership, but this fresh unifying theory integrates both scientific domains. Physicists frequently illustrate criticality using the classic illustration of a sand pile: As sand accumulates, the pile becomes increasingly steep until it eventually collapses. Just before that final grain precipitates chaos, the pile exists at a critical angle, one step away from instability.
Shew clarified that physicists initially developed a profound understanding of criticality to describe magnets and various materials. Around the dawn of the 21st century, these concepts were broadened to elucidate a wider array of complex systems, including avalanches, earthquakes, and ultimately, living systems and the brain.
A defining characteristic of critical systems is their consistent appearance at any scale: A sand pile on the verge of an avalanche maintains the same slope whether it is small or monumental. In the brain, criticality remains uniform whether measured in a handful of neurons or an entire region. Similarly, brain patterns that evolve over time show striking similarities when analyzed in milliseconds or hours. “This aligns with our intuitive perception of how brains function,” Hengen remarked. “Our internal experiences range from milliseconds to months. They lack a specific scale.”
Hengen and Shew argue that criticality is more than a theoretical idea; it is a condition that can be accurately measured and quantified through fMRI brain imaging technology. “Criticality represents the optimal computational state of the brain,” Hengen stated. “We’ve formulated a mathematical approach to assess how close the brain is to criticality, which should aid in addressing fundamental inquiries about human brain functionality.”
A revised understanding of disease
The criticality framework provides a fresh lens for comprehending neurological diseases. Instead of concentrating on specific impaired brain regions or accumulated proteins, Hengen asserts that conditions like Alzheimer’s undermine something more fundamental: the brain’s capability to preserve criticality.
“Alzheimer’s and other neurodegenerative disorders not only harm neurons, they also disrupt the brain’s overall ability to process by gradually eroding criticality,” Hengen elaborated. “As a brain drifts further from criticality, it loses the capability to adapt and effectively manage information.”
This framework elucidates a perplexing characteristic of brain diseases: Patients frequently seem entirely normal until they have lost a significant number of neurons. “The brain possesses remarkable compensatory mechanisms that can obscure functional issues even as criticality starts to deteriorate,” Hengen noted. “Traditional evaluations overlook the early phases because they emphasize well-established endpoints that the brain strives to maintain through alternative strategies.”
As criticality progressively declines, the brain exerts greater effort to achieve the same cognitive results, Hengen commented. “It’s akin to an engine that continues to function but requires more fuel and generates extra heat. By the time we observe memory challenges or other symptoms, criticality has probably been compromised for years.”
Hengen’s collaboration with David M. Holtzman, MD, the Barbara Burton and Reuben M. Morriss III Distinguished Professor at WashU Medicine, has uncovered that tau protein accumulation in Alzheimer’s directly hampers criticality, establishing a clear connection between the disease’s molecular signatures and cognitive decline.
This linkage between criticality and Alzheimer’s presents thrilling diagnostic opportunities. In theory, a straightforward fMRI could help identify breakdowns in criticality well before symptoms manifest. “In conjunction with advanced blood tests, we could pinpoint individuals at risk and intervene prior to irreversible harm occurring,” Hengen indicated.
In another partnership, Hengen has collaborated with Deanna Barch, the Gregory B. Couch Professor of Psychiatry at WashU Medicine and a professor of psychological and brain sciences in Arts & Sciences, for a longitudinal study examining how criticality at birth influences cognitive development and abilities during childhood. “From the very start, some children are closer to criticality than others, which, according to our theory, implies they may become superior learners,” Hengen stated. “Numerous external factors can influence their academic success, but criticality could account for a significant portion of the variation observed among children.”
The sleep-mind connection
In early 2024, Hengen and co-author Ralf Wessel, a professor of physics in Arts & Sciences at WashU, leveraged the concept of criticality to reexamine an age-old inquiry:“`html
Why is sleep necessary? By monitoring cerebral activity over several weeks, they discovered that sleep rejuvenates a state of criticality. “Staying awake and engaged takes us away from criticality, and sleep functions as a reset mechanism,” Hengen articulated.
This revelation could assist scientists in harnessing the therapeutic potential of sleep for Alzheimer’s and other neurological disorders that push the brain beyond its ideal condition. Prior investigations by Holtzman and colleagues have shown that individuals who do not obtain adequate sleep — perhaps due to shift work or chronic sleeplessness — face a significantly elevated risk of developing Alzheimer’s as they grow older. Furthermore, there exists some evidence indicating that sleep interventions may aid in slowing the advancement of Alzheimer’s symptoms.
Hengen is optimistic that focused, intensive sleep-based treatments could restore criticality and enhance learning and memory in individuals affected by brain disorders. Research involving mice, conducted by Holtzman and James McGregor, a postdoctoral researcher in Hengen’s team, provides a glimpse into the possibilities: Mice specially bred showing Alzheimer’s symptoms become quicker learners following a tailored sleep intervention that strengthens criticality.
Vital Future
There is substantial work ahead, but Hengen aspires to ultimately comprehend how criticality elucidates complex aspects of human neurobiology. “We might discover that an exceptional artist, for instance, could be very close to criticality in brain regions associated with creative thinking,” he remarked. It’s also conceivable that a thorough examination of criticality could unveil hidden tendencies or abilities that merely require an outlet. “Perhaps they never explored art, yet we can identify that the potential exists.”
In the interim, Hengen, Shew, and others are raising awareness about the significance of criticality. Hengen delivered a TEDx talk on the topic in 2024 and presented his findings at Arts & Sciences’ inaugural research pitch competition, where he secured second place. He hopes that the new Neuron publication will spark discussions among neurologists, physicians, journalists, and the general public.
A cohesive theory of the mind could transform the world, but first, it needs to bring together the experts. “Woody (Shew) and I genuinely believe we’re onto something significant,” Hengen stated. “And, gradually, it seems that others are starting to concur.”
WashU has proven to be the perfect setting for a novel concept of the brain to develop, according to Hengen. “We are surrounded by brilliant individuals from varied disciplines, including physics, biology, psychology, mathematics, and neuroscience, and the community here is exceptionally supportive,” he noted. “Everyone is eager to assist.”
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