A recent study published in Nature Neuroscience suggests that the brain is more mechanically connected to the body than previously appreciated. Scientists found that abdominal muscle contractions compress blood vessels connected to the spine and brain, pushing fluid that gently moves the brain within the skull. This physical swaying provides evidence for how exercise might benefit brain health by washing away cellular waste.
Scientists set out to understand the specific mechanical origins of brain motion in awake animals. The central nervous system is encased in thick bone, making it seem isolated from the physical forces of the rest of the body. However, the work builds on previous studies detailing how sleep and neuron loss can influence how and when cerebrospinal fluid flushes through the brain, according to Patrick Drew, a professor of engineering science and mechanics, neurosurgery, biology and biomedical engineering at Penn State.
“Our research explains how just moving around might serve as an important physiological mechanism promoting brain health,” said Drew, corresponding author on the paper. “In this study, we found that when the abdominal muscles contract, they push blood from the abdomen into the spinal cord, just like in a hydraulic system, applying pressure to the brain and making it move.”
“Simulations show that this gentle brain movement will drive fluid flow in and around the brain,” Drew said. “It is thought the movement of fluid in the brain is important for removing waste and preventing neurodegenerative disorders. Our research shows that a little bit of motion is good, and it could be another reason why exercise is good for our brain health.”
To observe these microscopic movements, the authors used two-photon microscopy, which allows for high-definition imaging of living tissue. They examined 24 awake mice that had their heads temporarily secured in place above a spherical treadmill. The mice had a special transparent window surgically placed into their thinned skulls, which allowed the scientists to see the outer surface of the brain.
The scientists rapidly switched the microscope’s focus between glowing microscopic beads placed on the skull and specific cells within the brain tissue. They measured these shifts exactly, capturing video frames roughly forty times per second. The authors found that the brain shifted slightly forward and to the side during running.
Interestingly, the researchers observed the brain shifting in the moments before the mouse moved, but right after the tightening of the abdominal muscles needed to spur the body into further movement. Because the brain moved right before the legs did, the scientists suspected that the core muscles might be responsible. Sensors implanted in the mice recorded spikes in abdominal muscle activity that perfectly predicted the timing of the brain’s movement.
Drew, who also holds the title of associate director of the Huck Institutes of the Life Sciences at Penn State, explained how in a hydraulic system, a pump creates pressure that drives fluid flow. In this case, the pump is the abdominal contraction, which can be as light as the tensing prior to sitting up or taking a step.
To understand the physical connection, the scientists mapped the blood vessels connecting the belly to the spine. They injected a special dye into two mice and scanned the animals using microcomputed tomography, which enables high-resolution 3D examination of whole organs. The scans revealed a specialized network of veins called the vertebral venous plexus.
The contraction puts pressure on the vertebral venous plexus, a network of veins that connect the abdominal cavity to the spinal cavity, causing the brain to move. When abdominal muscles contract, they squeeze blood out of the belly and up into the spinal column. The added volume inside the spine pushes fluid upward, which creates a pressure wave that physically moves the brain.
To confirm that it was abdominal contractions rather than other movement that acted as the pump, the researchers applied gentle and controlled pressure to the abdomens of lightly anesthetized mice. They built a custom pneumatic belt, similar to a miniature blood pressure cuff. With no other movement other than a localized mechanical pressure less than a human would experience with a blood pressure cuff, the mice’s brains shifted.
“Importantly, the brain began moving back to its baseline position immediately upon relief of the abdominal pressure,” Drew said. “This suggests that abdominal pressure can rapidly and significantly alter the position of the brain within the skull.”
With the abdominal contraction-brain movement link confirmed, Drew said the next step was to understand the fluid’s movement in the brain and if the brain’s movement could induce fluid flow. However, there previously were no existing imaging techniques to visualize the rapid, nuanced dynamics of such fluid flows.
“Luckily, our interdisciplinary team at Penn State was able to develop these techniques, including conducting the imaging experiments of living mice and creating computer simulations of fluid motion,” Drew said. “That combination of expertise is so important for understanding these types of complicated systems and how they impact health.”
Francesco Costanzo, a professor of engineering science and mechanics, biomedical engineering, mechanical engineering and mathematics at Penn State, led the computational modeling. This model represented the simplified geometry of the mouse central nervous system.
“Modeling fluid flow in and around the brain offers unique challenges because there are simultaneous, independent movements, as well as time-dependent, coupled movements,” Costanzo said. “Accounting for all of them requires accounting for the special physics that happens every time a fluid particle crosses one of the many membranes in the brain.”
“So, we simplified it,” Costanzo said. “The brain has a structure similar to a sponge, in the sense that you have a soft skeleton and fluid can move through it.”
By simplifying the geometry of the brain to that of a sponge, Costanzo explained that the team could model how fluid flows through a structure with varied spaces, like wrinkles in the brain, or pores in the sponge.
“Keeping with the idea of the brain as a sponge, we also thought of it as a dirty sponge, how do you clean a dirty sponge?” Costanzo asked. “You run it under a tap and squeeze it out. In our simulations, we were able to get a sense of how the brain moving from an abdominal contraction can help induce fluid flow over the brain to help clear waste products.”
The simulation indicated that the sudden movement of the brain forces interstitial fluid, the liquid found in the microscopic spaces around cells, out of the brain tissue. This outward flow is the exact opposite of what happens during sleep, when fluid washes deeply into the brain to remove waste.
While these findings provide insights, there are a few limitations to consider. The experiments required the mice to have their heads held perfectly still. In a freely moving animal, the physical forces generated by moving the head up and down would also act on the brain, adding another layer of complexity.
Additionally, the scientists only imaged the very top portion of the brain’s cortex. Deeper brain regions tend to experience different types of stretching or shifting during abdominal contractions. The computer simulation also relied on a simplified geometry of the brain and spinal cord, which might not capture how fluids navigate the intricate real-world anatomy of the nervous system.
Drew emphasized that while more work is needed to understand the full implications in humans, this study suggests that body movement may help to cycle cerebrospinal fluid around and in the brain, removing waste and helping to protect against neurodegenerative disorders associated with waste buildup.
“This kind of motion is so small,” Drew said. “It’s what’s generated when you walk or just contract your abdominal muscles, which you do when you engage in any physical behavior. It could make such a difference for your brain health.”
The study, “Brain motion is driven by mechanical coupling with the abdomen,” was authored by C. Spencer Garborg, Beatrice Ghitti, Qingguang Zhang, Joseph M. Ricotta, Noah Frank, Sara J. Mueller, Denver I. Greenawalt, Kevin L. Turner, Ravi T. Kedarasetti, Marceline Mostafa, Hyunseok Lee, Francesco Costanzo, and Patrick J. Drew.
