Good afternoon everybody. I am Mayank Kaushal and I am very excited to the ANS to give me this opportunity to present on the research that we have been undertaking for the last four years. So the purpose of my talk is to talk about changes that we have seen using resting state fMRI. Essentially the information transmission changes that we see in the brain networks following a distant insult to the cord. A bit about the epidemiology. It's a significant problem in the United States with more than 90% cases caused by a traumatic event. You have about 12,000 new cases per year. I'm quoting 2013 numbers. The 2017 numbers are about 17,000 new cases and the prevalence around 282,000. Depending on the age and the severity of the injury, the lifetime costs vary in the millions. When we talk about the pathophysiology of spinal cord injury, you have this force that is transmitted to the spinal column which leads to disruption of bony and ligamentous structures surrounding the cord and the disruption further causes neural injury and that can have manifestations which could be sensory motor and autonomic. There are two separate mechanisms that are often elicited. One is the primary mechanism and the other is the secondary. Primary being the initial blood force trauma, the initial trauma and the secondary being the cascading of cellular events that happens including edema. So, so far it has been shown that the entire So, so far it has been shown that the entire neural axis is affected when you have injury to the cord. You have anatomical evidence of retrograde valerian degeneration as we also have imaging evidence in the form of DTI, that is diffusion tensor imaging, which shows microstructural changes in the spinal tracts, corticospinal tracts on the dorsal columns. You have changes in the gray matter of the brain. You have thinning that we have seen in various grades and in various severities of spinal cord injury. We have also used functional magnetic resonance imaging which has shown posterior shifts in activation in the sensory cortex. We thought that we should probably use resting state fMRI to see what changes, if any, are present following injury to the cord. The reason we chose resting state fMRI was to determine if any neuroplasticity that's not apparent on traditional activation-based sequences of fMRI. Also investigate multiple networks in the brain in a short span of time. And a lot of these subjects have limited mobility and cannot carry out tasks properly. So in those subjects it gives us an opportunity to see what's going on in the brain. The theory of resting fMRI, I'll touch it real quick. So glutamate is released by neurons which leads to changes in the blood flow. So your balance of paramagnetic hemoglobin and the deoxyhemoglobin, it changes. That leads to a signal that is picked up by fMRI and that is what we observe, the activation signal. This was the recruitment criteria we followed. Asia A is chronic injury more than two years in the making. The demographics of our subjects, imaging parameters. So we had 15 subjects and 15 controls. We used a functional atlas by a group based out of Washington University in St. Louis, which essentially segments the brain in 264 regions. And then we did a correlation analysis. We took the time series from each region, averaged it, and correlated with every other ROI. After that we grouped the connectivity matrices that we obtained to obtain one group for one matrix for the spinal cord injury and one for the normal group. And then we tried to run the brain connectivity toolbox to perform quantitative metric analysis. We tried to see betweenness centrality and transitivity. The betweenness centrality is essentially how many shortest paths go through a particular node. So you have no- you have ROI1, you have ROI2, and they are connected through ROI3. So how many of these important shortest paths are going through ROI3? And transitivity is if two ROIs are connected to each other, what are the chances that they are connected to a third person? We tried to see these quantitative group differences at incremental cost thresholds because there is no consensus yet as to a particular cost threshold which should be used when comparing for group differences with cost thresholds being the number of possible connections and the number of actual connections seen. So our results showed that in spinal cord injury both the matrices were reduced compared to controls and this difference was obvious at multiple cost thresholds. Similar to the other two matrices we also saw clustering coefficient and modularity. I thought of including this slide, I had presented it before. And all this points to a picture that the segregation potential of the brain, that is the ability to process information in specialized regions, is compromised. It is not as efficient as compared to a normal person. So the conclusions we drew were that this shows that we can use resting state to study neurosurgically relevant populations. The alterations that we saw were persistent because these are all chronic patients so these alterations stayed. And it could potentially spur the development of non-invasive biomarkers for potential prognostication and measurement of functional recovery as we move forward. Thank you.

brain networks

resting state fMRI

spinal cord injury

neuroplasticity

connectivity matrices