Pediatric Neuro Trauma


Most people tend to assume that children are near-Herculean in regards to injury. As an EMT I see this all the time. Kids are bouncy. Something that would knock me flat on my back they respond to with no more than giggles. As with any oversimplification, there are catches especially with the brain.

Here we have a paper that takes a look at the overall effect of traumatic cranial injuries in small children and the resulting trend in performance scores. The researchers lurked around an emergency room of a children’s hospital waiting for cases of cranial trauma. They included everything from kids taking a minor spill to those involved in car accidents to those pretending they were Superman. Upon admission they were categorized via age (infant 0-2, young 3-7, and old 8-12) and Glasgow coma score (scale of 3-15: If you’re reading this, you’re a 15) as a ranking of severity.

From there they tested the kids multiple cognitive scales to determine where they ranked verbally, globally, etc. They did this 24 hours post-injury, 12 months after, and at 30 months.

 

This graph is of particular interest to me as it shows every category simultaneously. The key lines to focus on are the old severe and infant moderate/severe. What we can see from this data is that age and severity both play an enormous role in the final outcome of the patient. The younger that the patient is at the time of insult the greater the long term detriment. Additionally, the severity of the insult is an important indicator of long term recovery (as one would expect).

This model does not hold true in all instances though. When examining people who require hemispherectomies to control severe seizure activity, we see a completely different result. Older is worse; younger is better. While in the above trauma example, the lack of developed pathways hampers recovery. Yet in removing an entire hemisphere of the brain this is actually beneficial. These pathways haven’t been strengthened and are thus more malleable to change. Huzzah plasticity!


Adventitious Synesthesia: Not Just from LSD Anymore


            The age-old philosophical question of perception, “Is my green the same as your green?” remains a problem that by its very nature science will never be able to answer.  This question addresses whether one solitary sensory system perceives input precisely as another’s.  But for some people, this question is a resounding no.  For these individuals one sensation is not limited to one sensory field.  Instead, a mixed wiring occurs between senses.  Sounds are given colors; shapes are given smells.   Synesthesia ensnares the senses in ways unfathomable to the average person.

            A common method to determine the cause of deviant attributes is to look for discrepancies between the abnormal structure and the typical structure.  In synesthetes sensory areas of the brain are wired to fire together.  In other words, one input fires two senses which give rise to artificial attributes (e.g.  green music).  For most synesthetes this misfiring has been present since birth.  The cause of this sensory blending is hereditary.

Not all synesthesia is the result of genetic predisposition though.  In some cases synesthesia can be induced, known as adventitious synesthesia.  The most popular form of this is often associated with lysergic acid diethylamide or LSD.  Patients who use this compound often report a temporary, psychedelic blending of various senses.  Other methods have been reported to elicit similar effects, both temporary and permanent.  Another temporary occurrence of synesthesia can be induced by seizures within the temporal lobe.  This is unsurprising as many studies of synesthetes show abnormal activity in this area.

Permanent synesthesia can be induced in people by a variety of sources.  In the case of neural damage inflicted by stroke, the effects can be seen as the result of plastic change attempting to offset the impacted areas.  Another example involving neuroplasticity is that of a sudden loss of a sensory system, such as blindness or deafness.  These sensory areas of the brain devoted to these processes are suddenly left without input and as a result begin to lose connections.  As the pathways dissolve, other systems begin to utilize this suddenly free space.  As a result, some processes wire together and fire erroneously when subjected to a sensory signal.

Much can be gleaned from adventitious synesthesia.  If looking for deviant processes, the best comparison would be to have a before and after image of the same individual.  While LSD is illegal in many countries and inducing seizures in patients is generally frowned upon some researchers have turned to a novel method to induce synesthesia, hypnosis.  This technique is a source of great controversy within the scientific community.  While some consider it to be an apt method of bridging the gap between the conscious and subconscious mind others consider it no more than well-played showmanship or suggestive influence from the researcher.

A group of researchers, Kosslyn et al., sought to find more concrete data that shows a controlled correlation between hypnotic techniques and actual changes sensory perception.  To do this they utilized an arrangement of colored squares in two conditions, normal and greyscaled.  Then they used PET imaging while subjects were under hypnosis and exposed them to these photos under four conditions: 1) perceive the greyscaled photo with color, 2) remove color from the normal photo, 3) view the grayscale as it appears, and 4) view the normal photo as it appears.  Individuals who were not sensitive to hypnotic techniques were also included as a control method.

What they found was a shift in blood flow to key areas generally associated with synesthesia, such as the fusiform gyrus.  While there was an increase in blood flow for nearly every parameter only the condition in which participants perceived grayscale with color proved significant.  A peculiar difference was noticed between left and right hemisphere activity.  Whereas the left hemisphere only changed in activity within the hypnotized group, the right hemisphere altered activity across both groups but in response to what the subjects were instructed to perceive.

This study shows that, at the very least, the induced effect of hypnosis to perceive color on a grey template has a physical basis within the brain.  While the other attributes may still certainly be open to bias from confounding variables, this small portion of synesthesia-like behavior has an explanation other than subjective perception or role-playing.  Although this shows that indeed something is occurring in this area of the brain it fails to provide any causal evidence.

Two hypotheses currently exist to describe the mechanism behind these abnormal interactions between senses.  The first suggests an over abundance of neuronal connections between areas and that this phenomena is due to said hyperconnectivity.  The other suggests a normal connectivity between areas.  Whereas normally signals are inhibited across these regions, in synesthetes these signals are dis-inhibited.  A study performed by Kadosh et al.  examined the likelihood of the first hypothesis within a short time frame of induced synesthesia-like activity.

A common test given to grapheme-color synesthetes (those who see numbers with a color) is to place the number on a background with either the same color as their perceived number or an opposing color and test for recognition.  This same test was given to a group of highly hypnotizable individuals who acted as their own controls.  Participants received the test under two randomized conditions, no suggestion and post-hypnotic suggestion, and then scored for speed and accuracy.  The suggestion received by subjects set the numbers 1 through 6 to uniform colors which corresponded with various backgrounds.  What a non-synesthete would see on a red background would be the number 1; however, when an induced-synesthete sees this image the 1 would blend into the background.  They tested the participants in four trials, ABBA and BAAB, with “A” being without hypnotic suggestion and “B” with the suggestions.  The trials were separated by a two week interval between the third and fourth testing.

The results of the study yielded a significant difference in test performance between suggested trials and those without.  The effects of the suggestion even carried over the two week gap in trial time.  Due to the extremely short length between trials of this study it is highly unlikely that the first hypothesis can be deemed appropriate for these results.  The initial hypothesis required a hyperconnectivity between key areas, but as the effects were quickly picked up and immediately dropped (BAAB condition) macroscopic growth and decay of connections is not plausible.  Plasticity of that magnitude takes place on a much larger time scale.  Instead focus should be placed upon the more micro-level changes associated with the latter hypothesis, dis-inhibition.

While this study neither disproves hyperconnectivity in congenital synesthetes nor proves disinhibition amongst induced-synesthetes, it does show that the brain is remarkably complex in its role of regulating our perception.  Subconscious processes alone can induce a phenomenon long thought to be solely the result of brain injury or congenital anomalies.  This event can help give insights into the microscopic realm of neuroplasticity by how small inconceivable changes in neuronal firing can result in the blending of sensory systems.

Hypnosis is a technique that has long been scrutinized if not simply seen as fraudulent, and not without good reason.  Yet, as the field comes under greater scrutiny and is applied to the proper field, such as synesthesia, we find that there is much to be learned.  It is in response to the latter study of induction that we can begin to wonder if instead of turning on this bridging of senses, might these techniques enable synesthetes to disconnect their senses from one another.  This experiment, at this time, appears not to have been attempted.  As the field of neuroscience continues its growth into new areas of interest a greater, more diverse array of techniques are becoming commonplace.

Cohen Kadosh, R., Henik, A., Catena, A., Walsh, V., Fuentes, L. J., 2009. Induced Cross-Modal Synaesthetic Experience Without Abnormal Neuronal Connections. Psychological Science. 20, 258-265.

Kosslyn, S. M., Thompson, W. L., Costantini-Ferrando, M. F., Alpert, N. M., Spiegel, D., 2000. Hypnotic Visual Illusion Alters Color Processing in the Brain. Am J Psychiatry. 157, 1279-1284.


A Continuous-Time Neural Network Model


Here’s a paper, co-authored by one of my frequently read neurologists Merzenich, regarding the brain’s ability to display sensory input in sync with time. Previously, studies only examined tasks that utilized spatially differentiated patterns. These studies neglected the influence of excitatory and inhibitory postsynaptic potential summation (ePSPs/iPSPs). Why did the authors choose these neural properties? It was a shot in the dark essentially. While well characterized, no one really knows how these contribute to information processing. This seems like a good way to find out.

They proceeded with a few sets of experiments. They examined ePSPs set with paired-pulse facilitation (PPF), iPSPs with PPF, and PPF with slow iPSPs. In the last category, they saw that when they sent two identical sequential signals down the same input channel the second reaction varied from the first. In fact, they saw that 25-50% of one cell layer showed time-sensitive behavior.

From here the authors fine tune their data using multiple time intervals as well as varying frequencies of the stimulus. The take home message here is that no major reconstruction of previous models was needed. All that was needed was to observe these overlooked properties in the proper context. The authors hope that with increasing complexity of study and incorporating a few other properties, like Hebbian plasticity, will further improve our understanding the transformation of temporal signaling into spatial signaling.

Perhaps next post I’ll take a look at Hebbian plasticity to better understand where this line of research could go. Cheers.


WHYCAN’TIHITYOU?!


Currently, there is a housefly buzzing around my head. Every single time it lands I attempt this futile clapping motion to destroy it. I fail. I fail time and time again. So, my question is, obviously, WHY CAN’T I HIT YOU!?

After a small amount of Google-sleuthing I found the answer here. It seems Drosophila contain a pair of large aptly named nerves, Giant Fiber. This bundle runs the entire length of the head and down to the thorax. At the endpoint it triggers the thoracic ganglion which then shoots elsewhere. What triggers this giant bundle to begin with? The eyes! It uses visual cues to initiate its escape sequence. I wonder why it would be associated with something like that…

Just an eye... NBDSo if the Giant Fibers end with the thoracic ganglion what happens next? The ganglion shoots the signal to the dorsal longitudinal muscle (DLM) and tergotrochanteral muscle (TTM or “jump muscles”). This moves two thing: the legs and the wings. What do the legs do? JUMP! Thus, the reason they’re called jump muscles. The wings do something a little more complex. Upon receiving a signal  the wings go from the closed position to the open position and slightly elevate. So really the one nerve bundle initiates a double whammy of legs and wings. The strange part is that the TTM does both of these functions. The DLM is only indirectly involved.

So the take away message is that a simple little pathway is why I can’t kill this damn fly.

Sidenote, the paper is a little dated as it was published in 1983 but the general workings are still the same.

*Update*

Flies didn’t evolve around flyswatters. Gotcha.Owned.


Notch and Delta in a Nutshell


Cell signaling is a very important process within multi-cellular organisms. Yet, many people grossly misunderstand how cells could communicate with one another. During the Answers in Genesis conference that stopped by Morris last year, one individual was under the impression that “cellular e-mail” must exist. “Why? Well, because it must!” *sigh* So, the pathway that I’m going to look at is Notch. Why? Well, because I must!  It’s also pretty cool, I swear.

So here we have the Notch pathway. http://www.humpath.com/IMG/jpg_notch_jagged_gs_01.jpg Notch is a transmembrane protein which means it goes straight through the cell membrane and protrudes on either side. This protein acts as a form of hair-trigger. When activated it cleaves the inside part which heads off to the nucleus to play with gene expression. Notch isn’t activated by just any protein flying into it, and this is where Delta comes into play. Now the specifics vary depending on species (humans don’t actually have Delta but it’s similar and therefore Delta-like) but the purpose remains relatively the same.

**Now, I’m grossly oversimplifying the Notch pathway. I do this not because the areas I’m overlooking are not important (they are!), but this is a neurology post and it’s far too easy to get bogged down in minutia of everything and overlook the cool stuff of one area. **

So Delta and Notch touch, part of Notch breaks off and heads off into the cell to make shenanigans. What does this shenaniganary have to do with cell signaling and the nervous system? These have two functions. One is to adhere the two cells to one another. The other function is in development, in this case neuro-development. Once the cell with Delta contacts the Notch cell the piece inside breaks off and heads for the nucleus. What it does here is stop the cell from differentiating while the Delta cell remains able to do so. Notch inhibits rather than induces. It’s a bit backwards from what you would expect, but the role of Notch in neural development is to say who cannot become neural tissue.  As for the Delta cell, eventually it will move out of the epithelial layer and differentiate into a neuroblast.

If you think about it, this makes sense. If something induces neural differentiation then something should also stop it to avoid something made entirely of nervous system. Now, I can’t emphasize enough that Notch does other things. Those things just reach beyond the scope of this class. This is just a quick look at how two little things poking out of a cell can have a big impact.


The Role of Neuroplasticity in Constraint-Induced Therapy


WOOHOO! I am finally done with my senior paper. As you may surmise from the title I chose to write it on the neuro-mechanics involved with CI therapy. It’s written with a more informal tone but nonetheless it still landed me high marks.  Comments, questions, and retweets (#revfrost) are always welcome. Enjoy!

ABSTRACT: The human brain is capable of extraordinary change. The impact of strokes can be devastating and often times seen as refractory. Constraint Induced (CI) therapy has proved beneficial in alleviating common symptoms caused by strokes. Recent evidence provides an insight in identifying the biological mechanisms exploited by CI-therapy: neurogenesis, gliosis, and synaptogenesis.

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A Brief History of the Brain: Ancient Egyptians


The brain has always been looked upon with reverence and awe for its power and capacity of conscious thought… right? Absolutely not. Not only is the brain the coolest thing in science (no bias, I swear) but historically it has been neglected or set aside as the “housing of the soul.” Well, that’s irritating.

So let’s start back in ye’ olden days of the pharaohs. It seems the Egyptians fall into a weird category of belief. They recognized the problems that would arise from head wounds but ignored it in terms of thought and consciousness. During the mummification process they would enter the nasal cavity, break through the thin-layered ethmoid bone, and draw out the contents of the skull. We’ve all heard this spiel since elementary school. The important parts to ask though are the why and how.

The why seems relatively straight forward. It was removed along with all the other organs excluding the heart to prepare the dead for their afterlife. The heart was left in place to be judged in Duat, the Egyptian underworld. Under supervision of Anubis, the heart was weighed against Ma’at’s feather of truth. The Declaration of Innocence: Spell 125 details a 42-part moral system which they were judged upon – similar to that of the 10 Commandments of Christianity but 2000 years prior (coincidence? >_>). If the heart was found to be unworthy it was eaten by the “devourer”, Ammut. If not, they proceeded to Aaru, the heavenly reed field.

That’s neat and all, but it’s not the whole story. Only 50% of recovered mummy skulls had the brain removed prior to mummification. In addition, the eyes had also been removed and replaced with various materials. Why? Because they rot and stay moist. The whole point of mummification is to remove as much water as possible to preserve the remaining tissue. The body needed to stay as recognizable as possible; I’ll explain in a minute. An example concoction used as a dehydrant consisted of 84.7% sodium carbonate or bicarbonate, 1.5% sodium chloride, and 13.8% sodium sulphate. While this prevents most bacterial decay it doesn’t stop it all. The brain and eyes start to leak fluid and rot. Quick fix? Take them out. Sure, it’s a little more difficult than the other organs, but it works better in the long-run. A dry mummy is a happy mummy.Credit goes to http://www.offbeatenough.com/

Another key part is how the brain was removed. Mummification was usually performed in a manner that minimized cosmetic damage as it was believe the soul (the Ba) needed to recognize the body to return to it every night. The  common belief of the process behind it seems to be a gross misconception. It is largely held that the brain was sucked out, scooped out with a hook or some variation thereof. For the most part, this is untrue. The tool used did indeed have a hook but it did not function in that fashion. The viscosity of the brain allowed it to stick to the entire tool. So, as the tool would be drawn out it would bring brain with it. With repeated entry from the tool the inside tissue would begin to liquefy and eventually could be poured out of the nasal cavity.

The Egyptians were pioneers of the medical realm. They were even recognized by Homer in the Odyssey: “In Egypt, the men are more skilled in medicine than any of human kind.” The Edwin Smith Surgical Papyrus details a great many of their accomplishments along with a few of their more… unique practices. Maybe with a bit more time they could have perfected the art of medicine a little more. Until next time, remember to “pour milk into both ears” for a wounded temple.

The Problem of Brain Removal during Embalming by the Ancient Egyptians
F. Filce Leek. The Journal of Egyptian Archaeology

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