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Using X-rays to Quantify Lesions and Find Electrodes in the Brain [Cox Lab]

Using X-rays to Quantify Lesions and Find Electrodes in the Brain [Cox Lab]

Lesioning (damaging) a particular brain region is one of the most important methods in neuroscience for determining the function of that region. Many groundbreaking discoveries were made through lesions, such as the fact that the prefrontal cortex, the area behind your forehead, is important for impulse control and for planning, and the hippocampus, an area nestled deep in the middle of your brain, is necessary for the formation of new memories.

These discoveries were made serendipitously. In one case, a man named Phineas Gage had a metal rod go through his prefrontal cortex and miraculously survived; in the other, a man named H.M. had his hippocampus removed surgically for medical reasons. When dealing with animal models, however, scientists have the freedom to induce lesions in areas of interest, and don’t have to wait for an unfortunate accident in order to study a particular part of the brain. That being said, the process of inducing precise lesions remains a challenging one. After inducing a lesion in an animal, the effect of that lesion will be assessed (typically some sort of change in its behavior). Because precise lesions are so challenging, scientists must then verify the location of that lesion in the brain, in order to make sure that the change in behavior is linked to the area they meant to lesion. This is where Masís and colleagues step in, during this verification step.

Masís et al. developed a new method to quantitatively verify the location of lesions in small animal brains. The conventional method for doing so involves cutting the brain into thin slices, staining the brain with chemicals that adhere to the cells, and then imaging every slice one by one in a microscope. This process is very laborious and prone to error, and the actual results require a substantial amount of estimation that cannot be compared across studies.

In their paper published in the open access journal Scientific Reports, Masis et al. decided instead to use x-rays to create a 3-D digital volume of the brain. X-rays, as most will know from broken bones during childhood, are good for imaging tissue that is very dense, such as bone. Brain tissue is not as dense as bone, so the first challenge was to make the brain visible to the X-rays. To do this, they incubated the brain in a heavy metal called osmium, effectively fossilizing it and making it visible to the X-rays. Once the brain could be scanned in a specialized X-ray machine called a micro-CT (similar to CT/CAT scans in a hospital), all the work could be done on a computer, without any risk of damaging important specimens. Moreover, any scientist who uses this technique could then compare their samples directly to those of other scientists.

This technique can find more than brain lesions. Neurons communicate with each other using electrical pulses. Scientists listen in on these pulses by inserting electrodes that can eavesdrop on this chatter. Similarly to lesions, verifying the location of recording electrodes is another challenge that neuroscientists face. Typically, tiny lesions will be induced at the tip of the electrodes, or the electrodes will be coated with a special dye that will then be searched for after slicing the brain and putting it under a microscope. Masís and colleagues found that their method was able to locate several types of electrodes in the brain without incurring the risks of slicing, staining and potentially damaging the brain.

This work shows the potential of applying existing techniques (such as X-ray imaging) to problems in other fields, emphasizing the importance of interdisciplinary departments and the diversity of scientific programs.


 David Cox faculty profileCox Lab website

(l to r) Steffen Wolff, Grigori Guitchounts, Javier Masis, and David Mankus

(l to r) Steffen Wolff, Grigori Guitchounts, Javier Masis, and David Mankus