Imaging the Relationship Between the Brain and Behavior after Spinal Cord Injury
A longtime collaboration between Miami Project and Marquette University researchers is shedding light on the relationship between the central nervous system and recovery from spinal cord injury.
Equipped with a new National Institutes of Health (NIH) federal award, Pantelis Tsoulfas, M.D., associate professor of neurological surgery and cell biology and anatomy at The Miami Project to Cure Paralysis, and Murray Blackmore, Ph.D., professor of biomedical sciences at Marquette University, will continue a long, fruitful collaboration.
The accomplished scientists are mapping the supraspinal, or brain, connections between the central nervous system (CNS) and functional recovery after spinal cord injury (SCI).
The Brain-SCI Connection
At first glance, it might not be obvious why the brain changes after SCI. Since trauma damaged the spinal cord, glia and fibrotic scar form there. But the reduction in sensory input from the body no longer transmitted to the brain leads to a reduction in brain regions that would typically process that input.
Known as cortical remapping, these changes occur in brain regions that receive information and also in regions that send information but no longer routinely activate. Drs. Tsoulfas and Blackmore have been diligently pursuing their goal of charting the entire network of brain connections — the supraspinal connectome — rather than focusing on just one or two. Their work will establish a neuroscientific framework for understanding the variations in functional outcomes after SCI.
Their new award integrates previously proven but separate approaches in a pivotal and thorough investigation, demonstrating the power of the model they have developed.
Drs. Tsoulfas’ and Blackmore’s supraspinal connectome journey began in 2018, when Dr. Blackmore was a postdoctoral fellow at The Miami Project.
“Science thrives on reciprocity and collaboration of different teams,” Dr. Tsoulfas said, “and the value of long-term professional relationships cannot be overstated.”
Drs. Blackmore and Tsoulfas implemented a novel, viral technique in SCI that labeled neurons projecting fibers to targets throughout the central nervous system. The method could label all intact brain connections with just a single application of a spinal cord tracer. Putting that capacity to productive use, though, requires imaging the entire, undamaged brain.
Light-sheet microscopy makes the supraspinal connectome paradigm possible. Rather than sectioning, light-sheet microscopy clears samples using a chemical process that makes tissue transparent. A sheet of light is then passed through the entire sample to illuminate and reconstruct in three dimensions the intact tissue. Combining a viral tracer with light-sheet microscopy allowed the researchers to label the entire CNS and then image the neurons.
The Next Step in Connectome Comprehension
Drs. Tsoulfas and Blackmore are now trying to understand how changes in the connectome relate to functional outcomes after SCI. By adopting a connectome approach, their research team aims to link changes in the brain regions with the restoration of motor function. In turn, their work may shed light on the cause of post-SCI recovery variability and why some smaller injuries lead to profound deficits while larger SCIs result in relatively minor impairments.
The team will deactivate certain brain regions that contribute to recovery after SCI. If deactivation generates the loss of a previously regained function, it will provide strong evidence that the region impacts function.
In addition to creating a comprehensive CNS labeling and imaging approach that integrates the supraspinal connectome with functional recovery after SCI, the work of Drs. Tsoulfas and Blackmore will also shed light on the complex relationship between the supraspinal connectome and functional outcomes, post-SCI, by attributing effects to specific nuclei, regardless of the of intervention type.
Tags: Dr. Pantelis Tsoulfas, spinal cord injury, The Miami Project to Cure Paralysis