“Our study suggests that patients with hidden consciousness can hear and comprehend verbal commands, but they cannot carry out those commands because of injuries in brain circuits that relay instructions from the brain to the muscles,” says study leader Jan Claassen, MD, associate professor of neurology at Columbia University Vagelos College of Physicians and Surgeons and chief of critical care and hospitalist neurology at NewYork-Presbyterian/Columbia University Irving Medical Center.

The findings could help physicians more quickly identify brain-injured patients who might have hidden consciousness and better predict which patients are likely to recover with rehabilitation.

Brain circuits disrupted in patients with hidden consciousness

Hidden consciousness, also known as cognitive motor dissociation (CMD), occurs in about 15% to 25% of patients with brain injuries stemming from head trauma, brain hemorrhage, or cardiac arrest.

In previous research, Claassen and colleagues found that subtle brainwaves detectable with EEG are the strongest predictor of hidden consciousness and eventual recovery for unresponsive brain-injured patients.

But the precise pathways in the brain that become disrupted in this condition were unknown.

In the new study, the researchers used EEG to examine 107 brain injury patients. The technique can determine when patients are trying, though unable, to respond to a command such as “keep opening and closing your right hand.”

The analysis detected CMD in 21 of the patients.

The researchers then analyzed structural MRI scans from all of the patients.

“Using a technique we developed called bi-clustering analysis, we were able to identify patterns of brain injury that are shared among patients with CMD and contrast to those without CMD,” says co-lead author Qi Shen, PhD, associate research scientist in the Claassen lab and an expert in signal processing, machine learning, and biostatistics.

The researchers found that all of the CMD patients had intact brain structures related to arousal and command comprehension, supporting the notion that these patients were hearing and understanding the commands but were unable to carry them out.

“We saw that all of the CMD patients had deficits in brain regions responsible for integrating comprehended motor commands with motor output, preventing CMD patients from acting on verbal commands,” says Claassen.

The findings may allow researchers to better understand which brain injury patients have CMD, which will be useful for clinical trials that support recovery of consciousness.

More research is required before these approaches can be applied to clinical practice. “However, our study shows that it may be possible to screen for hidden consciousness using widely available structural brain imaging, moving the detection of CMD one step closer to general clinical use,” Claassen says.

“Not every critical care unit may have resources and staff that is trained in using EEG to detect hidden consciousness, so MRI may offer a simple way to identify patients who require further screening and diagnosis.”

The researchers will present their results at the fall meeting of the American Chemical Society (ACS).

“For 20 years, my group has been developing methods to transform natural products — such as glucose obtained from sugar cane or trees — into degradable, digestible polymers that don’t persist in the environment,” says Karen Wooley, Ph.D., the project’s principal investigator. “But those natural products are harvested from resources that are also used for food, fuel, construction and transportation.”

So Wooley began searching for alternative sources that wouldn’t have these competing applications. Her colleague Jeffery Tomberlin, Ph.D., suggested she could use waste products left over from farming black soldier flies, an expanding industry that he has been helping to develop.

The larvae of these flies contain many proteins and other nutritious compounds, so the immature insects are increasingly being raised for animal feed and to consume wastes. However, the adults have a short life span after their breeding days are over and are then discarded. At Tomberlin’s suggestion, those adult carcasses became the new starting material for Wooley’s team. “We’re taking something that’s quite literally garbage and making something useful out of it,” says Cassidy Tibbetts, a graduate student working on the project in Wooley’s lab at Texas A&M University.

When Tibbetts examined the dead flies, she determined that chitin is a major component. This nontoxic, biodegradable, sugar-based polymer strengthens the shell, or exoskeleton, of insects and crustaceans. Manufacturers already extract chitin from shrimp and crab shells for various applications, and Tibbetts has been applying similar techniques using ethanol rinses, acidic demineralization, basic deproteinization and bleach decolorization to extract and purify it from the insect carcasses. She says her fly-sourced chitin powder is probably purer, since it lacks the yellowish color and clumpy texture of the traditional product. She also notes that obtaining chitin from flies could avoid possible concerns over some seafood allergies. Some other researchers isolate chitin or proteins from fly larvae, but Wooley says her team is the first that she knows of to use chitin from discarded adult flies, which — unlike the larvae — aren’t used for feed.

While Tibbetts continues to refine her extraction techniques, Hongming Guo, another graduate student in Wooley’s lab, has been converting the purified fly chitin into a similar polymer known as chitosan. He does this by stripping off chitin’s acetyl groups. That exposes chemically reactive amino groups that can be functionalized and then crosslinked. These steps transform chitosan into useful bioplastics such as superabsorbent hydrogels, which are 3D polymer networks that absorb water.

Guo has produced a hydrogel that can absorb 47 times its weight in water in just one minute. This product could potentially be used in cropland soil to capture floodwater and then slowly release moisture during subsequent droughts, Wooley says. “Here in Texas, we’re constantly either in a flood or drought situation,” she explains, “so I’ve been trying to think of how we can make a superabsorbent hydrogel that could address this.” And because the hydrogel is biodegradable, she says it should gradually release its molecular components as nutrients for crops.

This summer, the team is starting a project to break down chitin into its monomeric glucosamines. These small sugar molecules will then be used to make bioplastics, such as polycarbonates or polyurethanes, which are traditionally made from petrochemicals. Black soldier flies also contain many other useful compounds that the group plans to use as starting materials, including proteins, DNA, fatty acids, lipids and vitamins.

The products made from these chemical building blocks are intended to degrade or digest when they’re discarded, so they won’t contribute to the current plastic pollution problem. Wooley’s vision for that process would align it with the sustainable, circular economy concept: “Ultimately, we’d like the insects to eat the waste plastic as their food source, and then we would harvest them again and collect their components to make new plastics,” she says. “So the insects would not only be the source, but they would also then consume the discarded plastics.”

The researchers acknowledge support and funding from the Welch Foundation and a private donation.