Neurotechnology in motion

By Nicoletta Lanese

BOSTON — Supported by former President Barack Obama’s BRAIN (Brain Research through Advancing Innovative Neurotechnologies) Initiative, three neuroscientists have made significant advances in studying the brain in active subjects.

Julie Brefczynski-Lewis with AMPET helmet

Julie Brefczynski-Lewis wearing a mock-up AMPET helmet while standing in front of a traditional PET scan machine. Courtesy of Julie Brefczynski-Lewis/WVU.

Once upon a time, the only way to look at an animal’s brain was to remove it from its skull. With the advent of neuroimaging, such as CT and PET, scientists could view intact brains. As an x-ray images bone within the body, these techniques provide visual data about the brain. Unfortunately, neuroimaging is often limited in that it cannot be applied to a moving body.

Elizabeth M. C. Hillman, Sarah Stanley, and Julie Brefczynski-Lewis are looking to change that. Each has succeeded in studying the brain in the behaving body. They discussed their accomplishments February 17, 2017, at the American Association for the Advancement of Science (AAAS) annual meeting.

“The BRAIN Initiative [brought] brand new money to fuel technology that goes across a number of fields that … could have impact on all areas of neuroscience,” said session organizer Jane Roskams, of the University of British Columbia in Vancouver.

Hillman, professor of biomedical engineering and radiology at Columbia University in New York, developed SCAPE: Swept, Confocally-Aligned Planar Excitation microscopy. This microscope works up to 100 times the speed of other 3D microscopes, fast enough to record brain activity in real time.

SCAPE works by illuminating a plane of brain tissue with a sheet of light. The sheet moves over the subject, quickly constructing a 3D representation of the whole brain. The light catches GCaMP, a fluorescent protein that glows green in response to brain activity. The glow indicates increases in calcium during neural firing, enabling SCAPE to map brain activity on a holistic scale.

In this technique, the study subject has freedom of movement, which Hillman remarked is significant to model organism research. “People have only been able to image [fruit fly larvae] while they were stationary,” she said. “In my system, we can actually allow those little organisms to crawl along.”

SCAPE can enrich our understanding of disease, Hillman said. “[Fruit fly] larvae are actually used to understand diseases like Lou Gehrig’s disease and spinal muscular atrophy.” Movement deficits are hallmarks of these diseases, but before SCAPE, their neural underpinnings could not be studied in a moving body.

Stanley, professor of medicine at Icahn School of Medicine at Mount Sinai in New York, is also making waves in disease pathology. She developed a technique to remotely switch groups of neurons “on” and “off.” That action can illuminate the cells’ roles in complex behavior “just like you try and switch on and switch off a machine to try and work out what it’s doing,” Stanley said.

Her technique for remote cell control inserts ion channels, integral structures in neural activation, and the iron-storing protein ferritin into the target cell. Ferritin assembles into nanoparticles filled with iron oxide. When radio waves or magnetic fields pass through target cells, the nanoparticles absorb their energy and open associated ion channels. This trips the neuron’s firing mechanism, silencing or activating the cell depending on the channel type.

This technology modulates neural activity without interrupting normal behavior. This has implications in study and treatment of disease. Stanley postulates that “it may be used as an alternative for neuro-stimulation, currently done using electrical implants, such as for deep brain stimulation for treating Parkinson’s disease.”

Currently, Hillman and Stanley’s innovations find their place in animal research. In contrast, Brefczynski-Lewis adapted a technique used on rats for human application. Brookhaven National Laboratory in Upton, N.Y., recently developed a wearable PET scanner for rats. She and her team at West Virginia University in Morgantown developed a similar device for people called AMPET (Ambulatory Micro-dose Positron Emission Tomography).

PET scanners look like something from a sci-fi flick – giant, cylindrical tubes fitted with narrow beds. Brefczynski-Lewis calls them “head-shrinkers,” a nickname for the scary looking 1960s models. In contrast, AMPET is much less intimidating and allows its wearer significant mobility. There is a seated AMPET that allows full head rotation and one with a rolling exostructure. Looking forward, Brefczynski-Lewis plans to design a helmet-sized AMPET with its supporting devices housed in a backpack.

AMPET enables imaging that was impossible with any old school “giant doughnut of a scanner,” Brefczynski-Lewis said. It eases use of PET with those who have trouble lying still, including the elderly. It can assess deep brain structures involved in balance and walking as a patient moves. This is especially significant in stroke, multiple sclerosis, and Parkinson’s research.

These scientists have helped usher in a new era of neurotechnology. As they move forward with their research, their subjects can now move with them.

Nicoletta Lanese is a senior at the University of Florida majoring in Psychology: Behavioral and Cognitive Neuroscience and BFA Dance. Reach her at nicolettalanese619@gmail.com, and follow her on Twitter @NicolettaML.