7 remarkable technologies shaping the future of the brain

The brain is the most enigmatic structure in the universe. But every now and then, the brain malfunctions. And just like Humpty Dumpty, we struggle to put it back together again…at least not to its previous level of complex organisation. But we are remarkably ingenious creatures, obviously because we possess great brains, and we are ever-inventing brilliant schemes to fix the brain (or at least our brains are). And we, or our brains, often conjure up unthinkable technologies (pardon the intended pun!) Over the years this blog has tried to keep up with these improbable schemes, and you can check the veracity of this claim by looking up two of my very old blog posts on this:

6 exciting neuroscience discoveries that will shape neurology

 10 remarkable breakthroughs that will change neurology.

But the developments keep rolling in, so here are 7 remarkable technologies shaping the future of the brain.

Artificial neurones

What if you could just replace your damaged nerves with spare neurones-just as you would replace a faulty spark plug in your car (OK, wrong analogy for many people I know). Well, this may not be a fantasy for too long. This comes from a piece in Popular Science titled Artificial neurones could replace some real ones in your brain. The article says “Swedish researchers have developed a synthetic neuron that is able to communicate chemically with organic neurones, which could change the neural pathways and better treat neurological disorders”. This is just understandable enough for most people and I will go no further. But if you desire the hard science version, with references to biomimetic neurones, (or is it neurons?), you may check out the original study in the journal Biosensors and Bioelectronics ; it does come with a slightly shorter and less convoluted, but totally undecipherable title, An organic electronic biomimetic neuron enables auto-regulated neuromodulation. I will stick to the Popular Science version.

Brain 22. Affen Aljfe on Flickr. https://www.flickr.com/photos/142299342@N06/32794072623 http://www.modup.net/

Bionic memory

One major disorder everyone fears is dementia. The concept of forgetting, not just your experiences but family, friends, and eventually yourself, is frightening. But what if you could rely on an electronic memory. A start in this direction was a report that researchers have built a nano memory cell that mimics the way humans lay down memory. At 10,000 sizes smaller than a human hair, such an external memory will surely prove useful. But just take a breath and imagine what it will be like to be incapable of forgetting! Solomon Shereshevsky on my mind. Some way to go yet. This story is sourced from the website Mashable but the research itself is published in the journal Advanced Functional Materials with the, again, cryptic title Donor‐induced performance tuning of amorphous SrTiO3 memristive nanodevices: multistate resistive switching and mechanical tunability. Stick to the translated version in Mashable.

Artificial-intelligence-503593_1920. Many Wonderful Artists on Flickr. https://www.flickr.com/photos/alansimpsonme/34715802120

Memory implants

Most people do not want extraordinary memories and would just want to access the ones they have laid down. Some of these are however buried so deep in the crypts of their brains, they have become inaccessible. Again, technology may have something to promise them. And this comes in the form of a memory boosting brain implant. This device, developed by US Defence scientists, can detect how we retrieve memory, and predict when this will fail, and kick in to action to save the day. A sort of brain pacemaker you may say. The potential benefit is in head injury, but we can all do with a little help every now and then, when the ‘uhms’ and the ‘aahs’ kick in. This piece comes from Science Alert but the original article is on the website of the Defence Advanced Research Project Agency (DARPA), and it is titled Targeted Electrical Stimulation of the Brain Shows Promise as a Memory Aid. Not a bad one this time.

Machine Learning & Artificial Intelligence. Mike MacKenzie on Flickr. https://www.flickr.com/photos/mikemacmarketing/42271822770 www.vpnsrus.com

Neural prosthetics

Another technology promising to help memory is neural prosthetics. These serve to directly send our short-term memories into long-term storage, bypassing the hippocampus when it is too defective to do the job properly. This comes from a piece in Science Daily titled Scientists to bypass brain damage by re-encoding memories. What the prosthesis does is “to bypass a damaged hippocampal section and provide the next region with the correctly translated memory”. In effect it will make the hippocampus redundant. I’m sure the hippocampus does other things apart from encode memories… but we don’t want to think of that now.

Artificial Intelligence – Resembling Human Brain. Deepak Pal on Flikr. https://www.flickr.com/photos/158301585@N08/43267970922

Thought-evoked movements

Imagine being able to move a robotic limb by just thinking about it. No, not telepathy, but with your brain wired to the limb. This is what a prosthetic technology promises for people with brain damage who are unable to move. The prosthetic is implanted in the part of the brain that initiates our intention to move. The source for this story comes from USC News, and it is titled Neural prosthetic device yields fluid motions by robotic arm. In the example cited in the piece, the surgeons “implanted a pair of small electrode arrays in two parts of the posterior parietal cortex-one that controls reach and another that controls grasp“. You have to see the robotic arm in action. Sci-fi is becoming reality in a brain lab near you soon.

3D Brain Sculpture STL model. Misanthropic one on Flikr. https://www.flickr.com/photos/22902505@N05/14780918556

Behavioural remote control

Press a button and alter behaviour. Exciting and scary at the same time. But this is what chemogenetics promises, or threatens, depending on your point of view. This one comes from a piece on the website Neuroscience News titled Chemogenetics technique turns mouse behaviour on and off. The technique “achieves remote control by introducing a synthetic brain chemical messenger system that integrates with the workings of naturally-occurring systems”. ‘Integrate’ feels a tad extreme, almost like being assimilated by the Borg. But I suppose it will be no worse than the antipsychotics and sedatives we currently use to control the behaviour of people with schizophrenia and addictive disorders. It surely looks like it has potential, at least in mice for now.

artificial-intelligence-2167835_1280. Many Wonderful Artisits on Flickr. https://www.flickr.com/photos/alansimpsonme/34752491210

Cognitive enhancement

This technology goes beyond just increasing the ability to preserve or retrieve memory. It sets out to make the brain smarter. This piece comes from The Atlantic and is titled Why cognitive enhancement is in your future (and your past). The technology is transcranial direct current stimulation (TDCS) of the deeper reaches of the brain, using electrodes to send small and painless electrical currents. The currents are thought to increase neuroplasticity, and this enables neurons (or perhaps neurones?) to form the connections necessary for learning.

Brains. Neil Conway on Flickr. https://www.flickr.com/photos/neilconway/3792906411

***

It is mind-boggling enough just thinking that people out there are thinking of stuff like these! But it is equally reassuring that the future of the brain is bright.

7 epic historical rivalries that shaped neuroscience

I admit I have a keen interest in rivalries. I think they reveal something primal about the human psyche. Nothing beats professional conflicts in their sheer intensity, and the scientific world is particularly rife with fierce duels and petty jealousies. And the main driver for these squabbles, often prolonged and bruising, is the ambition to be recognised as the first and the best. And the fuel is often the tempting allure of a juicy patent, and perhaps a Nobel prize to boot. Some scientific feuds are legendary, such as the one between Isaac Newton and Robert Hooke, or the one between electricity giants Nicola Tesla and Thomas Edison.

By RollieBOwn work, CC BY-SA 3.0, Link

Coming closer home, the medical world has had, and continues to have, its share of rivalries. A look back at different stages of history reveals virulent feuds such as the one between polio vaccine pioneers Jonas Salk and Albert Sabin, and the HIV rivalry between Robert Gallo and Luc Montagnier. We can look even back further to the conflict between medical microbiologists Robert Koch and Louis Pasteur, or the wars between cardiac surgery giants Michael DeBakey and Denton Cooley.

 

By Hisland7Own work, Public Domain, Link

How has the field of neuroscience fared in the duelling arena? Here are our 7 epic historical rivalries that shaped neuroscience.

1. Wilder Penfield versus Francis Walshe

This is not a huge controversy, but there is enough hurt ego to class it a rivalry. Wilder Penfield, the brilliant neurosurgeon, was instrumental to mapping the representation of the motor and sensory cortex, defining the homonculus. He did this through his experiments during awake surgery for people with intractable epilepsy at the prestigous Canadian Neurological Institute. Francis Walshe, neurologist at the National Hospital for Neurology and Neurosurgery was, to say the least, unimpressed by Penfield’s surgical approach. And he said so to Penfield’s hearing at an Anglo-American Symposium which held in London. The controversy also played out in a series of letters between the two. But it is possible the rivalry goes further back in time; they probably never took to each other when they both trained under the great neurologist Gordon Holmes. And at the heart of the matter is the disdain with which neurologists regarded neurosurgeons at that time. How the tide has changed.

By Bureau of Land Management, U.S. Department of the Interior – http://www.blm.gov/pgdata/etc/medialib/blm/mt/blm_programs/whb.Par.51951.Image.-1.-1.1.gif, Public Domain, Link

2. Sigmund Freud versus Carl Jung

These are two of the leading figures in psychoanalysis. The older Sigmund Freud, and the younger Carl Jung, liked each other at the outset…until their scientific theories about the nature of the unconscious made them rivals. This resulted in the two distinct Jungian and Freudian concepts. Some go as far as to argue that sex and race were also driving their rivalry. Whatever the reasons, things got very heated with Freud claiming Jung wanted him dead. How much worse could a rivalry get?

Two Stallions Fighting Spanner Sculpture. Bushie on Flickr. https://www.flickr.com/photos/bushie/4083544951

3. Jean-Martin Charcot versus Charles Bouchard

The French Neurologist Jean-Martin Charcot is considered by many to be the father of modern neurology. Charles Bouchard on the other hand was a student of Charcot. Things fell apart between the two as soon as Bouchard became a professor. No Nobel prizes at stake here-their feud revolved around a brutal struggle for power and influence. Even though Bouchard got the upper hand, history hasn’t remembered him as well as it has Charcot. Just by the way, Charcot may have also had a simmering rivalry with Jules Joseph Dejerine! I am not quite sure what that says about the personalities at the crucible of neurology.

Fight of the Metal Stallions 4-15. Don Graham on Flickr. https://www.flickr.com/photos/23155134@N06/26855754985/

4. Vladimir Bekhterev versus Ivan Pavlov

Vladimir Bekhterev is not a household name, but the Russian neurologist is instrumental to defining the role of the hippocampus in memory, and indeed has an eponymous non-neurological disease known as Ankylosing spondylitis. Bekhterev had a simmering conflict with his fellow countryman and physiologist Ivan Pavlov. And this had to do, unsurprisingly, with their rather similar theories of conditioned reflexes. It did not help that they both had “oversized and confrontational personalities“. This is one rivalry that blew out of all proportions, spilling into open enmity.

Horse Fight. Sam Howzit on Flickr. https://www.flickr.com/photos/aloha75/4024092009

5. Camillo Golgi versus Santiago Ramon y Cajal

This rivalry is between two people who shared the Nobel Prize in Medicine in 1906. It was at the prize-giving ceremony that the Italian anatomist Camillo Golgi maliciously shredded his co-recipient, the Spanish Santiago Ramon y Cajal. The stakes in this rivalry were very high for neuroscience, as it concerned the fundamental structure of the nervous system. Golgi originally developed the staining method which made neurones visible, but Cajal refined and improved it. He then went on to demonstrate that neurones do not form seamless interconnected cells, firing in all directions, as Golgi argued. Rather, he found neurones to be individual cells firing in one direction. Cajal’s neuron doctrine was the eventual winner in this one.

By Albert de Balleroy – http://www.latribunedelart.com/spip.php?page=docbig&id_document=11895, Public Domain, Link

 6. Ambroise Pare versus Andreas Vesalius

This is a rivalry that played out in royalty. The French surgeon Ambroise Pare was already recognised for refining the treatment of battlefield wounds and amputations. And he later became the official surgeon to King Henry. The Spanish Andreas Vesalius, on the other hand, had established his fame with human anatomy, and he was the official physician to King Philip. His defining work is the highly regarded De Humani Corporis Fabrica. In this very scientific rivalry, devoid of ego, the two giants explored their different approaches to the diagnosis and treatment of head injury. And their vehicle for this was the fatal head injury sustained by King Henri during a jousting tournament. Pare’s countercoup injury theory won the day at post-mortem.

By George Stubbshere / здесь, Public Domain, Link

 7. Paul Broca versus Marc Dax

This is a rivalry between two giants of French neuroscience, and it is all about who got there first. Localisation of speech and language to the left hemisphere is now generally attributed to the work of Paul Broca. In recognition of this, the brain’s speech area, area 44, is named after Broca. By some accounts however, there was another pretender to the throne in the form of Marc Dax. It is argued that Dax sent his paper for publication six weeks before Broca published his. And it is even whispered that the establishment connived to delay publishing Dax’s paper, to the advantage of Broca. After his death, Dax’s son, Gustave, tried valiantly but unsuccessfully to convince French Academy of Sciences and to the French Academy of Medicine to acknowledge his father. Some are arguing that Broca and Dax should share the recognition, calling for the theory of lateralisation of language to be renamed ‘the theory of Dax-Broca‘.

By Hendrik Hondius I (Flanders, Duffel, 1573-circa 1649) – Image: http://collections.lacma.org/sites/default/files/remote_images/piction/ma-31723256-O3.jpgGallery: http://collections.lacma.org/node/234686 archive copy at the Wayback Machine (archived on 22 January 2019), Public Domain, Link

***

Undoubtedly similar rivalries are still playing out today, but perhaps in a more restrained way. As the low lying fruit have all been picked, current squabbles are frequently banal. But they are not always harmless as indicated by the St George’s Hospital heart unit feud. But healthy rivalries help the progress of science, pushing the competing rivals to better refine and defend their theories.

 

By Giuseppe Castiglionehttp://theme.npm.edu.tw/npmawards/langshining/pages/giuseppecastiglione/ch/page-4.html#main, Public Domain, Link

You may explore more rivalries in the following sources I used for this blog post:

Do you have any rivalries to share? Please drop a comment!

Depression and the shrinking seahorses in the brain

Seahorses are beautiful creatures. The biologists convince us that seahorses are fish, even if they don’t look anything like fish. They also tell us, intriguingly, that seahorses are monogamous and the males do the childbearing.

By © Hans Hillewaert, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=22106851
By © Hans Hillewaert, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=22106851

But why is a neurologist talking about seahorses. It’s all in the name. The Latin name for seahorse is hippocampus , derived from hippos for horse, and kampos for sea monster. Where biologists saw fish, the ancients saw monsters. And you really can’t blame them…take a closer look

By Gervais et Boulart - Les poissons Gervais, H., Public Domain, https://commons.wikimedia.org/w/index.php?curid=19157222
By Gervais et Boulart – Les poissons Gervais, H., Public Domain, https://commons.wikimedia.org/w/index.php?curid=19157222

Deep in the brain is a structure also called the hippocampus, one on each side. The hippocampus plays a central role in memory, and it is considered by some to be the brain’s emotional centre.

By Images are generated by Life Science Databases(LSDB). - from Anatomography, website maintained by Life Science Databases(LSDB).You can get this image through URL below. 次のアドレスからこのファイルで使用している画像を取得できますURL., CC BY-SA 2.1 jp, https://commons.wikimedia.org/w/index.php?curid=7887124
By Images are generated by Life Science Databases(LSDB). – from Anatomography, website maintained by Life Science Databases(LSDB).You can get this image through URL below. 次のアドレスからこのファイルで使用している画像を取得できますURL., CC BY-SA 2.1 jp, https://commons.wikimedia.org/w/index.php?curid=7887124

It is no mystery why neuroanatomists name this important part of the brain after the seahorse, the resemblance is eerily striking.

By Hippocampus_and_seahorse.JPG: Professor Laszlo Seressderivative work: Anthonyhcole (talk) - Hippocampus_and_seahorse.JPG, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=9451294
By Hippocampus_and_seahorse.JPG: Professor Laszlo Seressderivative work: Anthonyhcole (talk) – Hippocampus_and_seahorse.JPG, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=9451294

Neurologists are passionate about the hippocampus for various reasons. In people with memory complaints, for example, hippocampal atrophy may predict the development of Alzheimer’s disease . A shrunken hippocampus is also seen in some forms of epilepsy. Neurologists therefore endlessly harangue their neuroradiology colleagues to look closely at their patients’ brain MRI scans, and to tell them that the hippocampus is shrunken…even if it’s just a little bit smaller. Unfortunately for the neuroradiologists, the MRI scans do not come colour-coded as in the illustrative scan below.

By Amber Rieder, Jenna Traynor - Own work, CC0, https://commons.wikimedia.org/w/index.php?curid=16393748
By Amber Rieder, Jenna Traynor – Own work, CC0, https://commons.wikimedia.org/w/index.php?curid=16393748

This blog post is however about major depression, and not about epilepsy or dementia. Depression, that bad feeling we all feel every now and then is frustrating, but major depression is devastating. And we now know that it is accompanied by major alterations in the structure of the brain. And, yes, the changes are in the hippocampus. I got interested in this subject when I came across a piece in Neurology News reporting that people with depression have a smaller hippocampus. 

depression-242024_1280

The association of depression with hippocampal atrophy is however an old one. Proceedings of the National Academy of Science (PNAS) reviewed the relationship in an editorial from 2011 titled Depression, antidepressants, and the shrinking hippocampus. The author addressed the unresolved puzzle…which of the two came first. Reminiscent of the chicken and egg scenario, it is not clear if the hippocampal atrophy causes depression, or vice versa. To add to the puzzle, the paper conjectured the possibility of a third, unknown agent, causing both the depression and the small hippocampus.

Depression. Shattered.art66 on Flikr. https://www.flickr.com/photos/shattered_art/3369289879
Depression. Shattered.art66 on Flikr. https://www.flickr.com/photos/shattered_art/3369289879

This question was the focus of a meta-analysis published in Molecular Psychiatry this year. It reviewed the brain imaging data of 15 studies, involving about 1700 people with major depression. Titled Subcortical brain alterations in major depressive disorder, the authors confirmed the link between depression and hippocampal atrophy, and also showed that the shrinkage is worse in those who developed depression at an early age, and in those who have had frequent episodes of depression.

5 stages of grief (Depression) #4. COCOMARIPOSA on Flikr. https://www.flickr.com/photos/8463160@N08/1790592784
5 stages of grief (Depression) #4. COCOMARIPOSA on Flikr. https://www.flickr.com/photos/8463160@N08/1790592784

Does depression lead to hippocampal atrophy? The meta-analyses hinted so, but there were too many caveats for the authors to arrive at a definitive conclusion. They admit that more needs to be done to unravel depression….leaving the mystery of the shrinking seahorses to continue to another day.

 

How bright is the future for Alzheimer’s disease?

Alzheimer’s disease (AD) is scary. It is the most prevalent cause of dementia, and the name strikes terror, especially to those with a close family history of the condition. It is disturbing when a person loses the concept of ‘self’. It is devastating when parents fail to recognise their children.

Any progress in finding the cause or the cure for this neurodegenerative disease should therefore be celebrated. Following on my previous post, Alzheimer’s disease: a few curious things, here are my top 10 breakthroughs giving hope for Alzheimer’s disease.

Deep brain stimulation (DBS)

By Andreashorn - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=40251125
By AndreashornOwn work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=40251125

 

I have waxed lyrical on the widening influence of neurostimulation in the context of epilepsy, stroke and vagus nerve stimulation (VNS). I was however taken aback by the potential role of deep brain stimulation (DBS) in dementia. This headline from Alzheimers.net reports the Benefits of Deep Brain Stimulation for Alzheimer’sand refers to a study published in eLife. This doesn’t sound a very ‘peer-reviewed’ source, but the title is scientific enough: Ventromedial prefrontal cortex stimulation enhances memory and hippocampal neurogenesis in the middle-aged rats. I should warn you here that most of the studies in this post involve furry little creatures! The study reports that chronic electrical stimulation of the brain increases the activity of memory-related genes, and this in turn increases the number of memory nerves in the hippocampus. Alzheimers.net puts it bluntly-Using Deep Brain Stimulation to Create New Brain Cells.

Iron-reducing treatments

By Vaccinationist - PubChem, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=43392593
By VaccinationistPubChem, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=43392593

 

Based on a premise that high brain iron levels are related to the pathology in Alzheimer’s disease, researchers have looked at iron reducing therapies. This isn’t a new idea because an article in Lancet from 1991 was titled Intramuscular desferrioxamine in patients with Alzheimer’s disease. This study showed that the progression of Alzheimer’s disease could be slowed down by reducing the iron levels in the brain. New Scientist has brought this therapeutic strategy back into contention in its article titled Iron levels in brain predict when people will get Alzheimer’s. The article tantalisingly refers to a link between high iron levels and ApoE4, a gene associated with Alzheimer’s disease. Watch this space.

Ultrasound therapy

By Unknown - Popular Science Monthly Volume 13, Public Domain, https://commons.wikimedia.org/w/index.php?curid=11085835
By UnknownPopular Science Monthly Volume 13, Public Domain, https://commons.wikimedia.org/w/index.php?curid=11085835

 

New Alzheimer’s treatment fully restores memory function, so blares this headline in Science Alert. It refers to a study in mice which shows that focused therapeutic ultrasound stimulates microglia, the cells responsible for clearing the brain’s waste products. The paper, published in Science Translational Medicine, is titled Scanning ultrasound removes amyloid-β and restores memory in an Alzheimer’s disease mouse model. The authors report that that by clearing amyloid, this technique restored memory in about 75% of mice models of Alzheimer’s disease. Human trials must surely beckon.

Dampening amyloid production

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12274694
By NephronOwn work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=12274694

 

The idea of dampening the production of amyloid comes from the discovery of a new chemical pathway in the brain; I didn’t realise there were any more pathways left to discover! My ignorance was dispelled by this article in MNT titled A newly discovered molecular feedback process may protect the brain against Alzheimer’s. The article discusses WAVE-1, a protein which is central to a pathway involved in ß-amyloid production. How could scientists could suppress this pathway and improve the clearance of ß-amyloid? By somehow enhancing an inhibitory feedback loop thereby reducing WAVE-1 production. The scientific details are published in Nature Medicine titled APP intracellular domain–WAVE1 pathway reduces amyloid-β production

Monoclonal antibodies

B0007277 Monoclonal antibodies Anna Tanczos. Wellcome Images images@wellcome.ac.uk http://images.wellcome.ac.uk
B0007277 Monoclonal antibodies
Anna Tanczos. Wellcome Images
images@wellcome.ac.uk
http://images.wellcome.ac.uk

 

It would be surprising if monoclonal antibodies did not crop up in this post, being the rage in many other diseases. The monoclonal antibody raising hopes in Alzheimer’s disease is Solanezumab. I came across this in Russia Today (yes…RT) in an article titled Alzheimer’s breakthrough? First ever drug found that may slow disease. ‘First ever’ is obviously hype, but there does seem to be some benefit of Solanezumab, even if this is restricted to those with early disease.  The phase 3 trial of Solanezumab, called EXPEDITION 3, will study this effect further. More hope, less hype!

Boosting the brain’s immune system

B0007277 Monoclonal antibodies Anna Tanczos. Wellcome Images images@wellcome.ac.uk http://images.wellcome.ac.uk
B0007277 Monoclonal antibodies
Anna Tanczos. Wellcome Images
images@wellcome.ac.uk
http://images.wellcome.ac.uk

 

Microglia, the brain’s waste disposal cells, also play a key role in it’s immune system. In this way they protect the brain from damage by ß-amyloid. This immune function is however countered by EP2, a prostaglandin receptor protein found on the surface of the microglia. In other words EP2 functions to restrict the activity of the microglia. Researchers have now shown that the nuisance effect of EP2 could be blocked, as reported in an article titled Prostaglandin signaling suppresses beneficial microglial function in Alzheimer’s disease models, and published in Journal of Clinical Investigation. Enhancing the activity of microglia therefore raises hope for the treatment for Alzheimer’s disease… if it could be translated to humans.

Neurotrophic factors

Brain Aging. Kalvicio de las Nieves on Flikr. https://www.flickr.com/photos/118316968@N08/19444505382
Brain Aging. Kalvicio de las Nieves on Flikr. https://www.flickr.com/photos/118316968@N08/19444505382

 

What if we could boost the activity of cells that have not yet been affected by Alzheimer’s disease? An experimental drug called J147 might just do that. According to researchers, J147 is a neurotrophic drug which enhances nerve activity in mice. The research, appropriately published in the journal Aging, shows that J147 improves cognitive function in mice which have been modified to age fast. The article is titled A comprehensive multiomics approach toward understanding the relationship between aging and dementia. I personally prefer the headline in Neuroscience News which simply says Experimental Alzheimer’s Drug Slows Clock on Key Aspects of Aging. Too soon to speculate, but could we be talking age reversal here? Perhaps competition for klotho.

Enhancing proteasome activity

By User:KGH - User:KGH, <a href="http://creativecommons.org/licenses/by-sa/3.0/" title="Creative Commons Attribution-Share Alike 3.0">CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=552918
By User:KGHUser:KGH, <a href=”http://creativecommons.org/licenses/by-sa/3.0/&#8221; title=”Creative Commons Attribution-Share Alike 3.0 
“>CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=552918

 

We can’t get too far away from waste clearance in this post. This time it’s a drug called Rolipram which seems to enhance the brains waste disposal system. It does this by increasing the activity of proteasomes. Neuroscience News describes a proteasome as ‘a hollow, cylindrical structure which chews up defective proteins into smaller pieces that can be recycled into new proteins needed by a cell‘. The scientific paper is published in Nature Medicine titled Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling. The authors show that Rolipram also reduces the levels of tau, another toxic product involved in Alzheimer’s disease. For an easier read see the Neuroscience News article titled Slowing Alzheimer’s by Speeding Up Brain’s Waste Disposal.

Gene therapy

There is no getting away from it, and gene therapy had to crop up in this post. And yes, it may have a role in the future of Alzheimer’s disease. Researchers genetically treated 10 Alzheimer’s disease patients using nerve growth factor (NGF) gene, and then waited and waited, …and then studied the brains of the subjects. They reported their findings the Journal of the American Medical Association (JAMA) under the title Nerve Growth Factor Gene Therapy Activation of Neuronal Responses in Alzheimer Disease. The details of the study are rather complicated, but it appears the nerve growth factor treatment triggered nerve growth. Doesn’t sound like rocket science but imagine the potential. I only wished they had used a more straightforward title. I prefer the layman’s version in The Guardian simply titled Gene therapy rescues dying cells in the brains of Alzheimer’s patients. Scientific journals really need better headline writers!

Reprogramming astroglia

A cocktail mixture which transforms the brain’s supporting cells into proper nerve cells? Not science fiction it seems. A group of scientists have developed a mixture which could reprogram glial cells into functional brain cells. I came across this in Neurology Times under the title Transforming Glial Cells. For a change, the original research paper is well headlined; it is published in Cell under the title Small Molecules Efficiently Reprogram Human Astroglial Cells into Functional Neurons. The authors show that the cocktail of nine small molecules do the trick by inhibiting glial pathways and activating neuronal pathways. And this all happens within 8-10 days! Too good to be true? Hopefully not.

 

Looking for more? Here are 13 headlines to further raise the spirits of people with Alzheimer’s disease:

Please share your thoughts

Are magnets transforming neurological practice?

The armoury of the neurologist is traditionally a cocktail of tablets and injections. The neurosurgeons and neuroradiologists seem to have all the fancy gadgets. This may however be changing with techniques that are gradually creeping into neurological practice. One such technique is transcranial magnetic stimulation (TMS). This is a non-invasive method of stimulating specific parts of the brain using a magnetic field generator or coil.

"Transcranial magnetic stimulation" by Eric Wassermann, M.D. - Wassermann, Eric. Transcranial Brain Stimulation. Behavioral Neurology Unit. National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States Department of Health and Human Services. Archived from the original on 2013-10-29. Retrieved on 2013-10-29.. Licensed under Public Domain via Commons - https://commons.wikimedia.org/wiki/File:Transcranial_magnetic_stimulation.jpg#/media/File:Transcranial_magnetic_stimulation.jpg
“Transcranial magnetic stimulation” by Eric Wassermann, M.D. – Wassermann, Eric. Transcranial Brain Stimulation. Behavioral Neurology Unit. National Institute of Neurological Disorders and Stroke, National Institutes of Health, United States Department of Health and Human Services. Archived from the original on 2013-10-29. Retrieved on 2013-10-29.. Licensed under Public Domain via Commons – https://commons.wikimedia.org/wiki/File:Transcranial_magnetic_stimulation.jpg#/media/File:Transcranial_magnetic_stimulation.jpg

 

The classical neurological application of TMS is in the treatment and prevention of migraine. The role of TMS in migraine has been fairly well-studied although the impact on symptoms is modest. There is however enough evidence to convince the National Institute of Health and Care Excellence to issue NICE guidelines on TMS. These, as expected, prescribed hope and caution in equal measure.

A potential application of TMS is in Parkinson’s disease. A recent systematic review and meta-analysis in JAMA Neurology is fairly convincing that TMS improves the motor symptoms of Parkinson’s disease

"Basal ganglia in treatment of Parkinson's" by Mikael Häggström, based on image by Andrew Gillies/User:Anaru - Derivative of File:Basal ganglia circuits.png. Licensed under CC BY-SA 3.0 via Commons - https://commons.wikimedia.org/wiki/File:Basal_ganglia_in_treatment_of_Parkinson%27s.png#/media/File:Basal_ganglia_in_treatment_of_Parkinson%27s.png
“Basal ganglia in treatment of Parkinson’s” by Mikael Häggström, based on image by Andrew Gillies/User:Anaru – Derivative of File:Basal ganglia circuits.png. Licensed under CC BY-SA 3.0 via Commons – https://commons.wikimedia.org/wiki/File:Basal_ganglia_in_treatment_of_Parkinson%27s.png#/media/File:Basal_ganglia_in_treatment_of_Parkinson%27s.png

What of TMS as a cognitive enhancer? I came across the report that TMS may boost memory in Gizmag. OK it’s not a neurology journal but it made a more exciting headline than the original study published in Science  under the elusive title targeted enhancement of cortical-hippocampal brain networks and associative memory. In simple language, TMS may enhance the neural networks in the hippocampus, the brains memory hub. Whilst the study was carried out in people with normal memory, there are implications for cognitive disorders such as Alzheimer’s disease if the potential and promise of TMS are realised.

"Magnet0873" by Newton Henry Black - Newton Henry Black, Harvey N. Davis (1913) Practical Physics, The MacMillan Co., USA, p. 242, fig. 200. Licensed under Public Domain via Commons - https://commons.wikimedia.org/wiki/File:Magnet0873.png#/media/File:Magnet0873.png
“Magnet0873” by Newton Henry Black – Newton Henry Black, Harvey N. Davis (1913) Practical Physics, The MacMillan Co., USA, p. 242, fig. 200. Licensed under Public Domain via Commons – https://commons.wikimedia.org/wiki/File:Magnet0873.png#/media/File:Magnet0873.png

 

A further surprising application of TMS, potential of course, is in dyslexia. This is an emerging field, still under investigation, but imagine the potential this will unleash! There is a helpful review article in Neuroimmunology and Neuroinflammation which discusses the role of rapid rate TMS in the treatment of dyslexia.

"Dislexia nens" by cuidado infantil - cuidadoinfantil.net. Licensed under CC BY-SA 3.0 via Wikimedia Commons - https://commons.wikimedia.org/wiki/File:Dislexia_nens.jpg#/media/File:Dislexia_nens.jpg
“Dislexia nens” by cuidado infantil – cuidadoinfantil.net. Licensed under CC BY-SA 3.0 via Wikimedia Commons – https://commons.wikimedia.org/wiki/File:Dislexia_nens.jpg#/media/File:Dislexia_nens.jpg

 

We’re not quite there yet but there is hope for the neurological arsenal; who knows, we may soon dispense with all these difficult to swallow pills and cumbersome to deliver injections!

 

Medicine 01 by Taki Steve on Flikr. https://www.flickr.com/photos/13519089@N03/4746653392
Medicine 01 by Taki Steve on Flikr. https://www.flickr.com/photos/13519089@N03/4746653392

Interested in delving deeper into TMS?

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

neurochecklists-image

6 exciting neuroscience discoveries that will shape neurology

Allan Ajifo on Flikr. https://www.flickr.com/photos/125992663@N02/14601014695
Allan Ajifo on Flikr. https://www.flickr.com/photos/125992663@N02/14601014695

 

The brain is a mystery and that is why neurologists find it fascinating. The more we know, the more it tantalises us with its hidden gems. Great neurologists have waxed lyrical about the ability of the brain to elude all efforts to fully understand it. Santiago Ramon y Cajal for instance says:

“The brain is a world

consisting of a number of unexplored continents

and great stretches of unknown territory” 

Non-neurologists are similarly awed by the brain. Emerson M. Pugh for example says:

“If the human brain were so simple that we could understand it,

we would be so simple that we couldn’t”

Neuroscience and neuroanatomy are at the forefront of exploring this great unknown; the research output from these fields is mind-boggling (pardon the intended pun). But which recent findings are most likely to change neurological practice in the near future? Here are my top 6.

1. Newly discovered brain lymphatic system

"Gray602" by Henry Vandyke Carter - Henry Gray (1918) Anatomy of the Human Body (See "Book" section below)Bartleby.com: Gray's Anatomy, Plate 602. Licensed under Public Domain via Commons - https://commons.wikimedia.org/wiki/File:Gray602.png#/media/File:Gray602.png
“Gray602” by Henry Vandyke Carter – Henry Gray (1918) Anatomy of the Human Body (See “Book” section below)Bartleby.com: Gray’s Anatomy, Plate 602. Licensed under Public Domain via Commons – https://commons.wikimedia.org/wiki/File:Gray602.png#/media/File:Gray602.png

A recent report that researchers have discovered a previously unknown lymphatic system in the brain is to say the least shocking. That these lymphatic channels have eluded the sharpest eyes and most focussed microscopes for centuries goes to show how mysterious the brain indeed is. Why has it stayed undiscovered for so long? Apparently because it is tucked behind a major blood vessel! Hiding in plain sight says one review article. The discovery is so important that one article says it will have the scientists rewriting textbooks. 

The finding however raises hope of better treatments for some neurological diseases. Because the lymphatic system is closely linked to the immune system, multiple sclerosis (MS) is one potential beneficiary of this discovery. Because lymphatics also act as drainage systems, there are implications for conditions such as Alzheimer’s Disease (AD). Hopefully this brain lymphatic system could be manipulated to clear the accumulated abnormal proteins that cause AD and other neurodegenerative diseases.

2. Newly discovered brain networks

"White Matter Connections Obtained with MRI Tractography" by Xavier Gigandet et. al. - Gigandet X, Hagmann P, Kurant M, Cammoun L, Meuli R, et al. (2008) Estimating the Confidence Level of White Matter Connections Obtained with MRI Tractography. PLoS ONE 3(12): e4006. doi:10.1371/journal.pone.0004006. Licensed under CC BY 2.5 via Commons - https://commons.wikimedia.org/wiki/File:White_Matter_Connections_Obtained_with_MRI_Tractography.png#/media/File:White_Matter_Connections_Obtained_with_MRI_Tractography.png
“White Matter Connections Obtained with MRI Tractography” by Xavier Gigandet et. al. – Gigandet X, Hagmann P, Kurant M, Cammoun L, Meuli R, et al. (2008) Estimating the Confidence Level of White Matter Connections Obtained with MRI Tractography. PLoS ONE 3(12): e4006. doi:10.1371/journal.pone.0004006. Licensed under CC BY 2.5 via Commons – https://commons.wikimedia.org/wiki/File:White_Matter_Connections_Obtained_with_MRI_Tractography.png#/media/File:White_Matter_Connections_Obtained_with_MRI_Tractography.png

 

The brain’s extensive connections is one of its enduring and fascinating mysteries. The winding fibers and tracts, meandering and looping around each other, demonstrate the brain’s complexity. As soon as we think we have grasped it all, along comes a discovery that causes a paradigm shift. This is illustrated by the report of the discovery of a new brain network involved in memory processing. This Parietal Memory Network (PMN), in the brain’s left hemisphere, responds differentially to new and to old information. This may have relevance for cognitive disorders such as Alzheimer’s Disease (AD). For the more technical details of the network, the paper is published in the journal Trends in Cognitive Neuroscience.

3. Newly discovered brain connection

Synapse by Peter Morgan on Flikr. https://www.flickr.com/photos/moogan/5997439279
Synapse by Peter Morgan on Flikr. https://www.flickr.com/photos/moogan/5997439279

 

In a similar vein is the discovery of previously unknown brain fiber tracts called the vertical occipital fasciculus (VOF). This new ‘brain corridor‘ is involved in visual processing. The research paper, published in the Proceedings of the National Academy of Science (PNAS), says the VOF is important in the perception of words and faces, amongst other things, and is ‘involved in the control of eye movements, attention, and motion perception. The main benefit of this finding is the improvement of our understanding of how the brain learns to read.

4. Newly discovered brain activity in deep coma

By Wojder (Own work(own work by uploader)) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 4.0-3.0-2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/4.0-3.0-2.5-2.0-1.0)], via Wikimedia Commons
By Wojder (Own work(own work by uploader)) [GFDL (http://www.gnu.org/copyleft/fdl.html) or CC BY-SA 4.0-3.0-2.5-2.0-1.0 (http://creativecommons.org/licenses/by-sa/4.0-3.0-2.5-2.0-1.0)%5D, via Wikimedia Commons

The common assumption that the electrical activity of the comatose brain flatlines on the electroencephalogram (EEG) now appears to be a misconception. This is according to a report of the discovery of a previously unknown electrical brain activity in deep coma suggests. One journal reported this as the discovery of life after brain death!

These electrical waves, seen in deep coma, are called Nu complexes. They are well-described in the original paper in PLoS One. This finding will alter our definition of brain death which relies very much on the absence of organised brain electrical activity. Another implication is for patients whose medical conditions require that they are put into a coma; this finding will potentially guide the anaesthetist to apply the best form of induced coma. 

5. Newly discovered brain cell type 

 

I thought I learnt all the different types brain cells or neurones that exist when I was in medical school. The mysterious brain however has a joker at every corner. The report of the discovery of a new type of neurone should come as a surprise, but by now we have learnt not to be shocked by new brain discoveries. The strange thing about these cells, found in the hippocampus of the the brains of mice, is that they have direct connections between their axons (the single long tail) and their dendrites (the smaller hair like projections). This connection by-passes the nerve body; this direct connection enhances the strength of the signals the cell generates. The reason for this peculiarity is not clear but, because the hippocampus is the seat of memory, I guess there are implications for cognitive disorders.

6. Newly discovered brain repair enhancers

We know that the brain repairs itself (neuroplasticity), and that brain fibers make new connections even if this occurs very slowly. What is new is that these processes can be enhanced or accelerated by external agents. Two interesting substances recently reported are psilocybin and curry. Yes, healing mushrooms and spices!

It appears that Psilocybin (psychedelic mushrooms) can establish stable connections between parts of the brain which do not normally communicate well. The research on this is published under the title ‘Homological Scaffolds of Brain Functional Networks‘. The paper describes how psilocybin helps in nerve re-wiring with the potential implications for the treatment of depression and addiction. A bit paradoxical, using an addictive substance to treat addiction; but hey, this is the brain we are talking about!

"Curcuma longa roots" by Simon A. Eugster - Own work. Licensed under CC BY-SA 3.0 via Commons - https://commons.wikimedia.org/wiki/File:Curcuma_longa_roots.jpg#/media/File:Curcuma_longa_roots.jpg
“Curcuma longa roots” by Simon A. Eugster – Own work. Licensed under CC BY-SA 3.0 via Commons – https://commons.wikimedia.org/wiki/File:Curcuma_longa_roots.jpg#/media/File:Curcuma_longa_roots.jpg

 

Curry on the other hand contains tumeric which contains tumerone. Tumerone has now been shown to help with nerve growth repair, and it does this by causing proliferation of brain nerve cells. The research itself is titled ‘Aromatic-tumerone induces neural stem cell proliferation in vitro and in vivo‘. It is a study in rats, but are human brains very different? Potential beneficiaries are all the neurodegenerative diseases which neurologists have singularly failed to reverse.

Enough food for thought,  but if you want to keep up with neuroscience findings, here are the most popular neuroscience blogs.

+++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++++

neurochecklists-image