Since her undergraduate days, Elizabeth M. C. Hillman, Ph.D., said, “I’ve been obsessed with blood flow in the brain.” So she studied physics and engineering, a path whose logic became evident in her talk this past Wednesday, hosted by Columbia University’s Mind Brain Behavior Institute.
The blood flow that has attracted her particular attention for nearly a decade is in the infant brain, said Dr. Hillman, director of the Laboratory for Functional Optical Imaging at Columbia School of Engineering, who described research into a paradox that could point the way to new treatments for brain disorders in both children and adults.
Her presentation, part of a series supported by the Dana Foundation, also offered a window on the interaction between engineering and neuroscience central to modern brain studies.
In the adult brain, neural activity is accompanied by increased blood flow—the basis for functional MRI. But in infants, the opposite apparently happen: when they hear a sound, for example, blood flow in the auditory cortex declines.
“How can this possibly be? We have no idea,” Dr. Hillman said.
Engineers, she said, “are good at figuring out how things work. We ask different questions from people trained in neuroscience, and come up with very different answers.” From her perspective, blood flow is “a supply and demand question, an energy question.”
Dr. Hillman sought answer in animal brains. In adult rats, stimulation produces “an amazing inflow of blood; it drains out of surface vessels and dives into capillary beds where the neurons are.” But in the first two weeks of life, “the response looks upside down: blood flow is flat, then decreases, producing massive deoxygenation.”
At an intermediate age, the response is intermediate: blood flow increases, but not enough to overcome the negative bias.
Another series of experiments, using genes from fluorescent jellyfish, demonstrated that neurons are indeed firing in newborn rats when their brains are stimulated. “There’s a complete decoupling,” Dr. Hillman said. “The brain is using oxygen and should be hungry, but it’s not feeding itself.”
This is a skill the infant brain must learn, she concluded. “We know both neuronal networks and vasculature are developing over this time, and so is their interdependence.”
And if something goes wrong? Thinking as an engineer, Dr. Hillman said, leads to a vision of brain disorders as disruptions in what should be a dynamic, highly efficient system. “Blood is a finite resource that has to be shared—it can’t be everywhere at once. Brain vasculature in adult animals and humans is optimized to bring in blood when needed, high here for a while,then low, finely tuned to keep the brain functioning normally.”
A failure in this system’s development could lead to childhood-onset disorders like autism and ADHD, she said, citing studies showing altered temporal lobe blood flow in autism, for example. In later life, “there’s a lot of pathological evidence that vascular dysregulation is a component of Alzheimer’s and other dementias.”
Neurotransmitters like acetylcholine and norepinephrine, central to networks that regulate attention, memory, alertness and motivation, are potent vasodilators and vasoconstrictors, she pointed out. “It makes me think there’s a link between blood flow and the day-to-day working of the brain that’s been overlooked.”
Thinking about such “previously unconsidered” factors in diseases, she said, could bring to mind novel ways to treat them. “We’re good at fixing blood vessel dysfunctions, but no one’s explored this approach for these disorders.”
Understanding the infant’s brain mysterious resilience, which allows it to function apparently without adequate oxygen supplies, could also suggest new ways to help adult brains severely stressed by injury or stroke, she added.
The potential dividends of studying the brains of very young humans brought Dr. Hillman to the difficulties that frustrate it. Little subjects won’t sit still for fMRIs, she said, so new technology must be developed to track neuronal activity and blood flow while they play and rest.
“This led me to put my engineering hat on—it’s another problem to solve,” she said. A helmet using infrared spectroscopy? She’s working on it.