Wednesday, September 24, 2014

3D Printed Brain Saves A Life



We are constantly hearing about 3D printing in the media. Whether people are making 3D-printed cars, guns, or even organs, this technology is becoming wild with the thousands of different applications. My new favorite: a 3D printed brain.

A hemispherectomy is a [scary] surgical procedure in which an entire hemisphere of your brain is either entirely removed, partially removed, or surgically disconnected (termed: functional hemispherectomy because all electrical influence of the diseased hemisphere is removed) from a healthy hemisphere in order to protect the healthy brain from damage (picture below is an example brain scan of a 7-year old girl who underwent the procedure, note what is missing!).






Image Source: http://www.dailymail.co.uk

The removed or disconnected hemisphere is epileptic and damaging the healthy hemisphere of the brain. I have always found this procedure to be so barbaric but also astonishing at the same time. An entire half of your brain is removed! Unfortunately, this is currently one of the only effective treatments for such intractable epilepsies. But, what is so phenomenal about this is that not only do patients not present with any long-term deficits in language or intelligence, their IQ often improves. On average there is an increase of 10 IQ points!

Before I get into what all of these results mean in terms of the implications of brain function and its amazing plastic nature, I want to review some of the basic neuroanatomy that is truly incredible with human brains. Gyrencephalic brains (of which human brains are included) are often considered to be more ‘complex’ and contain a vast number of folds to obtain the surface area required for their high neuron count. The smallest mammal with a gyrencephalic brain for example is the ferret. Lissencephalic or ‘smooth’ brains are often observed in animals that are often considered to be more primitive (e.g. rodent brains) in nature and have lower neuron counts since the brain does not need the surface area to accommodate for an increased number of neurons. Now, why is this important? Brain tissue is incredibly weak! It’s really hard to convey this idea to people who haven’t held an unfixed brain. Here is a good example of an unfixed human brain:


The Unfixed Brain


Watch this video because it is pretty incredible; it is a demonstration of a human brain being handled immediately following its removal from an autopsy. It is important to understand how weak the brain is because if the brain were resting on any part of your skull, it would be damaged. As you can see in this video demonstration, just from having an unfixed human brain set on a table, it has deformed the tissue and compressed it immediately. So, how does the brain stay undamaged inside of the skull? Cerebrospinal fluid typically ‘floats’ the brain and this prevents it from being damaged. And, in order to prevent the cerebral hemispheres from crashing into each other or the cerebellum, we have evolved some incredible structures that are rarely covered in introductory neuroanatomy courses.

Inside the human skull we have what are called the falx cerebri (pictured below), a structure typically present within the skulls of species that possess gyrencephalic brains. These incredible extensions of the dura mater, a protective covering of brain tissue, plunge down in between the cerebral hemispheres to block them from damaging each other. An additional projection extends from the skull wall to separate the hemispheres from the cerebellum. These structures are so rigid that during an extreme trauma such as a car accident or a blast-traumatic brain injury, the rotational forces generated can cause the brain matter to contact the falx cerebri and sheer the brain tissue like a hot knife through warm butter. Brain tissue is that weak. Now, imagine the incredible task of the neurosurgeon. In the more commonly performed modern procedure, the functional hemispherectomy, the neurosurgeon must navigate and sever all connections of epileptic hemisphere from the healthy half of your brain. As I am sure you can imagine, an incredible dearth of complications are associated with this surgical procedure given the construction of the inside of the human skull. The entire skull cannot be removed and several sites are required to be severed in order to obtain complete functional disconnection of the unhealthy hemisphere. Normally, this is done with some mapping by a magnetic resonance imager but, in some ways, one might argue the operation is done somewhat blindly as there are enough individual variations in brain anatomy to cause problems.






Wikimedia Commons ©

On September 3rd, The Verge reported the incredible story of Gabriel Mandeville. At the age of 5 months, Gabriel started experiencing incredibly debilitating seizures and they only continued to get worse. After several treatment attempts failed, Gabriel’s neurologists quickly decided the only treatment option was a functional hemispherectomy. Understanding the incredible risk associated with this surgery, Boston Children’s hospital had a 3D printer replicate Gabriel’s brain to give the surgeon a practice run. Part of a growing program at Boston Children’s and Harvard’s Hospital, the Pediatric Simulator Program (called SIMPeds: http://simpeds.org/) creates extensive simulations for various procedures to allow physicians and surgeons to practice these operations in advance of the real thing. A variety of 3D printed objects are being produced to simulate more common procedures or for those as rare as the hemispherectomy performed by Gabriel’s neurosurgeons.

The happy ending to this story is that Gabriel is now seizure free. But, I still haven’t hit the nail on the head as to why I think this is an incredible story that gives us such powerful information about the brain. An entire half of a brain is either completely or partially removed during this incredibly uncommon surgical procedure. It seems that either through abnormal development, perhaps due to the presence of the diseased hemisphere, the healthy hemisphere is able to take over seemingly all of the functions of the diseased hemisphere. Again, further demonstrating that the neuromyth that we have hemispheric dominance is not true (if the myth were true all of the functions associated with some particular hemisphere should be completely lost). It’s almost hard to believe that we can still do so much with so much loss. Even further, the average improvement in IQ by 10 points is remarkable and suggests that the diseased hemisphere was almost putting some kind of brake or training wheels on the healthy one and hindering its normal function.

The brain is truly the most remarkable organ. For most people, it might seem impossible that our brains could adapt to such a trauma but it prevails for reasons we are far from completely understanding. A fact that makes this field so exciting; so much is left to be learned. 3D printed ‘practice brains’ are making this procedure far safer and a more viable option to let the healthy brain do what its designed to do best during development: thrive.



NeuroscienceDC




References:

The Verge, "Doctor turns to 3D printers in a race to save a toddler's mind." September 3rd, 2014: http://goo.gl/gV7a5g


Tinuper, P., Andermann, F., Villemure, J.G., Rasmussen, T.B., and Quesney, L.F. (1988). Functional hemispherectomy for treatment of epilepsy associated with hemiplegia: rationale, indications, results, and comparison with callosotomy. Annals of neurology 24, 27-34.

Tuesday, June 17, 2014

The Neurogenesis Saga

Similar to the once wildly popular anime, Dragon Ball Z, science too has its own sagas.
Webster defines ‘dogma’ as, “a belief or set of beliefs that is accepted by the members of a group without being questioned or doubted.” Science is no different than any other field in terms of having its own dogmas. Anyone who has taken a biology course is probably familiar with the central dogma of molecular biology. In 1958 it was thought that information transfer occurs in the following order:
As with most ‘rules’ in biology, viruses tend to break them [and they do so in some of the coolest ways]. Like Apple’s slogan, “There’s an app for that,” there’s often a virus that breaks a biological rule you think you know (Author’s note: if biology textbooks pick up the phrase, “There’s a virus for that” you can say you saw it here first). The discovery of RNA-based tumor viruses demonstrated that viruses with an RNA-based genome can actually insert their information into the nucleus in a fashion reverse that of the central dogma (RNA --> DNA). This discovery led to a major change in the way we think about the flow of biological information within the cell. Questioning some of the most basic assumptions about life have led to amazing, and important discoveries.
In neuroscience, a traditionally held dogma basically states that no new neurons are produced in the adult brain. This dogma is part of a constantly evolving saga in neuroscience: the neurogenesis saga. Some may have heard of the Neuromyth that whenever you drink alcohol, you lose brain cells. Aside from being dispelled as a neuroscience myth, logically this doesn’t seem to make sense. If this were true, this would mean the brains of a lot of college freshman everywhere might rapidly shrivel to nothing during their first semester in college. Thankfully neither of these pieces of information are true. Our brains are capable of producing new neurons, a processed called adult neurogenesis and alcohol–for the most part–does not kill them. There are two brain regions that are now associated with producing newborn neurons in the adult brain: the dentate gyrus of the hippocampus and the subventricular zone.
As it often happens in science, the story evolves and gets more complicated in light of new data. Ernst and colleagues published a paper in Cell that provides strong evidence that neurogenesis also takes place in the adult striatum–a structure well-known for its involvement in motor control. This begs the question, why would there be a need for newborn cells in the adult striatum? Huntington’s disease is typically associated with damage to the striatum and abnormal movements called chorea. Many more studies will need to be conducted to infer the role of striatal neurogenesis, but it is interesting to note that the authors of this paper also analyzed post-mortem brain tissue of patients who had Huntington’s disease. They found a dramatic reduction in the number of newborn cells produced in the striatum of these patients present in the disease. Why is this happening? It is unclear but the discovery could play an important role in understanding Huntington's disease and assist in treatment development.
In the hippocampus, a structure extremely well-known for its role in learning and memory, the answer for why there would be a need for newborn neurons in the adult might seem a little more straightforward. And, as it turns out, it appears that newborn neurons in the adult hippocampus are required for the formation of new memories. But, interestingly, the production of too many newborn neurons in the hippocampus may paradoxically induce forgetting. In a paper recently published in Science, Aker and colleagues suggest an explanation for the phenomenon of infantile amnesia. Don't vividly remember the first few years of your life? Based on the interesting evidence presented in the paper, the authors suggest that the production of new cells within the hippocampus actually regulates forgetting. When we are newborns, the process of neurogenesis is occurring at an alarming rate and because of this, we are not able to retain any of our first memories during early life. I found this particular study to be fascinating because I think the kinds of scientific questions like, "Why can't I remember being 2 years old?" are unique to neuroscience. Moreover, the fact that we're able to answer these questions now with modern lab techniques make this such an exciting field. I'm anxious to see where the neurogenesis saga goes next.

NeuroscienceDC

References:
Akers, K.G., Martinez-Canabal, A., Restivo, L., Yiu, A.P., De Cristofaro, A., Hsiang, H.L., Wheeler, A.L., Guskjolen, A., Niibori, Y., Shoji, H., et al. (2014). Hippocampal neurogenesis regulates forgetting during adulthood and infancy. Science 344, 598-602.

Crick, F. (1970). Central dogma of molecular biology. Nature 227, 561-563.

Ernst, A., Alkass, K., Bernard, S., Salehpour, M., Perl, S., Tisdale, J., Possnert, G., Druid, H., and Frisen, J. (2014). Neurogenesis in the striatum of the adult human brain. Cell 156, 1072-1083.

Saturday, March 22, 2014

Hope for the 1%ers

The rich are not the only 1%ers. About 1% of the world has epilepsy. Epilepsy is one of the most common neurological disease in the world and unfortunately, up to one-third of these patients are resistant to the current anti-epileptic medications. For these patients, there is little recourse. Epilepsy surgery, though an extreme form of medical intervention is one of the only options for patients whose epilepsy is drug-resistant. This past November, the FDA approved an implantable device made by NeuroPace that acts–as you might've guessed–similar to a pacemaker (pictured below).
Once NeuroPace detects the onset of abnormal electrical activity, it delivers short rounds of stimulation to prevent seizure activity from starting or arrest it in its tracks. This device is currently approved by the FDA for the treatment of partial epilepsy that is resistant to 2 or more current antiepileptic medications. Partial epilepsies are those that have seizures that do not spread to or occur throughout the entire brain but are localized to a specific area: the seizure focus. This device is not designed to treat those seizures that do spread throughout the brain (generalized epilepsies). 

The advent of this device highlights some of the more recent advancements for patients with this debilitating disease. But, this also represents hope for people who have a certain stigma associated with their disease. In the United States, patients with epilepsy have significant challenges. Depending on the state you live, there can be rather severe but understandable restrictions on how long you must be seizure-free before a driver's license may be issued (see this article for a review on driving issues and epilepsy). Alarmingly, the diagnosis of epilepsy can also be used in the consideration of divorce proceedings and these patients may be denied custody of their child based on this diagnosis. 

Depending on your culture and part of the world you live, the diagnosis of epilepsy can be a mark of disgrace, or even considered a form of madness. Attitudes towards disorders such as epilepsy are changing but, unfortunately in some languages, the word used for epilepsy derives from words that are demonstrative in regard to the cultural attitude experienced by these patients. For example, in Chinese the word for epilepsy is 癲癎 or dianxian, a word for madness. In Japanese, the word epilepsy is てんかん (tenkan) which also means madness. In a recent article in Epilepsia, Kim and colleagues discuss these cultural stigmas regarding the diagnosis of epilepsy in Asia and in an attempt to change these attitudes, Korea is leading the way by altering their current name for epilepsy: 간질 (Gan-jil) meaning mad sickness to 뇌전증 (Noi-jeon-jeung) a word meaning cerebroelectric disorder.

Changing the legal and cultural attitudes towards people with epilepsy will help these patients seek the medical treatment they desperately need. Treatments like the device by NeuroPace which represent a significant advancement in the treatment of drug resistant epilepsies.


NeuroscienceDC


References:
Thurman, D.J., Beghi, E., Begley, C.E., Berg, A.T., Buchhalter, J.R., Ding, D., Hesdorffer, D.C., Hauser, W.A., Kazis, L., Kobau, R., et al. (2011). Standards for epidemiologic studies and surveillance of epilepsy. Epilepsia 52 Suppl 7, 2-26.

Kim, H.D., Kang, H.C., Lee, S.A., Huh, K., and Lee, B.I. (2014). Changing name of epilepsy in Korea; cerebroelectric disorder (noi-jeon-jeung,,): My Epilepsy Story. Epilepsia 55, 384-386.


Monday, February 17, 2014

First Post-KickStarter Episode of NEURO.tv

After an extremely successful KickStarter campaign (https://www.kickstarter.com/projects/410389794/neurotv-discussion-among-scientists-and-philosophe) we raised enough money to meet our goal. It's too bad we didn't meet our stretch goal because I would've loved to have seen our President, Jean-Francois be taught how to dance dubstep. I am truly excited for our first episode (which you can find here: goo.gl/Q8D7HU) and hope this great concept for a show will last for many seasons to come.

For our first episode our special guest is Katherine Bryant (Twitter: @EvoNeuro). Katherine is neuroscience PhD student at Emory University studying primate cortical evolution, the main topic of conversation during our episode. Specifically we talk about the visual system across different primate species and how this system may have evolved. We also have a short chat about freedom of speech and activism within academia. I hope everyone enjoys this first episode and I am very excited for the rest of the season 1. I won't give away all of the guests but one of the our other guests is the famous neuroscientist, Dale Purves who is not only an expert in vision but has written one of the canonical introductory neuroscience textbooks used by many undergraduate and graduate neuroscience programs.

NeuroscienceDC